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Some Clarifying Data on ARBs

Two studies diminish concerns that angiotensin-receptor blockers might increase risk for myocardial infarction in some patients.

ACE inhibitors (ACEIs) prevent cardiovascular events in high-risk patients with heart failure or left-ventricular systolic dysfunction (LVSD). Angiotensin-receptor blockers (ARBs) also inhibit the renin-angiotensin system, but concerns have been raised that ARBs may increase MI risk in some patients. Two new studies address these concerns.

One study was a further analysis of the manufacturer-sponsored, double-blind, randomized CHARM trial, in which symptomatic heart failure patients received either the ARB candesartan (target dose, 32 mg once daily) or placebo (Journal Watch Cardiology Oct 10 2003). The 7599 subjects (62% with ischemic heart failure, 28% with diabetes) were randomized within three trial arms: one for subjects with LVSD who already were taking ACEIs, one for those with LVSD who could not tolerate ACEIs, and one for those without LVSD (19% of whom were taking ACEIs). In addition, 55% of CHARM subjects were taking beta-blockers, 56% aspirin, and 42% lipid-lowering therapy. The new CHARM report elucidates candesartan’s effects on several cardiovascular endpoints during a median follow-up of 38 months.

In CHARM, candesartan was significantly better than placebo in preventing the primary combined endpoint of cardiovascular death or nonfatal MI (20.4% vs. 22.9%; hazard ratio, 0.87; number needed to treat, 40), as well as cardiovascular death (18.2% vs. 20.3%) and nonfatal MI (3.1% vs. 3.9%) individually. Results were consistent across subgroups, including within each trial arm (by LVSD status and ACEI use) and by beta-blocker use. Risks for unstable angina and coronary revascularization were similar with candesartan and placebo.

The other study was a meta-analysis of 19 randomized, controlled ARB trials (including CHARM) that enrolled a total of 31,569 subjects with hypertension, heart failure, coronary disease, or diabetic nephropathy. In these trials, MI risk was statistically similar between ARB recipients and either placebo or ACEI recipients.

Comment: The meta-analysis findings suggest that ARBs do not increase MI risk in high-risk patients, and the CHARM data show that candesartan can prevent cardiovascular death and MI in a wide range of optimally treated heart failure patients. Pending issues include the relative benefits of ACEIs versus ARBs, as well as the potential preventive benefit of ARBs when added to ACEIs in patients with LVSD and when used as first-line therapy in heart failure patients without LVSD. Ongoing clinical trials (ONTARGET and TRANSCEND; both involving telmisartan) are likely to clarify the role of ARBs in preventing cardiovascular events in high-risk patients.

— Frederick A. Masoudi, MD, MSPH

Dr. Masoudi is Associate Professor of Medicine, University of Colorado Health Sciences Center, and a practicing clinician at the Denver Health Medical Center.

Published in Journal Watch Cardiology November 4, 2005

Citation(s):

Demers C et al. Impact of candesartan on nonfatal myocardial infarction and cardiovascular death in patients with heart failure. JAMA 2005 Oct 12; 294:1794-8.

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• Medline abstract (Free)

McDonald MA et al. Angiotensin receptor blockers and risk of myocardial infarction: Systematic review. BMJ 2005 Oct 15; 331:873-6.

• Original article (Subscription may be required)
• Medline abstract (Free)