Friday, October 29, 2010
dabigatran warfarin
Dabigatran Is Approved for Atrial Fibrillation
Will dabigatran replace warfarin?
On October 19, 2010, dabigatran (Pradaxa; an oral thrombin inhibitor) was approved by the FDA to lower risk for thrombus and stroke in patients with atrial fibrillation. Unlike warfarin, dabigatran is given in fixed twice-daily doses and does not require international normalized ratio (INR) monitoring. The approval comes on the heels of the RE-LY trial, in which >18,000 people were randomized to one of two twice-daily doses of dabigatran (110 mg or 150 mg) or to dose-adjusted warfarin and were followed for a median of 2 years (JW Cardiol Sep 1 2009).
In RE-LY, risk for systemic embolism or stroke was 1.7% in the warfarin group, 1.5% in the 110-mg group, and significantly lower — 1.1% — in the 150-mg group. The rate of major bleeding was significantly lower in the 110-mg group (2.7% annually) than in the warfarin group (3.4%) or in the 150-mg group (3.1%). Dyspepsia was almost twice as common with dabigatran as with warfarin, and the rate of myocardial infarction (MI) was higher in both dabigatran groups (0.5% annually for warfarin vs. 0.7% in both dabigatran groups).
Comment: The FDA's action gives physicians an alternative to warfarin in patients with atrial fibrillation who are at excess risk for stroke. Interestingly, only the 75-mg and 150-mg capsules were approved for this indication. Dabigatran should not be used in patients with renal dysfunction, severe heart-valve disorders, liver disease, recent stroke, or other conditions that raise risk for hemorrhage; data for other indications, such as mechanical valves, are lacking. MI risk should be monitored closely. Dabigatran also should not be given to pregnant women or patients with clinically significant dyspepsia.
But who should be treated with dabigatran instead of warfarin? Some experts suggest that we have little reason to switch patients with stable INRs who are doing well on warfarin, especially because the yearly cost of dabigatran likely will be thousands of dollars, whereas generic warfarin now is available at some U.S. pharmacies for pennies a day. Of course, the costs of INR monitoring are also relevant, although these might be less important to patients than out-of-pocket drug costs. Only time will tell to what extent dabigatran displaces warfarin and to what extent other emerging alternatives to warfarin (e.g., oral factor Xa inhibitors, such as rivaroxaban) will compete with dabigatran. But, in the meantime, anticipate frank discussions with — and many questions from — patients about the pros and cons of this new drug.
— Kirsten E. Fleischmann, MD, MPH
Published in Journal Watch General Medicine October 28, 2010
Will dabigatran replace warfarin?
On October 19, 2010, dabigatran (Pradaxa; an oral thrombin inhibitor) was approved by the FDA to lower risk for thrombus and stroke in patients with atrial fibrillation. Unlike warfarin, dabigatran is given in fixed twice-daily doses and does not require international normalized ratio (INR) monitoring. The approval comes on the heels of the RE-LY trial, in which >18,000 people were randomized to one of two twice-daily doses of dabigatran (110 mg or 150 mg) or to dose-adjusted warfarin and were followed for a median of 2 years (JW Cardiol Sep 1 2009).
In RE-LY, risk for systemic embolism or stroke was 1.7% in the warfarin group, 1.5% in the 110-mg group, and significantly lower — 1.1% — in the 150-mg group. The rate of major bleeding was significantly lower in the 110-mg group (2.7% annually) than in the warfarin group (3.4%) or in the 150-mg group (3.1%). Dyspepsia was almost twice as common with dabigatran as with warfarin, and the rate of myocardial infarction (MI) was higher in both dabigatran groups (0.5% annually for warfarin vs. 0.7% in both dabigatran groups).
Comment: The FDA's action gives physicians an alternative to warfarin in patients with atrial fibrillation who are at excess risk for stroke. Interestingly, only the 75-mg and 150-mg capsules were approved for this indication. Dabigatran should not be used in patients with renal dysfunction, severe heart-valve disorders, liver disease, recent stroke, or other conditions that raise risk for hemorrhage; data for other indications, such as mechanical valves, are lacking. MI risk should be monitored closely. Dabigatran also should not be given to pregnant women or patients with clinically significant dyspepsia.
But who should be treated with dabigatran instead of warfarin? Some experts suggest that we have little reason to switch patients with stable INRs who are doing well on warfarin, especially because the yearly cost of dabigatran likely will be thousands of dollars, whereas generic warfarin now is available at some U.S. pharmacies for pennies a day. Of course, the costs of INR monitoring are also relevant, although these might be less important to patients than out-of-pocket drug costs. Only time will tell to what extent dabigatran displaces warfarin and to what extent other emerging alternatives to warfarin (e.g., oral factor Xa inhibitors, such as rivaroxaban) will compete with dabigatran. But, in the meantime, anticipate frank discussions with — and many questions from — patients about the pros and cons of this new drug.
— Kirsten E. Fleischmann, MD, MPH
Published in Journal Watch General Medicine October 28, 2010
Wednesday, October 27, 2010
folium zuur
J Psychopharmacol. 2005 Jan;19(1):59-65.
Treatment of depression: time to consider folic acid and vitamin B12.
Coppen A, Bolander-Gouaille C.
MRC Neuropsychiatric Research Laboratory, Epsom, Surrey, UK. acoppen@globalnet.co.uk
Abstract
We review the findings in major depression of a low plasma and particularly red cell folate, but also of low vitamin B12 status. Both low folate and low vitamin B12 status have been found in studies of depressive patients, and an association between depression and low levels of the two vitamins is found in studies of the general population. Low plasma or serum folate has also been found in patients with recurrent mood disorders treated by lithium. A link between depression and low folate has similarly been found in patients with alcoholism. It is interesting to note that Hong Kong and Taiwan populations with traditional Chinese diets (rich in folate), including patients with major depression, have high serum folate concentrations. However, these countries have very low life time rates of major depression. Low folate levels are furthermore linked to a poor response to antidepressants, and treatment with folic acid is shown to improve response to antidepressants. A recent study also suggests that high vitamin B12 status may be associated with better treatment outcome. Folate and vitamin B12 are major determinants of one-carbon metabolism, in which S-adenosylmethionine (SAM) is formed. SAM donates methyl groups that are crucial for neurological function. Increased plasma homocysteine is a functional marker of both folate and vitamin B12 deficiency. Increased homocysteine levels are found in depressive patients. In a large population study from Norway increased plasma homocysteine was associated with increased risk of depression but not anxiety. There is now substantial evidence of a common decrease in serum/red blood cell folate, serum vitamin B12 and an increase in plasma homocysteine in depression. Furthermore, the MTHFR C677T polymorphism that impairs the homocysteine metabolism is shown to be overrepresented among depressive patients, which strengthens the association. On the basis of current data, we suggest that oral doses of both folic acid (800 microg daily) and vitamin B12 (1 mg daily) should be tried to improve treatment outcome in depression.
PMID: 15671130 [PubMed - indexed for MEDLINE]
Treatment of depression: time to consider folic acid and vitamin B12.
Coppen A, Bolander-Gouaille C.
MRC Neuropsychiatric Research Laboratory, Epsom, Surrey, UK. acoppen@globalnet.co.uk
Abstract
We review the findings in major depression of a low plasma and particularly red cell folate, but also of low vitamin B12 status. Both low folate and low vitamin B12 status have been found in studies of depressive patients, and an association between depression and low levels of the two vitamins is found in studies of the general population. Low plasma or serum folate has also been found in patients with recurrent mood disorders treated by lithium. A link between depression and low folate has similarly been found in patients with alcoholism. It is interesting to note that Hong Kong and Taiwan populations with traditional Chinese diets (rich in folate), including patients with major depression, have high serum folate concentrations. However, these countries have very low life time rates of major depression. Low folate levels are furthermore linked to a poor response to antidepressants, and treatment with folic acid is shown to improve response to antidepressants. A recent study also suggests that high vitamin B12 status may be associated with better treatment outcome. Folate and vitamin B12 are major determinants of one-carbon metabolism, in which S-adenosylmethionine (SAM) is formed. SAM donates methyl groups that are crucial for neurological function. Increased plasma homocysteine is a functional marker of both folate and vitamin B12 deficiency. Increased homocysteine levels are found in depressive patients. In a large population study from Norway increased plasma homocysteine was associated with increased risk of depression but not anxiety. There is now substantial evidence of a common decrease in serum/red blood cell folate, serum vitamin B12 and an increase in plasma homocysteine in depression. Furthermore, the MTHFR C677T polymorphism that impairs the homocysteine metabolism is shown to be overrepresented among depressive patients, which strengthens the association. On the basis of current data, we suggest that oral doses of both folic acid (800 microg daily) and vitamin B12 (1 mg daily) should be tried to improve treatment outcome in depression.
