GI bleeding less frequent with ticagrelor, prasugrel vs clopidogrel

In the first year following percutaneous coronary intervention (PCI) for acute coronary syndrome (ACS), ticagrelor and prasugrel cuts the risk of gastrointestinal (GI) bleeding by more than 30 percent compared with clopidogrel, as shown in a large real-world study.

“Our finding of a reduction in GI bleeding adverse events associated with ticagrelor prescription is novel … [and helps to] clarify the risk reduction associated with the [drug] that has previously been difficult to ascertain in a real-world population,” according to the investigators.

Reports from randomized clinical trials of P2Y12 inhibitors (eg, PLATO, TRITON-TIMI 38, ISAR-REACT) showed variable GI bleeding risks in the post-ACS population, whereas prior real-world studies examined the overall risk of bleeding and failed to establish the risk in the GI tract. [Int J Cardiol 2013;168:1739-1744; N Engl J Med 2007;357:2001-2015; Aliment Pharmacol Ther 2019;49:7-19; N Engl J Med 2019;381:1524-1534; Clin Gastroenterol Hepatol 2020;18:337-346.e19; Eur Heart J Acute Cardiovasc Care 2016;5:13-22]

The current analysis included 37,019 real-world ACS patients (70 percent male) who underwent PCI, of whom 25,715 used clopidogrel (69.5 percent), 5,985 used prasugrel (16.1 percent), and 5,319 used ticagrelor (14.4 percent). The mean age of the population was 63 years, and roughly 20 percent of patients were ≥75 years old. Cardiac comorbidity was prevalent, with the majority of patients having a CHA2DS2VASC score of ≥2.

Pharmacological risk modifiers (including concomitant anticoagulant and aspirin prescription), nonsteroidal anti-inflammatory drug (NSAID) use, and history of GI bleeding were well-balanced among the three exposure groups.

GI bleeding events occurred less frequently with prasugrel than with clopidogrel (4.1 percent vs 5.1 percent), with the difference corresponding to a 21-percent risk reduction in the overall population (hazard ratio [HR], 0.79, 95 percent confidence interval [CI], 0.64–0.97). In patient subgroups defined by ACS type, prasugrel reduced the risk by 36 percent among ST-elevated myocardial infarction (STEMI) patients (HR, 0.64, 95 percent CI, 0.49–0.85) but conferred no significant protection among those with non-ST elevated ACS (NSTE-ACS). [Aliment Pharmacol Ther 2020;doi:10.1111/apt.15790]

Likewise, ticagrelor users had fewer GI bleeding events compared with clopidogrel users, with the difference indicating a >30-percent risk reduction in the overall population (HR, 0.66, 95 percent CI, 0.54–0.81) and in subgroups of STEMI (HR, 0.63, 95 percent CI, 0.42–0.93) and NSTE-ACS patients (HR, 0.66, 95 percent CI, 0.52–0.83). For every 62 patients overall given clopidogrel, as opposed to ticagrelor, one developed GI bleeding.

There was no marked difference in GI bleeding events seen between ticagrelor and prasugrel in the overall population and in the two ACS subgroups.

On all three P2Y12 inhibitors, upper was more common than lower GI bleeding (p<0.0001). The number of related transfusions was lowest with ticagrelor (18 events per 43.8 person years), corresponding to a 41-percent reduction in overall transfusion burden when compared with clopidogrel (HR, 0.59, 95 percent CI, 0.35–1.00); there was no significant difference between prasugrel and clopidogrel. Patients in all three exposure groups had similar hospital stay duration (clopidogrel, 6.5 days; prasugrel, 5.2 days; ticagrelor, 6.5 days; p=0.46).

“Taken together our results are compelling because, despite significant reductions in major adverse cardiac events in ACS patients undergoing PCI, many clinicians remain reticent to use ticagrelor due to concerns for increased risk of bleeding,” the investigators said, adding that limiting the use of the drug due to such concerns may be unnecessary.

“Our ability to ascertain outcomes in a large, geographically diverse, national cohort of patients of different backgrounds [ie, patients of all ages and with concomitant prescription of NSAIDs, aspirin, or anticoagulants] provides clinically relevant data for physicians as they choose between the three P2Y12 inhibitors following coronary reperfusion therapy,” they said.