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)

Holman, John R.

Jamieson, Barbara

Lin, Victor

University of Missouri: MOspace

Evidence-based answers from the Family Physicians Inquiries Network527JFPONLINE.COM VOL 59, NO 9  |  SEPTEMBER 2010  |  THE JOURNAL OF FAMILY PRACTICEStarting aspirin soon after an acute MI reduces mortality, reinfarction, and stroke at 1 month.Victor Lin, MD; John R. Holman, MD, MPHCamp Lejeune, NC (Dr. Lin); Dewert Branch Clinic, Bridgeport, Calif (Dr. Holman)Barbara Jamieson, MLSMedical College of Wisconsin, MilwaukeeEVIDENCE-BASED ANSWERWhich drugs should post-MIpatients routinely receive?      patients should be placed on     the following medications           (TABLE): •   antiplatelet agents (strength of recom-mendation [SOR]: A, meta-analysis for aspirin; A, multiple randomized controlled trials [RCTs] for aspirin plus clopidogrel)•   a statin; atorvastatin has the best evi-dence (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).AEvidence summaryA systematic review of 9 RCTs demonstrated that aspirin (75-325 mg) started soon after the onset of acute MI signifi cantly reduced mortality, reinfarction, and stroke at 1 month compared with placebo (absolute risk reduc-tion [ARR]=3.8%; number needed to treat [NNT]=26; 95% confi dence interval [CI], 23-30).1One 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 vas-cular deaths at 35 days compared with place-bo.2 Th e survival benefi t persisted for as long as 10 years. Th e RCT also found no signifi -cant diff erence between aspirin and placebo in rates of cerebral hemorrhage or bleeding requiring transfusions. Patients who have had an MI without ST segment elevation should take clopidogrel (75 mg/d) and aspirin (81 mg/d) for 12 months. Th e combination has been shown to result in a 2.1% ARR (NNT=48) in deaths, recurrent MI, and stroke compared with aspirin alone.3 Pa-tients who have had an ST segment elevation MI should take clopidogrel in combination with aspirin for at least 2 weeks.4 Intensive atorvastatin therapy lowers risk of deathTh e PROVE IT-TIMI 22 trial showed the ben-efi t of early intensive therapy with the hy-droxymethyl glutaryl coenzyme A reductase inhibitor atorvastatin to lower low-density lipoprotein <70 mg/dL post-MI.5 At 30 days af-ter 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 signifi cantly decrease late mortalityOne systematic review of 63 RCTs showed that, in long-term trials, use of a beta-blocker signifi cantly 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 mor-tality 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 deathAn ACE inhibitor should be started regard-528 THE JOURNAL OF FAMILY PRACTICE  |   SEPTEMBER 2010  |   VOL 59, NO 9Patients who have had an MI without ST segment elevation should take clopidogrel and aspirin for 12 months.less of the ejection fraction or the presence or absence of left ventricular systolic dysfunc-tion. 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 inhibi-tors signifi cantly 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 Eplerenone + ACE inhibitor benefi t patients with post-MI heart failureTh e selective aldosterone blocker eplerenone appears to benefi t patients with a decreased ejection fraction post-MI. Th e EPHESUS study demonstrated that eplerenone, when added to an ACE inhibitor, reduced all-cause mortality (ARR=1.4%; NNT=71; 95% CI, 47-200; RR=0.69; 95% CI, 0.54-0.89) and sud-den cardiac death (ARR=0.5%; NNT=200; 95% CI, 125-∞; RR=0.63; 95% CI, 0.40-1.00) up to 30 days in patients with post-MI heart fail-ure. Benefi ts were also seen after 16 months of treatment.9 Recommendations Th e American College of Cardiology (ACC) and American Heart Association (AHA) provide the following recommendations in their joint 2006 Guidelines for Secondary Prevention for Pa-tients with Coronary and Other Atherosclerotic Vascular Disease:10•   Low-dose aspirin should be used, as well as clopidogrel in combination with aspirin for up to 12 months after a non-ST elevation MI•   ACE inhibitors or angiotensin recep-tor blockers should be considered in all patients, and an aldosterone antago-nist should be prescribed for