As regards the use of antithrombotic agents, the risk of bleeding will always be an issue, and in the case of aspirin this risk is twice as big: it does have the desired antiaggregation effect, but on top of the increased bleeding risk, it has a damaging effect on stomach lining that increases the risk of stomach bleeding in particular. Can we mitigate this effect? Several studies are looking into free aspirin cardioembolic stroke prevention, even after PCI.

Aspirin could lose its undisputed status as the cornerstone of antiplatelet therapies, if one of the new, more powerful, antithrombotic agents proved to be enough.

This is just a theory; we should wait for the outcomes of studies such as the GLOBAL-LEADERS and the TWILIGHT before even thinking of stop using or indicating aspirin.

During these past years, many studies have tested the efficacy of drugs in trying to maintain the desired antithrombotic effect without increasing the risk of bleeding. Unfortunately, the greater the efficacy, the higher the bleeding risk; and this complication involves a worse prognosis, even death.

Read also: NSAIDs and Risk of Bleeding in Patients with Atrial Fibrillation.

This study revisited 10 trials testing aspirin-sparing regimes in different scenarios, including post PCI, atrial fibrillation patients and post TAVR.

The WOEST was the first study to test a strategy free of aspirin in the context of patients with atrial fibrillation undergoing PCI. Compared to the triple therapy (aspirin, clopidogrel and anticoagulation) an aspirin-sparing strategy (clopidogrel and anticoagulation) resulted as effective and yielded less bleeding.  

After that came the PIONEER AF-PCI and the RE-DUAL PCI, that suggested the same: stopping aspirin reduces bleeding without an excessive trade-off in terms of efficacy.

Read also: Post Carotid Stenting Cerebral Hyperperfusion: a Preventable Complication.

These studies, together with the few currently in place (AUGUSTUS and ENTRUST AF-PCI), have encouraged us to manage without aspirin, at least with atrial fibrillation patients undergoing PCI.

Next, we will have to wait for the GLOBAL-LEADERS outcomes, currently randomizing 16000 patients treated with DES to ticagrelor plus aspirin for one month followed by ticagrelor for just 23 months vs. dual APT (ticagrelor or clopidogrel plus aspirin) for 12 months, followed by aspirin alone for 12 more months.

The TWILIGHT is planning to include 9000 patients to answer the question on the safety and efficacy of aspirin plus ticagrelor vs. placebo plus ticagrelor in patients undergoing PCI that remain event free the first three months.

Read also: Far from a Being a Pun, Malnutrition Tips the Scales in TAVR.

The aspirin paradigm could eventually shift, especially after PCI, something we deemed impossible 3 or 4 years ago.

The need of aspirin after TAVR is also being examined and several studies are including patients to test this hypothesis (GALILEO, ATLANTIS y TICTAVI).

Time will attest to the future of aspirin in cardiology, but for now, all we have is questions, conjectures, speculation and expectations.

Original title: Aspirin-free strategies in cardiovascular disease and cardioembolic stroke prevention.

Reference: Capodanno D et al. Nat Rev Cardiol. 2018; Epub ahead of print.

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