Less Bleeding With Dual Than Triple Therapy for Atrial Fibrillation After PCI

By Will Boggs MD

March 19, 2020

NEW YORK (Reuters Health) - Triple antithrombotic therapy for atrial fibrillation (AF) after percutaneous coronary intervention (PCI) increases bleeding compared with dual therapy, according to a new systematic review and meta-analysis.

"Dual therapy is safe and perhaps provides an optimal balance between safety (in terms of bleeding) and ischemic profile (in terms of ischemic endpoints)," Dr. Safi U. Khan of West Virginia University, in Morgantown, told Reuters Health by email.

For the 5% to 10% of PCI patients who have AF, evidence has favored direct oral anticoagulant agents (DOACs) over vitamin K antagonists (VKAs), but whether dual or triple antithrombotic strategies provide better outcomes remains unclear.

Dr. Khan and colleagues examined the effects of dual therapy (DOAC plus P2Y12 inhibitor) versus triple therapy (VKA plus aspirin and P2Y21) on bleeding and ischemic outcomes in their meta-analysis of contemporary randomized clinical trials in adults with AF after PCI. The analysis included four trials (PIONEER AF-PCI, RE-DUAL PCI, AUGUSTUS, and ENTRUST-AF PCI) with nearly 8,000 patients in total.

High-certainty evidence demonstrated that patients given dual therapy had significantly lower risks of major bleeding, major and minor bleeding, and trial-defined bleeding, than did those given triple therapy.

There was no significant difference between dual and triple therapy in terms of intracerebral hemorrhage, based on moderate-certainty evidence, the researchers report in Annals of Internal Medicine.

Dual therapy did not differ statistically from triple therapy in the risks for all-cause mortality, cardiovascular mortality, myocardial infarction, stent thrombosis, major adverse cardiovascular events, or stroke.

"For most patients and those having high bleeding risk, dual therapy is the optimal approach, compared to triple therapy, in patients with recent percutaneous coronary intervention and atrial fibrillation," Dr. Khan said. "For patients with very high ischemic risk and low bleeding risk, one might consider an extended (1-3 months) course of triple therapy, keeping in mind that effects of dual therapy on ischemic endpoints are uncertain in this scenario."

He added that further trials are needed to examine the anti-ischemic benefits of these strategies.

Dr. John U. Doherty of Sidney Kimmel Medical College at Thomas Jefferson University, in Philadelphia, who wrote an accompanying editorial, told Reuters Health by email, "These are complex patients and the use of combined antiplatelet therapy and anticoagulation should be a joint decision of the entire care team. For example, the interventional cardiologist would provide a unique and valuable perspective based on the individual patient. Likewise, since we are balancing risk and benefit, the patient should be involved in shared decision-making."

"DOAC-based regimens are overall preferred over warfarin-based triple therapy in patients with AF and PCI," he said. "The case-by-case judgment is how long dual antiplatelet agents need to be continued and when it is safe to 'de-escalate' to a single antiplatelet, usually a P2Y12. Other mitigating factors are whether the stenting was elective or the lesion was less complex angiographically, or the patient is at increased bleeding risk (in which transition to a single antiplatelet agent may be preferred sooner)."

Dr. Renato D. Lopes of Duke Clinical Research Institute, in Durham, North Carolina, whose recent network meta-analysis also favored a DOAC plus a P2Y12 inhibitor without aspirin in most AF patients undergoing PCI, told Reuters Health by email, "Based on this and prior published data, triple therapy with warfarin plus clopidogrel plus aspirin should generally be avoided. If one needs to use triple therapy, then it needs to be with a DOAC (instead of warfarin) and keeping aspirin for 30 days only. So, triple therapy for few cases and only for 30 days at the most."

"For most patients, double therapy, with a DOAC plus clopidogrel, should be enough by the time of hospital discharge and should be the way to go," said Dr. Lopes, who was not involved in the new analysis. "After 12 months from the acute coronary syndrome/PCI, the P2Y12 inhibitor can be dropped and oral anticoagulation should be the only antithrombotic treatment for these patients."

SOURCE: https://bit.ly/33pNWyg Annals of Internal Medicine, online March 17, 2020.