PMID: 15671130 [PubMed - indexed for MEDLINE]
Tuesday, October 26, 2010
dementia
October 18, 2010 — The serum level of bioavailable testosterone (BT) can predict risk for Alzheimer's disease (AD) in older men, new research suggests.
Although low levels of BT were associated with the onset of AD, higher levels may offer protective value against the disease, report the researchers, led by Leung-Wing Chu, MD, chief of geriatric medicine at Queen Mary Hospital at the University of Hong Kong.
"The take home message is we should pay more attention to low testosterone, particularly in people who have signs of cognitive impairment," coinvestigator John Morley, MD, professor of gerontology and director of the Division of Geriatric Medicine at Saint Louis University School of Medicine in Missouri, told Medscape Medical News.
"We found that low testosterone did predict a pretty rapid decline in memory and conversion to Alzheimer's," added Dr. Morley. "So this opens up the possibility of using testosterone as a potential treatment in males who are having early memory problems."
However, he noted that the findings should be viewed with some caution. "We thought the same thing was true with estrogen and then the Women's Health Initiative suggested that at least in some subgroups of women estrogen made them worse not better. So until we have further studies, we just don't know for sure. But we do think it's exciting."
The study was published in the October issue of the Journal of Alzheimer's Disease
Although low levels of BT were associated with the onset of AD, higher levels may offer protective value against the disease, report the researchers, led by Leung-Wing Chu, MD, chief of geriatric medicine at Queen Mary Hospital at the University of Hong Kong.
"The take home message is we should pay more attention to low testosterone, particularly in people who have signs of cognitive impairment," coinvestigator John Morley, MD, professor of gerontology and director of the Division of Geriatric Medicine at Saint Louis University School of Medicine in Missouri, told Medscape Medical News.
"We found that low testosterone did predict a pretty rapid decline in memory and conversion to Alzheimer's," added Dr. Morley. "So this opens up the possibility of using testosterone as a potential treatment in males who are having early memory problems."
However, he noted that the findings should be viewed with some caution. "We thought the same thing was true with estrogen and then the Women's Health Initiative suggested that at least in some subgroups of women estrogen made them worse not better. So until we have further studies, we just don't know for sure. But we do think it's exciting."
The study was published in the October issue of the Journal of Alzheimer's Disease
Monday, October 25, 2010
atrial fibrillation A.F.
Steroids may help prevent post-ablation AF recurrence
21 October 2010
MedWire News: Short-term, low-dose corticosteroid therapy may be a useful adjunct to catheter ablation for atrial fibrillation (AF), offering a reduction in both short- and medium-term AF recurrence, a clinical study suggests.
The research was undertaken by a Japanese team and tested the value of corticosteroid administration in patients undergoing pulmonary vein isolation (PVI) for paroxysmal AF.
There is much evidence of a mechanistic link between inflammatory processes and the development of AF, explain Takashi Koyama (University of Tsukuba, Japan) and co-authors. Yet, to date, no study has examined the hypothesis that corticosteroids given after PVI might negate AF recurrence by preventing the post-ablation inflammatory response.
To investigate, the team recruited 125 patients with paroxysmal treatment-refractory AF and randomly assigned them to receive intravenous hydrocortisone 2 mg/kg immediately after the procedure plus oral prednisolone 0.5 mg/kg/day for 3 days post-procedure, or a placebo.
Writing in the Journal of the American College of Cardiology, Koyama et al report that body temperature and C-reactive protein levels – both indicative of inflammatory processes – were significantly lower in the corticosteroid group than in the placebo group in the 3 days following ablation.
In the placebo group, body temperature during the initial 3 days was significantly higher in patients with an immediate recurrence of AF than in other participants. By contrast, in the steroid group there was no difference in body temperature between patients with and without an immediate recurrence.
When comparing AF recurrence between treatment and placebo groups, the rate was significantly lower in the corticosteroid group up to 3 days after the procedure (7% vs 31%) but similar in each group between 4 and 30 days post-procedure (20% vs 18%). Between day 31 and 14 months, the rate was again significantly lower in the corticosteroid group (15% vs 29%).
Kaplan-Meier survival analysis confirmed that the rate of freedom from AF without antiarrhythmic drugs was significantly greater with corticosteroids than with placebo; in multivariate analysis, corticosteroid therapy was an independent predictor of AF recurrence, at a hazard ratio of 0.46.
The authors conclude: “Corticosteroid treatment administered shortly after PVI might halt the relationship between inflammation and rapid atrial arrhythmia formation, which may represent a vicious cycle.”
In an accompanying editorial, Bernard Belhassen (Tel Aviv Sourasky Medical Center, Israel) said the study offers “the first objective evidence that the immediate atrial tachyarrhythmias occurring during the first 3 days after AF ablation are due to an inflammatory response and can be decreased by a short course of corticosteroid therapy.”
However, he admitted that the question of whether corticosteroid therapy should now be used in routine clinical practice or whether to wait for confirmatory studies “is difficult to answer.”
MedWire (www.medwire-news.md) is an independent clinical news service provided by Current Medicine Group, a trading division of Springer Healthcare Limited. © Springer Healthcare Ltd; 2010
J Am Coll Cardiol 2010; 56: 1463–1472
21 October 2010
MedWire News: Short-term, low-dose corticosteroid therapy may be a useful adjunct to catheter ablation for atrial fibrillation (AF), offering a reduction in both short- and medium-term AF recurrence, a clinical study suggests.
The research was undertaken by a Japanese team and tested the value of corticosteroid administration in patients undergoing pulmonary vein isolation (PVI) for paroxysmal AF.
There is much evidence of a mechanistic link between inflammatory processes and the development of AF, explain Takashi Koyama (University of Tsukuba, Japan) and co-authors. Yet, to date, no study has examined the hypothesis that corticosteroids given after PVI might negate AF recurrence by preventing the post-ablation inflammatory response.
To investigate, the team recruited 125 patients with paroxysmal treatment-refractory AF and randomly assigned them to receive intravenous hydrocortisone 2 mg/kg immediately after the procedure plus oral prednisolone 0.5 mg/kg/day for 3 days post-procedure, or a placebo.
Writing in the Journal of the American College of Cardiology, Koyama et al report that body temperature and C-reactive protein levels – both indicative of inflammatory processes – were significantly lower in the corticosteroid group than in the placebo group in the 3 days following ablation.
In the placebo group, body temperature during the initial 3 days was significantly higher in patients with an immediate recurrence of AF than in other participants. By contrast, in the steroid group there was no difference in body temperature between patients with and without an immediate recurrence.
When comparing AF recurrence between treatment and placebo groups, the rate was significantly lower in the corticosteroid group up to 3 days after the procedure (7% vs 31%) but similar in each group between 4 and 30 days post-procedure (20% vs 18%). Between day 31 and 14 months, the rate was again significantly lower in the corticosteroid group (15% vs 29%).
Kaplan-Meier survival analysis confirmed that the rate of freedom from AF without antiarrhythmic drugs was significantly greater with corticosteroids than with placebo; in multivariate analysis, corticosteroid therapy was an independent predictor of AF recurrence, at a hazard ratio of 0.46.
The authors conclude: “Corticosteroid treatment administered shortly after PVI might halt the relationship between inflammation and rapid atrial arrhythmia formation, which may represent a vicious cycle.”
