REVIEW

URRENT C OPINION

Should b-blockers still be routine after myocardial infarction?

Peter L. Thompson a,b

Purpose of review This review will assess whether the 25-year-old evidence base to support routine prescribing of b-blockers after myocardial infarction (MI) is relevant to modern management. Recent findings The evidence base to support the recommendation for the widespread use of b-blockers after MI was nearfinalized in the mid-1980s. Whereas the use of intravenous b-blockers is waning, the routine use of oral b-blockers after MI is still regarded as evidence based. In the past 25 years, the introduction of coronary reperfusion and of effective nonreperfusion therapies has changed the natural history of MI and there have been substantial changes in the definition of MI. The relevance of old clinical trial data collected in patients who bear little resemblance to todays MI patients is questioned. Recent analyses have shown that there is no convincing evidence for the use of b-blockers as first-line therapy in hypertension or in patients with stable coronary heart disease. In contrast, the evidence base for the use of b-blockers in heart failure is strong and contemporary. Summary A rational recommendation for the modern treatment of MI would be to limit the use of b-blockers in the post-MI patient to higher-risk patients with evidence of ongoing ischemia, heart failure, or left ventricular dysfunction. There is no evidence to support the routine use of oral b-blockers in low-risk MI patients. Keywords b-blockers, myocardial infarction, outcomes, prognosis

INTRODUCTION
The evidence base to support the use of b-blockers after myocardial infarction (MI) is over 25 years old. This review will assess whether this evidence is still relevant to the modern management of patients with MI and will challenge the current recommendation that most postinfarction patients should be considered for b-blockers.

INTRAVENOUS b-BLOCKERS
Although both the ISIS (International Study of Infarct Survival) [1] and MIAMI (Metoprolol in Acute Myocardial Infarction) [2] trials of the 1980s commenced b-blockade via the intravenous (i.v.) route, the evidence to support the early i.v. use of b-blockers in the modern era is weak. Guidelines have recognized this and have progressively backed away from earlier recommendations for their routine use in MI. The evidence base for i.v. b-blockers in patients receiving reperfusion therapy is even more limited. With thrombolytic therapy, a single small trial within a larger trial in patients treated

with alteplase compared i.v. and oral with oral b-blockers and showed an apparent benefit of commencing treatment with i.v. [3]. Two other relatively small randomized trials of i.v. b-blockade [4,5] and a post-hoc analysis of the use of atenolol in the GUSTO-I [Global Utilization of Streptokinase and TPA (alteplase) for Occluded Coronary Arteries] trial [6] all failed to provide any evidence to support the routine use of i.v. b-blockers with thrombolysis. There have been no trials of the use of i.v. b-blockers in the percutaneous coronary intervention (PCI) era of treatment of ST elevation myocardial infarction (STEMI), although such a trial is planned [7]. When the available data were examined in a 1999

Heart Research Institute, Sir Charles Gairdner Hospital and bUniversity of Western Australia, Perth, Western Australia, Australia Correspondence to Professor Peter L. Thompson, Director, Heart Research Institute, R Block, Sir Charles Gairdner Hospital, Nedlands, Western Australia, Australia. E-mail: peterlthompson@bigpond.com Curr Opin Cardiol 2013, 28:399404 DOI:10.1097/HCO.0b013e328361e97a

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KEY POINTS
 The evidence base to support the routine use of oral b-blockers after MI is 25 years out of date.  The widespread uptake of reperfusion therapy for STEMI, introduction of effective nonreperfusion therapies, subsequent dramatic improvements in the outcomes of MI, and changes in the definition of MI have changed the clinical profile of MI so substantially that evidence from the mid-1980s is not relevant to the modern management of MI.  Recent observations have challenged the rationale for the use of b-blockers in hypertension and stable coronary heart disease, weakening the assumption that all post-MI patients should be on oral b-blockers.  In contrast, the evidence base to support b-blockers in cardiac failure and left ventricular dysfunction is strong and contemporary.  The routine use of b-blockers after MI should be reconsidered and limited to high-risk post-MI patients (cardiac failure, left ventricular dysfunction, or ongoing myocardial ischemia).

