β-Blockers in the Post–Myocardial Infarction Patient
2002; Lippincott Williams & Wilkins; Volume: 106; Issue: 4 Linguagem: Inglês
10.1161/01.cir.0000019582.39797.ef
ISSN1524-4539
AutoresMihai Gheorghiade, Sidney Goldstein,
Tópico(s)Antiplatelet Therapy and Cardiovascular Diseases
ResumoHomeCirculationVol. 106, No. 4β-Blockers in the Post–Myocardial Infarction Patient Free AccessReview ArticlePDF/EPUBAboutView PDFView EPUBSections ToolsAdd to favoritesDownload citationsTrack citationsPermissions ShareShare onFacebookTwitterLinked InMendeleyReddit Jump toFree AccessReview ArticlePDF/EPUBβ-Blockers in the Post–Myocardial Infarction Patient Mihai Gheorghiade and Sidney Goldstein Mihai GheorghiadeMihai Gheorghiade From the Division of Cardiology (M.G.), Northwestern Feinberg Medical School, Chicago, Ill; and Division of Cardiovascular Medicine (S.G.), Henry Ford Heart and Vascular Institute, Henry Ford Hospital, Detroit, Mich. and Sidney GoldsteinSidney Goldstein From the Division of Cardiology (M.G.), Northwestern Feinberg Medical School, Chicago, Ill; and Division of Cardiovascular Medicine (S.G.), Henry Ford Heart and Vascular Institute, Henry Ford Hospital, Detroit, Mich. Originally published23 Jul 2002https://doi.org/10.1161/01.CIR.0000019582.39797.EFCirculation. 2002;106:394–398Case 1: A 76-year-old man was diagnosed with an ST-segment elevation anterior wall myocardial infarction (MI) and underwent primary percutaneous coronary intervention with stent placement. After 3 days, the left ventricular ejection fraction was 35%. He was prescribed aspirin, clopidogrel, an angiotensin-converting enzyme (ACE) inhibitor, and a statin.Case 2: A 67-year-old woman with history of hypertension was diagnosed with a non–ST-elevation MI. The left ventricular ejection fraction was 50%. She initially was given an intravenous β-blocker, nitrates, aspirin, an ACE inhibitor, and a statin.Should long-term β-blockers be recommended for both of these patients?The 2001 American Heart Association and American College of Cardiology (AHA/ACC) guidelines for secondary prevention of MI and death recommend initiating β-blockade in all post-MI patients and continuing therapy indefinitely.1Despite strong evidence supporting the use of β-blockers in the post-MI period, less than half of MI patients are prescribed β-blockers in the chronic setting.2,3 Physician reluctance to use β-blockers after acute MI may be related to: (1) a perceived decline of benefits due to the introduction of antiplatelet agents, ACE inhibitors, statins, and revascularization procedures; (2) concerns about safety in patients with heart failure (HF), chronic obstructive pulmonary disease (COPD), diabetes mellitus, and/or old age; (3) side effect profile; and (4) perceived lack of benefit in non–ST-elevation MI.Use of β-Blockade in Contemporary Management of Post-MI PatientsSince it was first reported in 1965 that administration of propranolol after acute MI reduced mortality,4 a number of studies have been conducted to confirm this observation.5 The largest were the β-Blocker Heart Attack Trial (BHAT)6 and the Norwegian Multicenter Study Group7 trial studying nonselective β-blockers. In the BHAT trial (which monitored 3837 post-MI patients for 27 months), propranolol significantly reduced overall mortality by 26% compared with placebo.8 The Norwegian Multicenter Study Group (which monitored 1884 post-MI patients for 12 to 33 months) demonstrated a 39% reduction in mortality and a 28% reduction in the reinfarction rate with timolol (Table 1).7TABLE 1. Comparison of Major β-Blocker Trials in the Chronic Post-MI PeriodTrialCAPRICORN11BHAT8Norwegian7Carvedilol (n=975)Placebo (n=984)Propranolol (n=1916)Placebo (n=1921)Timolol (n=945)Placebo (n=939)N/A indicates not available; NP, not performed.Starting dose, titration, and target dose6.25 mg starting dose, increased progressively to max 25 mg twice daily during 4- to 6-wk period180–240 mg daily5 mg starting