Dose de-escalation of prasugrel 1 month after percutaneous coronary intervention (PCI) in patients with acute coronary syndrome (ACS) was found to lower the risk for adverse clinical outcomes, according to a study published in The Lancet.

Although potent P2Y12 receptor inhibition is an integral part of dual antiplatelet regimens following PCI, its efficacy in preventing ischemia during the early phase (ie, 30 days post-procedure) tends to be countered by bleeding concerns over the course of the chronic maintenance phase.

In the Harmonizing Optimal Strategy for Treatment of Coronary Artery Diseases Trial – Comparison of REDUCTION of PrasugrEl Dose & POLYmer TECHnology in ACS Patients trial ( Identifier: NCT02193971), a South Korean multicenter, randomized, parallel-group, open-label, non-inferiority study, 2338 patients with ACS who underwent PCI between September 2014 and December 2018 were enrolled. Participants were randomly assigned 1:1 to receive prasugrel dose de-escalation therapy (n=1170; mean age, 58.7±9.0 years; 89.7% men) or conventional therapy (n=1168; mean age, 58.9±9.1 years; 88.8% men), with adjudicators blinded to this allocation. All participants received prasugrel 10 mg plus aspirin 100 mg daily for the first month after PCII. After 1 month, the prasugrel dose was lowered to 5 mg daily in the de-escalation group, and was maintained at 10 mg per day in the conventional group. Aspirin therapy continued in both groups at 100 mg.

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The study’s primary outcome was the incidence of net adverse clinical events at 1 year (ie, all-cause mortality, stroke, non-fatal myocardial infarction, repeat revascularization, stent thrombosis, or a Bleeding Academic Research Consortium [BARC] criteria-based bleeding event graded ≥2), with a non-inferiority margin of 2.5%. Secondary outcomes included safety (grade ≥2 BARC events) and efficacy (cardiovascular death, myocardial infarction, ischemic stroke, and stent thrombosis) endpoints, to assess bleeding and ischemic risks, respectively.

The primary outcome occurred in 82 (Kaplan-Meier estimate, 7.2%) and 116 (10.1%) patients in the de-escalation and conventional groups, respectively (absolute risk difference, -2.9%; Pnon-inferiority <.0001; hazard ratio [HR], 0.70; 95% CI, 0.52-0.92; Pequivalence =.012).

At 1 year, bleeding risk was reduced in the de-escalation vs conventional group (HR, 0.48; 95% CI, 0.32-0.73; P =.0007) with a comparable ischemic risk in both groups (HR, 0.76; 95% CI, 0.40-1.45; P =.40).

Study strengths include high rates of protocol adherence and clinical follow-up. Study limitations include analysis of a single arm from the larger HOST-REDUCE-POLYTECH-ACS trial, broad margin and low statistical power, open-label design, potential non-generalizability to other ethnicities, and absence of pharmacodynamic testing to determine uniform dose reductions.

“Our results suggest that a de-escalation strategy using a potent P2Y12 inhibitor could be the optimal strategy in East Asian patients with acute coronary syndrome after PCI,” noted the authors.

Funding and Conflicts of Interest Disclosures:

This study was supported by Daiichi Sankyo, Boston Scientific, Terumo, Biotronik, Qualitech Korea, and Dio.

H-SK has received research grants or speaker’s fees from Daiichi Sankyo, Boston Scientific, Terumo, Biotronik, Dio, Medtronic, Abbott Vascular, Edwards Life Science, Amgen, and Behringer Ingelheim, outside of the submitted work. KWP reports speaker’s fees from Daiichi Sankyo, AstraZeneca, Sanofi, Bristol-Myers Squibb, Bayer, and Pfizer outside of the submitted work. All other authors declare no competing interests.


Kim H-S, Kang J, Hwang D, et al. Prasugrel-based de-escalation of dual antiplatelet therapy after percutaneous coronary intervention in patients with acute coronary syndrome (HOST-REDUCE-POLYTECH-ACS): an open-label, multicentre, non-inferiority randomised trial. Lancet. 2020;396(10257):1079-1089. doi:10.1016/s0140-6736(20)31791-8