In patients at high bleeding risk who had undergone percutaneous coronary intervention (PCI), 1 month of dual antiplatelet therapy (DAPT) was associated with a similar rate of major adverse cardiac or cerebral events but a lower bleeding risk than a longer duration of DAPT, even in patients undergoing complex PCI, a new analysis of the MASTER DAPT study shows.
The results of this subgroup analysis of complex PCI cases were presented by Pascal Vranckx, MD, Hartcentrum Hasselt, Belgium, at the Congress of European Association of Percutaneous Cardiovascular Interventions (EuroPCR 2022), being held this week in Paris.
The findings were also simultaneously published online in the European Heart Journal.
“These latest results show that, regardless of PCI-complexity, the discontinuation of DAPT at a median of 34 days compared with continuation of treatment for a median of 193 days [6.5 months] after PCI was consistently associated with similar rates of net adverse clinical events and major adverse cardiac or cerebral events and a lower rate of major or clinically relevant nonmajor bleeding,” Vranckx reported.
“Results remained consistent with an alternative complex PCI definition, and in complex PCI and/or ACS as well as complex PCI and ACS,” he added.
Vranckx explained that the main MASTER DAPT trial, conducted in patients at high bleeding risk undergoing PCI with the sirolimus-eluting biodegradable polymer Ultimaster stent (Terumo), 1 month of dual antiplatelet therapy (DAPT) was noninferior compared with 2 or more months of DAPT in terms of major adverse clinical events and net clinical events, but the 1 month of DAPT was associated with reduced major or clinically relevant nonmajor bleeding.
The current study is a prespecified substudy of the MASTER DAPT trial focusing on patients who underwent complex PCI. “These patients who have more advanced coronary artery disease have a higher short- and long-term risk of ischemic events,” Vranckx noted.
The definition of complex PCI for this study was one of the following criteria: three vessels treated, three or more stents implanted, three or more lesions treated, bifurcation with two stents implanted, total stent length over 60 mm, or chronic total occlusion as the target lesion. For a sensitivity analysis, two extra definitions were also added: left main stenting and graft stenting.
Of the 4579 patients in the overall MASTER DAPT trial, 1196 (26%) underwent a complex PCI.
The baseline angiographic and procedural characteristics, stratified by PCI complexity, were well balanced between the two antiplatelet regimens.
Although the majority (74%) of the patients classified a having complex PCI had just one criterion to qualify as complex, there was a significant minority with two or more criteria, showing that this was truly a complex PCI population, Vranckx said.
The trial had three coprimary endpoints to be tested in a hierarchical order:
Major adverse cardiac and cerebral events: the composite of all-cause death, MI, and stroke; and
Major or clinically relevant nonmajor bleeding: the composite of BARC type 2, 3 and 5 bleeding.
Results showed that the outcomes of net adverse clinical outcomes and major adverse cardiovascular events were similar for both antiplatelet treatment groups, and there was no difference between the results in patients receiving complex PCI and those receiving noncomplex PCI.
For net adverse clinical outcomes, the hazard ratio was 1.03 (95% CI, 0.69 – 1.52) for the complex PCI population and 0.90 (95% CI, 0.71 – 1.15) for the noncomplex PCI population, with an interaction P value of .60.
For major adverse cardiac and cerebral events, the hazard ratio was 1.24 (95% CI, 0.79 – 1.92) for the complex PCI population and 0.91 (95% CI, 0.69 – 1.21) for the noncomplex PCI population, with an interaction P value of .26.
But the abbreviated DAPT group showed a lower rate of major of clinically relevant nonmajor bleeding. In the complex PCI patients, the hazard ratio for this endpoint was 0.64 (95% CI, 0.42 – 0.98). And in the noncomplex patients, the hazard ratio was 0.70 (0.55 – 0.89), with an interaction P value of .72.
Vranckx noted that the study had some limitations. These included an open label design, no stratification for PCI complexity, and the absence of a universally accepted definition for complex PCI.
He also pointed out that these results may not apply to patients not treated with biodegradable-polymer sirolimus eluting stents, and the type of monotherapy after discontinuing dual antiplatelet therapy was at the discretion of the treating physicians.
At a EuroPCR press conference on the study, lead investigator of the main MASTER DAPT study, Marco Valgimigli, MD, Instituto Cardiocentro Ticino, Lugano, Switzerland, pointed out that these results were in line with previous studies suggesting shorter durations of DAPT were better than longer durations, but he noted that in the current study, many patients were continued on monotherapy with a P2Y12 inhibitor antiplatelet rather than aspirin monotherapy, which could be the reason for the positive results with just one month of DAPT.
Asked if one month of DAPT was now recommended for all patients at high bleeding risk after PCI, Valgimigli replied: “If patients are high bleeding risk, this is the now the standard of care I am implementing more and more in my practice, with the exception of patients with stent thrombosis or in-stent restenosis — these were two exclusion criteria in this study and for these patients probably a slightly longer duration of DAPT treatment may be reasonable.”
Co-moderator of the EuroPCR session, Chaim Lotan, MD, head of The Heart Institute of the Hadassah University Medical Center, Jerusalem, Israel, congratulated Vranckx on the study. “These results would have a lot of influence on our daily work in the cath lab, especially in complex patients,” Lotan said.
Commenting on the study, panel discussant, Petr Widimsky, MD, University Hospital Kralovske Vinohrady, Prague, Czech Republic, pointed out that the trial randomly assigned patients 1 month after PCI to stop or to continue on DAPT. “For me the main message is that we can decide about DAPT duration at 1 month rather than at the end of PCI or the day after as we do now,” he said.
Another panel discussant, Eliano Navarese, MD, Nicolaus Copernicus University, Poland suggested that there was still some uncertainty about such a short duration of DAPT in patients with acute coronary syndrome (ACS).
“Given the wide noninferiority margins in the main trial with lower than expected event rates, and the large use of clopidogrel monotherapy which is a less potent drug not recommended as first choice in ACS, before extrapolating the use of monotherapy in pure ACS patients which were lower than half of the MASTER DAPT population, more powered data in ACS are needed based on P2Y12 type,” Navarese told theheart.org | Medscape Cardiology.
“Among the spectrum patients at ischemic risk, ACS poses the greatest risk,” he added. “In these patients however, the risk clusters in the first month, and is then reduced, while bleeding risk continues to increase stepwise. Novel approaches such as drug de-escalation with the more potent ticagrelor therapy can thus be tested in ACS.”
Navarese noted that the ongoing ELECTRA-SIRIO trial is evaluating such a strategy.
The study was funded by a grant from Research Grant from Terumo. Vranckx reports consulting fees from Daiichi Sankyo, Novartis, CSL Behring and Bayer AG; honoraria from Daiichi Sankyo and Servier; and participating on an advisory board for Daiichi Sankyo. Valgimigli reports grants and personal fees from Abbott; personal fees from Chiesi, Bayer, Biotronik, Daiichi Sankyo, Amgen, Alvimedica, Biosensors, Idorsia; grants and personal fees from Terumo; and personal fees from AstraZeneca, and personal fees from Vesalio.
EuroPCR-2022. Presented May 17, 2022.
Eur Heart Journal. Published online May 17, 2022. Abstract