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Use of antihypertensive drugs had no consistent association with cancer risk, according to a review of 33 clinical studies.

Patients treated with any of five different classes of antihypertensive drugs had essentially the same cancer risk as that of placebo-treated patients. Comparisons of each antihypertensive class against all the others showed no association with an increased risk of cancer, with the exception of calcium channel blockers (CCBs), which had only a modestly higher risk versus the other drug classes (HR 1.06, 95% CI 1.01-1.11).

Though reassuring, the data do not close the door on the issue, as some comparisons had insufficient data to rule out the possibility of excess cancer risk, reported Kazem Rahimi, DM, of the University of Oxford in England, and colleagues in .

"Our study has addressed an ongoing controversy about the safety of blood pressure-lowering medication with respect to cancer risk, using the largest sample of individual-level randomized evidence on blood pressure-lowering treatment to date, to our knowledge," they wrote. "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."

The findings could have reflected the play of chance, noted the author of an . The number of trials per drug class varied substantially, and analyses by type of cancer involved small sample sizes.

"Taken together, these limitations raise a more fundamental question about how the findings of randomized controlled trials should be interpreted," wrote Laurent Azoulay, PhD, of McGill University in Montreal.

Although randomized trials represent the "gold standard" for assessing drug efficacy, they usually are not designed to assess safety, he continued. The point is particularly relevant for outcomes that have delayed onset, such as cancer. Given that the meta-analysis had a relatively brief median follow-up of 4.2 years, "a potential association between cancer and the long-term use of antihypertensive drugs cannot be ruled out."

"Such analyses are necessary to understand the short-term effects of these drugs on cancer incidence," Azoulay concluded. "However, 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."

Several meta-analyses of data from randomized controlled clinical trials have examined the association between antihypertensive therapy and cancer risk, but the analyses yielded conflicting evidence, Rahimi and colleagues stated. The Blood Pressure Lowering Treatment Trialists' Collaboration (BPLTTC) is a collaboration among principal investigators in global trials of blood pressure lowering and has accumulated the world's largest individual patient-level data on blood pressure-lowering trials. BPLTTC data formed the basis for the meta-analysis.

The authors performed a literature review that covered the period from Jan. 1, 1966 to Sept. 1, 2019. They identified 33 trials for inclusion in the meta-analysis, which comprised 260,447 patients for whom data on cancer outcomes were available. CCBs were the antihypertensive class most commonly represented in the trials (n=19), followed by ACE inhibitors (15), angiotensin-receptor blockers (ARBs, 11), thiazide diuretics (six), and beta-blockers (five). Median follow-up ranged from 4.0 to 5.0 years across the trials, grouped by drug class.

Patient age ranged between 64 and 68 by drug class. Patients ages 65 or older constituted a majority of participants (56%-65%) by type of medication, with the exception of beta-blockers (54% younger than age 65). Pretreatment systolic blood pressure ranged from 147 mm Hg (ACE inhibitors) to 166 mm Hg (beta-blockers).

Across the five classes of antihypertensive drugs, individual comparisons for cancer risk versus the other drug classes yielded hazard ratios of 0.96 for ARBs (95% CI 0.92-1.01), 0.98 for beta-blockers (0.89-1.07), 0.99 for ACE inhibitors (0.95-1.04), 1.01 for thiazide diuretics (0.95-1.07), and 1.06 for CCBs (1.01-1.11). A network meta-analysis of individual drug classes versus placebo resulted in HRs of 0.99 for ARBs and beta-blockers, 1.00 for ACE inhibitors and thiazide diuretics, and 1.04 for CCBs. Confidence intervals for all the comparisons included 1.00.

"We found no consistent evidence that antihypertensive medication use had any effect on cancer risk," the authors stated.

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