Key Points
- Combination therapy versus angiotensin-converting enzyme (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.
- Moderate- to high-strength evidence from 7 randomized control trials (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).
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.
Randomized controlled trial (RCT) results were selected for inclusion to assess potential benefits if the trial included at
least 75 patients, patients with stable ischemic heart disease, and patients with preserved LV function. They also had to
have followed patients for at least 6 months, compared ACE inhibitor or ARB therapy with placebo or active control or compared
combination therapy with an ACE or ARB with either alone, and reported data on at least one prespecified efficacy outcome
including total mortality, cardiovascular mortality, nonfatal MI, stroke, or a composite of the last 3 endpoints. RCTs were
selected for the harms evaluation if they satisfied all of these criteria except for reported data on efficacy and instead
reported data on a prespecified harm, that is, withdrawals due to adverse events, hypotension, syncope, or cough. Some observational
studies were also included. Eight RCTs with a total of 37,148 participants met the inclusion criteria. 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].
Practice Tools
