ARBs linked to modest increase in cancer risk, researchers report

Angiotensin II receptor blockers (ARBs) are associated with a modestly increased risk of cancer, according to data from a recent meta-analysis. Dr. Ilke Sipahi of Case Western Reserve University in Cleveland, Ohio, and colleagues analyzed data from trials published before November 2009 that evaluated any of the 7 currently available ARBs. Their analysis included randomized controlled trials in which an ARB was given in >=1 patient group, >=1 year of follow-up data were available, and...

Angiotensin II receptor blockers (ARBs) are associated with a modestly increased risk of cancer, according to data from a recent meta-analysis.

Dr. Ilke Sipahi of Case Western Reserve University in Cleveland, Ohio, and colleagues analyzed data from trials published before November 2009 that evaluated any of the 7 currently available ARBs. Their analysis included randomized controlled trials in which an ARB was given in >=1 patient group, >=1 year of follow-up data were available, and >=100 patients were enrolled.

Data pertaining to new cancer were available for 61,590 patients from 5 trials, data on solid organ cancers were available for 68,402 patients from 5 trials, and data on cancer-related deaths were available for 93,515 patients from 8 trials.

For the primary outcome of cancer occurrence, telmisartan was the main ARB used as the study drug (used by 85.7%, or 30,014 patients). Other drugs included in the analysis were losartan potassium, valsartan, candesartan cilexetil, irbesartan, eprosartan mesylate, and olmesartan medoxomil.

The researchers discovered that the patients randomized to receive ARBs had a significantly increased risk of new cancer occurrence as compared with those who were randomized to receive control therapies (risk ratio [RR], 1.08 [95% CI, 1.01-1.15]; P=.016). Cancer was diagnosed in 7.2% of the patients treated with ARBs and in 6% of the patients treated with control therapies.

In the evaluation of specific solid organ cancers, only the incidence of new lung cancer was significantly higher among the recipients of ARBs than among the recipients of control treatments (0.9% vs 0.7%; RR, 1.25 [95% CI, 1.05-1.49]; P=.01).

No statistically significant difference in cancer deaths was observed between the patients who received ARBs and those who received a control treatment (1.8% vs 1.6%; RR, 1.07 [95% CI, 0.97-1.18]; P=.183).

The study authors noted important limitations in their analysis, including a lack of patient-level data that would have allowed them to adjust for the effects of age, sex, and smoking status. In addition, the trials they evaluated were not designed specifically to explore cancer outcomes as the primary goal, although an increased risk of cancer remained significant in an analysis limited to 3 trials in which cancer was a prespecified endpoint and cancer data were rigorously collected.

"Given limited data, it is not possible to draw conclusions about the exact risk of cancer associated with each particular ARB," the authors wrote. "Our findings warrant further investigation."

The study was published online June 14 ahead of print in The Lancet Oncology.

In an accompanying commentary, Dr. Steven Nissen, chairman of the department of cardiovascular medicine at Cleveland Clinic, provided his thoughts on the analysis.

He said regulators need to review the possible association between ARB therapy and cancer risk, and "[i]n the interim, we should use ARBs, particularly telmisartan, with greater caution. These drugs are often overprescribed, as a result of aggressive marketing and in the absence of evidence that they are better than angiotensin-converting enzyme (ACE) inhibitors. ARBs can be reserved for patients with intolerance to ACE inhibitors," he recommended.

Boehringer Ingelheim Pharmaceuticals Inc., the firm that sells telmisartan under the brand name Micardis, refuted the findings and said its "comprehensive internal safety data analysis of primary data contradicts the conclusions about an increased risk of potential malignancies mentioned by Sipahi et al."