New Consensus Statement: NOAC and Clopidogrel for Most A-fib Patients Treated With PCI

The management of antithrombotic therapy in patients with atrial fibrillation undergoing PCI for coronary artery disease remains a challenge in clinical practice, but a new North American consensus statement should help provide some clarity in this complex patient population.

Based on the results of recent clinical trials, including PIONEER AF-PCI and RE-DUAL PCI, experts now suggest that individuals with atrial fibrillation undergoing PCI should be treated with oral anticoagulation—preferably with one of the non-vitamin K antagonist oral anticoagulants (NOACS)—and a P2Y12 inhibitor upon discharge from hospital.

“This is our third time we have put together a North American consensus statement and it’s the first time we have had pretty convincing data, which we really did not have in the past,” Dominick Angiolillo, MD, PhD (University of Florida College of Medicine, Jacksonville), lead author of the new statement published online July 31, 2018, ahead of print in Circulation, told TCTMD.

While the default treatment strategy of a NOAC plus single antiplatelet therapy is sufficient for most patients, extending the use of aspirin beyond hospital discharge can be considered for selected patients at high risk for ischemic or thrombotic events and a low risk for bleeding. This triple therapy combination—oral anticoagulation, aspirin, and a P2Y12 inhibitor—should only be prescribed for a limited period, say experts.

No matter how many trials there will be in the area—and there are at least two large studies still ongoing—we will always be faced with the dilemma on what is the optimal choice for the individual patient. Dominick Angiolillo

Additionally, given its lower risk of bleeding complications, clopidogrel should be prioritized as the P2Y12 inhibitor of choice for most patients with atrial fibrillation undergoing PCI and receiving concomitant oral anticoagulation. Ticagrelor (Brilinta; AstraZeneca) can be considered a reasonable treatment option in patients with high ischemic/thrombotic risk and a low risk of bleeding, but prasugrel (Effient; Eli Lilly) is to be avoided.

“While we understand our recommendations are to be considered ‘recommendations based on the available evidence,’ ultimately, the decision on how to manage antithrombotic therapy in these patients needs to be individualized,” said Angiolillo. “No matter how many trials there will be in the area—and there are at least two large studies still ongoing—we will always be faced with the dilemma on what is the optimal choice for the individual patient.” He added that the consensus statement provides a framework for treatment, while leaving enough room to adapt models of antithrombotic regimens to fit best for each patient.

Angiolillo pointed out that all patients are treated with aspirin in the periprocedural PCI period. “We just recommend an early withdrawal of aspirin,” said Angiolillo. If a patient has a high risk of ischemic/thrombotic events, aspirin can be continued for up to 1 month after hospital discharge, bearing in mind that physicians should minimize the duration of triple therapy, he added.

“One thing is clear: prolonging triple therapy does increase the risk of bleeding,” said Angiolillo.

Less Bleeding, No Excess Risk of Ischemic Events

In PIONEER AF-PCI and RE-DUAL PCI, use of rivaroxaban (Xarelto; Bayer/Janssen Pharmaceuticals) and dabigatran (Pradaxa; Boehringer Ingelheim), respectively, with a P2Y12 inhibitor alone was superior to triple therapy with warfarin and dual antiplatelet therapy for reducing the risk of bleeding complications. Dropping aspirin did not increase the risk of ischemic or thrombotic events in those trials. In the WOEST study, oral anticoagulation with warfarin and single antiplatelet therapy with clopidogrel reduced the risk of bleeding but did not affect efficacy when compared with triple therapy (oral anticoagulation, aspirin, and clopidogrel).

The AUGUSTUS and ENTRUST-AF PCI trials are both ongoing. Those studies are similar in design and will compare apixaban (Eliquis; Bristol-Myers Squibb) and edoxaban (Savaysa; Daiichi Sankyo), respectively, against a vitamin K antagonist in atrial fibrillation patients undergoing PCI. The AUGUSTUS trial, however, is also testing aspirin versus no aspirin in a factorial design and will provide more data on the relative risks and benefits of dropping aspirin at hospital discharge.

