Examining the Risks of Major Bleeding Events in Older People Using Antithrombotics

Prasad S. Nishtala,Sarah N. Hilmer,Hamish A. Jamieson,Te-yuan Chyou,H. Carl Hanger

doi:10.1007/s10557-019-06867-z

Abstract

BackgroundReal-world evidence for the safety of using antithrombotics in older people with multimorbidity is limited. We investigated the risks of gastrointestinal bleeding (GI-bleeding) and intracranial (IC-bleeding) associated with antithrombotics either as monotherapy, dual antiplatelet therapy (DAPT) or as triple therapy (TT) [DAPT plus anticoagulant] in older individuals aged 65 years and above.MethodsWe identified all individuals, 65 years and above, who had a first-time event of either IC- or GI-bleeding event from the hospital discharge data. We employed a case-crossover design and conditional logistic regression analyses to estimate the adjusted relative risks (ARR) of bleeding.ResultsWe found 66,500 individuals with at least one event of IC- or GI-bleeding between 01/01/2005 and 31/12/2014. DAPT use was associated with an increased risk relative to non-use of any antithrombotics in IC-bleeding (ARR = 3.13, 95% CI = [2.64, 3.72]) and GI-bleeding (ARR = 1.34, 95% CI = [1.14, 1.57]). The increased bleeding risk relative to non-use of any antithrombotics was highest with TT use (IC-bleeding, ARR = 17.28, 95% CI = [6.69, 44.61]; GI-bleeding, ARR = 4.85, 95% CI = [1.51, 15.57]).ConclusionsUsing population-level data, we were able to obtain estimates on the bleeding risks associated with antithrombotic agents in older people often excluded from clinical trials because of either age or comorbidities.

Highlights

IntroductionStudies that have examined the risk of bleeding using dual antiplatelet therapy (DAPT) and triple therapy (TT) regimens have reported mixed findings
Dual antiplatelet therapy (DAPT) combines aspirin and clopidogrel, ticagrelor or other antiplatelet drugs, and is Electronic supplementary material The online version of this article contains supplementary material, which is available to authorized users.Studies that have examined the risk of bleeding using dual antiplatelet therapy (DAPT) and triple therapy (TT) regimens have reported mixed findings
We excluded 1079 individuals as they did not receive any prescription of aspirin, AC, AP or any effect-modifiers of interests, and 3221 of them were further excluded because at least one IC- or GI-bleed had occurred within 12 months from 01/01/2005, implying a potentially less reliable date of firsttime bleeding (Fig. 2)

Summary

Introduction

Studies that have examined the risk of bleeding using DAPT and TT regimens have reported mixed findings. Others reported no association of an increased risk of bleeding [9, 10]. Older people prescribed DAPT or TT because of a percutaneous intervention and AF are excluded from clinical trials because of comorbidities or extremes of age. In the absence of clear guidance from clinical trials and head-tohead comparisons, there remains an ongoing research gap on the bleeding risks associated with antithrombotics in older people with multimorbidity. We investigated the risks of gastrointestinal bleeding (GI-bleeding) and intracranial (IC-bleeding) associated with antithrombotics either as monotherapy, dual antiplatelet therapy (DAPT) or as triple therapy (TT) [DAPT plus anticoagulant] in older individuals aged 65 years and above

Methods

Results

Conclusion