continued indefinitely or at least for several years [11 ,12,13 ]. Although the guidelines generally acknowledge that the data were collected over 25 years ago, the lack of relevant modern evidence has not prevented adherence to these guidelines being championed as the standard of care in modern cardiology practice. Programs to encourage guideline adherence have been launched irrespective of whether the evidence base is sufficiently robust in the modern era. The Get With The Guidelines (GWITG) programs of the AHA [14] and the Guidelines Applied in Practice (GAP) program of the ACC [15] have promoted high levels of b-blocker prescribing as quality measures for patients with acute MI, and some hospital reimbursement programs penalize hospitals which do not achieve adequate levels of adherence to b-blocker prescribing on discharge [16].
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ORAL b-BLOCKERS
The collection of evidence from randomized clinical trials of oral b-blockade after MI commenced in the late 1970s, reached a peak in the mid-1980s, and was essentially complete by the early 1990s (Fig. 1). Since 1985, there have been major changes in MI and its management. We have seen the reperfusion era introduced into coronary care, initially with thrombolysis as a result of the ISIS-2 [17] and GUSTO trials [18], later with primary PCI [19,20], the near universal use of aspirin [21], high-dose statins [22], and dual antiplatelet therapy [23,24]. Although there is no doubt that the evidence collected in the mid-1980s was relevant to the treatment of patients at that time, there are four important reasons to question the relevance of the old b-blocker evidence to modern cardiology practice. First, most patients in the modern era receive reperfusion therapy. Early reperfusion changes the pathophysiology of MI [25] with the net result being far less and sometimes no damage to the myocardium, in contrast to persistent ischemia resulting in extensive myocardial necrosis, scarring, and adverse remodeling. The uptake of reperfusion therapies, initially with thrombolytic therapy and later with PCI, was rapid during the late 1980s and has accelerated into the modern reperfusion era for the treatment of STEMI. The clinical judgment and availability of resources determine use of lytic therapy or PCI in almost all patients. In the Perth MONICA (Multinational Monitoring of Trends and Determinants in Cardiovascular Disease) study conducted from the mid-1980s to the early 1990s, the use of thrombolysis increased from 12 to 49% and coronary revascularization therapy in the year postinfarction increased from 2 to 38% [26 ]. These
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systematic review of 54 234 patients with STEMI, there was no significant reduction in mortality with the i.v. use of b-blockers [8]. More recent data raise serious concerns about the i.v. use of b-blockers. The recent large Chinese COMMIT (Clopidogrel and Metoprolol in Myocardial Infarction Trial) trial of i.v. followed by oral b-blocker in STEMI with limited use of reperfusion therapy (just over half received urokinase) [9] showed some benefits on re-infarction and ventricular fibrillation, but a 30% increase in cardiogenic shock. An updated meta-analysis of the clinical trials including the COMMIT trial confirmed the lack of efficacy for early b-blockers [10 ]. The 2012 update of the American College of Cardiology/American Heart Association (ACC/AHA) guidelines for the treatment of STEMI concludes that the evidence for i.v. b-blockers is only of evidence level B and makes a class IIa recommendation for their use, that is, reasonable, but not strongly recommended [11 ], with the recommendation limited to patients who are hypertensive or with ongoing ischemia. The latest European guidelines for STEMI reach a similar conclusion [12].
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LONG-TERM ORAL b-BLOCKERS AFTER MYOCARDIAL INFARCTION

Although support for i.v. b-blockers has waned in recent years, practice guidelines still recommend the use of oral b-blockers. All international guidelines recommend that b-blockers should be commenced as soon as possible after the onset of MI, and
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b-Blockers and myocardial infarction Thompson

Long-term post-AMI Beta blockers vs. placebo trials Cumulative deaths Number of deaths
1400 1200 1000 800 600 400 200 0 1975 1980 1985 1990 1995 2000 2005 2010 Placebo Treatment 15 10 5 0
Thrombolysis Aspirin Primary PCI Dual antiplatelet therapy High dose statins

