NEW ORLEANS – Rivaroxaban plus P2Y12 inhibitor monotherapy or rivaroxaban plus dual antiplatelet therapy (DAPT) was associated with a reduced risk of all-cause mortality or recurrent hospitalization for adverse events compared with vitamin K antagonists (VKA) plus DAPT in patients with atrial fibrillation (AF) undergoing intracoronary intervention, according to results of the PIONEER AF-PCI trial.1
C. Michael Gibson, MS, MD, presented the findings at the 2016 American Heart Association Scientific Sessions in New Orleans on behalf of the study investigators, which were also simultaneously published in Circulation.2
In PIONEER AF-PCI (An Open-label, Randomized, Controlled, Multicenter Study Exploring 2 Treatment Strategies of Rivaroxaban and a Dose-Adjusted Oral Vitamin K Antagonist Treatment in Subjects With Atrial Fibrillation Who Undergo Percutaneous Coronary Intervention; ClinicalTrials.gov identifier: NCT01830543), patients with nonvalvular AF (n=2124; median age: 71; 25.6% women) were randomly assigned 1:1:1 to receive a reduced-dose of rivaroxaban (15 mg/d) plus a P2Y12 inhibitor for 1 year (group 1); rivaroxaban (2.5 mg twice daily) with stratification to a prespecified duration of DAPT of 1, 6, or 12 months; (group 2) or the reference arm of dose-adjusted VKA daily with similar DAPT stratification (group 3).
All-cause mortality or recurrent hospitalization for an adverse event were designated as the primary end points. Adverse events, defined by the International Conference on Harmonization guidelines, were subsequently classified by researchers as either “potentially attributable to bleeding, cardiovascular causes, or other causes through consensus.”
The first group, rivaroxaban (15 mg/d) plus P2Y12 inhibitor, had a 34.9% risk of all-cause mortality or recurrent hospitalization (hazard ratio [HR]: 0.79; 95% confidence interval [CI]: 0.66-0.94; P =.008 vs the group 3; number need to treat [NNT]: 15). Meanwhile, the second group, rivaroxaban (2.5 mg twice daily), had 31.9% risk of the primary end point (HR: 0.75; 95% CI, 0.62-0.90; P =.002 vs group 3; NNT: 10). Finally, group 3 had a 41.9% risk of the primary end point.
All-cause death plus hospitalization possibly from bleeding were reduced in both rivaroxaban groups compared with the reference group (group 1: 8.6%, P =.032 vs group 3; group 2: 8.0%, P =.012 vs group 3; group 3: 12.4%), as well as hospitalization from a possible cardiovascular cause (group 1: 21.4%, P= .001 vs group 3; group 2: 21.7%, P =.011 vs group 3; group 3: 29.3%), but other forms of hospitalization were not.
While there was a reduction in bleeding events, there was no difference in any of the designated composite secondary end points, including death, myocardial infarction [MI], and stroke. It is important to note that recurrent hospitalization is a more frequent end point, obtained with greater sensitivity but with less specificity than the “traditional adjudicated end point of death/MI and stroke.” This means that the present analysis had a greater statistical power (90%) to determine a 20% difference in treatment strategies compared to the end points of cardiovascular death/MI and stroke (16.8% to determine a 20% treatment difference).
“The fact that bleeding and cardiovascular events differed among the strategies but other causes of hospitalization did not, supports the acceptable specificity of rehospitalization as an end point,” the authors wrote.
In an accompanying editorial,3 Deepak L.Bhatt, MD, MPH, of Brigham and Women’s Hospital Heart & Vascular Center in Boston, wrote, “This paper may be one of those rare circumstances where the secondary post hoc analysis is more insightful than the primary pre-specified analysis, having both greater statistical power and a more clinically relevant end point.”
Dr Bhatt explained that while some may view this circumstance as a drastic departure from statistical standards, clinicians need to make complicated decisions with the best data available.
In addition, regardless of the cause, hospitalization is still associated with higher costs and poor quality of life. For example, the cost of a bleeding event associated with a VKA was estimated at approximately $8000 in 2011, and other common cardiovascular conditions, such as chest pain, heart failure, and PCI carry similar costs ($8000-$25,000).2 Therefore, a 10% absolute and 25% relative reduction in hospitalization risks would likely be associated with a reduction in healthcare costs.2
Finally, the dosing regimen of rivaroxaban 2.5 mg/d plus DAPT is currently indicated and available in Europe and elsewhere for the secondary prevention of acute coronary syndrome (ACS) events, but the 15/10 mg/d dose is not approved for patients with either ACS or AF.
Disclosures: All of the authors have received research grant support from Janssen Scientific Affairs, LLC and Bayer, the study sponsors. Drs Burton and Wildgoose are Janssen employees and Dr Eickels is an employee of Bayer AG. Dr Gibson has received consulting fees from Janssen Scientific Affairs, LLC and Bayer. Drs Lip and Halperin have received consulting fees from Janssen, and Dr Cohen is part of the Janssen speakers bureau and has received research support and advisory board honoraria. Dr Bhatt has received research funding from several pharmaceutical companies including, Amgen, AstraZeneca, Medtronic, Pfizer, Roche, Sanofi Aventis, and The Medicines Company.
- Gibson CM, on behalf of the PIONEER AF-PCI investigators. An open-label, randomized, controlled, multicenter study exploring 2 treatment strategies of rivaroxaban and a dose-adjusted oral VKA treatment strategy in subjects with atrial fibrillation who undergo percutaneous coronary intervention. LBCT.02: Pioneering the future of heart interventions. Presented at: the 2016 American Heart Association Scientific Sessions. November 12-16, 2016; New Orleans, LA.
- 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. 2016 Nov 14. doi:10.1161/CIRCULATIONAHA.116.025783 [Epub ahead of print].
- Bhatt DL. O PIONEERS – the beginning of the end of full dose triple therapy with warfarin? Circulation. 2016 Nov 14. Doi:10.1161/CIRCULATIONAHA.116.025923 [Epub ahead of print].