patients with a diminished ejection fraction post-MI•   Beta-blockers should be used in all post-MI patients without contraindications. Th e ACC/AHA 2007 Guidelines for the Management of Patients with Unstable An-gina/Non–ST-Elevation Myocardial Infarction recommend the same medication combina-tions.11 So does the 2007 Focused Update of the ACC/AHA 2004 Guidelines for the Man-Drug type Examples Precautions ContraindicationsAntiplatelet agents Aspirin 81 mg/d;clopidogrel 75 mg/dRisk for bleeding;use caution in patients taking warfarinActive bleeding;hypersensitivity RAAS blockers Lisinopril 20 mg/d;losartan 50 mg/d;eplerenone 50 mg/dHypotension, hyperkalemia, renal failureUse eplerenone only with decreased ejection fractionHypersensitivity;systolic blood pressure 90 mm HgBeta-blockers Metoprolol 100 mg bidHypotension, bradycardia, reactive airwaysSystolic blood pressure 90 mm Hg;pulse rate 50 bpmStatins Atorvastatin 80 mg/dElevated AST/ALT, myositisActive liver disease;pregnancy/nursing ALT, alanine aminotransferase; AST, aspartate aminotransferase; BPM, beats per minute; RAAS, renin-angiotensin-aldosterone system.TABLERecommended drugs for post-MI patients529JFPONLINE.COM VOL 59, NO 9  |  SEPTEMBER 2010  |  THE JOURNAL OF FAMILY PRACTICEWHICH DRUGS FOR POST-MI PATIENTS?Atorvastatin has been found to decrease the risk of death and recurrent acute coronary syndrome.References 1.  Collaborative overview of randomized trials of antiplatelet ther-apy: 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 myo-cardial 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. Eff ects of clopidogrel in addi-tion to aspirin in patients with acute coronary syndromes with-out 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: ran-domised placebo-controlled trial. Lancet. 2005;366:1607-1621. 5.  Ray KK, Cannon CP, McCabe CH, et al. Early and late ben-efi ts of high-dose atorvastatin in patients with acute coro-nary 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 myo-cardial infarction: systematic review and meta regression analy-sis. BMJ. 1999;318:1730-1737.  8.  Domanski MJ, Exner DV, Borkowf CB, et al. Eff ect of angioten-sin converting enzyme inhibition on sudden cardiac death in patients following acute myocardial infarction. A meta-anal-ysis 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 up-date 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 Asso-ciation 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.agement of Patients with ST-Elevation Myo-cardial Infarction, with the exception that clopidogrel in combination with aspirin is rec-ommended for at least 14 days.12Similarly, the British National Institute for Clinical Excellence Clinical Guideline 48 recommends that all post-MI patients be off ered a combination of an ACE inhibitor, aspirin with clopidogrel, a beta-blocker, and a statin.13                JFPACKNOWLEDGMENTThe opinions and assertions contained herein are the private views of the authors and should not be construed as offi cial or as refl ecting the views of the US Department of the Navy or the Department of Defense.Late-onset male hypogonadism and testosterone replacement therapy in primary careThis CME supplement and supporting webcast discuss: • The defi nition, epidemiology, and key signs and symptoms of late-onset hypogonadism • The role of lab measurements • Considerations in selecting patients for testosterone replacement therapy • The best treatment strategies for each patientFACULTY>>  Stephen A. Brunton, MD, FAAFP>>  Richard Sadovsky, MDClick on Supplements/CME at jfponline.com. Or, visit www.jfponline.com/supplements.asp?id=8754FREE1.0 CME CREDITFREE0.5 CME CREDITTo earn an additional 0.5 CME credit, listen to an engaging interview between 2 family physicians—Clinical conversations: Late-onset male hypogonadism and testosterone replacement therapy. www.jfponline.com/Pages.asp?AID=8794AUDIOCASTThe supplement and audiocast were submitted by the Primary Care Education Consortium and supported by an educational grant from Endo Pharmaceuticals, Inc.

Which drugs should post-MI patients routinely receive?

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