Prucalopride does not appear to increase cardiovascular risk in patients with chronic constipation

WASHINGTON — Patients with constipation who received prucalopride did not show an increased risk for major cardiovascular events, according to research presented at Digestive Disease Week.

Alicia Gilsenan, MD, of RTI Health Solutions in North Carolina, and colleagues conducted a trial to determine if there was any difference in risk for major adverse cardiovascular events (MACE) for patients treated with the drug — a selective, high-affinity serotonin 5-HT4 receptor agonist — compared with patients treated with polyethylene Glycol 3350 (PEG).

“PEG was chosen for this study because it was the most commonly reimbursed prescribed medication for chronic constipation in Europe,” Gilsenan said in her presentation. “It was also considered neutral for cardiovascular risk.”

While prucalopride has not shown any risk for cardiovascular events during its development or use in Europe, Gilsenan said the FDA requested an observational study of the drug to support its new drug application in the United States.

Gilsenan and colleagues analyzed data from 35,087 patients with chronic constipation treated with either prucalopride (n = 5,715) or PEG (n = 29,372). The patients were based in the United Kingdom, as well as Sweden.

The investigators searched patient history for MACE, including hospitalization for acute myocardial infarction or stroke, as well as in-hospital cardiovascular death. They calculated adjusted incidence rate ratio (IRR) for MACE after using propensity score matching to compare the two drugs.

They found that the standardized incidence rate of MACE per 1,000 person-years (6.57; 95% CI, 3.9–10.39) was lower compared with PEG (10.3; 95% CI, 7.03-14.19). The pooled incidence rate ratio (0.64; 95% CI, 0.36-1.13) indicated that there was no evidence of an increased risk for MACE for patients treated with prucalopride compared with patients treated with PEG, according to Gilsenan.

“The main results were consistent with no evidence of increased risk of MACE in new users of prucalopride compared with new users of PEG in the overall study population,” she said. Because the study population comprised mostly women and had a large proportion of patients younger than 55 years, it already had a lower risk for cardiovascular events. Therefore, Gilsenan said future studies that include more older men are needed to determine the incidence rates for that subgroup of patients. – by Alex Young

Reference:

Gilsenan A, et al. Abstract 386. Presented at: Digestive Disease Week; June 2-5, 2018; Washington, D.C.

Disclosures: Gilsenan is employed by RTI Health Solutions and reports financial ties to Shire Pharmaceuticals. Please see the DDW faculty disclosure index for a list of all other authors’ relevant financial disclosures.