P2Y12 Monotherapy Better Than Continued DAPT Even After Complex PCI

Among patients undergoing PCI, regardless of their procedural complexity, dropping aspirin after 1-3 months of dual antiplatelet therapy (DAPT) is associated with no increase in fatal and ischemic events and less bleeding compared with continuing standard DAPT, according to a meta-analysis.

Several studies have already shown the potential benefits of using a short course of DAPT followed by P2Y12 inhibitor monotherapy for general PCI patients receiving modern DES. However, many clinicians have remained cautious in their approach for those undergoing complex procedures.

Thus, “it was important to assess whether this holds true also for patients with higher ischemic risks, such as those who underwent complex PCI who suffer more frequently from recurrent ischemic events than those without,” senior author Marco Valgimigli, MD, PhD (Cardiocentro Ticino, Lugano, Università della Svizzera italiana (USI); University of Bern, Switzerland), told TCTMD in an email.

Previously, Allen Jeremias, MD (St. Francis Hospital and Heart Center, Roslyn, NY), who commented on the results for TCTMD, said he had been inclined to give DAPT for at least 6 months in complex patients—meaning those with chronic total occlusions (CTOs), bifurcations, or longer than 60 mm of total stent length. “Now, with this new data, I feel certainly more confident that we can shorten it even in this complex population,” he said.

Same Ischemic Risk, Less Bleeding

For the meta-analysis, published in the February 14, 2023, issue of the Journal of the American College of Cardiology, Valgimigli, Felice Gragnano, MD, PhD (University of Campania Luigi Vanvitelli, Caserta, Italy), and colleagues pooled data on 22,941 PCI patients from five trials (mean age 65 years), 20.4% of whom had complex PCI. Complex cases were defined as three vessels treated, at least three stents implanted, at least three lesions treated, bifurcation with two stents implanted, total stent length > 60 mm, or CTO.

Over a median follow-up of 334 days, the primary efficacy endpoint—all-cause mortality, MI, and stroke—occurred more often in those receiving complex compared with noncomplex PCI (3.86% vs 2.95%; HR 1.28; 95% CI 1.04-1.59). However, there was no increased risk of this endpoint for those who received P2Y12 inhibitor monotherapy compared with continued DAPT in either the complex PCI group (HR 0.87; 95% CI 0.64-1.19) or noncomplex PCI group (HR 0.91; 95% CI 0.76-1.09; P for interaction = 0.770).

Also, while the risk of the key safety endpoint of BARC 3 or 5 bleeding was numerically higher in the complex PCI group (1.66% vs 1.31%; HR 1.18; 95% CI 0.87-1.59), P2Y12 inhibitor monotherapy consistently reduced this endpoint in complex (HR 0.51; 95% CI 0.31-0.84) and noncomplex PCI patients (HR 0.49; 95% CI 0.37-0.64) compared with DAPT (P for interaction = 0.920).

In a subgroup analysis, it was suggested that P2Y12 inhibitor monotherapy reduced the risk of the primary endpoint for females but not males receiving noncomplex PCI (P for interaction = 0.010), but no significant interaction was found for individual outcomes by sex. Additionally, there was no effect of the type of P2Y12 inhibitor used—clopidogrel or newer agent—on the primary endpoint, and an additional analysis looking at only those receiving clopidogrel monotherapy across all subgroups confirmed this.

Valgimigli said he was “not surprised [but] rather very pleased” at the results.

“P2Y12 monotherapy should become the default treatment after 1-3 months of DAPT in all PCI patients, not just in those at high bleeding risk and irrespective of the ischemic risks,” he said. “I would be curious to see if now guidelines will be brave enough to walk away from the old and now unsupported standard 12-month DAPT regimen as the default option post-PCI. This still comes from opinions more than data and it is, at least to me, no longer justified and justifiable in 2023.”

New Guidelines Needed?

Deepak L. Bhatt, MD, MPH (Icahn School of Medicine at Mount Sinai Health System, New York, NY), who authored an accompanying editorial, seems to agree. This study “strongly suggests that a strategy of initial DAPT followed by P2Y12 inhibitor monotherapy provides adequate protection against ischemic events with a substantially lower risk of bleeding,” he writes. “These findings are consistent with the prior body of published data that shows P2Y12 inhibitor monotherapy is more potent than aspirin monotherapy.”

One caveat, Bhatt notes, is that while the median duration of follow-up for this meta-analysis was 334 days, “the benefit of DAPT with ticagrelor plus aspirin over aspirin monotherapy in THEMIS, for example, did not even emerge until after 1 year of follow-up. Additionally, THEMIS-PCI found a benefit of DAPT vs aspirin that was statistically significant out to at least 6 to 7 years from the time of the prior PCI.” COMPASS-PCI also found an ischemic benefit of two antithrombotics over aspirin monotherapy at 10 years post-PCI, Bhatt says.

Even so, “it does seem very plausible that using a P2Y12 inhibitor instead of aspirin may strike the best balance for many patients,” he writes. “The present data raise the possibility that such a de-escalation strategy to P2Y12 inhibitor monotherapy should perhaps be the default strategy, including for complex PCI, and not reserved for use only in those at perceived high bleeding risk.”

Jeremias said these data lead him to want to shorten DAPT to 1 month for “the most straightforward” patients and 3 months for “the most complex,” but then proceed with P2Y12 inhibitor monotherapy. Still, even though the results don’t support the practice of routine clopidogrel responsiveness testing, he might consider doing so if patients are not on one of the more-potent agents like ticagrelor or prasugrel, just to check that they are protected after aspirin is removed.

He would also like to see “a more detailed analysis on that just to make sure that it is in fact okay for these complex patients to just be on clopidogrel monotherapy as opposed to maybe one of the more-potent agents. . . . It does not seem that the patient population that has received clopidogrel monotherapy had any issues, which is a little bit counterintuitive, but certainly before we change the practice, that should be analyzed a little bit more carefully.”

A comprehensive intravascular imaging protocol for PCI patients can also go a long way in helping with “the comfort level in terms of stopping aspirin,” Jeremias said.

He, too, thinks it might be time for recommendations to change. “There is good prospective data already. I do not know if this is going to be sufficient for guideline changes,” said Jeremias. “But I feel the guideline committees should start looking at the data, including this meta-analysis, and certainly I think we have enough data to make some basic recommendations.”