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hart aspirine en clopidogrel
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From Journal of the American Board of Family Medicine
An Appraisal of Dual Antiplatelet Therapy with Clopidogrel and Aspirin for Prevention of Cardiovascular Events
Posted 03/10/2009
Chris Terpening, PhD, PharmD
Author Information
Information from Industry
NAMENDA® (memantine HCl) ––The first and only NMDA–receptor antagonist for the treatment of moderate to severe Alzheimer's disease. NAMENDA has been used by over 2 million patients worldwide.Read Important Safety Information and Prescribing Information.
Abstract and Introduction
Abstract
Combination antiplatelet therapy, typically with clopidogrel and aspirin, is commonly used for the prevention of cardiovascular events. When used for appropriate indications and duration, its benefits clearly outweigh its risks. However, it is not uncommon for the combination to be used outside of recommended indications or for longer than recommended durations. In these circumstances data are at best unclear and, at worst, indicative of harm. Furthermore, use for one of its indications—prevention of cardiac events after deployment of a coronary stent—is complicated by the type of stent used. This report reviews the evidence surrounding combination antiplatelet therapy with clopidogrel and aspirin, with an emphasis on identifying appropriate indications for and durations of therapy.
Introduction
Primary care physicians (PCPs) often find themselves in the situation in which a patient's cardiologist institutes therapy with clopidogrel in combination with low-dose aspirin, but then defers routine follow-up back to the PCP. This combination offers certain theoretical benefits. Platelet activation is a critical step in the formation of thrombotic clots. Aspirin inhibits the production of thromboxanes, which play a prominent role in platelet activation. Clopidogrel, a thienopyridine, acts by inhibiting adenosine receptors, which play a major role at a different step in platelet activation. Thus, their mechanisms are complementary and may decrease clot formation over either agent alone. Furthermore, resistance to the effects of each agent has been well reported,[1] but resistance to both agents in a given patient should be less frequent. Although this combination of antiplatelet agents has been demonstrated to offer clinical benefits under certain circumstances, it does raise problems as well. Most significantly, the reiterative platelet inhibition increases the likelihood of bleeding. Thus, it is incumbent on the PCP to understand the evidence behind the use of combination therapy and the point at which potential benefits may be offset by its risks. Only then can the PCP make an informed decision about when to return the patient to monotherapy with antiplatelets. Unfortunately, although the literature on this combination of agents is extensive, data regarding the benefits and risks of long-term use are often conflicting. Newer thienopyridines, such as prasugrel, seem to offer both greater benefit and greater risk and may confuse the situation further.[2] This article will outline what is known and make reasonable recommendations for the PCP.
Section 1 of 5
Next Page: Indications for Combination Therapy
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References
1. Gladding P, Webster M, Ormiston J, Olsen S, White H. Antiplatelet drug nonresponsiveness. Am Heart J 2008;155:591–9.
2. Wiviott SD, Braunwald E, McCabe CH, et al. Prasugrel versus clopidogrel in patients with acute coronary syndromes. N Engl J Med 2007;357:2001–15.
3. Bhatt DL, Fox KAA, Hacke W, et al. Clopidogrel and aspirin versus aspirin alone for the prevention of atherosclerotic events. N Engl J Med 2006;354: 1706–17.
4. Fraker TD Jr, Fihn SD, Gibbons RJ. 2007 chronic angina focused update of the ACC/AHA 2002 Guidelines for the management of patients with chronic stable angina: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines Writing Group to develop the focused update of the 2002 Guidelines for the management of patients with chronic stable angina. Circulation 2007;116:2762–72.
5. Diener H-C, Bogousllovsky J, Brass LM, et al. Aspirin and clopidogrel compared with clopidogrel alone after recent ischaemic stroke or transient ischaemic attack in high-risk patients (MATCH): randomised, double-blind, placebo-controlled trial. Lancet 2004;364:331–7.
6. Sabatine MS, Cannon CP, Gibson CM, et al. Addition of clopidogrel to aspirin and fibrinolytic therapy for myocardial infarction with ST-segment elevation. N Engl J Med 2005;352:1179–89.
7. Chen ZM, Jiang LX, Chen YP, et al. Addition of clopidogrel to aspirin in 45,852 patients with acute myocardial infarction: randomised placebo-controlled trial. Lancet 2005;366:1607–21.
8. Antman EM, Hand M, Armstrong PW, et al. 2007 Focused Update of the ACC/AHA 2004 Guidelines for the Management of Patients with ST-Elevation Myocardial Infarction: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines: developed in collaboration with the Canadian Cardiovascular Society endorsed by the American Academy of Family Physicians: 2007 Writing Group to Review New Evidence and Update the ACC/AHA 2004 Guidelines for the Management of Patients with ST-Elevation Myocardial Infarction, writing on behalf of the 2004 Writing Committee. Circulation 2008;117: 296–329.