In an accompanying editorial, Bernard Belhassen (Tel Aviv Sourasky Medical Center, Israel) said the study offers “the first objective evidence that the immediate atrial tachyarrhythmias occurring during the first 3 days after AF ablation are due to an inflammatory response and can be decreased by a short course of corticosteroid therapy.”
However, he admitted that the question of whether corticosteroid therapy should now be used in routine clinical practice or whether to wait for confirmatory studies “is difficult to answer.”
MedWire (www.medwire-news.md) is an independent clinical news service provided by Current Medicine Group, a trading division of Springer Healthcare Limited. © Springer Healthcare Ltd; 2010
J Am Coll Cardiol 2010; 56: 1463–1472
Saturday, October 23, 2010
vitamine B12 folium zuur
October 18, 2010 — Both serum homocysteine (tHcy), an amino acid associated with vitamin B12, and holotranscobalamin (holoTC), the biologically active fraction of vitamin B12, may have a role in the development of Alzheimer's disease (AD), the findings of a new Finnish study suggest.
Among a group of elderly subjects followed up for 7 years, elevated baseline serum tHcy concentrations were independently associated with an increased risk of developing AD, whereas higher baseline holoTC values were independently related to a reduced risk for incident AD. No association was observed with folate.
"Our results indicate that vitamin B12 and related metabolites may have a role in Alzheimer's disease, but more research is needed before we can get conclusion on the role of vitamin B12 supplements on neurodegenerative diseases such as Alzheimer's disease," first study author Babak Hooshmand, MD, MSc, of the Aging Research Center, Karolinska Institutet, Stockholm, Sweden, noted in an email to Medscape Medical News.
Their results are published October 19 in Neurology.
Cardiovascular Risk Factors, Aging and Dementia Study
"Most available studies have so far considered tHcy and its main determinants separately in relation to AD," Dr. Hooshmand and colleagues note in their report. Few studies, they add, have investigated the association between holoTC and AD.
Here, they investigated serum tHcy, holoTC, and folate levels simultaneously, as well as putative interactions between them, in relation to AD risk in a subsample of the population-based Cardiovascular Risk Factors, Aging and Dementia study.
The sample comprised 271 community-dwelling subjects, 65 to 79 years old, who were dementia free at baseline and were followed up for up to 7 years for incident AD. During that period, 17 (6.2%) developed the disease.
As expected, subjects who developed AD were older at baseline and had lower body mass index (BMI), lower blood pressure, and a higher frequency of the APOE ε4 allele than those who did not. They also had higher tHcy levels (14.9 vs 12.6 µmol/L) and lower holoTC levels (61.6 vs 93.3 pmol/L) compared with subjects who did not develop AD.
According to the investigators, for each 1-µmol/L increase in the baseline concentration of tHcy, the risk for AD increased by 16% (odds ratio [OR], 1.16; 95% confidence interval [CI], 1.04 – 1.31). On the other hand, for each 1-pmol/L increase in baseline holoTC, the risk for AD was reduced by 2% (OR, 0.980; 95% CI, 0.965 – 0.995).
The results held up in analyses adjusted for several potential confounding factors, including age, sex, education APOE e4 allele, body mass index, Mini-Mental State Examination score, smoking, stroke, and blood pressure.
Adjusting for holoTC attenuated the tHcy-AD link; the OR changed from 1.16 to 1.10 (95% CI, 0.96 – 1.25). The holoTC-AD relationship was less influenced by controlling for tHcy; the OR changed from 0.980 to 0.984 (95% CI, 0.986 – 1.000).
A significant interaction between holoTC and age was observed; the protective effect of holoTC became more pronounced with increasing age (adjusted OR for the interaction, 0.994; 95% CI, 0.989 – 0.998). Adding folate to the analysis did not change any of the results.
Important First Step
This study is "an important initial step relating plasma holoTC to risk of incident dementia and AD," Sudha Seshadri, MD, of Boston University School of Medicine in Massachusetts, writes in a commentary published with the study.
By way of background, Dr. Seshadri notes that, in the 1990s, several observational and cohort studies linked elevated tHcy level with an increased risk for stroke, cognitive decline, and dementia, including AD. Homocysteine can directly promote cerebrovascular disease and neuronal injury through a variety of mechanisms.
The associations with tHcy were "generally more robust than those for B12 levels (vitamin B12 levels indirectly elevating tHcy), so tHcy replaced B12 as the putative risk factor of greater interest," Dr. Seshadri explains.
However, it was subsequently found in clinical trials that lower tHcy levels (via folate administration) did not seem to have a beneficial effect on cognitive outcomes, whether assessed in healthy persons, those with mild cognitive impairment, or those with mild dementia. "Ironically, these results turned scientific interest back to a renewed emphasis on direct adverse effects of B12 deficiency, independent of plasma tHcy," Dr. Seshadri notes.
Going Forward
Dr. Hooshmand and Dr. Seshadri both agree that further study is needed to unravel the vitamin B12 story as it relates to AD, including clinical studies that directly relate holoTC to clinical AD or comprehensively address the relative importance of the interlinked players (B12, tHcy, holoTC, and folate).
"I think that it is an advantage if future studies on B12 and AD include other vitamin B12 indicators, including holotranscobalamin," Dr. Hooshmand told Medscape Medical News.
Dr. Seshadri thinks future vitamin B12 researchers should "either measure holoTC levels or store serum samples to permit this to be done," the researcher said. "I would support further observational studies and clinical trials that relate B12, folate to brain function and look comprehensively at possible intermediate metabolites."
The study was supported by the Karolinska Institutet, the Swedish Research Council for Medical Research, the European Commission Seventh Framework Programme, the Academy of Finland, the Ragnhild and Einar Lundströms Minne Lindhés Foundation, the Stohnes Foundation, the Gamla Tjanarinnor Foundation, and the Dementia Foundation of Sweden. Dr. Hooshmand has disclosed no relevant financial relationships. A complete list of disclosures for the other authors of the study are published with the original article. Dr. Seshadri discloses serving as an editor for the Journal of Alzheimer's Disease and on the editorial board of Stroke and receives research support from the National Institutes of Health.
Neurology. 2010;75:1408-1414.
Among a group of elderly subjects followed up for 7 years, elevated baseline serum tHcy concentrations were independently associated with an increased risk of developing AD, whereas higher baseline holoTC values were independently related to a reduced risk for incident AD. No association was observed with folate.
"Our results indicate that vitamin B12 and related metabolites may have a role in Alzheimer's disease, but more research is needed before we can get conclusion on the role of vitamin B12 supplements on neurodegenerative diseases such as Alzheimer's disease," first study author Babak Hooshmand, MD, MSc, of the Aging Research Center, Karolinska Institutet, Stockholm, Sweden, noted in an email to Medscape Medical News.
Their results are published October 19 in Neurology.
Cardiovascular Risk Factors, Aging and Dementia Study
"Most available studies have so far considered tHcy and its main determinants separately in relation to AD," Dr. Hooshmand and colleagues note in their report. Few studies, they add, have investigated the association between holoTC and AD.
Here, they investigated serum tHcy, holoTC, and folate levels simultaneously, as well as putative interactions between them, in relation to AD risk in a subsample of the population-based Cardiovascular Risk Factors, Aging and Dementia study.
The sample comprised 271 community-dwelling subjects, 65 to 79 years old, who were dementia free at baseline and were followed up for up to 7 years for incident AD. During that period, 17 (6.2%) developed the disease.
As expected, subjects who developed AD were older at baseline and had lower body mass index (BMI), lower blood pressure, and a higher frequency of the APOE ε4 allele than those who did not. They also had higher tHcy levels (14.9 vs 12.6 µmol/L) and lower holoTC levels (61.6 vs 93.3 pmol/L) compared with subjects who did not develop AD.
