An Open-Label, Randomized, Controlled, Multicenter Study Exploring Two Treatment Strategies of Rivaroxaban and a Dose-Adjusted Oral Vitamin K Antagonist Treatment Strategy in Subjects With Atrial Fibrillation Who Undergo Percutaneous Coronary Intervention - PIONEER AF-PCI

Nov 14, 2016
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Presenter/Author:
C. Michael Gibson, MD, FACC
Author/Summarized by Author:
Anthony A. Bavry, MD, MPH, FACC
Summary Reviewer:
Deepak L. Bhatt, MD, MPH, MBA, FACC
Trial Sponsor:
Janssen Scientific Affairs and Bayer Pharmaceuticals
Date Presented:
11/14/2016
Date Published:
11/14/2016
Date Updated:
11/14/2016
Original Posted Date:
11/14/2016
References

Contribution To Literature:

The PIONEER AF-PCI trial showed that a rivaroxaban-based strategy was associated with less bleeding compared with a warfarin-based strategy after PCI.

Description:

The goal of the trial was to evaluate three strategies of anticoagulation/antiplatelet therapy in patients with atrial fibrillation (AF) undergoing percutaneous coronary intervention (PCI).

Study Design

  • Randomized
  • Parallel
  • Stratified (type of P2Y12 inhibitor and duration of dual antiplatelet therapy [DAPT])

Patients with AF who underwent PCI were randomized to one of the following groups:

  • Group 1: Rivaroxaban 15 mg (10 mg if creatinine clearance 30-50 cc/min) daily plus P2Y12 inhibitor monotherapy for 12 months (n = 709).
  • Group 2: Rivaroxaban 2.5 mg twice daily plus DAPT for 1, 6, or 12 months (n = 709). After completion of the 1 or 6 months of DAPT, patients received rivaroxaban 15 mg daily plus low-dose aspirin monotherapy.
  • Group 3: Warfarin plus DAPT for 1, 6, or 12 months (n = 706). After completion of 1 or 6 months of DAPT, patients received warfarin plus low-dose aspirin monotherapy.
  • Total number of enrollees: 2,124
  • Duration of follow-up: 12 months
  • Mean patient age: 70 years
  • Percentage female: 25%

Inclusion criteria:

  • Patients at least 18 years of age with AF and recent PCI

Exclusion criteria:

  • Stroke or transient ischemic attack
  • Significant gastrointestinal bleed in last 12 months
  • Creatinine clearance <30 cc/min
  • Hemoglobin <10 g/dl

Other salient features/characteristics:

  • Index event: ST-segment elevation myocardial infarction (STEMI) 12%, non-STEMI 19%, unstable angina 21%
  • P2Y12 inhibitor at baseline: clopidogrel 93%, prasugrel 2%, ticagrelor 5%
  • Type of stent: drug-eluting stent (DES) 65%, bare-metal stent (BMS) 33%

Principal Findings:

The primary outcome, incidence of clinically significant bleeding, occurred in 16.8% of group 1 vs. 18.0% of group 2 vs. 26.7% of group 3 (hazard ratio [HR] 0.59, p < 0.001 for group 1 vs. 3; HR 0.63, p < 0.001 for group 2 vs. 3). Results were the same in multiple tested subgroups.

Secondary outcomes:

  • Major bleeding: 2.1% of group 1 vs. 1.9% of group 2 vs. 3.3% of group 3 (HR 0.66, p = 0.23 for group 1 vs. 3; HR 0.57, p = 0.11 for group 2 vs. 3)
  • Major adverse cardiac events: 6.5% of group 1 vs. 5.6% of group 2 vs. 6.0% of group 3 (HR 1.08, p = 0.75 for group 1 vs. 3; HR 0.93, p = 0.76 for group 2 vs. 3)
  • Stent thrombosis: 0.8% of group 1 vs. 0.9% of group 2 vs. 0.7% of group 3 (HR 1.20, p = 0.79 for group 1 vs. 3; HR 1.44, p = 0.57 for group 2 vs. 3)
  • Stent thrombosis in group 2 patients who received DAPT for 1 month, 1.9%; 6 months, 1.7%; 12 months, 0
  • Stent thrombosis in group 3 patients who received DAPT for 1 month, 1.1%; 6 months, 0.4%; 12 months, 0.8%
  • All-cause death or recurrent hospitalization: 35% of group 1 vs. 32% of group 2 vs. 42% of group 3 (HR 0.79, p = 0.008 for group 1 vs. 3; HR 0.75, p = 0.002 for group 2 vs. 3)

Interpretation:

Among patients with nonvalvular AF who underwent PCI, a rivaroxaban-based strategy was associated with a lower frequency of clinically significant bleeding (TIMI [Thrombolysis in Myocardial Infarction] major or minor bleeding) compared with a warfarin/DAPT strategy. However, TIMI major bleeding was similar between the three groups. Major adverse cardiac events including stent thrombosis appeared to be similar between the three groups. All-cause death or rehospitalization was lower with a rivaroxaban-based strategy compared with a warfarin/DAPT strategy.

The trial design was complex and warrants a summary: Group 1 evaluated rivaroxaban 15 mg daily and clopidogrel monotherapy (resembles the WOEST trial). Group 2 evaluated rivaroxaban 2.5 mg twice daily plus aspirin/clopidogrel for 1, 6, or 12 months, while group 3 evaluated warfarin plus aspirin/clopidogrel for 1, 6, or 12 months (current standard of care). The duration of DAPT was nonrandomized and determined by provider discretion. For example, in the 1-month stratum, 67% received a BMS, while in the 12-month stratum, 72% received a DES.

In summary, several lines of evidence now suggest that it is safe to treat patients with an increased risk for bleeding with anticoagulation (warfarin studied in WOEST, rivaroxaban studied in PIONEER AF-PCI) and clopidogrel monotherapy.

References:

Gibson CM, Mehran R, Bode C, et al. Prevention of Bleeding in Patients With Atrial Fibrillation Undergoing PCI. N Engl J Med 2016;375:2423-34.

Gibson CM, Pinto DS, Chi G, et al. Recurrent Hospitalization Among Patients With Atrial Fibrillation Undergoing Intracoronary Stenting Treated with 2 Treatment Strategies of Rivaroxaban or a Dose-Adjusted Oral Vitamin K Antagonist Treatment Strategy. Circulation 2017;135:323-33.

Editorial: Bhatt DL. O PIONEERs! – The Beginning of the End of Full Dose Triple Therapy With Warfarin? Circulation 2017;135:113-5.

Presented by Dr. C. Michael Gibson at the American Heart Association Annual Scientific Sessions (AHA 2016), New Orleans, LA, November 14, 2016.

Keywords: Acute Coronary Syndrome, Administration, Oral, AHA Annual Scientific Sessions, Anticoagulants, Aspirin, Atrial Fibrillation, Drug-Eluting Stents, Hemorrhage, Percutaneous Coronary Intervention, Platelet Aggregation Inhibitors, Secondary Prevention, Stents, Thrombosis, Vitamin K, Warfarin


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