9. Yusuf S, Zhao F, Mehta SR, et al. Effects of clopidogrel in addition to aspirin in patients with acute coronary syndromes without ST-segment elevation. N Engl J Med 2001;345:494 –502.
10. Bertrand ME, Rupprecht H-J, Urban P, Gershlick AH, CLASSICS Investigators. Double-blind study of the safety of clopidogrel with and without a loading dose in combination with aspirin compared with ticlopidine in combination with aspirin after coronary stenting: the Clopidogrel Aspirin Stent International Cooperative Study (CLASSICS). Circulation 2000;102:624 –9.
11. Steinhubl SR, Berger PB, Mann JT 3rd, et al. Early and sustained dual oral antiplatelet therapy following percutaneous coronary intervention. A randomized controlled trial. JAMA 2002;288:2411–20.
12. Mehta SR, Yusuf S, Peters RJ, et al. Effects of pretreatment with clopidogrel and aspirin followed by long-term therapy in patients undergoing percutaneous coronary intervention: the PCI-CURE study. Lancet 2001;358:527–33.
13. Airoldi F, Colombo A, Morici N, et al. Incidence and predictors of drug-eluting stent thrombosis during and after discontinuation of thienopyridine treatment. Circulation 2007;116:745–54.
14. Iakovou I, Schmidt T, Bonizzoni E, et al. Incidence, predictors, and outcome of thrombosis after successful implantation of drug-eluting stents. JAMA 2005; 293):2126 –30.
15. Finn AV, Nakazawa G, Joner M, et al. Vascular responses to drug eluting stents: importance of delayed healing. Arterioscler Thromb Vasc Biol 2007; 27:1500–10.
16. Lagerqvist B, James SK, Stenestrand U, et al. Longterm outcomes with drug-eluting stents versus baremetal stents in Sweden. N Engl J Med 2007;356: 1009–19.
17. Kastrati A, Mehilli J, Pache J, et al. Analysis of 14 trial comparing sirolimus-eluting stents with baremetal stents. N Engl J Med 2007;356:1030 –9.
18. Grines CL, Bonow RO, Casey DE Jr, et al. Prevention of premature discontinuation of dual antiplatelet therapy in patients with coronary artery stents: a science advisory from the American Heart Association, American College of Cardiology, Society for Cardiovascular Angiography and Interventions, American College of Surgeons, and American Dental Association, with representation from the American College of Physicians. Circulation 2007;115: 813–8.
19. Eisenstein EL, Anstrom KJ, Kong DF, et al. Clopidogrel use and long-term clinical outcomes after drugeluting stent implantation. JAMA 2007;297:159–68.
20. Daemen J, Wenaweser P, Tsuchida K, et al. Early and late coronary stent thrombosis of sirolimus-eluting and paclitaxel-eluting stents in routine clinical practice: data from a large two-institutional cohort study. Lancet 2007;369:667–78.
21. Bhatt DL, Flather MD, Hacke W, et al. Patients with prior myocardial infarction, stroke, or symptomatic peripheral areterial disease in the CHARISMA trial. J Am Coll Cardiol 2007;49:1982– 8.
22. Hallas J, Dall M, Andries A, et al. Use of single and combined antithrombotic therapy and risk of serious upper gastrointestinal bleeding: population based case-control study. BMJ 2006;333:726 –30.
23. Delaney JA, Opatrny L, Brophy JM, Suissa S. Drugdrug interactions between antithrombotic medications and the risk of gastrointestinal bleeding. CMAJ 2007;177:347–51.
24. Verheugt FW, Clappers N. Incidence of severe bleeding with long-term clopidogrel-aspirin combination: comparison with chronic warfarin therapy [abstract]. Circulation 2007;116(suppl II):441.
25. Ebell MH, Siwek J, Weiss BD, et al. Strength of recommendation taxonomy (SORT): a patient-centered approach to grading evidence in the medical literature. J Am Board Fam Pract 2004;17:59–67.
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Author Information
Chris Terpening, PhD, PharmD, from the Departments of Family Medicine and Clinical Pharmacy, West Virginia University, Charleston Division
J Am Board Fam Med. 2009;22(1):51-56. ©2009 American Board of Family Medicine
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Medscape MedscapeCME eMedicine Drugs MEDLINE All
J Goossens
Account Settings | Log Out | Newsletters
Gastroenterology
* Latest
* News
* Conferences
* Journals
* Resource Centers
* Viewpoints
IN THIS ARTICLE
* Abstract and Introduction
* Indications for Combination Therapy
* Benefits of Long-Term Use of Combination Therapy
* Bleeding Risks with Combination Therapy
* Conclusions
* Tables
* References
* Printer-Friendly Printer-Friendly
* Email This Email This
* Discuss This Discuss This
From Journal of the American Board of Family Medicine
An Appraisal of Dual Antiplatelet Therapy with Clopidogrel and Aspirin for Prevention of Cardiovascular Events
Posted 03/10/2009
Chris Terpening, PhD, PharmD
Author Information
Information from Industry
NAMENDA® (memantine HCl) ––The first and only NMDA–receptor antagonist for the treatment of moderate to severe Alzheimer's disease. NAMENDA has been used by over 2 million patients worldwide.Read Important Safety Information and Prescribing Information.
