Age Modifies Intracranial and Gastrointestinal Bleeding Risk from P2Y₁₂ Inhibitors in Patients Receiving Dialysis.

Area of Science:

• Nephrology
• Cardiology
• Geriatrics

Background:

• End-stage kidney disease (ESKD) patients, particularly those ≥75 years, are a growing population requiring dialysis.
• ESKD and P2Y12 inhibitor (P2Y12-I) antiplatelet therapy increase bleeding risk.
• Age-specific bleeding complication rates in dialysis patients on P2Y12-I are not well understood.

Purpose of the Study:

• To investigate age-specific bleeding risks associated with P2Y12-I use in patients with ESKD.
• To analyze how age modifies bleeding risk from different P2Y12-I medications.

Main Methods:

• Retrospective cohort study of 40,972 patients on maintenance dialysis prescribed P2Y12-I.
• Data sourced from the USRDS registry (2011-2015).
• Analysis of time to first bleed and age-P2Y12-I interactions.

Main Results:

• Twenty percent of the cohort were aged ≥75 years.
• Higher incidence of GI bleeds (9%) and IC bleeds (3%) in those ≥75 years compared to <55 years.
• Increased risk of IC bleeds per decade of age: clopidogrel (9%), prasugrel (55%), ticagrelor (59%).
• Increased risk of GI bleeds per decade of age: clopidogrel (21%), prasugrel (28%), ticagrelor (39%).
• Prasugrel showed higher IC bleed risk than clopidogrel at age ≥75 years.
• Ticagrelor showed higher GI bleed risk than clopidogrel at age ≥60 years.

Conclusions:

• More potent P2Y12-Is (prasugrel, ticagrelor) are associated with disproportionately higher intracranial bleeding risks with increasing age.
• All P2Y12-Is showed modest increases in GI bleed risk with age, with ticagrelor being worse than clopidogrel at ≥60 years.
• Head-to-head trials are needed to determine age cutoffs where bleeding risks outweigh benefits for P2Y12-I use in ESKD patients.