Shorter DAPT post-PCI noninferior to longer duration in high bleeding risk
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Dual antiplatelet therapy for 1 month or 3 months was noninferior to a 12-month duration with regard to all-cause mortality and MI in patients with high bleeding risk undergoing PCI, researchers found.
Data from the XIENCE 90 and XIENCE 28 trials, which were presented at TCT Connect, also determined that a short DAPT regimen after PCI resulted in similar rates of clinically relevant bleeding and very low incidence of stent thrombosis compared with longer duration therapy.
The XIENCE Short DAPT program includes the XIENCE 90 with 3-month DAPT (n = 2,047) and XIENCE 28 with 1-month DAPT (n = 1,605).
“We’ve had recent trials with current-generation DES that have shown an acceptable safety profile with a short course of DAPT, but how long the optimal duration is, is really unclear in high bleeding risk patients,” Roxana Mehran, MD, professor of medicine and director of interventional cardiovascular research and clinical trials at the Zena and Michael A. Wiener Cardiovascular Institute at Icahn School Medicine at Mount Sinai, said during the press conference.
Both trials were prospective, single-arm, multicenter, open-label, nonrandomized trials, and all patients had high bleeding risk and underwent PCI with an everolimus-eluting stent (Xience, Abbott Vascular).
“This multilink design cobalt chromium alloy that is 81 µm in strut thickness, with a durable fluoropolymer coating that selectively retains albumin and minimizes platelet adhesion, with everolimus drug-eluting,” Mehran said during the presentation. “It has been very well studied, and is incredibly safe and effective.”
In addition, patients from both trials were aged at least 75 years, were on chronic oral anticoagulation therapy, had major bleeding in the past 12 months and a history of stroke. Exclusion criteria included STEMI presentation, left ventricular ejection fraction less than 30% and planned surgery within 1 month or 3 months of PCI.
For the XIENCE 90 trial, patients were treated with a P2Y12 inhibitor and aspirin after PCI for 3 months. After the 3 months, if patients were free from events, the P2Y12 inhibitor was stopped and aspirin therapy continued from 3 to 12 months. The primary analysis period was between 3 and 12 months, during which patients were followed up at 6 and 12 months.
The XIENCE 28 trial had a similar design but with a shorter DAPT duration. Patients were treated with a P2Y12 inhibitor and aspirin after PCI for 1 month, which changed to aspirin only if patients were event-free during that time. Patients received aspirin during the primary analysis period from 1 to 6 months, during which patients were followed up at 3 and 6 months.
The historical control in this program was data from XIENCE V USA, a prospective, multicenter, post-approval study that assessed the safety and effectiveness of the Xience stent in 8,061 patients from 2008 to 2011.
The primary endpoint was all-cause death or MI, which was compared with control in each trial. Key secondary endpoints included Bleeding Academic Research Consortium (BARC) types 2 to 5 bleeding, which was compared with control in each trial, and definite/probable stent thrombosis, which was assessed only in the XIENCE 90 trial.
There were 1,693 patients (mean age, 75 years; 35% women) from the XIENCE 90 trial who were event-free at 3 months and 1,392 patients (mean age, 76 years; 33% women) from the XIENCE 28 trial event-free at 1 month.
From 3 to 12 months, all-cause death or MI occurred in 5.4% of patients in the XIENCE 90 trial and 5.4% in the historical control group. The primary endpoint was met in the XIENCE 90 trial (P for noninferiority = .0063).
From 1 to 6 months, all-cause death or MI occurred in 3.5% of patients in the XIENCE 28 trial and 4.3% in the historical control group. The primary endpoint was also met in this trial (P for noninferiority = .0005).
The secondary endpoint of BARC types 2 to 5 bleeding did not meet superiority in both the XIENCE 90 (P for superiority = .0687) and XIENCE 28 trials (P for superiority = .19). There were trends toward less bleeding in the XIENCE 90 (5.1% vs. 7%) and the XIENCE 28 trial (4.9% vs. 5.9%) compared with the historical control group.