Abstract and Introduction
Abstract
Combination antiplatelet therapy, typically with clopidogrel and aspirin, is commonly used for the prevention of cardiovascular events. When used for appropriate indications and duration, its benefits clearly outweigh its risks. However, it is not uncommon for the combination to be used outside of recommended indications or for longer than recommended durations. In these circumstances data are at best unclear and, at worst, indicative of harm. Furthermore, use for one of its indications—prevention of cardiac events after deployment of a coronary stent—is complicated by the type of stent used. This report reviews the evidence surrounding combination antiplatelet therapy with clopidogrel and aspirin, with an emphasis on identifying appropriate indications for and durations of therapy.
Introduction
Primary care physicians (PCPs) often find themselves in the situation in which a patient's cardiologist institutes therapy with clopidogrel in combination with low-dose aspirin, but then defers routine follow-up back to the PCP. This combination offers certain theoretical benefits. Platelet activation is a critical step in the formation of thrombotic clots. Aspirin inhibits the production of thromboxanes, which play a prominent role in platelet activation. Clopidogrel, a thienopyridine, acts by inhibiting adenosine receptors, which play a major role at a different step in platelet activation. Thus, their mechanisms are complementary and may decrease clot formation over either agent alone. Furthermore, resistance to the effects of each agent has been well reported,[1] but resistance to both agents in a given patient should be less frequent. Although this combination of antiplatelet agents has been demonstrated to offer clinical benefits under certain circumstances, it does raise problems as well. Most significantly, the reiterative platelet inhibition increases the likelihood of bleeding. Thus, it is incumbent on the PCP to understand the evidence behind the use of combination therapy and the point at which potential benefits may be offset by its risks. Only then can the PCP make an informed decision about when to return the patient to monotherapy with antiplatelets. Unfortunately, although the literature on this combination of agents is extensive, data regarding the benefits and risks of long-term use are often conflicting. Newer thienopyridines, such as prasugrel, seem to offer both greater benefit and greater risk and may confuse the situation further.[2] This article will outline what is known and make reasonable recommendations for the PCP.
Section 1 of 5
Next Page: Indications for Combination Therapy
* Printer-Friendly Printer- Friendly
* Email ThisEmail This
[ CLOSE WINDOW ]
References
1. Gladding P, Webster M, Ormiston J, Olsen S, White H. Antiplatelet drug nonresponsiveness. Am Heart J 2008;155:591–9.
2. Wiviott SD, Braunwald E, McCabe CH, et al. Prasugrel versus clopidogrel in patients with acute coronary syndromes. N Engl J Med 2007;357:2001–15.
3. Bhatt DL, Fox KAA, Hacke W, et al. Clopidogrel and aspirin versus aspirin alone for the prevention of atherosclerotic events. N Engl J Med 2006;354: 1706–17.
4. Fraker TD Jr, Fihn SD, Gibbons RJ. 2007 chronic angina focused update of the ACC/AHA 2002 Guidelines for the management of patients with chronic stable angina: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines Writing Group to develop the focused update of the 2002 Guidelines for the management of patients with chronic stable angina. Circulation 2007;116:2762–72.
5. Diener H-C, Bogousllovsky J, Brass LM, et al. Aspirin and clopidogrel compared with clopidogrel alone after recent ischaemic stroke or transient ischaemic attack in high-risk patients (MATCH): randomised, double-blind, placebo-controlled trial. Lancet 2004;364:331–7.
6. Sabatine MS, Cannon CP, Gibson CM, et al. Addition of clopidogrel to aspirin and fibrinolytic therapy for myocardial infarction with ST-segment elevation. N Engl J Med 2005;352:1179–89.
7. Chen ZM, Jiang LX, Chen YP, et al. Addition of clopidogrel to aspirin in 45,852 patients with acute myocardial infarction: randomised placebo-controlled trial. Lancet 2005;366:1607–21.
8. Antman EM, Hand M, Armstrong PW, et al. 2007 Focused Update of the ACC/AHA 2004 Guidelines for the Management of Patients with ST-Elevation Myocardial Infarction: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines: developed in collaboration with the Canadian Cardiovascular Society endorsed by the American Academy of Family Physicians: 2007 Writing Group to Review New Evidence and Update the ACC/AHA 2004 Guidelines for the Management of Patients with ST-Elevation Myocardial Infarction, writing on behalf of the 2004 Writing Committee. Circulation 2008;117: 296–329.
