Friday, June 22, 2012
statines
SUMMARY
AND COMMENT
June 12,
2012 | Seemant
Chaturvedi, MD | Neurology
An
observational study suggests that statin use before and during
hospitalization for stroke improves short-term outcomes.
Reviewing:
Flint AC et al. Neurology 2012 May 22; 78:1678
Thursday, June 21, 2012
statines
Should Anyone Not Take a Statin?
In a meta-analysis, benefits of statins outweighed risks, even in the healthiest patients.Meta-analyses have shown that statins safely lower the incidence of major vascular events (MVEs, including nonfatal myocardial infarction or coronary death, any stroke, or coronary revascularization) by about 20% for every 40 mg/dL reduction in LDL cholesterol level. But the net benefit of statin therapy in patients at low vascular risk has been unclear.
In a new meta-analysis of patient-level data from 27 randomized trials of statins versus control treatments or high- versus low-dose statins, researchers stratified 170,000 participants by their pretrial 5-year risk for MVEs (from <5% to
30%).
Overall, statins lowered 5-year relative risk for MVEs by 21% per 40
mg/dL reduction in LDL cholesterol level, and risk reductions were more
pronounced in the lowest risk categories (as much as 38% per 40 mg/dL
reduction in LDL cholesterol level for participants with 5-year vascular
risk <5%). Similar relative risk reductions occurred when patients
with prior vascular disease, diabetes, or chronic kidney disease were
excluded. Statins lowered 5-year relative risk for vascular death by at
least 12% and did not raise risk for nonvascular death in patients with
or without histories of vascular disease.Comment: Among patients with 5-year MVE risk of <10%, statins lowered the absolute 5-year MVE risk by about 11 events per 1000 patients for each 40 mg/dL of reduction in LDL cholesterol level. This benefit substantially outweighs any known risk of statin therapy. The authors and editorialists suggest that current guidelines, which generally do not recommend statin therapy for low-risk patients, should be reevaluated. However, lingering questions include the following: In the general population, are statins tolerated as well as was reported in the randomized trials? Among the lowest-risk patients in real-life practice, is the long-term balance of benefits and harms as favorable as predicted from the trials? And, if low-risk patients choose to take statins, what are the appropriate ages to start and stop?
— Bruce Soloway, MD
Published in Journal Watch General Medicine June 12, 2012
Citation(s):
Cholesterol Treatment Trialists'
(CTT) Collaborators. The effects of lowering LDL cholesterol with statin
therapy in people at low risk of vascular disease: Meta-analysis of
individual data from 27 randomised trials. Lancet 2012 May 17; [e-pub ahead of print]. (http://viajwat.ch/KqxJye)
Ebrahim S and Casas JP. Statins for all by the age of 50 years? Lancet 2012 May 17; [e-pub ahead of print]. (http://dx.doi.org/10.1016/S0140-6736(12)60694-1)
Wednesday, June 13, 2012
CRP as a Predictor of Statin Efficacy: Time to Move On?
- An Interview With Peter S. Sever, MB BChir, PhD
- Background to the Interview
- The Interview
An Interview With Peter S. Sever, MB BChir, PhD
statins
The Study
Sever PS, Poulter NR, Chang CL, et al; ASCOT Investigators. Evaluation of C-reactive protein prior to and on-treatment as a predictor of benefit from atorvastatin: observations from the Anglo-Scandinavian Cardiac Outcomes Trial. Eur Heart J. 2012;33:486-494.About the Interviewee
Peter S. Sever, MB BChir, PhD, is Professor of Clinical Pharmacology and Therapeutics at Imperial College London; Honorary Consultant Physician at the Imperial Healthcare NHS Trust; and Co-director of the International Centre for Circulatory Health, London, United Kingdom. During the past decade, he established a major research program in the pathogenesis and treatment of cardiovascular disease. He is joint editor-in-chief of Journal of the Renin-Angiotensin-Aldosterone System and has been a member of the editorial boards of several journals, including Journal of Hypertension, Journal of Human Hypertension, and Clinical Science.Professor Sever is past president of the British Hypertension Society (1989-1991) and past president of the European Council for Blood Pressure and Cardiovascular Research. He is also a Fellow of the European Society of Cardiology and past Chairman of the Fellowships Committee of the British Heart Foundation.
