Angiotensin receptor blockers and risk of cancer: cohort study among people receiving antihypertensive drugs in UK General Practice Research Database

Abstract

Objectives: To investigate whether there is an association between use of angiotensin receptor blockers and risk of cancer.

Design: Cohort study of risk of cancer in people treated with angiotensin receptor blockers compared with angiotensin converting enzyme (ACE) inhibitors. Effects were explored with time updated covariates in Cox models adjusted for age, sex, body mass index (BMI), diabetes and metformin/insulin use, hypertension, heart failure, statin use, socioeconomic status, alcohol, smoking, and calendar year. Absolute changes in risk were predicted from a Poisson model incorporating the strongest determinants of risk from the main analysis.

Setting: UK primary care practices contributing to the General Practice Research Database.

Participants: 377,649 new users of angiotensin receptor blockers or ACE inhibitors with at least one year of initial treatment.

Main outcome measures: Adjusted hazard ratios for all cancer and major site specific cancers (breast, lung, colon, prostate) by exposure to angiotensin receptor blockers and by cumulative duration of use.

Results: Follow-up ended a median of 4.6 years after the start of treatment; 20,203 cancers were observed. There was no evidence of any increase in overall risk of cancer among those ever exposed to angiotensin receptor blockers (adjusted hazard ratio 1.03, 95% confidence interval 0.99 to 1.06, P = 0.10). For specific cancers, there was some evidence of an increased risk of breast and prostate cancer (1.11, 1.01 to 1.21, P = 0.02; and 1.10, 1.00 to 1.20, P = 0.04; respectively), which in absolute terms corresponded to an estimated 0.5 and 1.1 extra cases, respectively, per 1000 person years of follow-up among those with the highest baseline risk. Longer duration of treatment did not seem to be associated with higher risk (P>0.15 in each case). There was a decreased risk of lung cancer (0.84, 0.75 to 0.94), but no effect on colon cancer (1.02, 0.91 to 1.16).

Conclusions: Use of angiotensin receptor blockers was not associated with an increased risk of cancer overall. Observed increased risks for breast and prostate cancer were small in absolute terms, and the lack of association with duration of treatment meant that non-causal explanations could not be excluded.

Fig 1 Assignation of time varying variable for ever exposed to angiotensin receptor blocker (ARB) and duration of angiotensin receptor blocker use during follow-up under four example scenarios

Fig 2 Inclusion and exclusion of study participants. ARB=angiotensin receptor blocker

Fig 3 Effect of cumulative duration (from end of initial one year qualifying treatment period) of angiotensin receptor blocker (ARB) use on risk of all cancer and specific cancers. Hazard ratios are from Cox models with cumulative duration of use treated as time updated covariate, adjusted for age, sex (except models for breast/prostate cancers), BMI, smoking, alcohol, diabetes, metformin use, index of multiple deprivation score, and calendar year. Effect estimate for “ever used” is from primary analysis model ignoring number of prescriptions and is shown for comparison