9. Yusuf S, Zhao F, Mehta SR, et al. Effects of clopidogrel in addition to aspirin in patients with acute coronary syndromes without ST-segment elevation. N Engl J Med 2001;345:494 –502.
10. Bertrand ME, Rupprecht H-J, Urban P, Gershlick AH, CLASSICS Investigators. Double-blind study of the safety of clopidogrel with and without a loading dose in combination with aspirin compared with ticlopidine in combination with aspirin after coronary stenting: the Clopidogrel Aspirin Stent International Cooperative Study (CLASSICS). Circulation 2000;102:624 –9.
11. Steinhubl SR, Berger PB, Mann JT 3rd, et al. Early and sustained dual oral antiplatelet therapy following percutaneous coronary intervention. A randomized controlled trial. JAMA 2002;288:2411–20.
12. Mehta SR, Yusuf S, Peters RJ, et al. Effects of pretreatment with clopidogrel and aspirin followed by long-term therapy in patients undergoing percutaneous coronary intervention: the PCI-CURE study. Lancet 2001;358:527–33.
13. Airoldi F, Colombo A, Morici N, et al. Incidence and predictors of drug-eluting stent thrombosis during and after discontinuation of thienopyridine treatment. Circulation 2007;116:745–54.
14. Iakovou I, Schmidt T, Bonizzoni E, et al. Incidence, predictors, and outcome of thrombosis after successful implantation of drug-eluting stents. JAMA 2005; 293):2126 –30.
15. Finn AV, Nakazawa G, Joner M, et al. Vascular responses to drug eluting stents: importance of delayed healing. Arterioscler Thromb Vasc Biol 2007; 27:1500–10.
16. Lagerqvist B, James SK, Stenestrand U, et al. Longterm outcomes with drug-eluting stents versus baremetal stents in Sweden. N Engl J Med 2007;356: 1009–19.
17. Kastrati A, Mehilli J, Pache J, et al. Analysis of 14 trial comparing sirolimus-eluting stents with baremetal stents. N Engl J Med 2007;356:1030 –9.
18. Grines CL, Bonow RO, Casey DE Jr, et al. Prevention of premature discontinuation of dual antiplatelet therapy in patients with coronary artery stents: a science advisory from the American Heart Association, American College of Cardiology, Society for Cardiovascular Angiography and Interventions, American College of Surgeons, and American Dental Association, with representation from the American College of Physicians. Circulation 2007;115: 813–8.
19. Eisenstein EL, Anstrom KJ, Kong DF, et al. Clopidogrel use and long-term clinical outcomes after drugeluting stent implantation. JAMA 2007;297:159–68.
20. Daemen J, Wenaweser P, Tsuchida K, et al. Early and late coronary stent thrombosis of sirolimus-eluting and paclitaxel-eluting stents in routine clinical practice: data from a large two-institutional cohort study. Lancet 2007;369:667–78.
21. Bhatt DL, Flather MD, Hacke W, et al. Patients with prior myocardial infarction, stroke, or symptomatic peripheral areterial disease in the CHARISMA trial. J Am Coll Cardiol 2007;49:1982– 8.
22. Hallas J, Dall M, Andries A, et al. Use of single and combined antithrombotic therapy and risk of serious upper gastrointestinal bleeding: population based case-control study. BMJ 2006;333:726 –30.
23. Delaney JA, Opatrny L, Brophy JM, Suissa S. Drugdrug interactions between antithrombotic medications and the risk of gastrointestinal bleeding. CMAJ 2007;177:347–51.
24. Verheugt FW, Clappers N. Incidence of severe bleeding with long-term clopidogrel-aspirin combination: comparison with chronic warfarin therapy [abstract]. Circulation 2007;116(suppl II):441.
25. Ebell MH, Siwek J, Weiss BD, et al. Strength of recommendation taxonomy (SORT): a patient-centered approach to grading evidence in the medical literature. J Am Board Fam Pract 2004;17:59–67.
[ CLOSE WINDOW ]
Related Links
[ CLOSE WINDOW ]
Author Information
Chris Terpening, PhD, PharmD, from the Departments of Family Medicine and Clinical Pharmacy, West Virginia University, Charleston Division
J Am Board Fam Med. 2009;22(1):51-56. ©2009 American Board of Family Medicine
Medscape MedscapeCME eMedicine Drugs MEDLINE All
* About Medscape
* Privacy Policy
* Terms of Use
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* Help
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All material on this website is protected by copyright, Copyright © 1994-2009 by Medscape. This website also contains material copyrighted by 3rd parties.
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# posted by roodbont @ 11:32 AM 
