No Blaming Common Antihypertensives for Pancreatic Cancer, Study Suggests

Long-time users of dihydropyridine calcium channel blockers (CCBs) were not at disproportionately high risk of pancreatic cancer, according to a large observational cohort study.

Based on primary care records from the U.K. in recent decades, the incidence of pancreatic cancer was similar between dihydropyridine CCB initiators and controls who started a thiazide diuretic instead (37.2 vs 39.4 per 100,000 person-years, weighted HR 0.93, 95% CI 0.80-1.09).

In fact, the Kaplan-Meier curves diverged at 10 years to suggest less pancreatic cancer with CCBs, albeit without reaching statistical significance (weighted HR 0.77, 95% CI 0.47-1.26).

"Future population-based studies with additional years of follow-up should further explore this finding," according to epidemiologist Laurent Azoulay, PhD, of Jewish General Hospital in Montreal, and colleagues reporting in the Journal of the American Heart Association.

Amlodipine (Norvasc) and other dihydropyridine CCBs comprise a drug subclass preferred for the treatment of hypertension because of their more potent vasodilatory effects.

"Given the long-term use of [dihydropyridine CCBs] in patients with hypertension, this observational study provides much needed evidence, as well as reassurance to physicians and patients, regarding the safety of this drug class with respect to pancreatic cancer," according to Azoulay's group.

While CCBs weren't part of the nitrosamine impurity recalls that hit certain antihypertensive classes in recent years over potential cancer risk, prior observational studies had flagged a potential association between CCBs and pancreatic cancer. A recent meta-analysis found the evidence insufficient to rule out excess cancer risk among CCB users.

Azoulay and colleagues pointed out that none of the older studies distinguished between dihydropyridine and non-dihydropyridine CCBs in their association with pancreatic cancer, and some were subject to prevalent user bias, latency bias, recall bias, and confounding by indication by comparing CCB users with nonusers or the general population.

"Although our study represents the largest study to date on [dihydropyridine CCBs] and pancreatic cancer, additional large, population-based studies would be needed to confirm our findings," the authors said.

Their population-based cohort study relied on primary care records from the U.K. CPRD GOLD database.

Participants were people age 40 and older who initiated either a dihydropyridine CCB (n=344,480) or a thiazide diuretic (n=357,968) from Jan. 1, 1990 to March 31, 2018. The comparison group was chosen because thiazide diuretics, another commonly prescribed antihypertensive drug class, have not previously been associated with pancreatic cancer.

The study cohort averaged 64 years of age. Before weighting, initiators of dihydropyridine CCBs were more likely than thiazide diuretic users to be male (54.3% vs 40.2%) and to be prescribed statins (33.5% vs 18.2%), angiotensin-converting enzyme inhibitors (34.2% vs 20.7%), and proton pump inhibitors (36.8% vs 22.7%). Baseline characteristics were well balanced after weighting.

CCB and control group patients were followed for a median of 4.1 and 5.0 years, respectively, which included a 1-year lag period to allow for a minimum cancer latency period and to minimize picking up prevalent pancreatic cancer at baseline.

Study authors noted that their main results were supported by secondary analyses accounting for individual CCBs and long-term cumulative use of this drug class. Results remained generally unchanged following sensitivity analyses using different lag periods and a different weighting method.

Even so, the study had the limitation of only counting prescriptions from primary care, which excluded specialists' prescriptions. There was also not enough information for the investigators to adjust for drug adherence or stratify by the various subtypes of pancreatic cancer.

CCBs are not the only antihypertensive drugs suspected of causing cancer. Long-term exposure to angiotensin-receptor blockers has also been linked to cancer, particularly lung cancer.

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