According to the investigators, for each 1-µmol/L increase in the baseline concentration of tHcy, the risk for AD increased by 16% (odds ratio [OR], 1.16; 95% confidence interval [CI], 1.04 – 1.31). On the other hand, for each 1-pmol/L increase in baseline holoTC, the risk for AD was reduced by 2% (OR, 0.980; 95% CI, 0.965 – 0.995).
The results held up in analyses adjusted for several potential confounding factors, including age, sex, education APOE e4 allele, body mass index, Mini-Mental State Examination score, smoking, stroke, and blood pressure.
Adjusting for holoTC attenuated the tHcy-AD link; the OR changed from 1.16 to 1.10 (95% CI, 0.96 – 1.25). The holoTC-AD relationship was less influenced by controlling for tHcy; the OR changed from 0.980 to 0.984 (95% CI, 0.986 – 1.000).
A significant interaction between holoTC and age was observed; the protective effect of holoTC became more pronounced with increasing age (adjusted OR for the interaction, 0.994; 95% CI, 0.989 – 0.998). Adding folate to the analysis did not change any of the results.
Important First Step
This study is "an important initial step relating plasma holoTC to risk of incident dementia and AD," Sudha Seshadri, MD, of Boston University School of Medicine in Massachusetts, writes in a commentary published with the study.
By way of background, Dr. Seshadri notes that, in the 1990s, several observational and cohort studies linked elevated tHcy level with an increased risk for stroke, cognitive decline, and dementia, including AD. Homocysteine can directly promote cerebrovascular disease and neuronal injury through a variety of mechanisms.
The associations with tHcy were "generally more robust than those for B12 levels (vitamin B12 levels indirectly elevating tHcy), so tHcy replaced B12 as the putative risk factor of greater interest," Dr. Seshadri explains.
However, it was subsequently found in clinical trials that lower tHcy levels (via folate administration) did not seem to have a beneficial effect on cognitive outcomes, whether assessed in healthy persons, those with mild cognitive impairment, or those with mild dementia. "Ironically, these results turned scientific interest back to a renewed emphasis on direct adverse effects of B12 deficiency, independent of plasma tHcy," Dr. Seshadri notes.
Going Forward
Dr. Hooshmand and Dr. Seshadri both agree that further study is needed to unravel the vitamin B12 story as it relates to AD, including clinical studies that directly relate holoTC to clinical AD or comprehensively address the relative importance of the interlinked players (B12, tHcy, holoTC, and folate).
"I think that it is an advantage if future studies on B12 and AD include other vitamin B12 indicators, including holotranscobalamin," Dr. Hooshmand told Medscape Medical News.
Dr. Seshadri thinks future vitamin B12 researchers should "either measure holoTC levels or store serum samples to permit this to be done," the researcher said. "I would support further observational studies and clinical trials that relate B12, folate to brain function and look comprehensively at possible intermediate metabolites."
The study was supported by the Karolinska Institutet, the Swedish Research Council for Medical Research, the European Commission Seventh Framework Programme, the Academy of Finland, the Ragnhild and Einar Lundströms Minne Lindhés Foundation, the Stohnes Foundation, the Gamla Tjanarinnor Foundation, and the Dementia Foundation of Sweden. Dr. Hooshmand has disclosed no relevant financial relationships. A complete list of disclosures for the other authors of the study are published with the original article. Dr. Seshadri discloses serving as an editor for the Journal of Alzheimer's Disease and on the editorial board of Stroke and receives research support from the National Institutes of Health.
Neurology. 2010;75:1408-1414.
Sunday, October 17, 2010
aspirin colorectal cancer
Aspirin for Colorectal Cancer Protection?
Use of low-dose aspirin for 5 years was associated with significantly diminished risk for CRC.
Long-term use of aspirin or other nonsteroidal anti-inflammatory drugs (NSAIDs) is associated with a reduction in colorectal cancer (CRC) incidence and a reduced risk for adenomatous polyps (JW Gastroenterol Mar 28 2008). However, uncertainty remains about the dose and duration of use required for NSAIDs to provide a benefit.
To address this issue, researchers in Scotland prospectively studied aspirin use in 2279 patients with newly diagnosed CRC and 2907 matched controls from the general population. Low-dose aspirin (75 mg) was used by 15.5% of CRC patients and by 18.1% of controls.
Use of low-dose aspirin was associated with diminished risk for CRC, which was evident after 1 year and significant after 5 years (P=0.004 for trend). The effect seemed to increase until 10 years of intake and then leveled off. Taking low-dose aspirin or NSAIDs reduced relative risk for CRC by 20% to 30%; taking low-dose aspirin plus other NSAIDs reduced relative risk even further, by up to 50%. Use of NSAIDs had no effect on CRC-specific survival.
Comment: The results of this study are consistent with findings in terms of the magnitude of risk reduction and the impact of duration of aspirin therapy. They also indicate a significant protective effect even from low-dose aspirin. Previous cost analyses have suggested that the use of aspirin to prevent CRC in the general population is less cost-effective than colonoscopy because of its lower effectiveness and the substantial costs associated with gastrointestinal complications. However, patients (especially those at high risk for CRC) who take low-dose aspirin for cardiovascular protection or other reasons can expect diminished risk for CRC. Although this study did not show any benefit in survival, studies of longer duration have shown that low-dose aspirin use was associated with an overall improvement in CRC mortality. In addition, prior data have suggested that patients who had not previously been taking aspirin, and who then developed prostaglandin-producing CRCs, achieved a survival benefit from aspirin therapy that was initiated after cancer diagnosis.
— Douglas K. Rex, MD
Published in Journal Watch Gastroenterology October 15, 2010
Use of low-dose aspirin for 5 years was associated with significantly diminished risk for CRC.
Long-term use of aspirin or other nonsteroidal anti-inflammatory drugs (NSAIDs) is associated with a reduction in colorectal cancer (CRC) incidence and a reduced risk for adenomatous polyps (JW Gastroenterol Mar 28 2008). However, uncertainty remains about the dose and duration of use required for NSAIDs to provide a benefit.
To address this issue, researchers in Scotland prospectively studied aspirin use in 2279 patients with newly diagnosed CRC and 2907 matched controls from the general population. Low-dose aspirin (75 mg) was used by 15.5% of CRC patients and by 18.1% of controls.
Use of low-dose aspirin was associated with diminished risk for CRC, which was evident after 1 year and significant after 5 years (P=0.004 for trend). The effect seemed to increase until 10 years of intake and then leveled off. Taking low-dose aspirin or NSAIDs reduced relative risk for CRC by 20% to 30%; taking low-dose aspirin plus other NSAIDs reduced relative risk even further, by up to 50%. Use of NSAIDs had no effect on CRC-specific survival.
Comment: The results of this study are consistent with findings in terms of the magnitude of risk reduction and the impact of duration of aspirin therapy. They also indicate a significant protective effect even from low-dose aspirin. Previous cost analyses have suggested that the use of aspirin to prevent CRC in the general population is less cost-effective than colonoscopy because of its lower effectiveness and the substantial costs associated with gastrointestinal complications. However, patients (especially those at high risk for CRC) who take low-dose aspirin for cardiovascular protection or other reasons can expect diminished risk for CRC. Although this study did not show any benefit in survival, studies of longer duration have shown that low-dose aspirin use was associated with an overall improvement in CRC mortality. In addition, prior data have suggested that patients who had not previously been taking aspirin, and who then developed prostaglandin-producing CRCs, achieved a survival benefit from aspirin therapy that was initiated after cancer diagnosis.
— Douglas K. Rex, MD
Published in Journal Watch Gastroenterology October 15, 2010
Friday, October 15, 2010
carotis hart coronair bloedvaten
Carotid endarterectomy (CEA) is a surgical procedure used to prevent stroke, by correcting stenosis (narrowing) in the common carotid artery. Endarterectomy is the removal of material on the inside (end-) of an artery.
SummaCarotid endarterectomy (CEA) is a surgical procedure used to prevent stroke, by correcting stenosis (narrowing) in the common carotid artery. Endarterectomy is the removal of material on the inside (end-) of an artery.
and Comment
Endarterectomy Is Still Safer Than Stenting in Symptomatic Carotid Stenosis
But stenting might be an acceptable alternative in patients younger than 70.
