Abstract
The association between angiotensin receptor blockers (ARBs) and cancer is controversial with meta-analyses of randomized controlled trials and observational studies reporting conflicting results. Thus, the objective of this study was to determine whether ARBs are associated with an overall increased risk of the four most common cancers, namely, lung, colorectal, breast and prostate cancers, and to explore these effects separately for each cancer type. We conducted a retrospective cohort study using a nested case-control analysis within the United Kingdom (UK) General Practice Research Database. We assembled a cohort of patients prescribed antihypertensive agents between 1995, the year the first ARB (losartan) entered the UK market, and 2008, with follow-up until December 31, 2010. Cases were patients newly-diagnosed with lung, colorectal, breast and prostate cancer during follow-up. We used conditional logistic regression to estimate adjusted rate ratios (RRs) and 95% confidence intervals (CIs) of cancer incidence, comparing ever use of ARBs with ever use of diuretics and/or beta-blockers. The cohort included 1,165,781 patients, during which 41,059 patients were diagnosed with one of the cancers under study (rate 554/100,000 person-years). When compared to diuretics and/or beta-blockers, ever use of ARBs was not associated with an increased rate of cancer overall (RR: 1.00; 95% CI: 0.96–1.03) or with each cancer site separately. The use of angiotensin-converting enzyme inhibitors and calcium channel blockers was associated with an increased rate of lung cancer (RR: 1.13; 95% CI: 1.06–1.20 and RR: 1.19; 95% CI: 1.12–1.27, respectively). This study provides additional evidence that the use of ARBs does not increase the risk of cancer overall or any of the four major cancer sites. Additional research is needed to further investigate a potentially increased risk of lung cancer with angiotensin-converting enzyme inhibitors and calcium channel blockers.
Highlights
The association between angiotensin receptor blockers (ARBs) and cancer is controversial
An increased risk of cancer was observed in the subgroup of patients who received a combination of ARBs and angiotensin-converting-enzyme inhibitors (ACEIs) (odds ratio (OR): 1.14; 95% confidence interval (CI): 1.04–1.24), though this effect was driven largely by the ONTARGET trial and was no longer significant when analyzed with a random-effects model [2]
Entering the exposure groups as nonmutually exclusive groups in the models did not materially change the results (ARBs: adjusted rate of cancer overall (RR): 0.99; 95% CI: 0.96–1.02; ACEIs: adjusted RR: 0.99; 95% CI: 0.97–1.01; calcium channel blocker (CCB): adjusted RR: 1.04; 95% CI: 1.01–1.06; other antihypertensives: adjusted RR: 0.98; 95% CI: 0.93–1.03; diuretics and/or beta-blockers: adjusted RR: 1.00; 95% CI: 0.97–1.03). The results of this large population-based study involving close to 1.2 million patients treated with antihypertensive agents do not support the hypothesis that the use of ARBs, when compared to diuretics and/or beta-blockers, is associated with an increased risk of cancer overall or with any of the four most common cancers
Summary
The association between angiotensin receptor blockers (ARBs) and cancer is controversial. A meta-analysis of eight randomized controlled trials (RCTs) published in 2010 found ARBs to be associated with a modest increase in the risk of new cancer diagnoses (relative risk: 1.08; 95% confidence interval (CI): 1.01– 1.15) [1]. A larger meta-analysis of 70 RCTs published later that year did not find that ARBs or any other antihypertensive agent, when used in monotherapy, was associated with an increased risk of cancer [2]. The aforementioned meta-analyses have several methodological limitations They were based on RCTs where cancer was not the primary outcome of interest. While lung cancer may appear to stand out, the magnitudes of the risks do not rule out a possible association with cancer overall and other cancers in particular
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