FIGURE 1. Cumulative evidence for mortality benefit of postmyocardial infarction (MI) b-blockers in randomized controlled trials (RCTs) from the 1970s to the present. The bars show the number of trials (scale on right) and the curves show the number of deaths with 95% confidence intervals (scale on left) in each 5-year period in the RCTs, which compared b-blockers with placebo. The evidence for superiority of b-blockers was evident by the late 1980s with minimal additional evidence since then. The horizontal bars below show the significant changes in therapy that have been introduced since then. The evidence for the timing of introduction of new therapies is based on [17,18] (thrombolysis), [17,21] (aspirin), [19,20] (primary PCI), [23,24] (dual anti-platelet therapy) and [22] (high dose statins).

trends have accelerated since. The US National Registry of Myocardial Infarction (NRMI) documented the patterns of care in over 2.5 million patients with MI in 2157 hospitals in the United States between 1990 and 2006 and showed that the use of revascularization procedures with PCI increased from 37 to 73% for STEMI and 25 to 44% for non-STEMI [27 ]. Second, other highly effective nonreperfusion therapies have been introduced into practice on the basis of evidence accumulated in the past 20 years. The use of antiplatelet therapies and statins now approaches 100 and 90%, respectively [28]. Third, there is evidence that the abovementioned changes in therapy, with efficacy proven in RCTs, have been effective when applied in practice and have contributed to an improved natural history and better outcomes for patients with MI. Patients with MI have fewer complications and better outcomes in 2012 compared with the mid-1980s when the b-blocker clinical trials were conducted. Within coronary care units, the incidence of cardiogenic shock and heart failure during MI has declined significantly [29 ,30], and, in a unique long-term study of the trends in mortality in patients treated in a coronary care unit, the 30-day mortality reduced by two-thirds and the 5-year mortality reduced by half from 1985 to 2008 [31]. Community-wide studies have also
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confirmed declines in mortality from MI. In Perth, the adjusted odds ratio for acute myocardial infarction (AMI) mortality declined by 36% in the decade from the mid-1980s to the mid-1990s, with similar trends observed in 12-year mortality in 1-year survivors [26 ]. Nationwide studies show the same pattern. In the United States, STEMI and non-ST elevation myocardial infarction (NSTEMI) mortality rates have declined dramatically from the 1980s to the 2000s. In over 1.3 million patients with STEMI, total mortality rates declined from 15 to 10% and age-adjusted rates nearly halved from 406 to 286 per 100 000 between 1988 and 2004 [32 ]. In 1.4 million patients with NSTEMI, total mortality rates decreased from 29.6% in 1988 to 11.3% in 2004 and age-adjusted mortality more than halved from 727 to 305 per 100 000 [33]. These trends have accelerated into the 2000s with a 24% decline between 1999 and 2008 [34 ]. In patients represented in large clinical trials of MI, early mortality rates over the period mid-1980s to mid2000s have declined by up to 70% [35 ]. Finally, the definition of myocardial has changed dramatically since the mid-1980s. At that time, the clinical trials used a variety of definitions to include patients in the b-blocker trials. The most common definition was the WHO definition, which required the development of Q waves or serial ECG changes, and an increase in creatine kinase level to twice the
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upper limit of normal [36]. The latest Universal Definition allows the diagnosis of AMI when the highsensitivity troponin level shows a rise and fall outside the normal range [37 ], significantly increasing the sensitivity of the diagnostic criteria. Patients being diagnosed with MI today include many patients with lower risk than in previous definitions [38 ]. In brief, the introduction of reperfusion therapy for STEMI has changed the pathophysiology of the condition for the better, nonreperfusion therapies have been introduced on the basis of proven efficacy in large randomized controlled trials (RCTs), the natural history has consequently changed to fewer complications and deaths, and changes in the definition of MI have widened the diagnosis to include patients with lower risk. Patients with MI who were being treated in the mid-1980s were so different in their pathophysiology, treatment profile, and natural history and definition that the b-blocker trials conducted at that time bear little relevance to those being treated for AMI in the modern era of coronary care. This raises the question of whether there is any relevant modern evidence to support the widespread prescribing of b-blockers after MI.
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cardiovascular disease (CVD) was 12% lower for first-line b-blockers compared with placebo, this was primarily due to a significant 20% decrease in stroke and there was no difference in CHD outcomes [40]. The latest update of this evidence confirms these findings, with the additional finding that b-blockers are less effective in reducing CHD endpoints than calcium channel blockers and concluding that the evidence is generally weak, with the potential for bias [41 ].
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LIMITED EVIDENCE IN STABLE CORONARY HEART DISEASE PATIENTS