His current research interests include all aspects of cardiovascular disease, including the pathophysiology of vascular disease, the evaluation of antihypertensive drug therapy, and multiple risk factor intervention in hypertensive populations. He is also interested in the epidemiology of hypertension, with particular reference to environmental influences on blood pressure and ethnic differences. Professor Sever was co-chair, along with Björn Dahlöf, MD (Sahlgrenska University Hospital, Göteborg, Sweden), of the Anglo-Scandinavian Cardiac Outcomes Trial (ASCOT) executive committee.
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STATINS
Oxford, UK - New data from an individual patient meta-analysis of
27 large statin trials shows that statin treatment is clearly
beneficial in much lower-risk patients than are currently recommended
for such therapy in most guidelines [1].
And authors of an accompanying comment suggest
that with this new data, everyone over 50 should now be eligible for
statin treatment.
The meta-analysis, published online May 16, 2012 in the Lancet, was conducted by the Cholesterol Treatment Trialists' (CTT) Collaborators.
They analyzed data from 175 000 individuals and grouped participants
into five baseline categories of cardiovascular risk. Outcomes were
studied in trials comparing statin with no statin treatment and of more
vs less intensive statin regimens.
Results showed that statins reduced the risk
of serious vascular events by around 21% for each 1-mmol/L reduction in
LDL cholesterol in each of the five baseline risk groups, including
those people with the lowest risk of vascular disease.
Benefits greatly exceeded harms
One of the senior authors on the paper, Prof Colin Baigent (Clinical Trial Service Unit, Oxford, UK), commented to heartwire: "Last year Cochrane published a review of statins in primary prevention
that was somewhat unclear in its conclusions. They showed that although
there was a clear reduction in mortality with statins, they were
uncertain about adverse effects. We wanted to clarify the situation, so
we looked at all the available individual patient data from all trials
that included low-risk patients. As well as all the primary-prevention
trials, these include some trials where both primary- and
secondary-prevention patients were included, such as the Heart Protection Study. This was a much more thorough analysis than the Cochrane review, which only had access to the overall trial results."
Baigent continued: "We found the relative
reduction in risk of cardiovascular events with a statin is just as good
in the lowest-risk group as in higher-risk groups. Even in the very
lowest-risk group studied (those with a risk below 10% in 10 years), the
benefits greatly exceeded the harms."
Primary prevention is obviously needed.
"Half of cardiac deaths happen in people who
have not previously had heart disease, so there is a limit to what can
be achieved just with secondary prevention. So primary prevention is
obviously needed. The question is where we set the threshold. And our
data suggest this should be lowered to a risk of 10% over 10 years."
Baigent believes the decision on whether to
take a statin needs to be made on the basis of risk of the patient
rather than on their cholesterol level. "Typically, at the moment, the
public and many doctors think that statins are necessary only if a
patient has high cholesterol. But the preferable view would be that a
statin is needed if you are at any increased risk of heart disease."
A statin is needed if you are at any increased risk of heart disease.
He added that everyone is supposed to have a
vascular check in middle age, and the current recommendation in the UK
is that if they are found to have a risk of a cardiovascular event of
more than 20% over 10 years they should be offered a statin. "But we
found in this current meta-analysis that the benefits of statins are
still obvious at a risk level of 10% over 10 years, and even below
that."
At present in the UK, five million patients
take statins, and another five million are eligible to take them but are
not receiving them, Baigent reported. "If the threshold were reduced to
a cardiac risk of 10% over 10 years, an additional five million people
would be eligible to receive these drugs. Simvastatin is off patent and atorvastatin
is now coming off patent, so this will not be an expensive exercise. It
is right and proper that there is an assessment of safety, but we have
now done that and shown the benefits to greatly outweigh the risks. If
the threshold were lowered to 10%, we could avoid 10 000 events,
including 2000 deaths every year."
If the threshold was lowered to 10%, we could avoid 10 000 events, including 2000 deaths every year.
