De-escalating Prasugrel Reduces Net Events in Complex PCI for ACS

De-escalating prasugrel at 1 month after complex PCI in ACS patients can reduce net adverse clinical events—lowering bleeding risk without increasing ischemic events—through 1 year compared with a conventional dual antiplatelet therapy (DAPT) strategy, according to a post hoc analysis of the HOST-REDUCE-Polytech-ACS trial.

On top of the main trial findings published last year, which showed a similar advantage in a general population of ACS patients undergoing PCI, Doyeon Hwang, MD (Seoul National University Hospital, Republic of Korea), said these results show that the benefit of dose de-escalation is seen “irrespective of PCI complexity.”

For this analysis, which was presented by Hwang as a “Key Abstract” online as part of a sneak peek at TCT 2021, researchers included 705 patients from the original trial who underwent complex PCI. The procedures included those with at least three vessels treated, three stents implanted, or three lesions treated, as well as bifurcation or left main PCI, a total stent length longer than 60 mm, or heavy calcification.

Commenting on the study following its presentation, Allen Jeremias, MD (St. Francis Hospital, Roslyn, NY), said the “conundrum” interventional cardiologists face is “that on the one hand, we obviously want to have as much antiplatelet therapy on board as possible to reduce MACE, but on the other hand of course we want to minimize bleeding because we know that also has very significant clinical impact, including mortality impact.”

A strategy involving de-escalation of prasugrel seems an appropriate “middle ground,” Jeremias said, though he observed that the analysis was not powered to show clinical outcomes.

De-escalation Wins Out

A total of 349 complex PCI patients in the analysis were randomized to de-escalation of prasugrel to 5 mg along with continued aspirin at 1 month, while 356 continued on both aspirin and prasugrel 10 mg.

Compared with those who had noncomplex PCI, patients included in this study were older, more likely to have diabetes or chronic kidney disease, had a lower LVEF, and more likely to present with unstable angina. Complex PCI was associated with double the risk of ischemic events at 1 year using the trial’s MACE endpoint (all-cause death, nonfatal MI, stent thrombosis, or clinically driven repeat revascularization), but there were no differences in BARC class ≥ 2 bleeding. The highest MACE risk was observed for patients with more than three stents implanted or more than three lesions treated.

Within the complex PCI population, patients in the de-escalation group were more likely to have diabetes, less likely to have prior revascularization, and more likely to present with STEMI compared with those who continued on conventional therapy. De-escalation was associated with a lower risk of net adverse clinical events at 1 year (all-cause death, nonfatal MI, stent thrombosis, clinically-driven revascularization, and BARC class ≥ 2 bleeding) compared with conventional DAPT, and this difference was driven by a lower risk of bleeding with no increase in ischemic events.

One-year Outcomes by Prasugrel Strategy

Prasugrel de-escalation was not associated with an increase in any specific ischemic event compared with continued conventional DAPT.

Despite his reservations about the analysis’ statistical power, Jeremias told TCTMD that he already practices in the manner of the study protocol for patients at high or even moderate risk of bleeding after complex PCI. “I usually decrease the dose from 10 to 5 mg,” he said. “Or sometimes a patient calls and they have bruising or minor bleeding, gum bleeding, and in those patients, I also reduce the dose to 5 at 1 month. Sometimes even sooner.”

IVUS guidance to confirm proper stent placement enables him to make these decisions, he added, noting that he uses imaging in more than 90% of his interventional procedures. About 40% of the complex PCI patients in the trial received IVUS, which Jeremias said is about double the US average.

Previous evidence has shown that “you don't necessarily need it,” he noted. But “I also think that imaging has been shown to reduce outcomes or adverse events. So when you [use IVUS to] achieve as perfect a result as possible and then de-escalate, you kind of get the best of both worlds.”