Aspirin for CV prevention—for which patients?

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Applied Evidence

Aspirin for CV prevention—for which patients?

J Fam Pract. 2011 September;60(9):518-523

By

Anita N. Jackson, PharmD

Anne L. Hume, PharmD, FCCP, BCPS

Put your patient on aspirin? Take him off? Here’s what you need to know to get it right.

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References

1. Sanchez DR, Diez Roux AV, Michos ED, et al. Comparison of the racial/ethnic prevalence of regular aspirin use for the primary prevention of coronary heart disease from the multi-ethnic study of atherosclerosis. Am J Cardiol. 2011;107:41-46.

2. Dwivedi G, Ball MC, Dilworth MP, et al. Use and misuse of aspirin in the hypertension clinic [letter]. BMJ. May 3, 2010. Available at: http://www.bmj.com/content/340/bmj.c1805.full/reply#bmj_el_235118. Accessed October 15, 2010.

3. American Diabetes Association. Standards of medical care in diabetes–2010. Diabetes Care. 2010;33(suppl 1):S11-S61.

4. US Preventive Services Task Force. Aspirin for the primary prevention of cardiovascular events: recommendation and rationale. Ann Intern Med. 2002;136:157-160.

5. Thrombosis prevention trial: randomised trial of low-intensity oral anticoagulation with warfarin and low-dose aspirin in the primary prevention of ischaemic heart disease in men at increased risk. The Medical Research Council’s General Practice Research Framework. Lancet. 1998;351:233-241.

6. Peto R, Gray R, Collins R. Randomised trial of prophylactic daily aspirin in British male doctors. BMJ. 1988;296:313-316.

7. Final report on the aspirin component of the ongoing Physicians’ Health Study. Steering Committee of the Physicians’ Health Study Research Group. N Engl J Med. 1989;321:129-135.

8. Hansson L, Zanchetti A, Carruthers SG. Effects of intensive blood-pressure lowering and low-dose aspirin in patients with hypertension: principal results of the Hypertension Optimal Treatment (HOT) randomised trial. Lancet. 1998;351:1755-1762.

9. de Gaetano G. Collaborative Group of the Primary Prevention Project. Low-dose aspirin and vitamin E in people at cardiovascular risk: a randomised trial in general practice. Lancet. 2001;357:89-95.

10. Wolff T, Miller T, Ko S. Aspirin for the prevention of cardiovascular disease: an update of the evidence for the US Preventive Services Task Force. Ann Intern Med. 2009;150:405-410.

11. Ridker PM, Cook NR, Lee IM. A randomized trial of low-dose aspirin in the primary prevention of cardiovascular disease in women. N Engl J Med. 2005;352:1293-1304.

12. Pearson TA, Blair SN, Daniels SR, et al. AHA guidelines for primary prevention of cardiovascular disease and stroke: 2002 update: consensus panel guide to comprehensive risk reduction for adult patients without coronary or other atherosclerotic vascular diseases. Circulation. 2002;106:388-391.

13. Wilson PW, D’Agostino RB, Levy D, et al. Prediction of coronary heart disease using risk factor categories. Circulation. 1998;97:1837-1847.

14. National Cholesterol Education Program. Risk assessment tool for estimating 10-year risk of developing hard CHD. Available at: http://hp2010.nhlbihin.net/atpiii/calculator.asp?usertype=prof. Accessed October 15, 2010.

15. Bhatt DL, Scheiman J, Abraham NS, et al. ACCF/ACG/AHA 2008 expert consensus document on reducing the gastrointestinal risks of antiplatelet therapy and NSAID use. Circulation. 2008;118:1894-1909.

16. Garcia Rodriguez LA, Lin KJ, Hernandez-Diaz S, et al. Risk of upper gastrointestinal bleeding with low-dose acetylsalicylic acid alone and in combination with clopidogrel and other medications. Circulation. 2011;123:1108-1115.

17. Lai KC, Lam SK, Chu Km, et al. Lansoprazole for the prevention of recurrences of ulcer complications from long-term low-dose aspirin use. N Engl J Med. 2002;346:2033-2038.

18. Antithrombotic Trialists’ (ATT) Collaboration. Aspirin in the primary and secondary prevention of vascular disease: collaborative meta-analysis of individual participant data from randomised trials. Lancet. 2009;373:1849-1860.

19. McQuaid KR, Laine L. Systematic review and meta-analysis of adverse events of low-dose aspirin and clopidogrel in randomized controlled trials. Am J Med. 2006;119:624-638.

