Harmonizing Optimal Strategy for Treatment of coronary artery diseases-comparison of REDUCtion of prasugrEl dose or POLYmer TECHnology in ACS patients - HOST-REDUCE-POLYTECH-ACS

Contribution To Literature:

Highlighted text has been updated as of March 28, 2022.

The HOST-REDUCE-POLYTECH-ACS trial showed that after 1 month of regular-dose DAPT, reduced-dose prasugrel (5 mg) is superior to regular-dose prasugrel (10 mg) when used along with low-dose aspirin for ACS PCI.


The goal of the trial was to assess the safety and efficacy of half-dose prasugrel compared with full-dose prasugrel (after 1 month of routine therapy) among east Asian patients undergoing percutaneous coronary intervention (PCI) for acute coronary syndrome (ACS).

Study Design

Patients were randomized in a 2x2 factorial design to: a) either prasugrel 5 mg daily (n = 1,170) or prasugrel 10 mg daily (n = 1,168), or b) durable polymer (DP) (n = 1,713) vs. bioabsorbable polymer (BP) (n = 1,700) drug-eluting stent (DES). Patients were stratified according to CHADS2 score (2 points or ≥3 points).

The recommended protocol was that all patients receive 300 mg aspirin and a loading dose of 60 mg prasugrel before PCI. After PCI, all patients in both groups were given aspirin 100 mg daily with 10 mg of maintenance prasugrel until the 1-month follow-up. Dual antiplatelet therapy (DAPT) was recommended for ≥1 year after PCI.

  • Total number of enrollees: a) 2,338; b) 3,413
  • Duration of follow-up: 1 year
  • Mean patient age: 63 years
  • Percentage female: 11%
  • Percentage with diabetes: 45%

Inclusion criteria:

  • Age ≥19 years
  • Clinical diagnosis of ACS
  • ≥1 culprit lesion in a native coronary artery with significant stenosis eligible for stent implantation

Exclusion criteria:

  • Hypersensitivity or contraindication to heparin, aspirin, clopidogrel, prasugrel, ticagrelor, or contrast media
  • Patients with any major or active pathologic bleeding
  • Women of childbearing potential
  • Presence of noncardiac comorbid conditions with life expectancy <1 year
  • Conditions that might result in protocol noncompliance
  • Exclusion criteria of prasugrel (age ≥75 years, bodyweight <60 kg, history of transient ischemic attack or stroke)

Other salient features/characteristics:

  • Mean body weight: 72 kg (159 lbs)
  • ST-segment elevation myocardial infarction (STEMI): 14%, NSTEMI: 25%
  • Mitral valve (MV) disease: 50%, MV intervention: 29%
  • Stents per patient: 1.6

In the DP-DES arm, the primary stents used were Promus Premier (40.3%), Resolute Onyx (30.1%), and Xience Alpine (29%).

In the BP-DES arm, the primary stents used were Ultimaster (31.9%), Orsiro (25.5%), Biomatrix Flex (21.7%), and Nobori (9.3%).

Principal Findings:

a) Prasugrel 5 mg vs. 10 mg: The primary endpoint, net adverse events (death, MI, stent thrombosis, clinically driven revascularization, stroke, and Bleeding Academic Research Consortium [BARC] 2 or higher bleeding) at 1 year for prasugrel 5 mg vs. 10 mg, was 7.2% vs. 10.1% (hazard ratio 0.70, 95% confidence interval 0.52-0.92, p = 0.012).

  • All-cause mortality: 0.9% vs. 1.2% (p = 0.41)
  • Nonfatal MI: 0.6% vs. 0.7% (p = 0.79)
  • Stent thrombosis: 0.1% vs. 0.3% (p = 0.34)
  • Repeat revascularization: 3.1% vs. 3.3% (p = 0.81)
  • Stroke: 0.9% vs. 0.7% (p = 0.65)
  • BARC ≥2 bleeding: 2.9% vs. 5.9% (p < 0.001)

Secondary outcomes:

  • BARC ≥3 bleeding: 0.8% vs. 0.7% (p = 0.82)
  • Cardiovascular death: 0.3% vs. 0.9% (p = 0.066)
  • Hemorrhagic stroke: 0.4% vs. 0.4% (p = 0.99)

Complex PCI (n = 705): Complex PCI was defined as having ≥1 of the following features: ≥3 stents implanted, ≥3 lesions treated, bifurcation PCI, total stent length ≥60 mm, left main PCI, or heavy calcification. Major adverse cardiovascular events (MACE) for complex vs. noncomplex PCI: 5.6% vs. 2.9% (p = 0.001). For patients undergoing complex PCI, MACE for 5 vs. 10 mg prasugrel: 5.3% vs. 6.0% (p = 0.70); stent thrombosis: 0% vs. 0.3% (p = NA); BARC class ≥2 bleeding: 1.8% vs. 6.9% (p = 0.0001).

b) DP vs. BP-DES: The primary endpoint (death, MI, stent thrombosis, and any repeat revascularization) for DP vs. BP-DES, was 5.2% vs. 6.4%, hazard ratio 0.81, 95% confidence interval 0.61-1.08 (p < 0.001 for noninferiority; p = 0.15 for superiority).

