Short-Acting CCBs May Increase Risk of Pancreatic Cancer

A large observational study found that use of short-acting calcium channel blockers (CCBs) for hypertension is associated with increased incidence of pancreatic cancer among postmenopausal women, when compared with the use of other types of antihypertensive medication and never-use of such agents.

“Pancreatic cancer is not very common in the United States, but it is a very lethal cancer. It is the third-leading cause of cancer death in the US,” said Zhensheng Wang, MPH, PhD, of the Dan L. Duncan Cancer Center at the Baylor College of Medicine in Houston, during a press conference.

Wang presented results of the new study, which investigated the associations between antihypertensive medications, a receptor known as sRAGE, and pancreatic cancer at the American Association for Cancer Research Annual Meeting (AACR), held April 14–18 in Chicago.

The soluble form of the receptor for advanced glycation end products (sRAGE) may have an anti-inflammatory effect on the body, and thus may have a protective effect on pancreatic cancer, while RAGE may promote cancer development. Other research has suggested that certain antihypertensive medications can downregulate the RAGE signaling pathway and increase sRAGE levels.

Wang et al evaluated data on 145,551 postmenopausal women included in the Women’s Health Initiative study. The mean follow-up period was 13.8 years, over which period of time 841 pancreatic cancer cases were identified. Among the full cohort, 14,105 women were ever-users of CCBs (4,338 users of short-acting CCBs); 25,076 women were ever-users of other antihypertensive medications, including beta-blockers, diuretics, or angiotensin-converting-enzyme (ACE) inhibitors; and 106,370 were never-users of these medications.

Compared with ever-users of other types of antihypertensive medications, users of short-acting CCBs had a hazard ratio (HR) for development of pancreatic cancer of 1.66, which was significant after adjustment for a number of relevant factors. When compared with never-users of any such agents, the short-acting CCB recipients had an HR for pancreatic cancer of 1.51 (95% CI, 1.08–2.11). None of the other types of agents showed a significant effect on pancreatic cancer risk, although there was a nonsignificantly lower risk with beta-blockers, diuretics, and ACE inhibitors.

Among a smaller cohort of patients for whom serum sRAGE levels were available, there were lower levels seen in those taking short-acting CCBs compared with any other type of antihypertensive medication (P = .032).

 “This is a very important finding, because previous studies reported that CCBs can reduce the RAGE and AGE [advanced glycation end products] interaction and can prevent pancreatic cancer, but they didn’t look at short-acting CCBs,” Wang said. “They increase the risk.” He stressed that this was an observational study, and only assessed postmenopausal women, so further investigation is needed to elucidate the potential risks.

Suzanne L. Topolian, MD, of the Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins University in Baltimore, moderated the press conference on Tuesday, and put the study findings into context. “I think this is potentially interesting, but very early,” she said. “It’s a relatively small number of people. There are other ways now to examine this question, [and] this [investigation] was an important first step but it needs more study.”