Meta-Analysis of Randomized Trials on the Efficacy and Safety of Angiotensin-Converting Enzyme Inhibitors in Patients ≥65 Years of Age.
The comparative efficacy and safety of angiotensin-converting enzyme inhibitors (ACEIs) with other agents in patients ≥65 years of age with cardiovascular diseases or at-risk are unknown. Electronic databases were systematically searched to identify all randomized controlled trials that compared ACEIs with control (placebo or active) and reported long-term cardiovascular outcomes. We required the mean age of patients in the studies to be ≥65 years. Random-effects model was used to pool study results. Sixteen trials with 104,321 patients and a mean follow-up of 2.9 years were included. Compared with placebo, ACEIs significantly reduced all outcomes except stroke. Compared with active controls, ACEIs had similar effect on all-cause mortality (relative risk [RR] 0.99, 95% confidence interval [CI] 0.95 to 1.03), cardiovascular mortality (RR 0.99, 95% CI 0.93 to 1.04), heart failure (RR 0.97, 95% CI 0.91 to 1.03), myocardial infarction (RR 0.94, 95% CI 0.88 to 1.00), and stroke (RR 1.07, 95% CI 0.99 to 1.15). ACEIs were associated with an increased risk of angioedema (RR 2.79, 95% CI 1.05 to 7.42), whereas risk for hypotension and renal insufficiency was similar compared with active controls. Meta-regression analysis showed that the effect of ACEIs on outcomes remained consistent with age increasing ≥65 years. Sensitivity analysis excluding trials comparing ACEIs with angiotensin receptor blockers and heart failure trials yielded similar results, except for reduction in myocardial infarction. In conclusion, the efficacy of ACEIs was similar to active controls for mortality outcomes. Compared with placebo, there was evidence for reduction in cardiovascular outcomes; however, ACEIs failed to prevent stroke and increased the risk of angioedema, hypotension, and renal failure.
Department of Cardiovascular Medicine, Mount Sinai St. Luke's & Mount Sinai West Hospitals, New York, New York.
Chirag
C
Bavishi
Department of Cardiovascular Medicine, Mount Sinai St. Luke's & Mount Sinai West Hospitals, New York, New York.
Mohammed
M
Ahmed
Division of Critical Care, Mayo Clinic, Rochester, Minnesota.
Vrinda
V
Trivedi
Division of Cardiovascular Medicine, University of Louisville, Louisville, Kentucky.
Abdur Rahman
AR
Khan
Department of Cardiovascular Medicine, Mount Sinai St. Luke's & Mount Sinai West Hospitals, New York, New York.
Carlos
C
Gongora
The Leon H. Charney Division of Cardiology, New York University School of Medicine, New York, New York.
Sripal
S
Bangalore
Division of Cardiology, Mount Sinai Medical Center, New York, New York; University of Bern, Switzerland; Jagiellonian University Krakow, Poland. Electronic address: messerli.f@gmail.com.
Franz H
FH
Messerli
D000367:Age Factors; D000368:Aged; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000627:therapeutic use*; D002318:Cardiovascular Diseases / Q000188:drug therapy*; D006801:Humans; D061214:Patient Safety; D016032:Randomized Controlled Trials as Topic
D000806:Angiotensin-Converting Enzyme Inhibitors