David B. Matchar, MD; Douglas C. McCrory, MD, MHS; Lori A. Orlando, MD, MHS; Manesh R. Patel, MD; Uptal D. Patel, MD; Meenal B. Patwardhan, MD, MHSA; Benjamin Powers, MD; Gregory P. Samsa, PhD; Rebecca N. Gray, DPhil
Disclaimer: The authors of this report are responsible for its content. Statements in the report should not be construed as endorsements by the Agency for Healthcare Research and Quality or the U.S. Department of Health and Human Services.
Grant Support: This project was funded under contract no. 290-02-0025 from the Agency for Healthcare Research and Quality, U.S. Department of Health and Human Services.
Potential Financial Conflicts of Interest:Honoraria: D.C. McCrory (AstraZeneca). Stock ownership or options (other than mutual funds): G.P. Samsa (Pfizer).
Requests for Single Reprints: David B. Matchar, MD, Duke Center for Clinical Health Policy Research, 2200 West Main Street, Suite 220, Durham, NC 27705; e-mail, email@example.com.
Current Author Addresses: Drs. Matchar, McCrory, Orlando, Patwardhan, Samsa, and Gray: Duke Center for Clinical Health Policy Research, 2200 West Main Street, Suite 220, Durham, NC 27705.
Dr. M.R. Patel: Duke Clinical Research Institute, North Pavilion, 2400 Pratt Street, Room 0311, Durham, NC 27705.
Dr. U.D. Patel: Department of Nephrology, Duke University Medical Center, DUMC Box 3646, Durham, NC 27710.
Dr. Powers: Duke University and Durham Veterans Affairs Medical Center, 2424 Erwin Road, Suite 1105, Durham, NC 27705.
The relative effectiveness of angiotensin-converting enzyme (ACE) inhibitors and angiotensin II receptor blockers (ARBs) for lowering blood pressure is unknown.
To compare the benefits and harms of ACE inhibitors versus ARBs for treating essential hypertension in adults.
MEDLINE (1966 to May 2006), the Cochrane Central Register of Controlled Trials (Issue 2, 2006), and selected reference lists were searched for relevant English-language trials. The MEDLINE search was updated to August 2007 to identify head-to-head trials that reported blood pressure outcomes and major cardiovascular events.
61 clinical studies that directly compared ACE inhibitors versus ARBs in adult patients with essential hypertension, reported an outcome of interest, lasted at least 12 weeks, and included at least 20 patients.
A standardized protocol with predefined criteria was used to extract data on study design, interventions, population characteristics, and outcomes; evaluate study quality and applicability; and assess the strength of the body of evidence for key outcomes.
ACE inhibitors and ARBs had similar long-term effects on blood pressure (50 studies; strength of evidence, high). No consistent differential effects were observed for other outcomes (few studies reported long-term outcomes), including death, cardiovascular events, quality of life, rate of single antihypertensive agent use, lipid levels, progression to diabetes, left ventricular mass or function, and kidney disease. Consistent fair- to good-quality evidence showed that ACE inhibitors were associated with a greater risk for cough. There were fewer withdrawals due to adverse events and greater persistence with therapy for ARBs than for ACE inhibitors, although this evidence was not definitive. Patient subgroups for whom ACE inhibitors or ARBs were more effective, associated with fewer adverse events, or better tolerated were not identified.
Few studies involved a representative sample treated in a typical clinical setting over a long duration, treatment protocols had marked heterogeneity, and substantive amounts of data about important outcomes and patient subgroups were missing.
Available evidence shows that ACE inhibitors and ARBs have similar effects on blood pressure control, and that ACE inhibitors have higher rates of cough than ARBs. Data regarding other outcomes are limited.
Are angiotensin-converting enzyme (ACE) inhibitors or angiotensin II receptor blockers (ARBs) more effective for treating essential hypertension?
This systematic review of trials that directly compared ACE inhibitors and ARBs in adults with essential hypertension found good evidence that the agents had similar long-term effects on blood pressure. There were no consistent differential effects for mortality, cardiovascular events, progression to diabetes, left ventricular function, or kidney disease. Cough was more frequent with ACE inhibitors than ARBs.
Both ACE inhibitors and ARBs have similar effects on blood pressure and may not have differential effects on other clinical outcomes, although ACE inhibitors do cause cough more often than ARBs.
Study flow diagram.
*See Appendix 1. ACE = angiotensin-converting enzyme; ARB = angiotensin II receptor blocker.
Table 1. Number of Included Studies and Publications Evaluating Various Treatment Comparisons*
Table 2. Summary of Reviewed Studies*
Successful monotherapy: angiotensin-converting enzyme (ACE) inhibitors versus angiotensin II receptor blockers (ARBs).
The first group is observational studies and the second group is randomized, controlled trials.
Cough as an adverse event: angiotensin-converting enzyme (ACE) inhibitors versus angiotensin II receptor blockers (ARBs).
Withdrawals due to adverse events: angiotensin-converting enzyme (ACE) inhibitors versus angiotensin II receptor blockers (ARBs).
Table 3. Studies of Persistence*
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Matchar DB, McCrory DC, Orlando LA, Patel MR, Patel UD, Patwardhan MB, et al. Systematic Review: Comparative Effectiveness of Angiotensin-Converting Enzyme Inhibitors and Angiotensin II Receptor Blockers for Treating Essential Hypertension. Ann Intern Med. 2008;148:16-29. doi: 10.7326/0003-4819-148-1-200801010-00189
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Published: Ann Intern Med. 2008;148(1):16-29.
Cardiology, Coronary Risk Factors, Hypertension, Nephrology.
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