New Review Probes Possibility of CVD Prevention Without Aspirin

To mitigate the risk of bleeding, several ongoing clinical trials are testing an aspirin-free antithrombotic treatment approach, including after PCI.

New Review Probes Possibility of CVD Prevention Without Aspirin

Aspirin could one day lose its treasured spot in the clinical toolbox of physicians treating patients with cardiovascular disease, including after PCI, if newer, more potent antithrombotic agents prove their mettle in a series of upcoming randomized clinical trials testing various aspirin-free strategies, according to a new review.   

However, experts stress that given aspirin’s “indisputable role” for managing and preventing cardiovascular disease, favorable results from these clinical trials—including GLOBAL-LEADERS and TWILIGHT—are needed before physicians can even consider opting for an aspirin-free approach in routine clinical practice.

“Over the past few years, there has been a lot of research on trying to identify antithrombotic strategies that reduce the risk of bleeding complications while maintaining efficacy,” said Dominick Angiolillo, MD, PhD (University of Florida, Jacksonville). “We’ve always been used to stacking on antithrombotic therapies, but this inevitably comes at a cost of increased bleeding. Bleeding complications are not trivial, and in fact are associated with very poor prognosis, including increased mortality. So the question becomes: what can we do?”

Angiolillo, senior author of the review published July 4, 2018, in Nature Reviews Cardiology, said stopping aspirin therapy has emerged as a potential means to reduce the risk of bleeding, particularly among patients with atrial fibrillation undergoing PCI. The review lists 10 studies currently underway testing various aspirin-free strategies in different clinical settings, including PCI, atrial fibrillation, and TAVR.

This “bench-to-bedside” review, stressed Angiolillo, does not promote dropping aspirin from therapy, but is intended to provide background information and the rationale for the number of studies underway. “We thought it was timely to put this together given the large number of ongoing trials,” he said.

Aspirin, Clopidogrel, and Oral Anticoagulation

To TCTMD, Angiolillo said the WOEST investigators were among the first to test an aspirin-free strategy in the setting of PCI in patients with atrial fibrillation. Compared with triple therapy—aspirin, clopidogrel, and oral anticoagulation—the use of clopidogrel and oral anticoagulation only was associated with a reduced risk of bleeding and no increased risk of thrombotic events.

Subsequent studies—PIONEER AF-PCI and RE-DUAL PCI—also suggested that not using aspirin as part of treatment could lower the risk of bleeding without worsening efficacy.

These trials, as well as others that are ongoing, including AUGUSTUS and ENTRUST AF-PCI, provide some direction for physicians wondering how to best treat patients with atrial fibrillation undergoing PCI, a group of patients at high risk for bleeding when treated with dual antiplatelet therapy and oral anticoagulation.

Later this month, an updated North American consensus document will be published and should provide some clarity, Angiolillo said. Last published in 2016, the new consensus statement will incorporate PIONEER AF-PCI and RE-DUAL PCI and will provide a framework for treatment in this everchanging field. Recommendations from European Society of Cardiology are also expected later this summer.

While the consensus statements are not yet published, Angiolillo said that data from randomized trials clearly support limited or no use of aspirin in patients treated with a P2Y12 inhibitor and oral anticoagulation. The exception is during the periprocedural PCI phase, he added.

What Antithrombotic Strategy for PCI and TAVR?

In the setting of PCI, where aspirin is a cornerstone of therapy, GLOBAL-LEADERS is randomizing 16,000 patients undergoing PCI with DES to ticagrelor plus aspirin for 1 month followed by ticagrelor alone for another 23 months, or to P2Y12 inhibition (ticagrelor or clopidogrel) and aspirin for 12 months, followed by aspirin alone for 12 months. The TWILIGHT trial is comparing the safety and efficacy of placebo versus aspirin for 12 months among 9,000 high-risk PCI patients on ticagrelor who are event free at 3 months.

Electing to skip aspirin at the time of PCI would raise eyebrows among cardiologists, especially since antithrombotic therapies have been developed by stacking treatments on top of the antiplatelet agent. “The results of the randomized clinical trials will dictate whether this should be a strategy considered in our clinical practice, and more specifically, in which subset it should be considered,” said Angiolillo.

Dropping aspirin, he added, would be a “paradigm-shifting” proposition, particularly following PCI, and one that wasn’t even considered up until 3 or 4 years ago. In addition to the development of newer antithrombotic agents, advances in stent technology have made it possible to avoid aggressive or prolonged antiplatelet therapy after PCI, said Angiolillo.

GLOBAL-LEADERS will be presented next month at the European Society of Cardiology Congress in Munich, Germany, while TWILIGHT results will be announced in 2019. Several trials testing an aspirin-free approach in TAVR are also underway, including GALILEO, ATLANTIS, and TICTAVI.

Sources
Disclosures
  • Angiolillo reports receiving consulting fees or honoraria from Amgen, Aralez, AstraZeneca, Bayer, Biosensors, Bristol-Myers Squibb, Chiesi, Daiichi-Sankyo, Eli Lilly, Janssen, Merck, PLx Pharma, Pfizer, Sanofi, and The Medicines Company. He also reports payment for participation in review activities from CeloNova and St. Jude Medical.

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