Asked if everyone should just receive a statin
at a certain age, Baigent said this was one possibility. "It is up to
the guidelines committees to decide on the strategy. We have called for NICE
to reconsider the threshold they recommend for statin treatment. All we
are saying is that we should at least treat everyone with a risk of 10%
or more over 10 years. But we actually showed benefit in patients with a
lower risk than this. People can be educated about risk. Everybody
knows their age and if they are overweight, smoke, or don't exercise
enough. It's not difficult to find out your cholesterol, blood
pressure, family history, or whether you are diabetic. These things then
should then trigger the thought that you might be able to benefit from a
statin."
Statins for everyone over 50?
In the comment article, Drs Shah Ebrahim and Juan P Casas
(London School of Hygiene and Tropical Medicine, UK) suggest that as
most people older than 50 years are likely to be at a >10% 10-year
risk of a cardiovascular event, it would be more pragmatic to use age as
the only indicator for statin prescription, which would avoid the costs
of vascular screening checks.
Major results for the new meta-analysis showed
that statin treatment reduced the risk of major vascular events by 21%
per 1.0-mmol/L reduction in LDL, and this was largely irrespective of
age, sex, baseline LDL cholesterol, previous vascular disease, and
baseline cardiovascular risk. The proportional reduction in major
vascular events was at least as big in the two lowest-risk categories as
in the higher-risk categories.
Risk reduction in major vascular events statin treatment according to baseline risk |
Baseline risk (risk of CV event over five years), %
|
Risk reduction (95% CI) per 1-mmol LDL reduction
|
|
<5
|
0.57 (0.36-0·89) |
|
5-10
|
0.61 (0.50-0·74) |
|
10-20
|
0.77 (0.69-0·85) |
|
20-30
|
0.77 (0.71-0·83) |
|
20-30
|
0.78 (0.72-0·84) |
|
Overall
|
0.76 (0.73-0·79) |
5% risk over five years=10% risk over 10 years
There was no evidence that reduction of LDL
cholesterol with a statin increased cancer incidence (RR per 1.0-mmol/L
LDL-cholesterol reduction 1.00, 95% CI 0.96-1.04), cancer mortality (RR
0.99, 95% CI 0.93-1.06), or other nonvascular mortality.
What about side effects?
In terms of side effects, the data show that
there was a small increased risk of myopathy (excess incidence of about
0.5 per 1000 over five years) and rhabdomyolysis (excess incidence of
about 0.1 per 1000 over five years). There was also an increase of
hemorrhagic strokes per 1.0-mmol/L LDL-cholesterol reduction of about
0.5 per 1000 people treated over five years. But the authors write that
"this was outweighed by the reduction in ischemic stroke (as well as the
reduction in other occlusive vascular events and deaths) even in
individuals whose five-year risk of major vascular events is lower than
5%."
They also report an absolute excess of
diabetes associated with statin treatment of about 0.1% per year. But
they estimate that the increased risk of cardiovascular events
associated with this excess in diabetes is more than 50 times smaller
than the absolute benefit observed with statin therapy in low-risk
patients.
Sunday, June 10, 2012
biphosphanate foamax alendroinezuur
June 7, 2012 | Andrew M. Kaunitz, MD | Women's Health
Mixed results from trials of extended bisphosphonate treatment leave treatment and monitoring guidelines uncertain.
Reviewing: Whitaker M et al. N Engl J Med 2012 May 31; 366:2048
Black DM et al. N Engl J Med 2012 May 31; 366:2051
Free Full-Text Article
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Tuesday, June 05, 2012
DEPRESSION
on line 31-5-2012
Hello. This is Dr. Scott Irwin, Chief of Psychiatry and Psychosocial Services at San Diego Hospice and The Institute for Palliative Medicine. I'd like to talk to you about the rapid treatment of depression in patients who don't have time to wait for standard antidepressant therapy to work.
Depression is not a normal part of end of life. Only 15% of patients in hospice and palliative care settings have major depressive episodes. These episodes are treatable, and if we don't treat them, depression causes a tremendous amount of suffering -- not only for the patient but for families as well.
The way we treat depression [at the end of life] is with psychostimulants. We often use methylphenidate, and we'll start by giving 5 mg in the morning. If, in an hour, the patient hasn't had any effects that they don't like, we'll give them another dose 4 hours later. As long as we are continuing to get benefit and no side effects, we'll continue to increase the dose; so the next day, we might go to 10 mg and 10 mg [later in the day], and the day after that, 15 mg and 15 mg [in a second daily dose]. We rarely see doses effective over 20 mg twice a day. In the home setting, we might go a little slower and increase the dose every 5-7 days instead.
