DAPT Interruption At Least 1 Month After ZES Implantation Appears Safe
Interruption of dual antiplatelet therapy (DAPT) in patients with second-generation zotarolimus-eluting stents (ZES) is unlikely to lead to stent thrombosis as long as it occurs at least 1 month after implantation, according to a retrospective study published online February 7, 2014, ahead of print in the European Heart Journal. However, earlier interruption is associated with a high risk of adverse events.
Researchers led by Sigmund Silber, MD, of the Heart Center at the Isar (Munich, Germany), reviewed data pooled from 4 trials totaling 4,896 patients with chronic stable CAD or ACS implanted with the Resolute ZES (Medtronic, Minneapolis, MN). Patients were split into 3 groups based on DAPT usage through 12 months:
- No interruption (n = 3,827)
- Interruption within 1 month (n = 166)
- Interruption from months 1 to 12 (n = 903; 60% of which were interrupted after 6 months)
Overall, 39 cases of stent thrombosis were reported with 82.1% of events occurring when patients were on DAPT and 17.9% when patients were off DAPT. There were 29 cases of early events (within the first 30 days; 25 on DAPT and 4 off DAPT) and 10 cases of late stent thrombosis (7 on DAPT and 3 off DAPT).
There were 6 (3.61%) stent thrombosis events among patients who interrupted DAPT within 1 month and 1 (0.11%) event among those who interrupted therapy between months 1 and 12; Kaplan-Meier estimates showed a higher cumulative incidence in the former at 1 year (log-rank P < 0.001). Patients with no DAPT interruption reported 32 events (0.84%).
Rates of cardiac death and target vessel MI were 6.84% in those who interrupted DAPT for longer than 14 days within 1 month, 1.41% in those with such interruptions between 1 and 12 months, and 4.08% in patients with no interruptions. Among the 2,309 patients with bleeding data available, there were 34 bleeding events (1.79%) in patients with continuous DAPT (n = 1,896); no patient with a DAPT interruption within the first month reported any bleeding, while 2 bleeding events (0.56%) occurred in patients with a DAPT interruption from 1 to 12 months.
Guideline Changes Not Justified
Dr. Silber and colleagues outline the current DAPT recommendations for DES: 6-months minimum in Europe and 12 months in the United States, although newer guidelines for STEMI (12 months and a strict minimum of 6 months in high-risk patients) and ACS (12 months irrespective of stent type) differ.
Although it would be inappropriate to suggest any changes in the current guidelines, the authors say this analysis “may provide reassurance for clinicians and patients implanted with an R-ZES who may need to interrupt or discontinue the medications before the recommended duration for a variety of unplanned reasons.” They add that “[r]andomized clinical trials are needed to determine whether early temporary or permanent interruption of DAPT is truly safe.”
Lends Clinical Equipoise
Study coauthor Ajay J. Kirtane, MD, SM, of Columbia University Medical Center (New York, NY), told TCTMD in a telephone interview that the study showed “that if a patient discontinued early, there did not appear to be a penalty paid. That’s reassuring because one is led to believe that if a patient discontinues dual antiplatelet therapy before 12 months, that patient is at extraordinarily high risk of stent thrombosis.”
Several studies have now demonstrated that in many cases 6 or even 3 months of therapy are adequate, he observed. However, “because [the current study] is not randomized, this should not give clinicians comfort enough to liberally discontinue patients from dual antiplatelet therapy at less than 6 months,” Dr. Kirtane cautioned.
“The way I look at it, from a clinician’s standpoint, is that [formerly] if someone came to my office and said they had stopped dual antiplatelet therapy 2 or 4 months in, [I would have told] them to go directly to their pharmacy and resume,” he explained. “Now, it gives us a little bit of equipoise in terms of whether patients ought to resume if they happened to have stopped.”
Although similar analyses have been published with everolimus-eluting stents, the data cannot be “generalized across all second-generation stents because that term can be used somewhat liberally,” Dr. Kirtane added. “So you need to see data with individual stents to feel secure. This really requires adequately sized trials, which are currently being proposed.”
ACS Still Needs a Year
Deepak L. Bhatt, MD, MPH, of Brigham and Women’s Hospital (Boston, MA), told TCTMD in a telephone interview that “the results are in keeping with all the data that seem to be coming out about second-generation drug-eluting stents both from randomized clinical trials and registries that show a fairly low rate of stent thrombosis compared with first-generation drug-eluting stents, or even compared, it seems, with bare metal stents.”
In his practice, he said, “if I have to stop [DAPT] at a month or interrupt at a month, for some good reason, I would still try to avoid it. But after that first month if there was surgery where DAPT absolutely had to be stopped, these data are reassuring.”
Still, “if possible it’s better to go longer with DAPT in accordance with the guidelines, in particular with patients who have acute coronary syndromes as the underlying cause of their stenting,” Dr. Bhatt commented. “There’s good data to support longer durations of dual antiplatelet therapy up to a year just for the ACS, not for the stent per se.”
Among patients with a classifiable reason for DAPT interruption, temporary DAPT interruption was usually prior to a medical/dental/surgical procedure (42.2%) or for another clinical indication (12.8%), whereas permanent discontinuation most often occurred because patients completed their prescribed course (46.0%). Stent thrombosis events were evenly distributed across the different reasons for DAPT interruption.
Roughly one-third of patients had diabetes and about 40% had ACS. Patients with a DAPT interruption in the first month were older and had lower LVEF.
Note: Study coauthor Dr. Kirtane is a faculty member of the Cardiovascular Research Foundation, which owns and operates TCTMD.
Silber S, Kirtane AJ, Belardi JA, et al. Lack of association between dual antiplatelet therapy use and stent thrombosis between 1 and 12 months following Resolute zotarolimus-eluting stent implantation. Eur Heart J. 2014;Epub ahead of print.
- The study was funded by Medtronic.
- Dr. Silber reports receiving grant, travel, and analysis support from Medtronic.
- Dr. Kirtane reports participating in studies through his institution, which receives institutional research support from Abbott Vascular, Abiomed, Boston Scientific, Medtronic, and St. Jude Medical.
- Dr. Bhatt reports receiving research grants from Amarin, AstraZeneca, Bristol-Myers Squibb, Eisai, Ethicon, Medtronic, Roche, Sanofi Aventis, and The Medicines Company.