Long term use of drugs affecting the renin‐angiotensin system and the risk of cancer: a population‐based case‐control study

WHAT IS ALREADY KNOWN ABOUT THIS SUBJECT • A recent meta‐analysis has suggested an increased risk of cancer among users of angiotensin receptor blockers. WHAT THIS STUDY ADDS • Within the limitations of an observational study there is no difference in the cancer incidence between users of drugs affecting the renin‐angiotensin system and users of other antihypertensives. • No consistent dose or duration dependency could be demonstrated for angiotensin reeptor blockers and angiotensin converting enzyme inhibitors. AIMS A recent meta‐analysis of clinical trials has demonstrated a small excess of cancers in persons who had been allocated to angiotensin receptor blockers (ARBs). We undertook this observational study to look at dose–response and dose–duration effects and look for specificity with respect to outcome. Use of angiotensin converting enzyme inhibitors (ACEIs) was included in the main analysis since ACEIs share pharmacological properties with ARBs. METHODS We identified 149 417 incident cancer cases in Denmark during the period 2000–2005. Four controls, matched by age and gender, were selected for each case by a risk‐set sampling. Data on medication were retrieved from the Danish National Prescription Registry. We defined long term exposure as at least 1000 defined daily doses redeemed within the past 5 years. Confounders were controlled by conditional logistic regression. RESULTS The odds ratio (OR) associating long term drug use with incident cancer was 1.12 (95% CI 1.06, 1.18), 1.17 (95% CI 1.14, 1.20), 1.23 (95% CI 1.20, 1.26), 1.18 (95% CI 1.14, 1.22), 1.25 (95% CI 1.22, 1.28), 1.37 (95% CI 1.21, 1.54), 1.29 (95% CI 1.22, 1.37) for ARBs, ACEIs, calcium channel blockers, β‐adrenoceptor blockers, thiazide diuretics and α‐adrenoceptor blockers. No consistent dose–duration or dose–response association could be demonstrated for ARBs or ACEIs. CONCLUSIONS The indication or possibly threshold for prescribing antihypertensives appears to be related to a small increase in cancer risk. The ARB‐cancer association is probably too weak to be addressed in observational studies, given their limitations.