A study of patients who have undergone PCI during their hospital treatment for STEMI showed no benefit for the use of postdischarge b-blockers in patients free of heart failure after adjustment for clinical and demographic factors [42 ]. A report on follow-up from the REACH (Reduction of Atherothrombosis for Continued Health) study on data collected in the early 1990s on 44 708 patients whose CHD was stable included a total of over 14 000 with known prior MI. A propensity-matched analysis failed to show any survival benefit for patients taking b-blockers [43 ].
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EVIDENCE FROM THE MODERN ERA ON THE EFFECTIVENESS OF b-BLOCKERS

As there are no RCTs examining the effect of b-blockers after AMI in the modern era, indirect evidence must be examined to decide whether the old evidence is relevant. Only guarded conclusions can be drawn from observational studies and RCTs in related conditions, but there is no clear support for the unrestricted use of b-blockers after MI.

STRONG EVIDENCE OF BENEFIT OF b-BLOCKERS IN HEART FAILURE

In contrast to the old evidence for post-MI b-blockers, and limited convincing evidence for their use in hypertension and stable CHD, the evidence for a benefit of b-blockers in heart failure is strong, relatively free of publication bias, and contemporary [44]. Multiple trials and meta-analyses have confirmed this conclusion, the latest indicating a likely reduction of 30% in 1-year mortality in patients with heart failure or left ventricular dysfunction treated with b-blockers [45 ]. One meta-analysis concluded that the probability that b-blocker therapy reduced total mortality and hospitalizations for congestive heart failure was almost 100% and that these benefits are clinically significant is 99% [46].
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LACK OF EFFICACY OF THE b-BLOCKERS IN THE HYPERTENSION TRIALS

Although the role of b-blockers as standard therapy after MI has been accepted with only minimal challenge, there has been a re-appraisal of the role of b-blockers as first-line treatment in hypertension. When the effect of b-blockers, primarily atenolol, was compared with other first-line antihypertensives, the effects on outcomes were less impressive for the b-blockers [39]. This led to a re-appraisal of the overall efficacy of b-blockers in all the hypertension trials, leading to disconcerting findings in their effect on coronary heart disease (CHD) events. In 13 RCTs with 91 561 participants with hypertension, the risk of all-cause mortality was not different between b-blockers used as first-line therapy and placebo [relative risk (RR) 0.99, 95% confidence interval (CI) 0.881.11]. Although the risk of total
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CONCLUSION
The following conclusions can be drawn: (1) The use of i.v. b-blockers in MI has little support and has been progressively downgraded in guidelines. (2) The data for long-term oral post-AMI b-blockers, collected in the 1980s in a different era, with a different pathophysiology, different treatment
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b-Blockers and myocardial infarction Thompson

(3)

(4)

(5)

(6)

profile, different natural history, and different definition of the condition, can no longer be used as a basis for current evidence-based practice. There is lack of evidence that b-blockers as first-line therapy in hypertension or use in patients with stable CHD can reduce coronary events. The data for the benefits of b-blockers in heart failure or left ventricular systolic dysfunction are persuasive. This review of the available evidence does not support routine prescribing of b-blockers for all patients with acute coronary syndromes and supports even less the use of adherence to high b-blocker target prescribing rates as a quality measure. An alternative interpretation of the available evidence is that the use of b-blockers in postMI patients should be restricted to patients at high risk, especially those who have ongoing evidence of myocardial ischemia, proven heart failure, or left ventricular dysfunction. The data to support b-blockers in low-risk patients in the modern era are lacking.

Acknowledgements None. Conflicts of interest There are no conflicts of interest.