20. Fowkes FG, Price JF, Stewart MCW, et al. Aspirin for the prevention of cardiovascular events in a general population screened for a low ankle brachial index: a randomized controlled trial. JAMA. 2010;303:841-848.

21. Kuliczkowski W, Witkowski A, Polonski L, et al. Interindividual variability in the response to oral antiplatelet drugs: a position paper of the working group on antiplatelet drugs resistance appointed by the section of cardiovascular interventions of the Polish Cardiac Society, endorsed by the working group on thrombosis of the European Society of Cardiology. Eur Heart J. 2009;30:426-435.

22. Hovens MM, Snoep JD, Eidenboom JC. Prevalence of persistent platelet reactivity despite use of aspirin: a systematic review. Am Heart J. 2007;153:175-181.

23. Gurbel PA, Bliden KP, DiChiara JD, et al. Evaluation of dose-related effects of aspirin on platelet function: results from the Aspirin-Induced Platelet Effect (ASPECT) study. Circulation. 2007;115:3156-3164.

24. Feher G, Geher A, Pusch G, et al. Clinical importance of aspirin and clopidogrel resistance. World J Cardiol. 2010;2:171-186.

25. Krasopoulos G, Brister SJ, Beattie WS, et al. Aspirin “resistance” and risk of cardiovascular morbidity: systematic review and meta-analysis. BMJ. 2008;336:195-198.

26. Hobikoglu GF, Norgaz T, Aksu H, et al. The effect of acetylsalicylic acid resistance on prognosis of patients who have developed acute coronary syndrome during acetylsalicylic acid therapy. Can J Cardiol. 2007;23:201-206.

27. Gasparyan AY, Watson T, Lip GYH. The role of aspirin in cardiovascular prevention: implications of aspirin resistance. J Am Coll Cardiol. 2008;51:1829-1843.

28. Arazi HC, Doiny DG, Torcivia RS, et al. Impaired anti-platelet effect of aspirin, inflammation and platelet turnover in cardiac surgery. Interact Cardiovasc Thorac Surg. 2010;10:863-867.

29. Hennekens CH, Schneider WR, Hebert PR, et al. Hypothesis formulation from subgroup analyses: nonadherence or nonsteroidal anti-inflammatory drug use explains the lack of clinical benefit of aspirin on first myocardial infarction attributed to “aspirin resistance.” Am Heart J. 2010;159:744-748.

30. Gengo FM, Rubin L, Robson M, et al. Effects of ibuprofen on the magnitude and duration of aspirin’s inhibition of platelet aggregation; clinical consequences in stroke prophylaxis. J Clin Pharmacol. 2008;48:117-122.

31. Belch J, MacCuish A, Campbell I, et al. The prevention of progression of arterial disease and diabetes (POPADAD) trial: factorial randomised placebo controlled trial of aspirin and antioxidants in patients with diabetes and asymptomatic peripheral arterial disease. BMJ. 2008;337:a1840.-

32. Ogawa H, Nakayama M, Morimoto T, et al. Low dose aspirin for primary prevention of atherosclerotic events in patients with type 2 diabetes: a randomized controlled trial. JAMA. 2008;300:2134-2141.

33. Pignone M, Alberts MJ, Colwell JA, et al. Aspirin for primary prevention of cardiovascular events in people with diabetes. A position statement of the American Diabetes Association, a scientific statement of the American Heart Association, and an expert consensus document of the American College of Cardiology Foundation. Circulation. 2010;121:2694-2701.

34. Barrett-Connor E, Giardina EG, Gitt AK, et al. Women and heart disease: the role of diabetes and hyperglycemia. Arch Intern Med. 2004;164:934-942.

35. Mosca L, Benjamin EJ, Berra K, et al. Effectiveness-based guidelines for the prevention of cardiovascular disease in women—2011 update. Circulation. 2011;123:1243-1262.

PRACTICE RECOMMENDATIONS

• Calculate a patient’s 10-year global risk of cardiovascular events using a risk-assessment tool before recommending aspirin for primary prevention. A

• Keep in mind that diabetes is not an indication for aspirin as primary cardiovascular protection, unless the patient’s calculated 10-year risk is >10%. A

Strength of recommendation (SOR)

A Good-quality patient-oriented evidence
B Inconsistent or limited-quality patient-oriented evidence
C Consensus, usual practice, opinion, disease-oriented evidence, case series

Among individuals at high risk (≥10%) for coronary heart disease (CHD) within 10 years, only 44% are taking aspirin.¹ In addition, for patients at high risk for CHD events, estimated aspirin use varies among ethnic groups: 53% for whites, 43% for African Americans, 38% for Hispanics, and 28% for Chinese Americans.¹

