Fewer Gastrointestinal Bleeds With Ticagrelor and Prasugrel Compared With Clopidogrel in Patients With Acute Coronary Syndrome Following Percutaneous Coronary Intervention

Neena S. Abraham; Eric H. Yang; Peter A. Noseworthy; Jonathan Inselman; Xiaoxi Yao; Jeph Herrin; Lindsey R. Sangaralingham; Che Ngufor; Nilay D. Shah


Aliment Pharmacol Ther. 2020;52(4):646-654. 

In This Article

Abstract and Introduction


Background: Gastrointestinal bleeding (GIB) frequently occurs following percutaneous coronary intervention (PCI) for acute coronary syndrome (ACS) with the prescription of P2Y12 inhibiting antiplatelet agents. Compared with clopidogrel, the newer P2Y12 inhibitors lower major adverse cardiac events with similar or possibly higher major bleeding events. The comparative GIB rates of these medications remain poorly understood.

Aim: To compare GIB rates associated with clopidogrel, prasugrel and ticagrelor using national medical and pharmacy claims data from privately insured and Medicare Advantage enrollees .

Methods: Propensity score and inverse probability treatment weighting were used to balance baseline characteristics among treatment groups. The 1-year GIB risk was calculated using weighted Cox proportional hazard models and expressed as hazard ratios (HR) with 95% confidence intervals (CI) and number needed to harm (NNH).

Results: We identified 37 019 patients with ACS (non-ST elevation ACS [NSTE-ACS] and ST-elevation myocardial infarction [STEMI]) within 14 days of a PCI (mean age 63 years and 70% male). Clopidogrel prescription was most common (69%) with prasugrel (16%) and ticagrelor (14%) prescribed less frequently. When compared with clopidogrel, ticagrelor was associated with a 34% risk reduction (HR 0.66; 95% CI: 0.54–0.81) in GIB overall and with NSTE-ACS, and a 37% GIB risk reduction (HR 0.63; 95% CI: 0.42–0.93) in STEMI patients. When compared with clopidogrel, prasugrel was associated with a 21% risk reduction (HR 0.79; 95% CI: 0.64–0.97) overall, a 36% GIB risk reduction (HR 0.64; 95% CI: 0.49–0.85) in STEMI patients but no reduction of GIB risk in NSTE-ACS patients.

Conclusions: In the first year following PCI, ticagrelor or prasugrel are associated with fewer GIB events than clopidogrel.


Following percutaneous coronary intervention (PCI), adjunctive platelet inhibition with a second-generation (ie clopidogrel) or newer (ie prasugrel, ticagrelor) thienopyridine agents is recommended for a minimum of 12 months in patients presenting with acute coronary syndromes (ACS).[1] This intense antiplatelet activity increases the risk of procedure and nonprocedure-related major bleeding complications. Compared to clopidogrel, the newer P2Y12 inhibitors lower major adverse cardiac events in patients undergoing PCI for ACS with similar or possibly higher major bleeding events.[2] Post-PCI bleeding is a serious event associated with increased morbidity and mortality.[3]

Gastrointestinal bleeding (GIB) is a frequent adverse event in the first year following PCI often necessitating temporary interruption of the antiplatelet regimen during identification and treatment of the bleeding source.[4] Systematic reviews of randomised clinical trials have suggested higher bleeding rates with the newer P2Y12 inhibitors compared to clopidogrel.[2] However, the comparative bleeding rates of these medications in real-world populations are poorly understood. This gap in the literature is noteworthy as there has been gradual uptake of these newer agents. More than one-third of patients receive these newer agents after PCI.[5,6]

We have previously demonstrated that the average 1-year GIB risk following initiation of P2Y12 inhibitors in routine clinical practice is 4.2% and increases to >8% for those over the age of 75.[4] However, it remains unclear if the risk of GIB differs among the three P2Y12 inhibitors. We aimed to compare the safety of clopidogrel, prasugrel and ticagrelor by quantifying the GIB risk in patients with ACS following PCI, using a real-world population.