乌鸦传媒

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SAN FRANCISCO -- People may have several stent options once it's been decided that they should undergo a shorter period of dual antiplatelet therapy (DAPT) after percutaneous coronary intervention (PCI), several studies suggested.

Whereas the headlining TWILIGHT trial showed the safety of taking away the aspirin component of DAPT, these studies presented the feasibility of several stent-DAPT timing combinations at the (TCT) meeting.

"I think we're going to see a number of trials beyond this with shorter durations of DAPT. We may see more trials now trying to whittle that 3 month period back down to a 1 month but we're going to need to see that it won't be at the expense of ischemia in these patients," B. Hadley Wilson, MD, of Sanger Heart & Vascular Institute in Charlotte, North Carolina, commented to 乌鸦传媒.

IDEAL-LM

In PCI for left main disease, the Synergy bioabsorbable-polymer drug-eluting stent (DES) worked with a shorter duration of DAPT to leave patients no worse off than a durable stent and 12 months of DAPT, although some suggested the researchers might have been too generous with the non-inferiority margin.

Major adverse cardiac events at 2 years -- death from any cause, MI, and ischemia-driven target vessel revascularization -- occurred in 14.6% of patients with Synergy and 4 months DAPT compared to 11.4% with Xience and 12 months DAPT (P=0.17) in the 818-person trial.

Thus, the experimental short-DAPT arm was deemed non-inferior to controls under a a margin of 7.5%, reported Robert Jan van Geuns, MD, PhD, of Erasmus Medical Center in Rotterdam, the Netherlands.

Such a relatively large non-inferiority margin was a point of contention among TCT press conference panelists, however.

"This does not provide very reassuring information where MI [6.0% for Synergy vs 3.5% for Xience, P=0.13], stent thrombosis [2.7% vs 1.3%, P=0.21] are doubled in one stent versus the other," commented Marco Valgimigli, MD, PhD, of Inselspital, Universitätsspital Bern, Switzerland.

"I think you need to be really careful on the interpretation. I think this is a classic case of type 2 error, where the failure to observe a difference is not the same as there not being a difference," said Robert Harrington, MD, of Stanford University in California and president of the American Heart Association.

"I think you should conclude that this is worrisome and more data are needed," Harrington said.

Additionally, there was the "absolutely" surprising finding that BARC 3 or 5 bleeding rates actually favored Xience and longer DAPT (2.7% vs 0.5%, P=0.02), though Van Geuns cautioned that this endpoint was not powered for a hard-and-fast interpretation and may have been due to chance.

IDEAL-LM participants were age 66.4 years on average, and 79.6% men. Nearly all had been eligible for surgery but received PCI instead for reasons such as a low SYNTAX score and certain comorbidities.

EVOLVE

The Synergy stent was separately tested with 3 months of DAPT and found to produce favorable outcomes in another group -- patients at high bleeding risk.

In the single-arm study, death and MI occurred in 5.8% of patients between DAPT cessation at 3 months and 15-month follow-up, a period when patients were only taking aspirin, reported Ajay Kirtane, MD, of Columbia University Medical Center/NewYork-Presbyterian Hospital in New York City.

After propensity-adjustment, Synergy was non-inferior for that endpoint against historical controls getting 12 months of DAPT in three other studies of people at high bleeding risk getting "-limus" drug-eluting stents (5.6% vs 5.7%, P=0.0016 for non-inferiority under a 2.52% margin).

The stent thrombosis rate with Synergy was 0.3%. The BARC 2/3/5 bleeding rate of 7.1% was no different than had been reported in the DAPT Study with 12 months of DAPT (6.26% vs 4.17%).

"These data support the use of Synergy with a 3-month duration of DAPT in HBR [high-bleeding risk] patients," Kirtane concluded.

EVOLVE participants totaled 1,487 people who all met at least one criterion for high bleeding risk. The average age was 75.7, and men comprised two-thirds of the group.

Overall, generalizability was limited by the limited lesion complexity and population without MI, Kirtane acknowledged.

It could also be debated whether study participants were truly at high bleeding risk given the bleeding rates were roughly half of what was observed in LEADERS FREE, commented Davide Capodanno, MD, PhD, of the University of Catania, Italy.

MODEL U-SES

Another bioresorbable-polymer DES showed positive results with 3 months of DAPT in Japan.

The number of patients experiencing ischemic or bleeding events at 12 months reached 4.3% among nearly 1,700 patients who received the Ultimaster sirolimus-eluting stent and stopped aspirin or P2Y12 inhibition therapy 3 months later.

This composite all-cause death, MI, stroke, stent thrombosis, BARC 3/5 bleeding rate met non-inferiority in a comparison with historical controls from CENTURY II (5.7%, P<0.0001 for non-inferiority), reported Ken Kozuma, MD, of Teikyo University Hospital in Tokyo.

An adjusted landmark analysis showed the same 2.5% event rate after 90 days between patients who went on with aspirin monotherapy and others who kept just the P2Y12 inhibitor (most commonly 3.75-mg prasugrel [Effient]).

This is the "most interesting" part, because not so many studies compare these two head-to-head, suggesting maybe we need to understand more about P2Y12 versus Cox-1 pathways, commented Capodanno during the TCT press briefing for the late-breaking clinical trial session.

Panelists were also struck by Kozuma's revelation that the decision to quit aspirin or P2Y12 inhibition was not so much a decision, but a matter of reimbursement: some Japanese districts couldn't be paid for prescribing P2Y12 inhibitor monotherapy, so hospitals would keep their patients on aspirin instead.

This suggests there's "probably less bias" in the analysis because it was not a decision made at the individual level, mimicking cluster randomization, Harrington said. "It lends some more credence, or reduces the risk of bias."

"It looks like it's not just the U.S. that has issues paying for drugs," quipped Ori Ben-Yehuda, MD, of NewYork-Presbyterian/Columbia University Medical Center and the Cardiovascular Research Foundation in New York City.

People included in the single-arm study had a mean age of 69.7 years. Over three-quarters were men. Nearly half were stented for stable coronary artery disease.

Onyx ONE

Finally, a randomized trial in patients at high bleeding risk found that DAPT could be brought down to 1 month with a durable-polymer DES, the Resolute Onyx, with outcomes matching those with a polymer-free drug-coated stent.

PCI was followed by 1 month of DAPT for the nearly 2,000 people randomly assigned to the Resolute Onyx and BioFreedom stents in the Onyx ONE trial.

Cardiac death, MI, or stent thrombosis at 12 months was ultimately similar between Resolute Onyx and BioFreedom (17.1% vs 16.9%, P=0.11 for non-inferiority under a 4.1% margin), according to Stephan Windecker, MD, of Bern University Hospital in Switzerland.

Rather than concluding that 1 month is the optimal duration of DAPT, it's better to interpret this as the Onyx stent being a viable option once the clinician has decided 1 month is the way to go, Valgimigli commented.

Landmark analysis showed that after DAPT discontinuation, the BioFreedom group was at greater risk of MI from 1 to 12 months (6.8% vs 4.3%, P=0.01).

Trial participants had an average age of 74; about one-third were women. Over half presented with acute coronary syndrome.

Crossover was more frequent with the BioFreedom arm (4.0% vs 0.2%).