Paradigm shift: DAPT loses out to P2Y12 inhibitor monotherapy

Cessation of aspirin and continuation of P2Y12 inhibitor monotherapy rather than ongoing dual antiplatelet therapy (DAPT) may be warranted within months of coronary revascularisation.

A meta-analysis of individual data from 23,308 patients in six RCTs compared P2Y12 inhibitor monotherapy versus DAPT following percutaneous or surgical revascularisation for stable or unstable coronary artery disease.

Most patients on P2Y12 monotherapy or DAPT were on ticagrelor (77.0% and 62.0%, respectively) compared to clopidogrel (22.2% and 36.8%) and prasugrel (0.8% and1.2%).

The meta-analysis, published in The BMJ, found the composite endpoint of all cause death, myocardial infarction, and stroke occurred in 2.95% of patients with P2Y12 inhibitor monotherapy and 3.27% patients with DAPT in the per protocol population (p=0.005 for non-inferiority, but not superiority p=0.38).

However in the safety endpoints, it found strong evidence for a reduction in the risk of BARC type 3 or type 5 bleeding among patients on P2Y12 inhibitor monotherapy compared with DAPT (0.89% v 1.83%; hazard ratio 0.49, 0.39 to 0.63; P<0.001; τ2=0.03).

The number needed to treat to benefit was 111.

Subgroup analysis suggested that P2Y12 inhibitor monotherapy lowers the risk of the primary ischaemic endpoint in women (hazard ratio 0.64, 0.46 to 0.89) but not in men (1.00, 0.83 to 1.19).

“Our analysis suggests that female patients may derive particular benefit from P2Y12 inhibitor monotherapy owing to the lower risk of major adverse cardiovascular events, largely driven by a reduction in cardiovascular death. P2Y12 inhibitor monotherapy was associated with lower bleeding rates consistently across subgroups, although the magnitude of this treatment effect varied by the potency of the P2Y12 inhibitor in the experimental and control groups, which has important implications for practice,” the investigators said.

“Our results, based on the totality of the available evidence, support a paradigm shift in antithrombotic management and question the central role of DAPT beyond one to three months after percutaneous coronary intervention.”

Associate Professor Sarah Zaman, from the Westmead Hospital and University of Sydney, agreed the findings warranted a paradigm shift in thinking.

“I think we probably do have enough evidence. We have got a couple of meta-analysis, this one included, and we have got several RCTs and they all point toward the same direction.”

However Australian cardiologists would probably wait for stronger direction from AHA/ACC and ESC guidelines. Associate Professor Zaman told the limbic the ESC did discuss a shortened duration of DAPT in their 2020 guidelines but AHA/ACC have not updated as yet.

“Patients with heart disease have been taking aspirin for decades and so I think there has to be a bit of a mental shift. There is a mental barrier. DAPT is so ingrained in our minds and that of patients.”

“I think that paradigm shift is the whole idea that cardiologists have been giving aspirin for so long and now we should look at the evidence and say it is not needed and in fact could be doing harm.”

She noted primary preventions trials such as ASCEND from 2018 had showed aspirin wasn’t necessary for primary prevention anymore.

“….and that has trickled down to practice now but it takes quite a few trials and a bit of a mindshift.”

“I guess the only caveat here is that most of the benefit was really weighted towards ticagrelor. Personally I would be more comfortable in an ACS patient on ticagrelor and aspirin, then after three months stopping the aspirin and just going forward with the ticagrelor.

She said there might be more evidence for prasugrel in the future.

Associate Professor Zaman said the major finding that women have a larger benefit than men on P2Y12 monotherapy was important but as yet unexplained.

In addition, interventional cardiologists should be reassured that the findings for P2Y12 monotherapy were irrespective of the complexity of the PCI.

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