Upper gastrointestinal bleeding in Japanese patients with ischemic heart disease receiving vonoprazan or a proton pump inhibitor with multiple antithrombotic agents: A nationwide database study

J Cardiol. 2020 Jul;76(1):51-57. doi: 10.1016/j.jjcc.2020.02.012. Epub 2020 Mar 14.

Abstract

Background: Vonoprazan has been launched as an alternative to proton-pump inhibitors (PPIs). This was the first study to compare the occurrence of upper gastrointestinal bleeding (UGIB) with vonoprazan treatment to that with PPI treatment in patients with ischemic heart disease (IHD) taking ≥2 antithrombotic agents, including those receiving dual antiplatelet therapy (DAPT).

Methods: Using Japanese Diagnosis Procedure Combination data from 2016 to 2017, we identified 16,415 patients with IHD who were prescribed ≥2 antithrombotic agents, including new antiplatelet medication with concurrent vonoprazan (n = 2226 or PPIs n = 14,189). UGIB occurrence was analyzed using an inverse probability-weighted Cox proportional hazards model. Non-inferiority of vonoprazan to PPI treatment for UGIB occurrence was assessed.

Results: Six-month incidence of UGIB in patients treated with vonoprazan and PPIs was 3.14% 70/2226 and 4.17% (591/14,189), respectively. The adjusted hazard ratio (aHR) of 0.84 was significantly below the non-inferiority margin (HR 2.06) (p < 0.0001), and thus demonstrated that vonoprazan treatment was non-inferior to PPIs in terms of occurrence of UGIB events. The difference between the 2 treatments was also not statistically significant [aHR 0.84; 95% confidence interval (CI): 0.65-1.07; p = 0.154). In a subgroup analysis, UGIB occurrence with vonoprazan and other PPI treatment in patients receiving DAPT was 2.82% (22/779) and 3.96% (209/5276) respectively; a non-significant difference (aHR 0.74; 95% CI: 0.48-1.16; p = 0.189) that demonstrated non-inferiority (p < 0.0001).

Conclusions: Vonoprazan was non-inferior to PPIs in terms of UGIB occurrence over 6 months in patients with IHD receiving ≥2 antithrombotic agents, including new antiplatelet medication.

Keywords: Antithrombotic; Gastrointestinal bleeding; Ischemic heart disease; Proton pump inhibitors; Vonoprazan.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Asian People
  • Databases, Factual
  • Female
  • Fibrinolytic Agents / adverse effects*
  • Gastrointestinal Hemorrhage / chemically induced*
  • Humans
  • Japan
  • Male
  • Myocardial Ischemia / drug therapy*
  • Platelet Aggregation Inhibitors / adverse effects*
  • Proton Pump Inhibitors / adverse effects*
  • Pyrroles / adverse effects*
  • Retrospective Studies
  • Sulfonamides / adverse effects*

Substances

  • 1-(5-(2-fluorophenyl)-1-(pyridin-3-ylsulfonyl)-1H-pyrrol-3-yl)-N-methylmethanamine
  • Fibrinolytic Agents
  • Platelet Aggregation Inhibitors
  • Proton Pump Inhibitors
  • Pyrroles
  • Sulfonamides