In several large trials involving patients with symptomatic carotid artery stenosis, endovascular stenting carried greater periprocedural risk than open endarterectomy, but no single trial was large enough to identify subgroups that might be at particular risk with either procedure. To gain statistical power, investigators combined patient-level data from three such trials, yielding a sample of 3454 patients with moderate-to-severe stenosis who were assigned randomly to stenting or endarterectomy.
In an intent-to-treat analysis, significantly more patients assigned to stenting than to endarterectomy reached the primary outcome of any stroke or death within 120 days after randomization (8.9% vs. 5.8%) — a difference that was driven primarily by nondisabling ischemic strokes. Patients younger than 70 had similar outcomes with both treatments, whereas those 70 and older had significantly more primary outcome events with stenting than with endarterectomy (12.0% vs. 5.9%). No significant differences were seen in any other predefined subgroup.
Comment: Unless contraindications to surgery exist, endarterectomy remains the treatment of choice for patients with symptomatic carotid artery stenosis. This study suggests that stenting might be an acceptable alternative in patients younger than 70. But another concern is that recurrent stenosis might be more common after stenting than after endarterectomy — an effect that would be important to these younger patients and that cannot be discerned in these short-term data.
— Bruce Soloway, MD
Published in Journal Watch General Medicine October 14, 2010
Citation(s):
Carotid Stenting Trialists' Collaboration. Short-term outcome after stenting versus endarterectomy for symptomatic carotid stenosis: A preplanned meta-analysis of individual patient data. Lancet 2010 Sep 25; 376:1062. (http://dx.doi.org/10.1016/S0140-6736(10)61009-4)
Medline abstract (Free)
SummaCarotid endarterectomy (CEA) is a surgical procedure used to prevent stroke, by correcting stenosis (narrowing) in the common carotid artery. Endarterectomy is the removal of material on the inside (end-) of an artery.
and Comment
Endarterectomy Is Still Safer Than Stenting in Symptomatic Carotid Stenosis
But stenting might be an acceptable alternative in patients younger than 70.
In several large trials involving patients with symptomatic carotid artery stenosis, endovascular stenting carried greater periprocedural risk than open endarterectomy, but no single trial was large enough to identify subgroups that might be at particular risk with either procedure. To gain statistical power, investigators combined patient-level data from three such trials, yielding a sample of 3454 patients with moderate-to-severe stenosis who were assigned randomly to stenting or endarterectomy.
In an intent-to-treat analysis, significantly more patients assigned to stenting than to endarterectomy reached the primary outcome of any stroke or death within 120 days after randomization (8.9% vs. 5.8%) — a difference that was driven primarily by nondisabling ischemic strokes. Patients younger than 70 had similar outcomes with both treatments, whereas those 70 and older had significantly more primary outcome events with stenting than with endarterectomy (12.0% vs. 5.9%). No significant differences were seen in any other predefined subgroup.
Comment: Unless contraindications to surgery exist, endarterectomy remains the treatment of choice for patients with symptomatic carotid artery stenosis. This study suggests that stenting might be an acceptable alternative in patients younger than 70. But another concern is that recurrent stenosis might be more common after stenting than after endarterectomy — an effect that would be important to these younger patients and that cannot be discerned in these short-term data.
— Bruce Soloway, MD
Published in Journal Watch General Medicine October 14, 2010
Citation(s):
Carotid Stenting Trialists' Collaboration. Short-term outcome after stenting versus endarterectomy for symptomatic carotid stenosis: A preplanned meta-analysis of individual patient data. Lancet 2010 Sep 25; 376:1062. (http://dx.doi.org/10.1016/S0140-6736(10)61009-4)
Medline abstract (Free)
Thursday, October 14, 2010
warfarin
SUMMARY AND COMMENT
Warfarin, Aspirin, and Clopidogrel in Atrial Fibrillation
October 7, 2010 | Thomas L. Schwenk, MD, and Kirsten E. Fleischmann, MD, MPH
Any combination raises risk for bleeding without lowering risk for ischemic stroke.
Reviewing: Hansen ML et al. Arch Intern Med 2010 Sep 13; 170:1433
Warfarin, Aspirin, and Clopidogrel in Atrial Fibrillation
October 7, 2010 | Thomas L. Schwenk, MD, and Kirsten E. Fleischmann, MD, MPH
Any combination raises risk for bleeding without lowering risk for ischemic stroke.
Reviewing: Hansen ML et al. Arch Intern Med 2010 Sep 13; 170:1433
Tuesday, October 12, 2010
CRP etnic differences.
From Heartwire CME
Ethnicity Could Muddy the Waters of CRP-Guided Statin Therapy CME
News Author: Lisa Nainggolan
CME Author: Laurie Barclay, MD
CME Released: 10/01/2010; Valid for credit through 10/01/2011
October 1, 2010 — A new meta-analysis shows that average C-reactive-protein (CRP) levels vary among races and that these differences were mostly unexplained by conventional cardiovascular risk factors [1]. The findings have led to debate over whether a single cutoff point for CRP across different ethnic groups is appropriate or not.
Lead author Dr Tina Shah (University College London, UK) told heartwire : "The average levels of CRP in different populations showed quite marked differences. We found that East Asians had quite substantially lower CRP levels compared, for example, with African American individuals. This may or may not reflect different levels of coronary risk; we don't know yet," she added.
The average levels of CRP in different populations showed quite marked differences.
And "if you're using CRP levels to perhaps prescribe statins, then it seems that this would have an impact on eligibility for statin treatment," she says, adding that these findings may be particularly relevant in the multiethnic melting pot that is the US. Shah and colleagues' study is published online September 28, 2010 in Circulation: Cardiovascular Genetics.
More Than 50% of Blacks and Hispanics Would Exceed 2 mg/L at Age 50
Earlier this year, the US FDA expanded the license for rosuvastatin (Crestor, AstraZeneca) to include its use in the prevention of cardiovascular disease in men over 50 years and women over 60 years who have one other risk factor and CRP greater than 2 mg/L, based on the findings of the JUPITER study.
But, as reported by heartwire , controversy surrounds JUPITER. Senior author of the new study, Dr Aroon D Hingorani (University College London), observes: "There is ongoing debate over the ability of CRP to predict the risk of heart disease over established cardiovascular risk factors, even in individuals of European origin, where there is the most evidence pertaining to the CRP–coronary disease association.”
And current advice on whether or not to measure CRP varies from country to country, he notes, with the US and Canada embracing the test more wholeheartedly than European countries at the moment. "The perspective from the European angle is that perhaps CRP doesn't add very much once you've already measured established risk factors," he says.
On this background, Shah et al conducted a systematic review and meta-analysis of data on 221 287 people from 89 published studies and discovered that CRP levels differed by ethnicity, even after adjustments for age, body-mass index, smoking, and polymorphisms in the CRP gene. African Americans had the highest CRP levels, with an average of 2.6 mg/L, followed by Hispanics (2.51 mg/L), South Asians (2.34 mg/L), and whites (2.03 mg/L). East Asians had the lowest CRP levels, at 1.01 mg/L.
Based on these figures, more than half of African Americans and Hispanics would likely exceed the 2-mg/L CRP threshold at 50 years of age, while less than half of East Asians would surpass this cutoff, the researchers say.
"What our study seems to indicate is that there are reasonably large differences in average CRP values between [people] of differing ancestry, and the differences are sufficiently large to have a potential impact on the eligibility for rosuvastatin treatment on the one hand and also on the interpretation of the CRP value for risk prediction on the other," says Hingorani.
This Is Nothing New, Says Ridker; A Single Cut Point Works Well
However, Dr Paul Ridker (Brigham and Women's Hospital, Boston, MA), the lead investigator of the JUPITER study, told heartwire : "There is not much new to talk about" in this study. "Just like LDL varies a bit between ethnic groups, it has long been known that CRP levels vary a bit between ethnic groups. What the authors seem to be missing here is that vascular event rates also vary between ethnic groups and that this variation tracks with CRP levels just as you would anticipate--for example, the observation that a somewhat larger proportion of African Americans have higher CRP levels is actually a good finding, since African Americans also have higher vascular-event rates than do age-matched whites. Similarly, those of Japanese or Chinese descent have somewhat lower CRP levels and also have somewhat lower vascular risk.