“It is important to note that XIENCE V USA protocol, unfortunately, did not mandate collection of BARC 2 bleeding,” Mehran said during the press conference.
To account for that, researchers also assessed BARC types 3 to 5 bleeding as a non-prespecified analysis. This resulted in a reduction in bleeding in the XIENCE 90 (2.2% vs. 6.3%; P for superiority < .0001) and XIENCE 28 trials (2.2% vs. 4.5%; P for superiority = .0156) compared with the historical control group.
Definite or probable stent thrombosis from 3 to 12 months occurred in 0.2% of patients in the XIENCE 90 trial (2-sided 95% upper CI = 0.63%; P < .0001).
Researchers also assessed stent thrombosis in the XIENCE 28 trial compared with the historical control, although it was not a powered secondary endpoint. From 1 to 6 months, stent thrombosis occurred in 0.3% of patients in the XIENCE 28 trial and 0.3% in the historical control.
“This is an important landmark trial,” Allen Jeremias, MD, director of interventional cardiology research and associate director of the cardiac catheterization laboratory at St. Francis Hospital in Roslyn, New York, said during the discussion at the press conference. “The reason ... is that this is an underserved population. High bleeding risk patients today don’t potentially get the best treatment. Those are difficult patients to treat, and to have more dedicated therapies available for them is important, in particular, because this is also a growing population. As the population ages and it’s a much more complex disease that we now treat, this is actually a common problem. To see that we can shorten DAPT to even 28 days is good news for these patients, and the outcomes are impressive.”
Perspective
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Amar Krishnaswamy, MD
There is significant clinical interest in how we can optimize post-PCI care for patients by minimizing risk and optimizing benefit of medical therapies. An important part of this management is the need for DAPT after stent implantation, most commonly with aspirin and clopidogrel. This dichotomy of risk and benefit is especially profound for those patients who present with high bleeding risk. While prolonged DAPT may be beneficial regarding long-term CV outcomes in some patients, those with high bleeding risk are especially prone to complications of the same. Therefore, minimizing the duration of DAPT is paramount to optimizing short- and long-term outcomes.
In this regard, the XIENCE 90/28 trial provides important outcomes data for high bleeding risk patients who received the durable polymer Xience EES with DAPT limited to either 1 or 3 months. Importantly, in comparison to a historical group of patients receiving the same stent under the XIENCE V protocol of 12-months DAPT, there was no increase in ischemic outcomes (importantly, no numerical increase in stent thrombosis) but a very clear reduction in significant bleeding with both of the shorter DAPT regimens. The data is congruent with other trials that have been recently published supporting 3-month DAPT for high bleeding risk patients using the biodegradable polymer Synergy (Boston Scientific) EES and 1-month DAPT for high bleeding risk patients using the durable polymer Resolute Onyx (Medtronic) zotarolimus-eluting stent.
These latter two stents have FDA approval for these respective shortened DAPT durations; the current data should provide evidence for a similar shorter DAPT indication among high bleeding risk patients for the Xience platform. It should be pointed out that the 3-month DAPT indication for the Synergy is due to the studied duration in the EVOLVE Short DAPT trial of that stent. Conjecturally, it would stand to reason that a 1-month DAPT duration could be equally effective with this stent, as its strut thickness is less than that of the other two stents and its biodegradable polymer (both of which are important considerations for stent thrombosis and restenosis), and future research could be beneficial in that regard.
In summary, XIENCE 90/28 is an important trial for physicians who take care of patients at high bleeding risk and have had a coronary drug-eluting stent implanted, as it provides reassurance with regard to coronary and stent safety outcomes with a shorter DAPT duration to minimize bleeding. Further, as many patients still undergo bare-metal stent implantation due to concerns of long-term bleeding and the desire to minimize DAPT as a result of stent thrombosis risks with prior generation DES, the current trial adds to the foundation of data that there appears to be less and less reason to implant a BMS with the current generation of DES even in high bleeding risk patients.
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Mehran R, et al. Late-Breaking Clinical Science Session II. Presented at: TCT Connect; Oct. 14-18, 2020 (virtual meeting).
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