Data Gap: Best Strategy Unknown for A-Fib Patients on Newer Anticoagulants Who Need PCI

Patients with A-fib who take newer alternatives to warfarin and who subsequently require PCI are at high risk for thrombosis and bleeding, according to a new analysis of ROCKET-AF. Optimal treatment strategies remain unclear, leaving physicians with knowledge gaps when faced with these vulnerable patients, researchers say.  

Previous studies have suggested that 1% to 2% of adults will develop A-fib and of these, 20% to 30% will, over time, need PCI, the authors note.

In an interview with TCTMD, the study’s lead author Matthew W. Sherwood, MD (Duke University School of Medicine, Durham, NC), said this is an area ripe for investigation because there is considerable variability in how clinicians approach the risk/benefit balance. Although randomized trials in this specific population are ongoing, he noted, data to help physicians decide on the best course of action are sparse.

“In the meantime, it’s hard to know what to do with our patients who are on direct oral anticoagulants who need PCI, because we don’t have studies looking at the combination of these agents with aspirin and clopidogrel, and certainly no data on combination with more potent agents such as ticagrelor and prasugrel,” Sherwood said. “The real question is, what is the antiplatelet therapy that should be added to the oral anticoagulation?”

Sherwood et al’s study, published August 15, 2016 in JACC: Cardiovascular Interventions, examined data from the ROCKET AF trial, which compared fixed-dose rivaroxaban and dose-adjusted warfarin in patients with electrocardiographically documented nonvalvular A-fib and moderate-to-high stroke risk. In the main trial, rivaroxaban was found to be noninferior to warfarin for the primary endpoint of stroke or systemic embolism.

Guidance on Antiplatelet Therapy Lacking

The new analysis focused on the 151 patients—a little over 1% of the ROCKET AF population—who underwent unplanned PCI during the trial. Compared with those randomized to rivaroxaban, patients randomized to warfarin had a shorter time to first PCI.

More than 80% of patients who underwent PCI remained on the anticoagulant they were randomized to in the trial after PCI.

“That highlights [the fact] that physicians understand that patients who are high risk for thrombosis who have A-fib do need to stay on oral anticoagulation even after an invasive procedure,” Sherwood said.

More striking, however, was the variation in oral antiplatelet therapy: 37% received clopidogrel and aspirin; 16% received aspirin alone; 18% received clopidogrel alone; 15% received no antiplatelet therapy; and 12% were switched at approximately 30 days post-PCI from DAPT to a monotherapy.

“This is showing that we can’t predict how physicians are going to act in this situation because there are no data to guide them,” Sherwood observed. He added that while personalized risk assessment of thrombotic and bleeding risk is important, so too is the understanding that patients need to remain on oral anticoagulants to prevent stroke.

Compared with those who did not undergo PCI during ROCKET AF, those who did experienced more stroke or systemic embolism, MI, vascular death, and major or non-major clinically relevant bleeding. While most stroke, MI, systemic embolic events, and major bleeding events occurred within the first 6 months after PCI, vascular deaths accrued across follow-up—a median of 806 days.

When the researchers compared the rivaroxaban and warfarin groups who underwent PCI, the latter had a numerically higher rate of stroke and vascular deaths, while the former had a numerically higher rate of major bleeding and the composite of major and clinically relevant non-major bleeding.

Looking Toward Future Data

In warfarin-only populations, the WOEST and ISAR-TRIPLE trials have suggested that less may be more when it comes to therapy, showing that “we might be able to use either a single antiplatelet agent or do a shorter duration of therapy with the current generation of drug-eluting stents,” Sherwood said. “But there are no such data for the direct oral anticoagulants.”

PIONEER AF-PCI and REDUAL PCI, which include patients on rivaroxaban and dabigatran, respectively, are two of the most promising trials from which Sherwood says he and others are pinning their hopes for more data in this vulnerable patient population. The former, he said, will provide information on safety, but is not powered for major clinical endpoints.

In an editorial accompanying the study, Jean-Philippe Collet, MD, PhD (Pitié-Salpêtrière Hospital, Paris, France), and colleagues note that lower doses of newer oral anticoagulants such as apixaban, rivaroxaban, and endoxaban are a possible solution for reducing the bleeding risk, but may not be effective enough to prevent stroke. They add that several large-scale outcome studies are looking at different combinations of these newer agents or warfarin with antiplatelet therapy in A-fib patients undergoing stenting, as well as varied dosing strategies, P2Y12 inhibitors, and exposure times.  

 

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Disclosures:

 

• The ROCKET AF trial was supported by Johnson & Johnson Pharmaceutical Research & Development, and Bayer HealthCare AG. 
• Sherwood reports no relevant conflicts of interest. 
• Collet reports institutional research grants or consulting/lecture fees from AstraZeneca, Bayer, Bristol-Myers Squibb, Daiichi Sankyo, Eli Lilly, Fédération Française de Cardiologie, Lead-Up, Medtronic, MSD, Sanofi, and WebMD. 

 

Related Stories:

 

• ROCKET AF Investigators Respond to New Questions About Point-of-Care Warfarin Monitoring Device
• Triple Therapy Yields No Thrombotic Benefit, More Bleeding in Older PCI Patients With A-fib
• ISAR-TRIPLE Published: No Net Gain for 6 Weeks vs 6 Months of Triple Therapy