Limited evidence to link antihypertensive use to cancer
medwireNews: An extensive meta-analysis of individual participant data has not found consistent evidence to indicate that antihypertensive use is associated with an increased risk for cancer.
“Although such findings are reassuring, evidence for some comparisons was insufficient to entirely rule out excess risk, in particular for calcium channel blockers,” write Kazem Rahimi (University of Oxford, UK) and co-authors in The Lancet Oncology.
They reviewed data for 260,447 participants from 33 randomized controlled trials (RCTs), published up to September 2019, that compared one blood pressure lowering drug class with a placebo, inactive control, or another blood pressure lowering drug. During a median 4.2 years of follow-up, 15,012 participants across all trials were diagnosed with cancer.
Rahimi and team report that there were no significant associations between cancer incidence and the use of angiotensin-converting enzyme (ACE) inhibitors, angiotensin II receptor blockers (ARBs), beta blockers, or thiazide diuretics relative to all other comparators.
There was, however, a significantly increased risk for cancer among people who used calcium channel blockers compared with any other group, at a hazard ratio (HR) of 1.06.
For cancer-related deaths, there was no significant link to ACE inhibitor, ARB, beta blocker, or calcium channel blocker use, but there was a significantly increased risk associated with the use of thiazide diuretics, at an HR of 1.14.
The researchers say that although these associations require further investigation, “the absence of plausible mechanisms suggest that calcium channel blockers or thiazides are unlikely to cause such cancers.”
Furthermore, when the team conducted a network meta-analysis comparing each of the drug classes against placebo only, they found no increased risk for developing or dying from cancer with any drug class.
For site-specific cancers, there was generally no evidence that antihypertensive drug use increased the risk for breast, colon, lung, prostate, or skin cancer. The only exception was with calcium channel blockers which were associated with a significantly increased risks for prostate (HR=1.15) and skin (HR=1.26) cancers that were driven by comparisons with ARB use, the researchers say.
Rahimi et al also report that their findings did not vary by age, sex, BMI, smoking status, or previous antihypertensive use, and the risk did not appear to increase significantly with treatment duration. They note, however, that the relatively short follow-up period “might not be sufficient for some cancers to develop.”
The authors say: “It is estimated that between 30% and 50% of individuals have poor adherence to [antihypertensive] drugs, partly because of concerns around the harmful effects that long-term use of antihypertensive medications might cause.”
They conclude: “The main implication of our study is that patients using antihypertensive medication should continue to take their medications because concerns about increased cancer risk seem to be unfounded.”
However, Laurent Azoulay, from McGill University in Montreal, Quebec, Canada, points out in an accompanying comment that RCTs “are generally not designed to assess safety [which] is particularly relevant for outcomes with delayed onset, such as cancer.”
He says: “As acknowledged by the authors, due to the relatively short median duration of follow-up of the antihypertensive drug trials, a potential association between cancer and the long-term use of antihypertensive drugs cannot be ruled out.”
Azoulay believes that “moving forward, these studies will need to be complemented with well designed, real-world studies in heterogeneous patient populations who are followed up for extended periods of time to fully understand their carcinogenic potential.”
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