New meta-analysis argues against a link between ARB use and increased cancer risk

The use of angiotensin-receptor blockers (ARBs) alone are not associated with increased odds of cancer or cancer-related death, according to a meta-analysis published in a recent edition of Lancet Oncology.

This finding is in direct contrast to a meta-analysis published only a few months ago by Ilke Sipahi, MD, and colleagues, which also appeared in the Lancet Oncology. The work by Dr Sipahi and colleagues reported an 8% (95% CI, 1%–15%; P=.02) increased risk of new cancer in patients receiving an ARB; however, their meta-analysis has been criticized for not including all the available data and for pooling trials with multiple different comparators together.

In this latest meta-analysis conducted by Dr Bangalore and colleagues, 70 randomized controlled trials (n=324,168 participants, mean follow-up of 3.5 years) of various antihypertensive agents were identified and analyzed as part of a sophisticated network of trials. Upon meta-analysis, no differences in the odds of new cancer development with ARBs (OR=1.01, 95% CI, 0.93–1.09), angiotensin-converting enzyme inhibitors (ACEi) (OR=1.00; 95% CI,  0.92–1.09), beta-blockers (OR=0.97, 95% CI, 0.88–1.07), calcium channel blockers (CCBs) (OR=1.05, 95% CI, , 0.96–1.13), diuretics (OR=1.00; 95% CI, 0.90–1.11), or other non-placebo active treatments (OR=0.97; 95% CI, 0.74–1.24) compared to placebo were observed.

Similarly, no differences were detected in cancer-related death rates with any individual class of antihypertensive agent (range of OR: 0.93–1.10, none statistically significant).

Consequently in their paper, the authors noted, “Our analysis refutes a 5.0 to 10.0% relative increase in the risk of cancer or cancer-related death with the use of ARBs, ACEi, beta-blockers, diuretics, and CCBs.”  They continued, “However, increased risk of cancer with the combination of ACEi and ARBs cannot be ruled out.”

Combination ARB and ACEi therapy was found to be associated with an increased odds of new cancer development (OR upon fixed-effect network meta-analysis, 1.14, 95% CI, 1.02 to 1.28 and upon random-effects network meta-analysis, 1.15, 95% CI: 0.92–1.38).  Combination ARB and ACEi therapy was not evaluated in Sipahi and colleagues meta-analyses.

Craig I. Coleman, MD, an associate professor at the University of Connecticut School of Pharmacy, Storrs, and co-director of a research group that specializes in the conduction of systematic reviews and meta-analyses remarked, “Dr Bangolore and colleagues provided a more complete and sophisticated analysis of the available data, and their use of network meta-analysis allowed them to overcome many of the limitations of the meta-analysis by Dr Sipahi.”  However, Dr Coleman also stressed, “Whenever you look at many different comparisons in many different ways in a meta-analysis, you always have to be concerned about identifying statistically significant findings-positive or negative-that are not true.” He concluded, “The increased odds of cancer seen with combination ACEi/ARB therapy may be real or may be statistical artifact, so future research is needed.”

The authors also concluded their report by suggesting to readers that further studies are needed to conclusively prove the association. Moreover, they warn readers to interpret findings cautiously due to the short duration of follow-up in included trials.

According to C. Michael White, PharmD, FCP, FCCP, a professor and cardiovascular pharmacology researcher at the University of Connecticut:  “We know that combination ACEi/ARB therapy reduces bad outcomes in patients with chronic heart failure and in patients with nephropathy and should be encouraged. In patients with a myocardial infarction but without heart failure, the use of combination ACEi/ARB therapy does not provide additional benefits, but has more adverse events and should not be used.” He explained, “As such, this new information about a possible cancer risk would only impact my choice of antihypertensive combination therapy. Instead of using a combination of an ACEi with an ARB, a combination of agents from a different class such as a thiazide diuretic or calcium channel blocker may be a better option.”