TOPLINE:

Concomitant use of potassium-competitive acid blockers (P-CABs) or proton pump inhibitors (PPI) with clopidogrel was associated with an increased risk for major adverse cardiovascular events (MACEs) and stroke recurrence compared with the use of clopidogrel alone in patients with a history of ischemic stroke, a new cohort study showed.

METHODOLOGY:

• A retrospective cohort study included data for more than 65,000 patients with incident ischemic stroke (median age, 66 years; 58% men) from the Korean National Health Insurance Service database.
• More than 40,000 patients received clopidogrel therapy between 2017 and 2021 and were classified into three cohorts: clopidogrel alone, clopidogrel plus P-CABs, and clopidogrel plus PPI.
• The P-CABs examined were tegoprazan, fexuprazan, vonoprazan, and revaprazan; PPI examined were esomeprazole, dexlansoprazole, omeprazole, pantoprazole, ilaprazole, and rabeprazole.
• Propensity score matching (PSM) compared outcomes between 536 patients each in the clopidogrel plus P-CAB and clopidogrel-only cohorts and between 5847 patients each in the clopidogrel plus PPI and clopidogrel-only cohorts.
• The primary outcome was the occurrence of MACEs, including myocardial infarction, stroke recurrence, and all-cause mortality, as well as gastrointestinal bleeding. All were assessed during a 180-day follow-up period.

TAKEAWAY:

• After PSM, the clopidogrel plus P-CAB cohort had a higher risk for MACE (hazard ratio [HR], 2.40) and stroke recurrence (HR, 2.64) than the clopidogrel-alone cohort as did the clopidogrel plus PPI cohort (HRs, 1.38 and 1.41, respectively).
• Among individual PPI, only esomeprazole was associated with a higher risk for MACEs (HR, 1.46) and stroke recurrence (HR, 1.50) compared with clopidogrel alone.
• No significant differences were observed in the incidence of myocardial infarction, death, or gastrointestinal bleeding among the three treatment cohorts.
• In additional analyses, women (but not men) in the clopidogrel plus PPI group had an increased risk for MACE and stroke recurrence (HRs, 1.61 and 1.58) compared with women in the clopidogrel-only group.

IN PRACTICE:

“This is the first study to show that P-CAB and esomeprazole may reduce the effectiveness of clopidogrel in patients with stroke,” the investigators wrote.

“Clinicians should exercise caution when prescribing a PPI or P-CAB to individuals receiving clopidogrel,” they added.

SOURCE:

This study was led by Jung-Hwa Hong and Seong-Hun Park, Chung-Ang University, Seoul, South Korea. It was published online on March 02 in Stroke.

LIMITATIONS:

The study was limited by the small sample size of the clopidogrel plus P-CAB cohort; the exclusion of patients with a history of myocardial infarction, atrial flutter, or atrial fibrillation within the previous year; and a short follow-up period. Additionally, P-CABs are relatively new agents and not available worldwide, limiting the generalizability of the findings.

DISCLOSURES:

This study was funded by the Republic of Korea Government. The investigators reported having no relevant conflicts of interest.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication.