Age Modifies Intracranial and Gastrointestinal Bleeding Risk from P2Y12 Inhibitors in Patients Receiving Dialysis. Issue 8 (25th August 2022)

• Record Type: Journal Article
• Authors: Jain, Nishank; Martin, Bradley C.; Dai, Junqiang; Phadnis, Milind A.; Al-Hindi, Layth; Shireman, Theresa I.; Hedayati, S. Susan; Rasu, Rafia S.; Mehta, Jawahar L.
• Is Part Of: Kidney360. Volume 3:Issue 8(2022)
• Page Start: 1374
• Page End: 1383
• Publication Date: 2022-08-25
• Subjects: dialysis -- age -- clopidogrel -- dialysis -- gastrointestinal bleeding -- intracranial bleeding -- P2Y12 inhibitors -- prasugrel -- ticagrelor; 616.61
• DOI: 10.34067/KID.0002442022
• Languages: English
• ISSNs: 2641-7650

Abstract

Key Points: In dialysis patients on P2Y12 inhibitors, annual incidence rates for intracranial bleeds were 2% in those aged <55 years and 3% in those ≥75 years, and gastrointestinal bleeds were 4% in those aged <55 years and 9% in those aged ≥75 years. On clopidogrel, prasugrel, and ticagrelor, for every decade increase in age of patients receiving chronic dialysis, risk of intracranial bleed increased by 9%, 55%, and 59%, and risk of gastrointestinal bleed increased by 21%, 28%, and 39%, respectively. Compared with clopidogrel, prasugrel was associated with a greater risk of intracranial bleed for those aged ≥75 years, and ticagrelor was worse for gastrointestinal bleeds for those aged ≥60 years. Visual Abstract: Abstract : Background: Individuals aged ≥75 years are the fastest-growing population starting dialysis for end-stage kidney disease (ESKD) due to living longer with coronary artery disease. ESKD alone can increase bleeding risk, but P2Y12 inhibitor (P2Y12-I) antiplatelet medications prescribed for cardiovascular treatment can exacerbate this risk in patients with ESKD. The age-specific rates of bleeding complications in dialysis patients with ESKD on P2Y12-I remain unclear, as does how age modifies the bleeding risk from P2Y12-I use in these patients. Methods: In a retrospective cohort study, we collected data on 40, 972 patients receiving maintenance hemo- or peritoneal dialysis who were newly prescribed P2Y12-I therapy between 2011 and 2015 from the USRDS registry. We analyzed the effect of age on the time to first bleed and the interactions between age and P2Y12-I type on modifying the effects of a bleed. Results: Twenty percent of the cohort were aged ≥75 years. There were 3096 (8%) gastrointestinal (GI) and 1298 (3%) intracranial (IC) bleeding events during a median follow-up of 1 year. Annual incidence rates for IC bleeds were 2% in those aged <55 years and 3% in those aged ≥75 years. Rates for GI bleeds were 4% in those aged <55 years and 9% in those aged ≥75 years. On clopidogrel, prasugrel, and ticagrelor, for every decade increase in age of the cohort members, the risk of IC bleed increased by 9%, 55%, and 59%, and the risk of GI bleed increased by 21%, 28%, and 39%, respectively. At age ≥75 years, prasugrel was associated with a greater risk of IC bleed than clopidogrel. At age ≥60 years, ticagrelor was associated with a greater risk of GI bleed than clopidogrel. Conclusions: More potent P2Y12-Is (prasugrel and ticagrelor) were associated with a disproportionately higher risk of IC bleed with increasing age compared with that of clopidogrel—prasugrel was much worse than clopidogrel at age ≥75 years. All three drugs were associated with only modest increase in the risk of GI bleed with every decade increase in age—ticagrelor was much worse than clopidogrel at ≥60 years of age. These results highlight the need for head-to-head clinical trials for the use of P2Y12-Is in patients with ESKD to determine age cutoffs where the risk of bleeding outweighs the benefits of thrombosis prevention.