In an individual participant data meta-analysis of randomized clinical trials reported in The Lancet Oncology, Emma Copland, MSc, and colleagues found “no consistent evidence” of an association between antihypertensive treatment and risk for cancer. A potential increase in risk was observed for calcium channel blockers (CCBs) vs all other comparators but not vs placebo.
Study Details
The meta-analysis included 260,447 participants from 33 randomized trials comparing an antihypertensive agent with placebo, inactive control, or another antihypertensive agent. Eligible trials had to have at least 1,000 participant-years of follow-up in each treatment group and had to include data on cancer events. Overall, 15 trials with 118,574 participants compared an angiotensin-converting enzyme inhibitor (ACEI) vs other; 11 trials with 99,711 participants compared an angiotensin II receptor blocker (ARB) vs other; 5 trials with 35,169 participants compared a β blocker vs other; 19 trials with 150,745 participants compared a CCB vs other, and 6 trials with 58,185 participants compared a thiazide diuretic vs other. The primary outcome measure was any cancer event, defined as the first occurrence of any cancer diagnosed after random assignment in the clinical trial.
We found no consistent evidence that antihypertensive medication use had any effect on cancer risk. Although such findings are reassuring, evidence for some comparisons was insufficient to entirely rule out excess risk, in particular for calcium channel blockers.— Emma Copland, MSc, and colleagues
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Key Findings
Median follow-up of participants was 4.2 years (interquartile range = 3.0–5.0 years).
Among the 260,447 participants, 15,012 had cancer events.
In the individual participant data meta-analysis comparing each drug class with all other comparators, no significant association with risk for any cancer was found for ACEIs (hazard ratio [HR] = 0.99, 95% confidence interval [CI] = 0.95–1.04), ARBs (HR = 0.96, 95% CI = 0.92–1.01), β blockers (HR = 0.98, 95% CI = 0.89–1.07), or thiazides (HR = 1.01, 95% CI = 0.95–1.07). A significant association was observed for CCBs (HR = 1.06, 95% CI = 1.01–1.11).
In a meta-analysis comparing drug classes vs placebo, individual data were available for 72,812 participants in 13 placebo-controlled trials, with 7 including an ACEI group, 3 an ARB group, 4 a CCB group, and 1 a thiazide group. No significant association with cancer risk was found for ACEIs (HR = 1.00, 95% CI = 0.93–1.09), ARBs (HR = 0.99, 95% CI = 0.92–1.06), β blockers (HR = 0.99, 95% CI = 0.89–1.11), CCBs (HR = 1.04, 95% CI = 0.96–1.13), or thiazides (HR = 1.00, 95% CI = 0.90–1.10).
In an analysis of antihypertensive drug classes vs all other comparators for risks of site-specific breast, colorectal, lung, prostate, and skin cancers, no evidence of any association was observed, except for an association of CCBs with increased risk of prostate and skin cancers; these increased risks were driven by comparison of CCBs with ARBs.
The investigators concluded, “We found no consistent evidence that antihypertensive medication use had any effect on cancer risk. Although such findings are reassuring, evidence for some comparisons was insufficient to entirely rule out excess risk, in particular for calcium channel blockers.”
Kazem Rahimi, FRCP, of Nuffield Department of Women’s and Reproductive Health, University of Oxford, is the corresponding author for The Lancet Oncology article.
Disclosure: The study was funded by the British Heart Foundation, National Institute for Health Research, and Oxford Martin School. For full disclosures of the study authors, visit thelancet.com.