REFERENCES AND RECOMMENDED READING

Papers of particular interest, published within the annual period of review, have been highlighted as: & of special interest && of outstanding interest Additional references related to this topic can also be found in the Current World Literature section in this issue (pp. 486487). 1. Randomised trial of intravenous atenolol among 16 027 cases of suspected acute myocardial infarction: ISIS-1. First International Study of Infarct Survival Collaborative Group Lancet 1986; 2:5766. 2. The MIAMI Trial Research Group. Metoprolol in acute myocardial infarction (MIAMI). A randomised placebo-controlled international trial. Eur Heart J 1985; 6:199226. 3. The TIMI Study Group. Comparison of invasive and conservative strategies after treatment with intravenous tissue plasminogen activator in acute myocardial infarction: results of the thrombolysis in myocardial infarction (TIMI) phase II trial. N Engl J Med 1989; 320:618627. 4. Roberts R, Rogers WJ, Mueller HS, et al. Immediate versus deferred betablockade following thrombolytic therapy in patients with acute myocardial infarction: results of the Thrombolysis in Myocardial Infarction (TIMI) II-B Study. Circulation 1991; 83:422437. 5. Van de Werf F, Janssens L, Brzostek T, et al. Short-term effects of early intravenous treatment with a beta-adrenergic blocking agent or a specic bradycardiac agent in patients with acute myocardial infarction receiving thrombolytic therapy. J Am Coll Cardiol 1993; 22:407 416. 6. Psterer M, Cox JL, Granger CB, et al. Atenolol use and clinical outcomes after thrombolysis for acute myocardial infarction: the GUSTO-I experience. Global Utilization of Streptokinase and TPA (alteplase) for Occluded Coronary Arteries. J Am Coll Cardiol 1998; 32:634640.

7. Ibanez B, Fuster V, Macaya C, et al. Study design for the effect of METOprolol in CARDioproteCtioN during an acute myocardial InfarCtion (METOCARDCNIC): a randomized, controlled parallel-group, observer-blinded clinical trial of early prereperfusion metoprolol administration in ST-segment elevation myocardial infarction. Am Heart J 2012; 164:473480. 8. Freemantle N, Cleland J, Young P, et al. Beta blockade after myocardial infarction: systematic review and meta regression analysis. BMJ 1999; 318:17301737. 9. Chen ZM, Pan HC, Chen YP, et al. Early intravenous then oral metoprolol in 45 852 patients with acute myocardial infarction: randomised placebocontrolled trial. Lancet 2005; 366:16221632. 10. Al-Reesi A, Al-Zadjali N, Perry J, et al. Do beta-blockers reduce short-term & mortality following acute myocardial infarction? A systematic review and metaanalysis. CJEM 2008; 10:215223. An update of the Freemantle meta-analysis of 1999, but including the results of the Chinese COMMIT trial, conrming limited value and signicant risk of i.v. b-blockers. 11. OGara PT, Kushner FG, Ascheim DD, et al. 2013 ACCF/AHA Guideline for & the Management of ST-Elevation Myocardial Infarction: a report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines. J Am Coll Cardiol 2013; 61:e78e140. Latest US guideline recommending only limited use of i.v. b-blockers. 12. Steg PG, James SK, Atar D, et al., Task Force on the management of ST-segment elevation acute myocardial infarction of the European Society of Cardiology (ESC). ESC Guidelines for the management of acute myocardial infarction in patients presenting with ST-segment elevation. Eur Heart J 2012; 33:25692619. 13. Hamm CW, Bassand JP, Agewall S, et al. ESC Guidelines for the manage& ment of acute coronary syndromes in patients presenting without persistent ST-segment elevation: the Task Force for the management of acute coronary syndromes (ACS) in patients presenting without persistent ST-segment elevation of the European Society of Cardiology (ESC). Eur Heart J 2011; 32:29993054. Latest European guidelines on NSTEMI recommending use of oral b-blockers in most patients. 14. Kumbhani DJ, Fonarow GC, Cannon CP, et al. Get With the Guidelines Steering Committee and Investigators. Predictors of adherence to performance measures in patients with acute myocardial infarction. Am J Med 2013; 126:74; e1e9. 15. Olomu AB, Grzybowski M, Ramanath VS, et al. American College of Cardiology Foundation Guidelines Applied in Practice Steering Committee. Evidence of disparity in the application of quality improvement efforts for the treatment of acute myocardial infarction: the American College of Cardiologys Guidelines Applied in Practice Initiative in Michigan. Am Heart J 2010; 159:377384. 16. Glickman SW, Ou FS, DeLong ER, et al. Pay for performance, quality of care, and outcomes in acute myocardial infarction. JAMA 2007; 297:23732380. 17. Randomised trial of intravenous streptokinase, oral aspirin, both, or neither among 17 187 cases of suspected acute myocardial infarction: ISIS-2. ISIS-2 (Second International Study of Infarct Survival) Collaborative Group Lancet 1988; 2:349360. 18. An international randomized trial comparing four thrombolytic strategies for acute myocardial infarction. The GUSTO Investigators N Engl J Med 1993; 329:673682. 19. Grines CL, Browne KF, Marco J, et al. A comparison of immediate angioplasty with thrombolytic therapy for acute myocardial infarction. The Primary Angioplasty in Myocardial Infarction Study Group. N Engl J Med 1993; 328:673 679. 20. A clinical trial comparing primary coronary angioplasty with tissue plasminogen activator for acute myocardial infarction. The Global Use of Strategies to Open Occluded Coronary Arteries in Acute Coronary Syndromes (GUSTO IIb) Angioplasty Substudy Investigators N Engl J Med 1997; 336:1621 1628. 21. Antithrombotic Trialists Collaboration. Collaborative meta-analysis of randomised trials of antiplatelet therapy for prevention of death, myocardial infarction, and stroke in high risk patients. BMJ 2002; 324:7186. 22. Cannon CP, Braunwald E, McCabe CH, et al. Intensive versus moderate lipid lowering with statins after acute coronary syndromes. N Engl J Med 2004; 350:14951504. 23. Yusuf S, Zhao F, Mehta SR, et al. Clopidogrel in Unstable Angina to Prevent Recurrent Events Trial Investigators. Effects of clopidogrel in addition to aspirin in patients with acute coronary syndromes without ST-segment elevation. N Engl J Med 2001; 345:494502. 24. 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; 366:16071621. 25. Pasotti M, Prati F, Arbustini E. The pathology of myocardial infarction in the pre and postinterventional era. Heart 2006; 92:15521556. 26. Briffa T, Hickling S, Knuiman M, et al. Long term survival after evidence based & treatment of acute myocardial infarction and revascularisation: follow-up of population based Perth MONICA cohort, 19842005. BMJ 2009; 338:b36. From efcacy to effectiveness. A clear demonstration in a long-term communitywide study of improved outcomes due to the application of evidence-based therapies.