We see very few side effects. We don't see tolerance, and you might actually get some adjunct analgesia as well.
So, if you have somebody who's depressed and they don't have time to wait for standard antidepressant therapies to work, think of using psychostimulants and titrate them effectively, safely, and rapidly. Be sure to treat depression so that we can relieve suffering in both patients and their families.
Thank you for listening. This is Dr. Scott Irwin, Chief of Psychiatry and Psychosocial Services at San Diego Hospice and The Institute for Palliative Medicine.
on line 31-5-2012
Hello. This is Dr. Scott Irwin, Chief of Psychiatry and Psychosocial Services at San Diego Hospice and The Institute for Palliative Medicine. I'd like to talk to you about the rapid treatment of depression in patients who don't have time to wait for standard antidepressant therapy to work.
Depression is not a normal part of end of life. Only 15% of patients in hospice and palliative care settings have major depressive episodes. These episodes are treatable, and if we don't treat them, depression causes a tremendous amount of suffering -- not only for the patient but for families as well.
The way we treat depression [at the end of life] is with psychostimulants. We often use methylphenidate, and we'll start by giving 5 mg in the morning. If, in an hour, the patient hasn't had any effects that they don't like, we'll give them another dose 4 hours later. As long as we are continuing to get benefit and no side effects, we'll continue to increase the dose; so the next day, we might go to 10 mg and 10 mg [later in the day], and the day after that, 15 mg and 15 mg [in a second daily dose]. We rarely see doses effective over 20 mg twice a day. In the home setting, we might go a little slower and increase the dose every 5-7 days instead.
We see very few side effects. We don't see tolerance, and you might actually get some adjunct analgesia as well.
So, if you have somebody who's depressed and they don't have time to wait for standard antidepressant therapies to work, think of using psychostimulants and titrate them effectively, safely, and rapidly. Be sure to treat depression so that we can relieve suffering in both patients and their families.
Thank you for listening. This is Dr. Scott Irwin, Chief of Psychiatry and Psychosocial Services at San Diego Hospice and The Institute for Palliative Medicine.
Saturday, June 02, 2012
Warfarin Ineffective for HF Without Atrial Fibrillation
In the WARCEF trial, reduced stroke rates were offset by increased bleeding.The benefits of chronic anticoagulation in patients with heart failure (HF) who do not have atrial fibrillation are controversial. Previous clinical trials were underpowered to generate conclusive evidence, and results of observational studies have conflicted.
In the international WARCEF trial, investigators compared warfarin with aspirin in 2305 patients without a contraindication to anticoagulation (mean age, 61; 80% men). All were in sinus rhythm and had systolic left ventricular ejection fractions less than 35% (mean, 25%). Patients were randomized to receive warfarin (target international normalized ratio [INR], 2.0–3.5; mean, 2.5) or aspirin (325 mg) daily. Sites received sham INR results for patients in the aspirin group.
At a mean follow-up of 3.5 years, the rate of the primary endpoint of ischemic stroke, intracerebral hemorrhage, or all-cause death did not differ significantly between the warfarin and aspirin groups (7.47 and 7.93 per 100 patient-years, respectively). Rates of ischemic stroke were significantly lower with warfarin than with aspirin (0.72 vs. 1.36 per 100 patient-years), but rates of major hemorrhage were twice as high (1.78 vs. 0.87 per 100 patient-years). During follow-up, patients in the warfarin group were within the target INR range 63% of the time.
Comment: WARCEF showed no net benefit of warfarin in patients in sinus rhythm with systolic heart failure. Up to now, in the absence of evidence, the use of anticoagulation in this patient population has presumably depended on the instincts of the treating clinician. This well-designed clinical trial injects much-needed evidence into the decision; however, whether clinicians will change their practices based on the results remains to be seen. Furthermore, we don't know whether newer agents, which may provide more reliable anticoagulation than warfarin, might be beneficial in this context.
— Frederick A. Masoudi, MD, MSPH, FACC, FAHA
Published in Journal Watch Cardiology May 9, 2012