There is not much new to talk about . . . . It has long been known that CRP levels vary a bit between ethnic groups.
"We obviously knew all of this back in 2003 when we started the JUPITER trial; picking a single cut point worked very well . . . as we got virtually identical risk reductions for our white and nonwhite subgroups," he says, adding that around 25% of the JUPITER population was nonwhite.
Hingorani told heartwire : "We think there is probably a positive association between CRP and [vascular] risk even in the non-European population, but whether that is sufficient for doctors to be able to interpret a CRP value in the clinical setting adequately to make decisions on statin targeting and risk prediction is uncertain."
Current Study Questions the Wisdom of a Universal Cut Point
Shah and colleagues say around five million high-sensitivity CRP tests were ordered in the US in 2007 and that the recent FDA decision to expand the label for rosuvastatin is likely to further increase the number of tests performed there.
Dr Sanjay Kaul (Cedars Sinai Medical Center, Los Angeles, CA)--who was on the FDA advisory panel deliberating on the expanded indication for rosuvastatin and who voted for approval--says this new research does complicate matters. "The current study muddies the water by suggesting an important impact of ethnic differences on CRP levels and questions the wisdom of using a universal CRP cutoff for identifying patients eligible for statin treatment.
The current study [suggests] an important impact of ethnic differences on CRP levels and questions the wisdom of using a universal CRP cutoff.
"The evidence base supporting the inclusion of CRP in CVD risk assessment is modest, incomplete, and overstated," Kaul asserts. "As with any other diagnostic or risk-prediction tests, one size does not fit all. The clinical and demographic contexts are important considerations. On the basis of the totality of evidence, calls for the widespread adoption of CRP measurement as a screening test must be regarded as premature and unwarranted."
Hingorani notes: "Whichever patient group you are seeing, it's important to focus your interest on established cardiovascular risk factors. . . . That should come first. If you are inclined to measure CRP values--which we wouldn't be in Europe--but if you are, then CRP levels need to be interpreted in the context of the ethnicity of the patient. To say much more than that is difficult at this stage.
"Hopefully, one of the aspects of this paper is that it might drive a little bit more research on the relationship between CRP and vascular risk in non-European populations," he concludes.
Shah and Hingorani have received research funding from the British Heart Foundation to study the potential role of CRP as a predictive test or therapeutic target in coronary heart disease. Hingorani has received research funding from the Medical Research Council relating to complement factor H as a potential biomarker for coronary disease; Pfizer is an industrial partner on this award. He has also received honoraria for speaking at educational meetings on coronary risk prediction, most or all of which have been donated to charity.
References
1. Shah T, Newcombe P, Smeeth L, et al. Ancestry as a determinant of mean population C-reactive protein values: implications for cardiovascular risk prediction. Circ Cardiovasc Genet 2010; DOI:10.1161/CIRCGENETICS.110.957431. Available at: http://circgenetics.ahajournals.org.
Clinical Context
Risk-prediction instruments such as the Framingham equation integrate information on established cardiovascular risk factors, but a large proportion of events occur among individuals with near-average levels of continuous risk factors or at intermediate Framingham risk. Because inflammation is increasingly implicated in the pathophysiology of atherosclerosis, CRP, a sensitive circulating biomarker of inflammation, may be potentially useful in predicting cardiovascular risk.
Statins are widely prescribed for the reduction of cardiovascular risk. One of the eligibility criteria for rosuvastatin treatment for cardiovascular disease prevention is a CRP concentration of more than 2 mg/L. To date, most observational studies of the association between CRP and cardiovascular disease risk have been performed in Europeans.
Ethnicity Could Muddy the Waters of CRP-Guided Statin Therapy CME
News Author: Lisa Nainggolan
CME Author: Laurie Barclay, MD
CME Released: 10/01/2010; Valid for credit through 10/01/2011
October 1, 2010 — A new meta-analysis shows that average C-reactive-protein (CRP) levels vary among races and that these differences were mostly unexplained by conventional cardiovascular risk factors [1]. The findings have led to debate over whether a single cutoff point for CRP across different ethnic groups is appropriate or not.
Lead author Dr Tina Shah (University College London, UK) told heartwire : "The average levels of CRP in different populations showed quite marked differences. We found that East Asians had quite substantially lower CRP levels compared, for example, with African American individuals. This may or may not reflect different levels of coronary risk; we don't know yet," she added.
The average levels of CRP in different populations showed quite marked differences.
And "if you're using CRP levels to perhaps prescribe statins, then it seems that this would have an impact on eligibility for statin treatment," she says, adding that these findings may be particularly relevant in the multiethnic melting pot that is the US. Shah and colleagues' study is published online September 28, 2010 in Circulation: Cardiovascular Genetics.
More Than 50% of Blacks and Hispanics Would Exceed 2 mg/L at Age 50
Earlier this year, the US FDA expanded the license for rosuvastatin (Crestor, AstraZeneca) to include its use in the prevention of cardiovascular disease in men over 50 years and women over 60 years who have one other risk factor and CRP greater than 2 mg/L, based on the findings of the JUPITER study.
But, as reported by heartwire , controversy surrounds JUPITER. Senior author of the new study, Dr Aroon D Hingorani (University College London), observes: "There is ongoing debate over the ability of CRP to predict the risk of heart disease over established cardiovascular risk factors, even in individuals of European origin, where there is the most evidence pertaining to the CRP–coronary disease association.”
And current advice on whether or not to measure CRP varies from country to country, he notes, with the US and Canada embracing the test more wholeheartedly than European countries at the moment. "The perspective from the European angle is that perhaps CRP doesn't add very much once you've already measured established risk factors," he says.
On this background, Shah et al conducted a systematic review and meta-analysis of data on 221 287 people from 89 published studies and discovered that CRP levels differed by ethnicity, even after adjustments for age, body-mass index, smoking, and polymorphisms in the CRP gene. African Americans had the highest CRP levels, with an average of 2.6 mg/L, followed by Hispanics (2.51 mg/L), South Asians (2.34 mg/L), and whites (2.03 mg/L). East Asians had the lowest CRP levels, at 1.01 mg/L.
Based on these figures, more than half of African Americans and Hispanics would likely exceed the 2-mg/L CRP threshold at 50 years of age, while less than half of East Asians would surpass this cutoff, the researchers say.
"What our study seems to indicate is that there are reasonably large differences in average CRP values between [people] of differing ancestry, and the differences are sufficiently large to have a potential impact on the eligibility for rosuvastatin treatment on the one hand and also on the interpretation of the CRP value for risk prediction on the other," says Hingorani.
This Is Nothing New, Says Ridker; A Single Cut Point Works Well
However, Dr Paul Ridker (Brigham and Women's Hospital, Boston, MA), the lead investigator of the JUPITER study, told heartwire : "There is not much new to talk about" in this study. "Just like LDL varies a bit between ethnic groups, it has long been known that CRP levels vary a bit between ethnic groups. What the authors seem to be missing here is that vascular event rates also vary between ethnic groups and that this variation tracks with CRP levels just as you would anticipate--for example, the observation that a somewhat larger proportion of African Americans have higher CRP levels is actually a good finding, since African Americans also have higher vascular-event rates than do age-matched whites. Similarly, those of Japanese or Chinese descent have somewhat lower CRP levels and also have somewhat lower vascular risk.
There is not much new to talk about . . . . It has long been known that CRP levels vary a bit between ethnic groups.
"We obviously knew all of this back in 2003 when we started the JUPITER trial; picking a single cut point worked very well . . . as we got virtually identical risk reductions for our white and nonwhite subgroups," he says, adding that around 25% of the JUPITER population was nonwhite.
