Systematic review: comparative effectiveness of angiotensin-converting enzyme inhibitors or angiotensin II-receptor blockers for ischemic heart disease.
BACKGROUND
Patients with ischemic heart disease and preserved ventricular function experience considerable morbidity and mortality despite standard medical therapy.


OBJECTIVE
To compare benefits and harms of using angiotensin-converting enzyme (ACE) inhibitors, angiotensin II-receptor blockers (ARBs), or combination therapy in adults with stable ischemic heart disease and preserved ventricular function.


METHODS
MEDLINE, EMBASE, Cochrane Central Register of Controlled Trials, and Cochrane Database of Systematic Reviews (earliest date, July 2009) were searched without language restrictions.


METHODS
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.


METHODS
Using standardized protocols, 2 independent investigators extracted information about study characteristics and rated the quality and strength of evidence. Disagreement was resolved by consensus.


RESULTS
41 studies met eligibility criteria. Moderate- to high-strength evidence (7 trials; 32 559 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; 25 620 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 (P < 0.001) and syncope (P = 0.035) with combination therapy compared with ACE inhibitors alone.


CONCLUSIONS
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.


CONCLUSIONS
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.


BACKGROUND
Agency for Healthcare Research and Quality.
Baker
William L
WL
University of Connecticut/Hartford Hospital Evidence-based Practice Center, 80 Seymour Street, Hartford, CT 06102, USA.
Coleman
Craig I
CI
Kluger
Jeffrey
J
Reinhart
Kurt M
KM
Talati
Ripple
R
Quercia
Robert
R
Phung
Olivia J
OJ
White
C Michael
CM
D047228:Angiotensin II Type 1 Receptor Blockers / Q000009:adverse effects / Q000627:therapeutic use*; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000009:adverse effects / Q000627:therapeutic use*; D002318:Cardiovascular Diseases / Q000401:mortality / Q000517:prevention & control; D003371:Cough / Q000139:chemically induced; D004359:Drug Therapy, Combination; D006801:Humans; D007022:Hypotension / Q000139:chemically induced; D017202:Myocardial Ischemia / Q000150:complications / Q000188:drug therapy* / Q000503:physiopathology; D013575:Syncope / Q000139:chemically induced; D016896:Treatment Outcome; D016276:Ventricular Function / Q000502:physiology
D047228:Angiotensin II Type 1 Receptor Blockers; D000806:Angiotensin-Converting Enzyme Inhibitors