Cardiovascular Risk with Prokinetics: A Self-Controlled Case Series Study Using a Korean Nationwide Health Claims Database

There have been concerns about potential adverse cardiovascular (CV) events associated with prokinetics that enhance gastrointestinal (GI) motility. To evaluate whether prokinetics use was associated with increased CV risk. We conducted a self-controlled case series (SCCS) study using the National Health Claims Database in South Korea. Age-adjusted incidence rate ratios (IRR) for the development of CV events (composite of myocardial infarction and stroke) were estimated by comparing the incidence during the risk period with prokinetics and the control period without prokinetics. This SCCS study included 15,621 participants who experienced CV events and exposure to prokinetics between 2004 and 2019. The risk period with prokinetics had a significantly increased risk for CV events compared to the control period (IRR 1.56, 95% CI 1.48–1.66). When the risk period was categorized according to the time from initiation of prokinetics, CV risk was highest in the first 7 days (IRR 2.29, 95% CI 2.13–2.47), and declined to non-significance in ≥ 15 days (IRR 1.03, 95% CI 0.94–1.13). In the analysis according to the class of prokinetics, CV risk was highest in the order of central dopamine type 2 (D2) receptor antagonist (IRR 2.14, 95% CI 1.95–2.34), peripheral D2 receptor antagonist (IRR 1.37, 95% CI 1.24–1.51), and selective 5-hydroxytryptamine 4 receptor agonist (IRR 1.29, 95% CI 1.17–1.42). The use of prokinetics was associated with an increased risk of CV adverse events, particularly in the early period following initiation of central D2 receptor antagonists.