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In 2003, the Candesartan in Heart failure Assessment of Reduction in Mortality and Morbidity (CHARM) investigators reported a small but significant elevation in the rate of cancer deaths in patients treated with candesartan versus placebo. Now, U.S. investigators have conducted a meta-analysis of randomized controlled trials of angiotensin-receptor blockers (ARBs) to learn more about their effect on cancer.
Telmisartan was the ARB used in most of the studies. Of the five trials that included data on new cancer occurrence, the overall cancer rate was higher in the ARB groups than in the control groups (7.2% vs. 6.0%; relative risk, 1.08; 95% confidence interval, 1.01–1.15). When the analysis was restricted to the three trials in which cancer was a prespecified endpoint, the excess risk associated with ARBs persisted (RR, 1.11; 95% CI, 1.04–1.18). In the one study in which patients received concomitant angiotensin-converting enzyme (ACE)-inhibitor treatment, ARBs were associated with a 13% increase in risk for incident cancer (95% CI, 1.03–1.24). The number needed to harm was estimated to be 143 with 4 years of treatment.
Sipahi I et al. Angiotensin-receptor blockade and risk of cancer: Meta-analysis of randomized controlled trials. Lancet 2010 Jun 14; [e-pub ahead of print]. (http://dx.doi.org/10.1016/S1470-2045(10)70106-6)
Nissen SE. Angiotensin-receptor blockers and cancer: Urgent regulatory review needed. Lancet 2010 Jun 14; [e-pub ahead of print]. (http://dx.doi.org/10.1016/S1470-2045(10)70142-X)
Comment
Nearly 7 years after the CHARM study raised questions about ARB-associated cancer risk, this analysis of the available evidence only heightens the concern. Unfortunately, we are no closer to understanding whether this is truly a problem than we were in 2003. Is the risk real? Is it restricted to certain drugs, is it a class effect of ARBs, or does it involve all drugs that affect the renin-angiotensin system? No similar elevation in cancer risk has yet been associated with ACE inhibitors, although more data on this drug class is also needed. The current results point to the importance of thorough and timely collection of safety data on drugs — and the necessity of analyzing all relevant data, published and unpublished. Clinicians and patients need more information to accurately weigh the benefits and risks of using ARBs.