Clinical Challenges: Aspirin’s Diminishing Role After PCI

With the advent of potent alternative antiplatelets and safer drug-eluting stents (DES), aspirin is losing its appeal as a standard antithrombotic medication after percutaneous coronary intervention (PCI). The question now confronting clinicians is when and in whom aspirin can be safely dropped.

To prevent stent thrombosis and other adverse events, guidelines generally recommend at least 12 months of dual antiplatelet therapy (DAPT) for acute coronary syndrome (ACS) patients, and 6 to 12 months after PCI for stable angina.

In practice, however, the tailoring of DAPT requires more thought, according to American College of Cardiology president Dipti Itchhaporia, MD, of Hoag Heart and Vascular Institute in Newport Beach, California.

“We’re being challenged with more complicated patients,” she said, citing an aging population with more complicated anatomy necessitating more complex PCI. “What if patients have atrial fibrillation too? All of those things are things to think about.”

There is interest in DAPT deescalation to accommodate people at high bleeding risk such as older people. This strategy keeps both aspirin and the P2Y12 inhibitor but reduces the intensity of the latter after the first few months — from ticagrelor (Brilinta) or prasugrel (Effient) to the weaker clopidogrel (Plavix), say, or to half-dose ticagrelor or prasugrel.

Yet there is a growing drumbeat for getting rid of the aspirin outright early on for some patients.

Studies such as GLOBAL LEADERS, STOP-DAPT2, and SMART-CHOICE have been consistent in showing the safety of switching to P2Y12 inhibitor monotherapy within months of revascularization. It appears that GLOBAL LEADERS’ approach, ticagrelor monotherapy after just 1 month of DAPT, reduced bleeding for ACS patients in particular.

The TWILIGHT trial from 2019 was a major win for strategy of cutting aspirin from ticagrelor-based DAPT after 3 months in high-risk stent recipients. Results were echoed in TICO-STEMI, which had the same short DAPT regimen tested in patients with ST-segment elevation myocardial infarction, a group excluded from TWILIGHT.

As for long-term post-stent maintenance, even clopidogrel monotherapy was superior to aspirin in this year’s HOST-EXAM trial, reducing ischemic and bleeding outcomes alike out to 2 years.

“Aspirin is taking a beating, and aspirin should take a beating,” Dean Kereiakes, MD, of the Christ Hospital in Cincinnati, said in an interview.

He suggested that the main appeal of aspirin is that it is cheap and familiar, and that most people in the U.S. with high bleeding risk are stopping the P2Y12 inhibitor and continuing aspirin when it should be the other way around.

“Watch out for bleeding. I’ve quit taking aspirin for primary prevention and quit prescribing it [for that]. I limit aspirin, and when I’m doing a short DAPT regimen, I’m more often than not likely to stop the aspirin at 1 to 3 months and continue the P2Y12 inhibitor,” he said.

“I’m not looking into a crystal ball. I’m looking at things that are yet to be published, and I can tell you that if you have to be on one [antiplatelet], be on the P2Y12 inhibitor if you have an increased risk of ischemia,” he emphasized.

Indeed, clinicians are starting to get more comfortable with the idea of dropping aspirin early, Itchhaporia told MedPage Today.

OPT-PEACE investigators recently reported that nearly all PCI recipients in the study developed some form of gastrointestinal injury after taking antiplatelets, and that being on one instead of two agents helped somewhat.

Whether short DAPT is the right strategy for patients should be based on careful consideration of their individual bleeding and thrombotic risks, Itchhaporia said. “I wish there was just one answer … This is where clinical judgment does play a role.”

Itchhaporia identified people at high ischemic and bleeding risk as being candidates for short DAPT. People at high bleeding risk but low ischemic risk are also good candidates, she said.

Kereiakes stressed the use of risk calculators in balancing bleeding risk and ischemic risk. He noted that his institution has the PRECISE-DAPT and DAPT risk scores incorporated into their EHR to help clinicians decide whether DAPT deescalation or short DAPT would be appropriate for a given PCI patient.

After all, he suggested, it would be a reach to say it’s time to say goodbye to standard DAPT for all PCI patients.

Many patients in the cardiac cath lab are still getting 12 months of DAPT, according to Kereiakes. The “significant minority” meeting criteria for high bleeding risk amount to roughly 30% of individuals. Other indications for deescalating or cutting DAPT short include older age, oral anticoagulant use, and chronic kidney disease, he said.

Notably, these bleed-reducing approaches have been compared to standard DAPT in multiple large-scale studies but never directly against each other in a head-to-head trial, he noted.

Kereiakes teased that a “sophisticated” network meta-analysis, currently in press at a peer-reviewed journal, indirectly compares short DAPT with deescalation and will help shed light on which antiplatelet regimen should be applied to which patients.

“The pieces of the puzzle are coming fast and furious. There will be more in the next several months,” he said.