William L. Baker, PharmD; Craig I. Coleman, PharmD; Jeffrey Kluger, MD; Kurt M. Reinhart, PharmD; Ripple Talati, PharmD; Robert Quercia, MS; Olivia J. Phung, PharmD; C. Michael White, PharmD
Patients with ischemic heart disease and preserved ventricular function experience considerable morbidity and mortality despite standard medical therapy.
To compare benefits and harms of using angiotensin-converting enzyme (ACE) inhibitors, angiotensin IIâ€“receptor blockers (ARBs), or combination therapy in adults with stable ischemic heart disease and preserved ventricular function.
MEDLINE, EMBASE, Cochrane Central Register of Controlled Trials, and Cochrane Database of Systematic Reviews (earliest date, July 2009) were searched without language restrictions.
Two independent investigators screened citations for trials of at least 6 months' duration that compared ACE inhibitors, ARBs, or combination therapy with placebo or active control and reported any of several clinical outcomes.
Using standardized protocols, 2 independent investigators extracted information about study characteristics and rated the quality and strength of evidence. Disagreement was resolved by consensus.
41 studies met eligibility criteria. Moderate- to high-strength evidence (7 trials; 32Â 559 participants) showed that ACE inhibitors reduce the relative risk (RR) for total mortality (RR, 0.87 [95% CI, 0.81 to 0.94]) and nonfatal myocardial infarction (RR, 0.83 [CI, 0.73 to 0.94]) but increase the RR for syncope (RR, 1.24 [CI, 1.02 to 1.52]) and cough (RR, 1.67 [CI, 1.22 to 2.29]) compared with placebo. Low-strength evidence (1 trial; 5926 participants) suggested that ARBs reduce the RR for the composite end point of cardiovascular mortality, nonfatal myocardial infarction, or stroke (RR, 0.88 [CI, 0.77 to 1.00]) but not for the individual components. Moderate-strength evidence (1 trial; 25Â 620 participants) showed similar effects on total mortality (RR, 1.07 [CI, 0.98 to 1.16]) and myocardial infarction (RR, 1.08 [CI, 0.94 to 1.23]) but an increased risk for discontinuations because of hypotension (PÂ < 0.001) and syncope (PÂ = 0.035) with combination therapy compared with ACE inhibitors alone.
Many studies either did not assess or did not report harms in a systematic manner. Many studies did not adequately report benefits or harms by various patient subgroups.
Adding an ACE inhibitor to standard medical therapy improves outcomes, including reduced risk for mortality and myocardial infarctions, in some patients with stable ischemic heart disease and preserved ventricular function. Less evidence supports a benefit of ARB therapy, and combination therapy seems no better than ACE inhibitor therapy alone and increases harms.
Agency for Healthcare Research and Quality.
Do patients already receiving standard therapy for ischemic heart disease benefit from additional treatment with angiotensin-converting enzyme (ACE) inhibitors or angiotensin II–receptor blockers (ARBs)?
Authors of this systematic review concluded that ACE inhibitors reduce risk for mortality, stroke, and myocardial infarction in patients with stable ischemic heart disease and preserved left ventricular function who already receive standard treatments, such as β-blockers, statins, and aspirin. Evidence about effects of ARBs was scant. Combining ACE inhibitors and ARBs increased risks for hypotension and syncope compared with ACE inhibitor therapy alone.
IHD = ischemic heart disease; LV = left ventricular; RCT = randomized, controlled trial.
* We included 3 citations at this step after a manual reference search.
† We included 27 citations from the outcomes search and evaluated them for harms data.
‡ We included 1 citation at this step after a manual reference search.
ACE = angiotensin-converting enzyme; ARB = angiotensin II–receptor blocker; CAMELOT = Comparison of Amlodipine vs. Enalapril to Limit Occurrences of Thrombosis; EUROPA = European Trial on Reduction of Cardiac Events with Perindopril in Stable Coronary Artery Disease; HOPE = Heart Outcomes Prevention Evaluation; MI = myocardial infarction; PART-2 = Prevention of Atherosclerosis with Ramipril 2; PEACE = Prevention of Events with Angiotensin Converting Enzyme Inhibition; RR = relative risk; SCAT = Simvastatin/Enalapril Coronary Atherosclerosis Trial; TRANSCEND = Telmisartan Randomised Assessment Study in ACE Intolerant Subjects with Cardiovascular Disease.
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December 22, 2009
Effectiveness of therapeutic reviews in search for efficiency.
Effectiveness of therapeutic reviews and search for efficiency.
For patients with stable ischemic heart disease, Baker et al finally showed that adding an Angiotensin-Converting Enzyme Inhibitor (ACEI) to standard medical therapy decrease mortality and morbidity while there was less evidence supporting a benefit of Angiotensin Receptor Blockers (ARB) therapy (1). However, I have concern for the effectiveness of this review.
For hypertension, ONTARGET is one of many studies showing that both classes give the same benefits in outcome for mortality and morbidity (2). In contrast, there are huge differences for prices: eg. in France, a daily treatment with Captopril or its generics costs 0.33 euro vs 0.67 to 0.74 euro for ARB. Prices are not related to the social value of the product: cost-effectiveness analysis (ie efficiency) seems inexistent and far beyond the capabilities of national pricing committees. Conflicts of interest in medicine are the subject of intensive and extensive debates. These debates divert us from the sad reality. The data are available to every one but very few professionals, either experts or practitioners, have concern for price. Price which is paid by the most deprived, the patient. We know what is wrong, why are we so weak that we cannot adjust our behavior and take back control.
1 Baker WL, Coleman CI, Kluger J, et al. Systematic review: comparative effectiveness of angiotensin-converting enzyme inhibitors or angiotensin II-receptor blockers for ischemic heart disease.Ann Intern Med. 2009;151:861-71.
2 Yusuf S, Diener HC, Sacco RL, Cotton D, Ounpuu S, Lawton WA, et al. Telmisartan to Prevent Recurrent Stroke and Cardiovascular Events. N Eng J Med 2008;358:1547-59.
3 http://www.has-sante.fr/portail/upload/docs/application/pdf/2008- 10/fiche_iec_sartans_011008.pdf accessed Dec. 22, 2009
Baker WL, Coleman CI, Kluger J, Reinhart KM, Talati R, Quercia R, et al. Systematic Review: Comparative Effectiveness of Angiotensin-Converting Enzyme Inhibitors or Angiotensin II–Receptor Blockers for Ischemic Heart Disease. Ann Intern Med. 2009;151:861-871. doi: 10.7326/0000605-200912150-00162
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Published: Ann Intern Med. 2009;151(12):861-871.
Cardiology, Coronary Heart Disease, Coronary Risk Factors, High Value Care, Hypertension.
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