Secondary outcomes for DP-DES vs. BP-DES:

  • Device-oriented outcome (cardiac death, target vessel MI, target lesion revascularization): 2.6% vs. 3.9% (p = 0.038)
  • Target lesion revascularization: 1% vs. 1.8% (p = 0.049)
  • All-cause mortality: 2.6% vs. 3.0% (p = 0.43)
  • Stent thrombosis: 0.1% vs. 0.4% (p = 0.17)


The results of this trial indicate that reduced-dose prasugrel (5 mg) is superior to regular-dose prasugrel (10 mg) when used along with low-dose aspirin for ACS PCI. All patients received 1 month of regular-dose DAPT; the dose de-escalation happened after 1 month. Among patients undergoing complex PCI, MACE rates at 12 months were higher overall, with preserved efficacy and safety of prasugrel de-escalation compared with conventional dosing. In addition, BP-DES met the primary criteria for noninferiority compared with DP-DES, but device-related endpoints, including the need for repeat procedures, were lower in the DP-DES arm.

We have seen several interesting trials in the DAPT space in the past few years. For a long time, the use of DAPT for 12 months post-ACS PCI was felt to be indisputable. Trials such as TWILIGHT have shown that it may be possible to continue ticagrelor monotherapy and drop aspirin after 3 months with no penalty in ischemic outcomes and a reduction in bleeding outcomes among patients undergoing PCI for NSTEMI. Similarly, the STOPDAPT-2 trial suggested that clopidogrel monotherapy could be continued after 1 month in patients undergoing PCI for stable ischemic heart disease and ACS. On the other hand, the SMART-DATE trial showed a concerning MI signal when DAPT was stopped at 6 months for ACS PCI. It is hard to directly compare across trials. Prasugrel and ticagrelor may be more reliable for modified use (for instance, low-dose prasugrel with low-dose aspirin after 1 month, or full-dose ticagrelor monotherapy after 3 months) due to high heterogeneity in clopidogrel responsiveness among patients.

One caveat is that the median body weight in this trial was ~72 kg and all patients were east Asian. It is unclear if this dose would have the same efficacy among similar patients in the United States.

On the stent side, these results are fairly similar to those noted in SORT OUT IX and other trials. BP-DES appear to be better than bare-metal stents, but efficacy is probably not as good as current-generation DP-DES.


Hwang D, Lim YH, Park KW, et al. Prasugrel Dose De-escalation Therapy After Complex Percutaneous Coronary Intervention in Patients With Acute Coronary Syndrome: A Post Hoc Analysis From the HOST-REDUCE-POLYTECH-ACS Trial. JAMA Cardiol 2022;Mar 9:[Epub ahead of print].

Kim HS, Kang J, Hwang D, et al., on behalf of the HOST-REDUCE-POLYTECH-ACS Randomized Clinical Trial Investigators. Durable Polymer Versus Biodegradable Polymer Drug-Eluting Stents After Percutaneous Coronary Intervention in Patients With Acute Coronary Syndrome: The HOST-REDUCE-POLYTECH-ACS Trial. Circulation 2020;396:1079-89.

Presented by Dr. Hyo-Soo Kim at the Transcatheter Cardiovascular Therapeutics Virtual Meeting (TCT Connect), October 17, 2020.

Kim HS, Kang J, Hwang D, et al., on behalf of the HOST-REDUCE-POLYTECH-ACS Investigators. 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;396:1079-89.

Presented by Dr. Hyo-Soo Kim at the European Society of Cardiology Virtual Congress, August 31, 2020.

Clinical Topics: Acute Coronary Syndromes, Cardiac Surgery, Invasive Cardiovascular Angiography and Intervention, Stable Ischemic Heart Disease, Vascular Medicine, Aortic Surgery, Cardiac Surgery and SIHD, Interventions and ACS, Interventions and Vascular Medicine, Chronic Angina

Keywords: Acute Coronary Syndrome, Aspirin, Constriction, Pathologic, Drug-Eluting Stents, ESC Congress, ESC20, Myocardial Infarction, ST Elevation Myocardial Infarction, Myocardial Ischemia, Myocardial Revascularization, Percutaneous Coronary Intervention, Platelet Aggregation Inhibitors, Stroke, Thrombosis, TCT20, Transcatheter Cardiovascular Therapeutics

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