Hingorani told heartwire : "We think there is probably a positive association between CRP and [vascular] risk even in the non-European population, but whether that is sufficient for doctors to be able to interpret a CRP value in the clinical setting adequately to make decisions on statin targeting and risk prediction is uncertain."
Current Study Questions the Wisdom of a Universal Cut Point
Shah and colleagues say around five million high-sensitivity CRP tests were ordered in the US in 2007 and that the recent FDA decision to expand the label for rosuvastatin is likely to further increase the number of tests performed there.
Dr Sanjay Kaul (Cedars Sinai Medical Center, Los Angeles, CA)--who was on the FDA advisory panel deliberating on the expanded indication for rosuvastatin and who voted for approval--says this new research does complicate matters. "The current study muddies the water by suggesting an important impact of ethnic differences on CRP levels and questions the wisdom of using a universal CRP cutoff for identifying patients eligible for statin treatment.
The current study [suggests] an important impact of ethnic differences on CRP levels and questions the wisdom of using a universal CRP cutoff.
"The evidence base supporting the inclusion of CRP in CVD risk assessment is modest, incomplete, and overstated," Kaul asserts. "As with any other diagnostic or risk-prediction tests, one size does not fit all. The clinical and demographic contexts are important considerations. On the basis of the totality of evidence, calls for the widespread adoption of CRP measurement as a screening test must be regarded as premature and unwarranted."
Hingorani notes: "Whichever patient group you are seeing, it's important to focus your interest on established cardiovascular risk factors. . . . That should come first. If you are inclined to measure CRP values--which we wouldn't be in Europe--but if you are, then CRP levels need to be interpreted in the context of the ethnicity of the patient. To say much more than that is difficult at this stage.
"Hopefully, one of the aspects of this paper is that it might drive a little bit more research on the relationship between CRP and vascular risk in non-European populations," he concludes.
Shah and Hingorani have received research funding from the British Heart Foundation to study the potential role of CRP as a predictive test or therapeutic target in coronary heart disease. Hingorani has received research funding from the Medical Research Council relating to complement factor H as a potential biomarker for coronary disease; Pfizer is an industrial partner on this award. He has also received honoraria for speaking at educational meetings on coronary risk prediction, most or all of which have been donated to charity.
References
1. Shah T, Newcombe P, Smeeth L, et al. Ancestry as a determinant of mean population C-reactive protein values: implications for cardiovascular risk prediction. Circ Cardiovasc Genet 2010; DOI:10.1161/CIRCGENETICS.110.957431. Available at: http://circgenetics.ahajournals.org.
Clinical Context
Risk-prediction instruments such as the Framingham equation integrate information on established cardiovascular risk factors, but a large proportion of events occur among individuals with near-average levels of continuous risk factors or at intermediate Framingham risk. Because inflammation is increasingly implicated in the pathophysiology of atherosclerosis, CRP, a sensitive circulating biomarker of inflammation, may be potentially useful in predicting cardiovascular risk.
Statins are widely prescribed for the reduction of cardiovascular risk. One of the eligibility criteria for rosuvastatin treatment for cardiovascular disease prevention is a CRP concentration of more than 2 mg/L. To date, most observational studies of the association between CRP and cardiovascular disease risk have been performed in Europeans.
atrium fibrillation AF
Freelance writer and reviewer, Medscape, LLC
Disclosure: Laurie Barclay, MD, has disclosed no relevant financial relationships.
Sarah Fleischman
CME Program Manager, Medscape, LLC
Disclosure: Sarah Fleischman has disclosed no relevant financial relationships.
Learning Objectives
Upon completion of this activity, participants will be able to:
1. Describe the efficacy of catheter ablation in patients younger than 45 years with atrial fibrillation, based on a large observational study.
2. Describe the risks associated with catheter ablation in patients younger than 45 years with atrial fibrillation, based on a large observational study.
Credits Available
Physicians - maximum of 0.25 AMA PRA Category 1 Credit(s)™
Family Physicians - maximum of 0.25 AAFP Prescribed credit(s)
All other healthcare professionals completing continuing education credit for this activity will be issued a certificate of participation.
Physicians should only claim credit commensurate with the extent of their participation in the activity.
Accreditation Statements
For Physicians
Medscape, LLC is accredited by the Accreditation Council for Continuing Medical Education (ACCME) to provide continuing medical education for physicians.
Medscape, LLC designates this educational activity for a maximum of 0.25 AMA PRA Category 1 Credit(s)™ . Physicians should only claim credit commensurate with the extent of their participation in the activity.
This activity, MedscapeCME Clinical Briefs has been reviewed and is acceptable for up to 300 Prescribed credits by the American Academy of Family Physicians. AAFP accreditation begins September 1, 2010. Term of approval is for 1 year from this date. Each issue is approved for .25 Prescribed credits. Credit may be claimed for 1 year from the date of this issue.
Note: Total credit is subject to change based on topic selection and article length.
Medscape, LLC staff have disclosed that they have no relevant financial relationships.
AAFP Accreditation Questions
Contact This Provider
For questions regarding the content of this activity, contact the accredited provider for this CME/CE activity noted above. For technical assistance, contact CME@medscape.net
CME Released: 09/28/2010; Valid for credit through 09/28/2011
Instructions for Participation and Credit
There are no fees for participating in or receiving credit for this online educational activity. For information on applicability and acceptance of continuing education credit for this activity, please consult your professional licensing board.
This activity is designed to be completed within the time designated on the title page; physicians should claim only those credits that reflect the time actually spent in the activity. To successfully earn credit, participants must complete the activity online during the valid credit period that is noted on the title page.
Follow these steps to earn CME/CE credit*:
1. Read the target audience, learning objectives, and author disclosures.
2. Study the educational content online or printed out.
3. Online, choose the best answer to each test question. To receive a certificate, you must receive a passing score as designated at the top of the test. MedscapeCME encourages you to complete the Activity Evaluation to provide feedback for future programming.
You may now view or print the certificate from your CME/CE Tracker. You may print the certificate but you cannot alter it. Credits will be tallied in your CME/CE Tracker and archived for 6 years; at any point within this time period you can print out the tally as well as the certificates by accessing "Edit Your Profile" at the top of your Medscape homepage.
*The credit that you receive is based on your user profile.
Hardware/Software Requirements
MedscapeCME is accessible using the following browsers: Internet Explorer 6.x or higher, Firefox 2.x or higher, Safari 2.x or higher. Certain educational activities may require additional software to view multimedia, presentation or printable versions of their content. These activities will be marked as such and will provide links to the required software. That software may be: Macromedia Flash, Adobe Acrobat, or Microsoft PowerPoint.
September 28, 2010 — A new study suggests that ablation may be the best choice for the first therapy for atrial fibrillation (AF) in younger patients [1].
Researchers led by Dr Peter Leong-Sit (London Health Science Hospital, ON) collected data from 1548 consecutive patients with drug-refractory AF who underwent 2038 AF ablation procedures over an eight-year period in the University of Pennsylvania Health System. They compared the outcomes of four age groups: <45 years, 45 to 54 years, 55 to 64 years, and >65 years. Results of the study are published online September 21, 2010 in Circulation: Arrhythmia & Electrophysiology.
The primary outcome, AF control, defined as no or rare AF on or off antiarrhythmic drugs, was similar in all groups (p=0.06). AF control was achieved in 87% of the youngest patients, 82% of the oldest patients, and 88% of both of the middle-aged groups. However, more patients younger than 45 demonstrated freedom from AF off of antiarrhythmic drugs (76%) compared with the 45-to-54-year-old group (68%), the 55-to-64-year-old group (65%), or the over-65 group (53%) (p<0.001).