dose, increased to 20 mg dailyMean no. days after entry from MI (range)10 (3–21)13.8 (5–21)11.5 (7–28)Inclusion criteriaDocumented MI Left ventricular ejection fraction ≤40% or wall motion score <1.3Documented MIDocumented MIExclusion criteriaContinued requirement for IV inotropic therapy or uncontrolled heart failure Blood pressure <90 mm Hg, heart rate <60 bpm, uncontrolled hypertensionMarked bradycardia History of HF or asthmaUncontrolled HF, heart rate <50 bpm, 2° or 3° atrioventricular block, blood pressure <100 mm Hg Unstable diabetes mellitus, COPD, intermittent claudicationMean age, y (range)63 (29–88)63 (25–90)54.7 (30–69)54.9 (30–69)60.3 (20–75)61.4 (20–75)Men/women, %73/2774/2684/1685/1580/2078/22Mean left ventricular ejection fraction, % (SD)33 (6.4)33 (6.4)NPNPNPNPPrevious MI, %312914131919Previous angina, %575436363838Previous hypertension, %555241401822Previous diabetes mellitus, %21231211N/AN/ARevascularization, %1211N/AN/AN/AN/AThrombolysis/percutaneous coronary intervention, %4547N/AN/AN/AN/AACE inhibitor, %9897N/AN/AN/AN/AAspirin-converting enzyme, %8686N/AN/AN/AN/AAnticoagulant, %63651415N/AN/ANitrates, %7373N/AN/AN/AN/AIV Diuretics, %3533N/AN/AN/AN/AAlthough the results of these studies represented a major advance in post-MI management, they predated the era of modern therapy and did not include patients with HF. With the addition of ACE inhibition into post-MI management algorithms, some clinicians questioned the added value of β-blockers. Nevertheless, the Survival and Ventricular Enlargement (SAVE) and Acute Infarction Ramipril Efficacy (AIRE) trials showed that β-blockers provided an additional reduction in cardiovascular mortality independent of the use of ACE inhibitors.9,10 In addition, a meta-analysis of 31 long-term β-blocker studies with follow-up lasting 1 to 4 years found marked benefits in terms of reducing mortality and morbidity in post-MI patients.5 The benefits of β-blockers were maintained in the era in which fibrinolytics and aspirin were used. In fact, the substantial effect of β-blockers in reducing mortality compared favorably with other therapies: The number of unselected patients needed to treat to avoid one death over 2 years was 24 for fibrinolytics and aspirin used for 4 weeks, 42 for β-blockers, 94 for statins, and 153 for antiplatelet agents.5The Carvedilol Post-Infarct Survival Control in LV Dysfunction (CAPRICORN) trial evaluated the effects of adding carvedilol (a nonselective β-blocker with α-blocking capability) to standard therapy in patients with acute MI and left ventricular systolic dysfunction (ejection fraction ≤0.40), with or without HF symptoms. In this study, mortality or nonfatal reinfarction (which was not the primary end point) was significantly reduced by carvedilol (Table 2).11 Almost all patients in CAPRICORN were given ACE inhibitors, ≥85% were on aspirin, and 45% received reperfusion therapy.11TABLE 2. Comparison of Major β-Blocker Trials in the Chronic Post-MI Period: Clinical OutcomesTrialCAPRICORN11BHAT6,8Norwegian7Carvedilol, %Placebo, %Reduction, %PPropranolo, %Placebo, %Reduction, %PTimolol, %Placebo, %Reduction, %PN/A indicates not analyzed; NS, not significant.*Coronary heart disease mortality and reinfarction.All-cause mortality11.915.3230.0317.29.826<0.00510.617.5390.0005Sudden death57280.0983.34.628<0.057.713.9450.0001Nonfatal reinfarction375400.0144.45.316NS14.420280.0006All-cause mortality and reinfarction1420300.00210*13*23 0.24 seconds, and moderate or severe left ventricular failure.35 Taken as a whole, this evidence leads to the conclusion that β-blockers should be administered to all post-MI patients without a contraindication and should be continued indefinitely, as recommended in the recent 2001 AHA/ACC Scientific Statement.1FootnotesCorrespondence to Mihai Gheorghiade, MD, Northwestern Feinberg Medical School, 201 E Huron St, Galter 10-240, Chicago, IL 60611. 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