ACE Inhibitor-Angiotensin-receptor Blocker Combination Poses Risks

Although the use of individual classes of antihypertensive medications does not increase a patient’s relative risk of cancer, those who take a combination of ACE inhibitors and angiotensin-receptor blockers (ARBs) may exhibit a 10% higher relative cancer risk, according to a meta-analysis published in Lancet Oncology.

In the study, Sripal Bangalore, MD, of New York University School of Medicine, and colleagues assessed the association between antihypertensive drugs and cancer risk in a comprehensive analysis of data from randomized clinical trials. “The risk of cancer from antihypertensive drugs has been much debated, with a recent analysis showing increased risk with angiotensin-receptor blockers (ARBs),” they wrote.

The investigators searched PubMed, Embase, and the Cochrane Central Register of Controlled Trials from 1950, to August, 2010, for randomized clinical trials of ARBs, angiotensin-converting-enzyme inhibitors [ACEi], beta-blockers, calcium-channel blockers [CCBs], or diuretics, with follow-up of at least one year. Primary outcomes included cancer and cancer-related deaths.

Meta-analyses of 70 randomized controlled trials covering 324,168 participants showed no significant difference in the risk of cancer with ARBs, ACEi, beta-blockers, CCBs, diuretics, or other controls versus placebo. Although there was an increased risk with the combination of ACEi plus ARBs, the risk was not apparent in the random-effects model, they noted.

Bangalore and colleagues noted no differences were detected in cancer-related mortality for ARBs, ACEi, beta-blockers, CCBs, diuretics, other controls, and ACEi plus ARBs. In direct comparison meta-analyses, similar results were recorded for all antihypertensive classes, except for an increased risk of cancer with ACEi and ARB combination and with CCBs. However, no significant differences were noted in cancer-related mortality.

“On the basis of trial sequential analysis, our results suggest no evidence of even a 5-10% relative risk (RR) increase of cancer and cancer-related deaths with any individual class of antihypertensive drugs studied,” they wrote. “However, for the ACEi and ARB combination, the cumulative Z curve crossed the trial sequential monitoring boundary, suggesting firm evidence for at least a 10% RR increase in cancer risk.”

The authors also noted that dual therapy with ACE inhibitors and ARBs is typically prescribed to patients with severe heart failure who have a higher mortality risk.

To access the Lancet Oncology study, click here.