Potent Antiplatelets Pre-CABG for ACS? Meta-analysis Stirs Debate

Giving potent antiplatelets up front to ACS patients, regardless of whether they may require CABG, could provide a survival benefit through early induction of platelet quiescence, according to results of a meta-analysis.

Senior study author Derek So, MD (University of Ottawa Heart Institute, Ontario, Canada), said the results build on data from the PLATO and TRITON-TIMI 38 trials, both of which suggested potent antiplatelets could bolster survival. Analysis of those two studies plus eight others found greater mortality overall when patients who were admitted for ACS and then underwent CABG had been given weaker antiplatelet strategies, such as aspirin alone or aspirin and clopidogrel, versus potent strategies like aspirin and P2Y12 inhibitors (OR 1.38; 95% CI 1.03-1.85).

“I think it really strikes home the point that we should not be holding back pretreating patients, which I find, unfortunately, is something that we're seeing more and more of these days,” So told TCTMD.

However, Faisal Bakaeen, MD (Cleveland Clinic Foundation, OH), a cardiac surgeon who was not involved in the study, told TCTMD he is not convinced, adding that the data are hypothesis-generating at best.

Despite the inclusion of four RCTs in the meta-analysis, he noted, none of them were designed to specifically look at antiplatelet regimens after ACS in patients undergoing CABG, rendering them essentially low-level observational data. Furthermore, Bakaeen said while the theory of platelet quiescence is suggestive with regard to possibly enhancing venous graft patency, the meta-analysis has multiple failings: among them no clear definition or timing of all-cause mortality, no precise breakdowns of when antiplatelets were stopped, and no information on whether patients resumed the aggressive antiplatelet regimen after the surgery.

If you put them on antiplatelet regimens, I can guarantee you that most surgeons, if they're afforded the opportunity, will wait. So, you actually delay the care. Faisal Bakaeen

“I would not advocate a more-liberal use of an aggressive antiplatelet regimen, especially in those where there is a high index of suspicion of a high atherosclerotic burden that may require CABG, because guess what, the best way to improve outcomes in those patients is to do an expeditious CABG,” he commented. “If you put them on antiplatelet regimens, I can guarantee you that most surgeons, if they're afforded the opportunity, will wait. So, you actually delay the care.”

The meta-analysis was published online February 18, 2021, ahead of print in the Journal of the American Heart Association.

RAPID-CABG May Provide Some Answers

The meta-analysis, led by Kiran Sarathy, MBBS (University of Ottawa Heart Institute), included four RCTs and six nonrandomized studies. Two compared glycoprotein IIb/IIIa inhibitors and aspirin with aspirin alone, four compared clopidogrel and aspirin with aspirin alone, and four compared ticagrelor or prasugrel with clopidogrel and aspirin. In all studies, antiplatelets except for aspirin were discontinued prior to surgery.

Analysis of the nonrandomized studies indicated a nonsignificant trend toward increased mortality with weaker antiplatelet strategies (OR 1.11; 95% CI 0.8-1.54), while analysis of the RCTs showed a significantly increased mortality rate for weaker versus stronger antiplatelet strategies (OR 1.79; 95% CI, 1.14-2.81).

So and colleagues hypothesize that having potent antiplatelets on board in the days prior to surgery may “quiet down” platelets, helping to prevent thrombotic complications, increase graft patency, and decreased platelet activation during bypass.

“For ticagrelor, its fast offset and reversibility may increase platelet availability postoperatively to minimize bleeding,” they write. “With respect to glycoprotein IIb/IIIa inhibitors, fibrinogen binding also preserves platelet function postoperatively.”

Current guidelines recommend stopping clopidogrel or ticagrelor for 5 days and prasugrel for 7 days prior to CABG. So said an ongoing study he is conducting, RAPID-CABG, should shed more light on the relationship between the antiplatelet benefits, the timing of the discontinuation, and potential bleeding risk. The study is randomizing ACS patients given ticagrelor to early surgery (2-3 days after antiplatelet discontinuation) or delayed surgery (5-7 days after antiplatelet discontinuation).

To TCTMD, Bakaeen said that, despite its flaws, the meta-analysis raises important questions about the benefits of individualized antiplatelet decisions and the research needed to validate this strategy. For example, he said, if point-of-care testing for platelet function was shown to inform antiplatelet strategies, which in turn allowed for expeditious CABG with documented downstream benefits thanks to potent antiplatelets, it could end up being the best of both worlds.

“That’s exactly what the future should be. It's about personalized, tailored care. Every patient reacts differently to different drugs,” he concluded.