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Copyright Lippincott Williams & Wilkins. Unauthorized reproduction of this article is prohibited.

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27. Peterson ED, Shah BR, Parsons L, et al. Trends in quality of care for patients with acute myocardial infarction in the National Registry of Myocardial Infarction from 1990 to 2006. Am Heart J 2008; 156: 10451055. From efcacy to effectiveness. A clear demonstration in a nationwide sample of improved outcomes due to the application of evidence-based therapies. 28. Mehta RH, Roe MT, Chen AY, et al. Recent trends in the care of patients with non-ST-segment elevation acute coronary syndromes: insights from the CRUSADE initiative. Arch Intern Med 2006; 166:20272034. 29. Jeger RV, Radovanovic D, Hunziker PR, et al. Urban P AMIS Plus Registry & Investigators. Ten-year trends in the incidence and treatment of cardiogenic shock. Ann Intern Med 2008; 149:618626. The study shows declines in the incidence of cardiogenic shock and heart failure in STEMI over the past decade and a half. 30. Fox KA, Steg PG, Eagle KA, et al. GRACE Investigators. Decline in rates of death and heart failure in acute coronary syndromes, 19992006. JAMA 2007; 297:18921900. 31. Nauta ST, Deckers JW, van Domburg RT, Akkerhuis KM. Sex-related trends in mortality in hospitalized men and women after myocardial infarction between 1985 and 2008: equal benet for women and men. Circulation 2012; 126:21842189. 32. Movahed MR, John J, Hashemzadeh M, et al. Trends in the age adjusted & mortality from acute ST segment elevation myocardial infarction in the United States (19882004) based on race, gender, infarct location and comorbidities. Am J Cardiol 2009; 104:10301034. The study shows that the outcomes after MI have improved dramatically since the b-blocker trials of the mid-1980s. 33. Movahed MR, John J, Hashemzadeh M, Hashemzadeh M. Mortality trends for non-ST-segment elevation myocardial infarction (NSTEMI) in the United States from 1988 to 2004. Clin Cardiol 2011; 34:689692. 34. Yeh RW, Sidney S, Chandra M, et al. Population trends in the incidence and & outcomes of acute myocardial infarction. N Engl J Med 2010; 362:2155 2165. The study shows that the outcomes after MI have improved dramatically since the b-blocker trials of the mid-1980s. 35. Van de Werf FJ, Topol EJ, Sobel BE. The impact of brinolytic therapy for & ST-segment-elevation acute myocardial infarction. J Thromb Haemost 2009; 7:1420. Patients included in clinical trials have shown a dramatic 70% decline in mortality rates since the mid-1980s. 36. Tunstall-Pedoe H, Kuulasmaa K, Amouyel P, et al. Myocardial infarction and coronary deaths in the World Health Organization MONICA Project. Registration procedures, event rates, and case-fatality rates in 38 populations from 21 countries in four continents. Circulation 1994; 90:583612.
&

