Which drugs should post-MI patients routinely receive?

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Clinical Inquiries

Which drugs should post-MI patients routinely receive?

J Fam Pract. 2010 September;59(9):527-529

By

Victor Lin, MD

John R. Holman, MD, MPH

Barbara Jamieson, MLS

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References

1. Collaborative overview of randomized trials of antiplatelet therapy: prevention of death, myocardial infarction, and stroke by prolonged antiplatelet therapy in various categories of people. Antiplatelet Trialists’ Collaboration. BMJ. 1994;308:81-106.

2. Randomized trial of intravenous streptokinase, oral aspirin, both, or neither among 17,187 cases of suspected acute myocardial infarction: ISIS-2. Second International Study of Infarct Survival (ISIS-2) Collaborative Group. Lancet. 1988;2:349-360.

3. 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.

4. 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;366:1607-1621.

5. Ray KK, Cannon CP, McCabe CH, et al. Early and late benefits of high-dose atorvastatin in patients with acute coronary syndromes: results from the PROVE IT-TIMI 22 trial. J Am Coll Cardiol. 2005;46:1405-1410.

6. Yusuf S, Peto R, Lewis J, et al. Beta-blockade during and after myocardial infarction: an overview of the randomized trials. Prog Cardiovasc Dis. 1985;27:335-371.

7. Freemantle N, Cleland J, Young P, et al. Beta blockade after myocardial infarction: systematic review and meta regression analysis. BMJ. 1999;318:1730-1737.

8. Domanski MJ, Exner DV, Borkowf CB, et al. Effect of angiotensin converting enzyme inhibition on sudden cardiac death in patients following acute myocardial infarction. A meta-analysis of randomized clinical trials. J Am Coll Cardiol. 1999;33:598-604.

9. Pitt B, White H, Nicolau J, et al. Eplerenone reduces mortality 30 days post-randomization following acute myocardial infarction in patients with left ventricular systolic dysfunction and heart failure. J Am Coll Cardiol. 2005;46:425-431.

10. Smith SC, Jr, Allen J, Blair SN, et al. AHA/ACC guidelines for secondary prevention for patients with coronary and other atherosclerotic vascular disease: 2006 update: endorsed by the National Heart, Lung, and Blood Institute. Circulation. 2006;113:2363-2372.

11. Anderson JL, Adams CD, Antman EM, et al. ACC/AHA 2007 guidelines for the management of patients with unstable angina/non–ST-elevation myocardial infarction. J Am Coll Cardiol. 2007;50:e1-e157.

12. Antman EM, Hand M, Armstron 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. J Am Coll Cardiol. 2008;51:210-247.

13. National Institute for Health and Clinical Excellence (NICE). Clinical guideline 48. Secondary prevention in primary and secondary care for patients following a myocardial infarction. London: NICE; 2007. Available at: http://guidance.nice.org.uk/CG48. Accessed March 7, 2010.

EVIDENCE-BASED ANSWER

PATIENTS SHOULD BE PLACED ON THE FOLLOWING MEDICATIONS :

antiplatelet agents (strength of recommendation [SOR]: A, meta-analysis for aspirin; A, multiple randomized controlled trials [RCTs] for aspirin plus clopidogrel)
a statin; atorvastatin has the best evidence (SOR: B, a single RCT)
a beta-blocker (SOR: A, meta-analysis)
renin-angiotensin-aldosterone system blockers, whether or not the ejection fraction is diminished after myocardial infarction (MI) (SOR: A, meta-analysis for angiotensin-converting enzyme [ACE] inhibitor; B, single RCT for ACE inhibitor plus aldosterone blocker). ( TABLE )

Evidence summary

A systematic review of 9 RCTs demonstrated that aspirin (75-325 mg) started soon after the onset of acute MI significantly reduced mortality, reinfarction, and stroke at 1 month compared with placebo (absolute risk reduction [ARR]=3.8%; number needed to treat [NNT]=26; 95% confidence interval [CI], 23-30).¹

One large RCT involving 17,187 patients with suspected acute MI showed that 162 mg aspirin given on the day of the MI resulted in a 2.6% ARR (NNT=38; 95% CI, 29-63) in vascular deaths at 35 days compared with placebo.² The survival benefit persisted for as long as 10 years. The RCT also found no significant difference between aspirin and placebo in rates of cerebral hemorrhage or bleeding requiring transfusions.

FAST TRACK

Starting aspirin soon after an acute MI reduces mortality, reinfarction, and stroke at 1 month.

Patients who have had an MI without ST segment elevation should take clopidogrel (75 mg/d) and aspirin (81 mg/d) for 12 months. The combination has been shown to result in a 2.1% ARR (NNT=48) in deaths, recurrent MI, and stroke compared with aspirin alone.³ Patients who have had an ST segment elevation MI should take clopidogrel in combination with aspirin for at least 2 weeks.⁴

TABLE
Recommended drugs for post-MI patients

Drug type	Examples	Precautions	Contraindications
Antiplatelet agents	Aspirin 81 mg/d; clopidogrel 75 mg/d	Risk for bleeding; use caution in patients taking warfarin	Active bleeding; hypersensitivity
RAAS blockers	Lisinopril 20 mg/d; losartan 50 mg/d; eplerenone 50 mg/d	Hypotension, hyperkalemia, renal failure Use eplerenone only with decreased ejection fraction	Hypersensitivity; systolic blood pressure <90 mm Hg
Beta-blockers	Metoprolol 100 mg bid	Hypotension, bradycardia, reactive airways	Systolic blood pressure <90 mm Hg; pulse rate <50 bpm
Statins	Atorvastatin 80 mg/d	Elevated AST/ALT, myositis	Active liver disease; pregnancy/nursing
ALT, alanine aminotransferase; AST, aspartate aminotransferase; BPM, beats per minute; RAAS, renin-angiotensin-aldosterone system.

Intensive atorvastatin therapy lowers risk of death

FAST TRACK

Patients who have had an MI without ST segment elevation should take clopidogrel and aspirin for 12 months.

The PROVE IT-TIMI 22 trial showed the benefit of early intensive therapy with the hydroxymethyl glutaryl coenzyme A reductase inhibitor atorvastatin to lower low-density lipoprotein <70 mg/dL post-MI.⁵ At 30 days after the event, atorvastatin 80 mg daily resulted in a 1.2% ARR in death and recurrent acute coronary syndrome (NNT=83; hazard ratio [HR]=0.72; 95% CI, 0.52-0.99). From 6 months to 24 months after the event, the ARR was 2.6% (NNT=38; HR=0.82; 95% CI, 0.69-0.99).

Beta-blockers significantly decrease late mortality
One systematic review of 63 RCTs showed that, in long-term trials, use of a beta-blocker significantly reduced the late mortality rate (NNT=48; odds ratio [OR]=0.77; 95% CI, 0.70-0.85).⁶ In another review of 82 RCTs, the mortality rate between 6 months and 4 years after MI decreased markedly in patients receiving a beta-blocker (OR=0.77; 95% CI, 0.69-0.85).⁷

ACE inhibitors decrease overall mortality, sudden cardiac death
An ACE inhibitor should be started regardless of the ejection fraction or the presence or absence of left ventricular systolic dysfunction. One systematic review that compared long-term mortality rates of patients started on an ACE inhibitor within 14 days of acute MI versus placebo found that ACE inhibitors significantly decreased overall mortality and sudden cardiac deaths between 2 and 42 months after the MI (NNT=42; OR=0.83; 95% CI, 0.71-0.97).⁸

Evidence-based answers from the Family Physicians Inquiries Network