In contrast to this underuse of aspirin by those who need it, patients who do not need aspirin have been told otherwise,² following widespread publicity of US Preventive Services Task Force (USPSTF) recommendations from 2002 (that have since been updated). Overuse of aspirin is also likely among individuals whose CHD risk has never been formally assessed but who take it on their own, based on direct-to-consumer advertising about the cardiovascular (CV) benefits of aspirin. Also, the American Diabetes Association (ADA) once recommended aspirin for all patients with diabetes. But it now advises avoiding the use of aspirin for primary prevention of CV events unless a patient’s calculated CV risk over 10 years is >10%.³

Our review summarizes the latest evidence on the use of aspirin for primary prevention of CV events, including the determination of benefit vs harm, the variability in aspirin responsiveness among individuals, and the efficacy of aspirin treatment in men vs women and in those with diabetes.

When does benefit outweigh risk?

In 2002, the USPSTF concluded that patients with a 5-year risk of coronary events ≥3% had the most favorable benefit-to-risk ratio with aspirin use.⁴ It based its recommendation on 5 randomized, controlled primary prevention studies with aspirin that demonstrated a reduction in the risk of a first myocardial infarction (MI) in men.^5-9 In 2009, the USPSTF updated its recommendations regarding the risks and benefits of aspirin for primary prevention of CHD,¹⁰ in part to include data from the Women’s Health Study¹¹ that demonstrated a 24% relative risk (RR) reduction of ischemic stroke without reducing the risk of MI.

The USPSTF now recommends aspirin for men ages 45 to 79 to prevent a first MI, and for women ages 55 to 79 to prevent an ischemic stroke when the potential benefit outweighs the increased risk of gastrointestinal (GI) hemorrhage.¹⁰ Evidence does not support the use of aspirin for primary CHD prevention in men younger than 45 years or women younger than 55. Evidence is insufficient to recommend aspirin for primary prevention of CHD for individuals ≥80 years of age in the absence of other compelling indications such as atrial fibrillation.

FAST TRACK

The AHA recommends low-dose aspirin for primary prevention of CV events in patients with a calculated 10-year risk ≥10%, taking into account risks for bleeding.

Calculating benefit. The American Heart Association (AHA) recommends low-dose aspirin for primary prevention of CV events in all individuals with a calculated 10-year CHD risk of ≥10%, while cautioning about its use in patients at increased risk for GI bleeding and hemorrhagic stroke.¹² The Framingham risk score¹³ is available online at http://hp2010.nhlbihin.net/atpiii/calculator.asp?usertype=prof to estimate an individual’s 10-year CHD risk (TABLE).¹⁴

Judging risk. There are no validated tools for assessing the long-term risk of intracranial or GI hemorrhage with low-dose aspirin. The risk factors for GI bleeding with nonsteroidal anti-inflammatory drugs (NSAIDs) are well known,¹⁵ but less data exist for low-dose aspirin. Likely risk factors include a history of peptic ulcer disease, concomitant NSAID therapy, high-dose corticosteroids or anticoagulants, dual antiplatelet therapy, age >60 years, and male sex.¹⁶ Although proton-pump inhibitors prevent recurrent peptic ulcers secondary to low-dose aspirin use, little data exist on their value or cost effectiveness for this purpose.¹⁷

Why the AHA recommendation makes sense. The 2009 USPSTF recommendations still identify different tiers of risk according to 3 age brackets within the range of 45 (or 55) to 79 years. Since then, however, further studies seem to favor a less aggressive approach to aspirin use, more in keeping with the AHA recommendation.

The Antithrombotic Trialists’ (ATT) Collaboration¹⁸ published a meta-analysis using individual participant data from the same studies that served as the basis of the USPSTF recommendations.^5-9,11 It found that aspirin did not reduce the risk of death due to CHD, stroke, or other vascular causes. The risk of nonfatal stroke also did not decline. Aspirin use decreased the risk of nonfatal MI (RR=0.77; 99% confidence interval [CI], 0.67-0.89), any major coronary event (RR=0.82; 95% CI, 0.75-0.90), and serious vascular events (RR=0.88; 95% CI, 0.82-0.94). The risk of extracranial hemorrhage, including GI bleeding, increased (RR=1.54; 95% CI, 1.30-1.82). Based on this analysis, the absolute reduction in serious ischemic events was partially offset by a small increase in serious bleeding. However, long-term disability from a nonfatal extracranial hemorrhage is likely less than that from a nonfatal stroke or MI.¹⁸