There were zero major complications in the patients younger than 45, but 10 major complications in the oldest (2.6%) group. There were 10 (1.7%) and 14 (1.4%) major complications in the 45- to 54-year-olds and 55- to 64-year-olds, respectively (p=0.01)
Previous studies show that younger patients with atrial fibrillation tend to be more symptomatic than older AF patients, but they are less compliant with long-term medications than their older counterparts. However, catheter ablation remains recommended as only second-line therapy for AF regardless of age, Leong-Sit and colleagues point out. The 2006 American College of Cardiology/American Heart Association/European Society of Cardiology guidelines on AF recommend ablation as a second-line therapy, and the 2007 Heart Rhythm Society/European Heart Rhythm Association/European Cardiac Arrhythmia Society expert consensus statement on AF ablation states that catheter ablation may be appropriate as a first-line therapy only in rare clinical situations.
Prior to this study, there were little data on the efficacy and risks of catheter ablation for AF in young patients, according to the authors. The new data at least demonstrate the feasibility of ablation instead of drugs as the first-line therapy in younger AF patients. "These data are strongly suggestive that ablation should be considered as a first-line strategy in young patients and reinforce the need for a randomized-controlled trial of first-line ablation vs antiarrhythmic medication in this young age group," the authors argue.
Disclosure: Laurie Barclay, MD, has disclosed no relevant financial relationships.
Sarah Fleischman
CME Program Manager, Medscape, LLC
Disclosure: Sarah Fleischman has disclosed no relevant financial relationships.
Learning Objectives
Upon completion of this activity, participants will be able to:
1. Describe the efficacy of catheter ablation in patients younger than 45 years with atrial fibrillation, based on a large observational study.
2. Describe the risks associated with catheter ablation in patients younger than 45 years with atrial fibrillation, based on a large observational study.
Credits Available
Physicians - maximum of 0.25 AMA PRA Category 1 Credit(s)™
Family Physicians - maximum of 0.25 AAFP Prescribed credit(s)
All other healthcare professionals completing continuing education credit for this activity will be issued a certificate of participation.
Physicians should only claim credit commensurate with the extent of their participation in the activity.
Accreditation Statements
For Physicians
Medscape, LLC is accredited by the Accreditation Council for Continuing Medical Education (ACCME) to provide continuing medical education for physicians.
Medscape, LLC designates this educational activity for a maximum of 0.25 AMA PRA Category 1 Credit(s)™ . Physicians should only claim credit commensurate with the extent of their participation in the activity.
This activity, MedscapeCME Clinical Briefs has been reviewed and is acceptable for up to 300 Prescribed credits by the American Academy of Family Physicians. AAFP accreditation begins September 1, 2010. Term of approval is for 1 year from this date. Each issue is approved for .25 Prescribed credits. Credit may be claimed for 1 year from the date of this issue.
Note: Total credit is subject to change based on topic selection and article length.
Medscape, LLC staff have disclosed that they have no relevant financial relationships.
AAFP Accreditation Questions
Contact This Provider
For questions regarding the content of this activity, contact the accredited provider for this CME/CE activity noted above. For technical assistance, contact CME@medscape.net
CME Released: 09/28/2010; Valid for credit through 09/28/2011
Instructions for Participation and Credit
There are no fees for participating in or receiving credit for this online educational activity. For information on applicability and acceptance of continuing education credit for this activity, please consult your professional licensing board.
This activity is designed to be completed within the time designated on the title page; physicians should claim only those credits that reflect the time actually spent in the activity. To successfully earn credit, participants must complete the activity online during the valid credit period that is noted on the title page.
Follow these steps to earn CME/CE credit*:
1. Read the target audience, learning objectives, and author disclosures.
2. Study the educational content online or printed out.
3. Online, choose the best answer to each test question. To receive a certificate, you must receive a passing score as designated at the top of the test. MedscapeCME encourages you to complete the Activity Evaluation to provide feedback for future programming.
You may now view or print the certificate from your CME/CE Tracker. You may print the certificate but you cannot alter it. Credits will be tallied in your CME/CE Tracker and archived for 6 years; at any point within this time period you can print out the tally as well as the certificates by accessing "Edit Your Profile" at the top of your Medscape homepage.
*The credit that you receive is based on your user profile.
Hardware/Software Requirements
MedscapeCME is accessible using the following browsers: Internet Explorer 6.x or higher, Firefox 2.x or higher, Safari 2.x or higher. Certain educational activities may require additional software to view multimedia, presentation or printable versions of their content. These activities will be marked as such and will provide links to the required software. That software may be: Macromedia Flash, Adobe Acrobat, or Microsoft PowerPoint.
September 28, 2010 — A new study suggests that ablation may be the best choice for the first therapy for atrial fibrillation (AF) in younger patients [1].
Researchers led by Dr Peter Leong-Sit (London Health Science Hospital, ON) collected data from 1548 consecutive patients with drug-refractory AF who underwent 2038 AF ablation procedures over an eight-year period in the University of Pennsylvania Health System. They compared the outcomes of four age groups: <45 years, 45 to 54 years, 55 to 64 years, and >65 years. Results of the study are published online September 21, 2010 in Circulation: Arrhythmia & Electrophysiology.
The primary outcome, AF control, defined as no or rare AF on or off antiarrhythmic drugs, was similar in all groups (p=0.06). AF control was achieved in 87% of the youngest patients, 82% of the oldest patients, and 88% of both of the middle-aged groups. However, more patients younger than 45 demonstrated freedom from AF off of antiarrhythmic drugs (76%) compared with the 45-to-54-year-old group (68%), the 55-to-64-year-old group (65%), or the over-65 group (53%) (p<0.001).
There were zero major complications in the patients younger than 45, but 10 major complications in the oldest (2.6%) group. There were 10 (1.7%) and 14 (1.4%) major complications in the 45- to 54-year-olds and 55- to 64-year-olds, respectively (p=0.01)
Previous studies show that younger patients with atrial fibrillation tend to be more symptomatic than older AF patients, but they are less compliant with long-term medications than their older counterparts. However, catheter ablation remains recommended as only second-line therapy for AF regardless of age, Leong-Sit and colleagues point out. The 2006 American College of Cardiology/American Heart Association/European Society of Cardiology guidelines on AF recommend ablation as a second-line therapy, and the 2007 Heart Rhythm Society/European Heart Rhythm Association/European Cardiac Arrhythmia Society expert consensus statement on AF ablation states that catheter ablation may be appropriate as a first-line therapy only in rare clinical situations.
Prior to this study, there were little data on the efficacy and risks of catheter ablation for AF in young patients, according to the authors. The new data at least demonstrate the feasibility of ablation instead of drugs as the first-line therapy in younger AF patients. "These data are strongly suggestive that ablation should be considered as a first-line strategy in young patients and reinforce the need for a randomized-controlled trial of first-line ablation vs antiarrhythmic medication in this young age group," the authors argue.
Friday, October 08, 2010
warfarin aspirine
Results A total of 82 854 of 118 606 patients (69.9%) surviving AF hospitalization had at least 1 prescription filled for warfarin, aspirin, or clopidogrel after discharge. During mean (SD) follow-up of 3.3 (2.6) years, 13 573 patients (11.4%) experienced a nonfatal or fatal bleeding. The crude incidence rate for bleeding was highest for dual clopidogrel and warfarin therapy (13.9% per patient-year) and triple therapy (15.7% per patient-year). Using warfarin monotherapy as a reference, the hazard ratio (95% confidence interval) for the combined end point was 0.93 (0.88-0.98) for aspirin, 1.06 (0.87-1.29) for clopidogrel, 1.66 (1.34-2.04) for aspirin-clopidogrel, 1.83 (1.72-1.96) for warfarin-aspirin, 3.08 (2.32-3.91) for warfarin-clopidogrel, and 3.70 (2.89-4.76) for warfarin-aspirin-clopidogrel.
Conclusions In patients with AF, all combinations of warfarin, aspirin, and clopidogrel are associated with increased risk of nonfatal and fatal bleeding. Dual warfarin and clopidogrel therapy and triple therapy carried a more than 3-fold higher risk than did warfarin monotherapy.
Conclusions In patients with AF, all combinations of warfarin, aspirin, and clopidogrel are associated with increased risk of nonfatal and fatal bleeding. Dual warfarin and clopidogrel therapy and triple therapy carried a more than 3-fold higher risk than did warfarin monotherapy.
