ACE inhibitors versus ARBs for ischemic heart disease: comparative effectiveness

A systematic review into the comparative effectiveness of angiotensin-converting enzyme (ACE) inhibitors or angiotensin II receptor blockers (ARBs), or both, for patients with stable ischemic heart disease and preserved left ventricular (LV) function found that adding an ACE inhibitor to standard treatment can improve outcomes.

Key Points

A systematic review into the comparative effectiveness of angiotensin-converting enzyme (ACE) inhibitors or angiotensin II receptor blockers (ARBs), or both, for patients with stable ischemic heart disease and preserved left ventricular (LV) function found that adding an ACE inhibitor to standard treatment can improve outcomes. ACE inhibitors reduce risk for mortality, stroke, and myocardial infarction (MI) in these patients, according to the report published in the Annals of Internal Medicine.

Combination therapy versus ACE inhibitor therapy alone appears to increase harms in some patients with stable ischemic heart disease and preserved LV function, by increasing risks for hypotension and syncope.

In order to compare benefits and harms of using these drugs alone or in combination in patients with stable ischemic heart disease and preserved LV function, two independent investigators screened citations for trials 6 months or longer in duration, which compared these agents alone or in combination with placebo or active control. Data sources included MEDLINE (1966-July 2009) and EMBASE (1990-July 2009), as well as the Cochrane Central Register of Controlled Trials and the Cochrane Database of Systematic Reviews (both second quarter 2009) with no language restrictions. The investigators reported any of several clinical outcomes. The Agency for Healthcare Research and Quality commissioned this report. Standard treatments for patients with stable ischemic heart disease and preserved LV function include aspirin, beta blockers, and aggressive modification of risk factors.

Moderate- to high-strength evidence from 7 RCTs with 32,559 study participants demonstrated that ACE inhibitors reduced total mortality risk (relative risk [RR], 0.87) compared with placebo. Similarly, 6 of these RCTs assessing ACE inhibitors reported data on MI that showed the drugs reduced the risk for nonfatal MI versus placebo (RR, 0.83). Also, data from the 7 RCTs showed that ACE inhibitors reduced the risk of stroke (RR, 0.78).

ARBs appear to reduce the composite end point of cardiovascular mortality, nonfatal MI, or stroke (RR, 0.88), according to low-strength evidence from the single RCT (5,926 participants) that investigated this class of drugs. ARBs do not reduce these risk factors individually, however.

There was only a single trial (including 25,620 participants) of combination therapy with ACE inhibitors and ARBs; this moderate-strength evidence found that combination therapy was associated with more study discontinuations (P<0.001) and discontinuations due to hypotension (P<0.001) and syncope (P=0.035) than ACE inhibitors alone. No significant difference was seen in total mortality (RR, 1.07) cardiovascular mortality (RR, 1.04), total MIs (RR, 1.08), stroke (RR, 0.93), or composite end points (RR, 1.00) between combination therapy and ACE inhibitors alone.

The authors note some limitations of their analysis regarding the effectiveness of ACE inhibitors versus ARBs in patients with stable ischemic heart disease and preserved LV function: they could only analyze data from published trials and data provided by the authors of these trials. Subgroup data was not reported consistently. The ability to test for statistical heterogeneity was limited, reducing the strength of resultant evidence. Finally, the harms data were both incomplete and inconsistent. They state that "Future trials are needed to more clearly define the role of ARBs in this population."

SOURCE

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;Oct 19 [Epub ahead of print].