Abstract & Commentary
Synopsis: The use of combination evidence-based pharmacologic therapy was associated with lower 6-month mortality in patients with ACS.
Source: Mukherjee D, et al. Circulation. 2004;109:745-749.
Several recent multicentered trials have exhibited the advantage of specific adjunctive medical therapy in acute coronary syndromes (ACS) for reducing major adverse cardiac events. The group from the University of Michigan sought to determine the impact on mortality of combining these agents in patients with unstable angina or acute myocardial infarction (MI). The patients were identified based upon discharge diagnoses and their charts reviewed to screen for entry criteria and document their therapy. Six-month mortality data were obtained by record review and phone calls. Based upon Class I recommendations of the ACC/AHA clinical practice guidelines, a medication appropriateness algorithm was developed for lipid-lowering, beta-blocker, ACE inhibitor, and antiplatelet therapy, which ranged from 0 for no indicated medications used to IV for all 4 indicated medications used. A total of 1358 patients were studied: 55% with non-ST segment elevation MI, 30% with unstable angina, and 15% with ST segment elevation MI. Coronary angiography was performed in two-thirds, and almost half had either percutaneous or surgical revascularization. Overall use of antiplatelet medications was 95%, beta-blockers 82%, lipid-lowering 84%, and ACE inhibitors 60%. When appropriate medications used at levels II-IV were compared to level 0, statistically significant reductions in mortality were noted. Level I vs 0 was not significant.
Age and ejection fraction were also powerful predictors of mortality at 6 months (P < .0001), as was biomarker positively (P = .007) and heart failure on admission (P = .004). Mukherjee and associates concluded that the use of combination evidence-based pharmacologic therapy was associated with lower 6-month mortality in patients with ACS.
Comment by Michael H. Crawford, MD
Although each of these 4 pharmacologic therapies has been shown individually to decrease subsequent events in patients with ACS, this is the first study to show their synergistic benefit in combination. Six-month mortality rates were decreased an impressive 72-87%, depending on how many drugs were combined, as compared to none of these drugs being used. One drug showed a beneficial trend but was not statistically significant (P = .08). These are important data since most of these drugs are generic, inexpensive, and well tolerated. Given that such secondary prevention therapies are often underutilized, these data underscore the value of efforts such as Guidelines Applied to Practice and Get With The Guidelines (ACC and AHA programs, respectively).
There are other interesting data in the paper. Early revascularization showed a strong trend toward lowered 6-month mortality (RR, .24; 95% CI, .05-1.24; P = .08). These data are consistent with the results of FRISC II, which showed improved survival with early revascularization at 2 years of follow-up. Some might be surprised by a 60% overall ACE inhibitor use at an academic medical center, but remember the Class I indications for ACE are heart failure due to systolic dysfunction, reduced LV ejection fraction, and hypertension in patients with ACS. Although there are compelling data to treat all patients with CAD with ACE inhibitors, they are not as robust as these Class I indications. Also, general surveys have shown that ACE use in ACS is usually 50%.
There are limitations to this study. It is based upon retrospective chart review, so information about previous use of the study drugs and reactions to them may not always be charted. Thus, some seeming drug omissions may be appropriate. Also, ARB substitution for ACE is not considered since this is not a Class I indication for ARB. In addition, newer therapies are not considered such as clopidogrel, enoxaparin, and platelet 11b/111a inhibitors. All 3 have demonstrated value in at least selected ACS patients. Finally, the impact of other strategies such as smoking cessation, folate, fish oils, weight loss, and exercise are not considered. However, despite these flaws, this is a powerful study for supporting the use of well-documented secondary preventive measures in ACS. A similar approach will be the subject of the next quality initiative on my cardiology inpatient service.
Dr. Crawford, Professor of Medicine, Associate Chief of Cardiology for Clinical Programs, University of California San Francisco, is Editor of Clinical Cardiology Alert.