Peter Kowey, MD (Thomas Jefferson University, Philadelphia, PA), who was not involved in drafting the consensus statement, said trials to date have provided reasonable reassurance that physicians do not need to use triple therapy in patients with atrial fibrillation undergoing PCI for a long period of time. Switching to double therapy with a NOAC and P2Y12 inhibitor soon after the intervention should be effective for preventing stent thrombosis and catastrophic coronary events, as well as result in a fairly low incidence of bleeding.

“What we probably will never be able to prove conclusively is if [double antithrombotic therapy] will definitely reduce vascular events, because there simply aren’t enough patients in these trials to be able to conclude that,” Kowey told TCTMD. PIONEER AF-PCI, for example, was not adequately powered for stroke events, and trial investigators used a relatively low dose of rivaroxaban compared with doses typically used for the prevention of stroke, he said. “Whether or not it’s effective for stroke prevention, you can’t know. You can’t power the studies because the event rates are too low. We didn’t see any major signal of danger in the data, but it’s not possible to be as confident as we’d like to be.”

In the North American consensus statement, Angiolillo and colleagues recommend using NOAC doses tested in the clinical trials and acknowledge that the dose of rivaroxaban suggested is lower than that tested in stroke prevention trials. They recommend that after antiplatelet therapy is stopped, oral anticoagulation should be continued at full stroke-prevention doses.

“I’m not really worried about using conventional doses of oral anticoagulation with a thienopyridine in an atrial fibrillation patient,” said Kowey. “Chances are very good you’ll be able to prevent stroke. My biggest concern is if we’re going with recommendations to use lower doses of oral anticoagulants. Then I’m worried if we have enough efficacy data.”

Overlap Between US and European Recommendations 

Davide Capodanno, MD, PhD (University of Catania, Italy), said there has been no shortage of expert consensus statements on both sides of the Atlantic for how to best to manage this complex patient population. Earlier this year, the European Heart Rhythm Association (EHRA) released a “practical guide” on the use of NOACs in patients with atrial fibrillation and this includes recommendations on antithrombotic therapy in patients undergoing PCI. An updated expert consensus document from the European Society of Cardiology is expected in the next few months.

“The recommendations from the available US and European documents overlap in some way, particularly because they leave ample room to physicians to follow a personalized strategy based on the individual risks of ischemia and bleeding,” Capodanno told TCTMD. “However, this is probably the first time that I have read such an explicit endorsement of dual antithrombotic therapy as a default approach for most of the patients, based on the results of PIONEER-AF and RE-DUAL PCI.”

This is probably the first time that I have read such an explicit endorsement of dual antithrombotic therapy as a default approach for most of the patients, based on the results of PIONEER-AF and RE-DUAL PCI. Davide Capodanno

In the EHRA practical guide, for example, triple antithrombotic therapy with a NOAC, aspirin, and clopidogrel is recommended for 3 months in patients with atrial fibrillation who have an ACS and undergo PCI. Like Angiolillo, Capodanno said the dual antithrombotic therapy strategy has consistently proven to be safer than the triple antithrombotic therapy strategy.

“However, the jury is still out on whether it is similarly effective in preventing thromboembolism,” said Capodanno. “There is some suggestion of no added harm with the dropping of aspirin, but I think we need to see AUGUSTUS and ENTRUST-AF PCI, and an updated meta-analysis, before closing the chapter.”

The new recommendations are an update to the 2016 expert consensus statement. In the past, experts said physicians could consider both a vitamin K antagonist oral anticoagulant, such as warfarin, and NOACs equally, and recommended physicians avoid prasugrel and ticagrelor. In the 2018 consensus statement, experts say physicians can stop antiplatelet therapy with clopidogrel 12 months after PCI in nearly all patients. If the patient is at high risk of bleeding, antiplatelet therapy can be stopped at 6 months.