37. Thygesen K, Alpert JS, Jaffe AS, et al. Joint ESC/ACCF/AHA/WHF Task Force for Universal Denition of Myocardial Infarction. Third universal denition of myocardial infarction. J Am Coll Cardiol 2012; 60:15811598. The latest denition of MI requirements is far more sensitive, the biochemical evidence of myocardial necrosis requiring only a rise and fall of high-sensitivity troponin outside the normal range. 38. Luepker RV, Duval S, Jacobs DR Jr, et al. The effect of changing diagnostic & algorithms on acute myocardial infarction rates. Ann Epidemiol 2011; 21:824829. A detailed analysis showing that the new denitions of MI with minimal rises in troponin make the diagnosis more sensitive. 39. Lindholm LH, Carlberg B, Samuelsson O. Should beta blockers remain rst choice in the treatment of primary hypertension? A meta-analysis. Lancet 2005; 366:15451553. 40. Wiysonge CS, Bradley H, Mayosi BM, et al. Beta-blockers for hypertension. Cochrane Database Syst Rev 2007; CD002003. 41. Wiysonge CS, Bradley HA, Volmink J, et al. Beta-blockers for hypertension. && Cochrane Database Syst Rev 2012; CD002003; doi: 10.1002/14651858. CD002003.pub4. This report reaches the disturbing conclusion that b-blockers as rst-line therapy in hypertension may be no better than placebo for the prevention of CHD events. 42. Ozasa N, Kimura T, Morimoto T, et al. j-Cypher Registry Investigators. Lack of && effect of oral beta-blocker therapy at discharge on long-term clinical outcomes of ST-segment elevation acute myocardial infarction after primary percutaneous coronary intervention. Am J Cardiol 2010; 106:12251233. Though not a randomized study, this study is one of the few to seriously examine the usefulness of b-blockers in the modern treatment of post-MI patients and provides no evidence to support their use. 43. Bangalore S, Steg G, Deedwania P, et al. REACH Registry Investigators. && b-Blocker use and clinical outcomes in stable outpatients with and without coronary artery disease. JAMA 2012; 308:13401349. Not only a randomized study, but also an examination of the role of b-blockers in the modern treatment of CHD and providing no support for the use of b-blockers in stable CHD. 44. Lechat P, Packer M, Chalon S, et al. Clinical effects of beta-adrenergic blockade in chronic heart failure: a meta-analysis of double-blind, placebocontrolled, randomized trials. Circulation 1998; 98:11841191. 45. Chatterjee S, Biondi-Zoccai G, Abbate A, et al. Benets of b blockers in && patients with heart failure and reduced ejection fraction: network metaanalysis. BMJ 2013; 346:f55; doi: 10.1136/bmj.f55. The latest meta-analysis conrming that b-blockers are central to the modern treatment of heart failure. 46. Brophy JM, Joseph L, Rouleau JL. Beta-blockers in congestive heart failure. A Bayesian meta-analysis. Ann Intern Med 2001; 134:550560.
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