Early stent thrombosis may be the deadliest among the ischemic and hemorrhagic events that can occur after getting a drug-eluting stent (DES), the ADAPT-DES study suggests. All-cause mortality at 2 years was most common in patients with stent thrombosis (27.2% versus 2.7% for those with no events, hazard ratio [HR] 11.37, 95% CI 7.61-16.98), Sorin J. Brener, MD, of New York Methodist Hospital in New York City, and colleagues found. Stent thrombosis occurring early, within 30 days in particular, was strongly associated, having a 38.5% mortality rate, the group reported online in JACC: Cardiovascular Interventions. Next most strongly associated with subsequent death were very late myocardial infarction (MI occurring after 1 year, 7.5% mortality) and late major bleeding (occurring between 1 month and 1 year, 7.3%). Exactly why early stent thrombosis is more likely to result in death than later stent thrombosis is hard to pin down, according to the authors. Advocating caution with the data was Donald E. Cutlip, MD, of Beth Israel Deaconess Medical Center in Boston, who warned against “complacency about the serious consequences of late and very late stent thrombosis.” In an accompanying editorial, he cited the 30-day mortality of very late stent thrombosis (20.0%) that was still nearly three-fold higher than that with spontaneous MI or clinically-relevant bleeding at any time point. In this context, percutaneous coronary intervention (PCI) safety seems to be a matter of optimal dual antiplatelet therapy (DAPT) duration, he suggested. “Personalized therapy that prolongs DAPT for patients at higher risk for stent thrombosis or MI and limits DAPT for patients at higher risk for bleeding might improve outcomes overall,” Cutlip wrote. The editorialist concluded: “Current DAPT regimens with mostly newer generation DES have lowered the risk of stent thrombosis, but it remains the most serious consequence of stenting and all efforts must be made to avoid any strategy or technology that might increase this risk, especially in the first 30 days.” “Beyond 30 days, MI and clinically relevant bleeding are equally important complications. To the extent that patients can be identified who have higher risk for one or the other, the goal should be a move away from dogmatic DAPT strategies toward adapting DAPT for personalized care and improved overall outcomes.” Brener’s study included 8,582 patients from the prospective ADAPT-DES study, 12.4% of whom had an event after successful DES placement. Patients were divided into those who had clinically-relevant bleeding (8.1%), MI (3.4%), stent thrombosis (0.9%), or no event (87.6%). As with stent thrombosis, MI and major bleeding were associated with 2-year mortality at all time points: an almost doubling of odds with MI (HR 1.84, 95% CI 1.24-2.72), and more than double with clinically relevant bleeding (HR 2.43, 95% CI 1.86-3.18). “Thus, one in eight patients successfully undergoing PCI with DES suffers clinically relevant bleeding, myocardial infarction, or stent thrombosis during the ensuing 2 years, which lead to increased mortality,” the investigators found. “These data provide additional impetus to further attempt to eliminate early stent thrombosis by improving PCI technique and using adequate antithrombotic therapy and [preventing] progression of coronary artery disease and plaque rupture with aggressive risk factor modification,” they concluded. Limitations of the study included that “significant bleeding in this analysis was based on site reporting, without independent adjudication, and included a rather broad range of events, albeit in tune with the recent efforts to standardize bleeding definitions,” Brener and colleagues acknowledged. In addition, “ADAPT-DES included a population of patients who had successful PCI with DES, and thus, may not represent the entire universe of PCI patients.” “Additional studies are needed to confirm the improved outcome resulting from prevention of both early stent thrombosis and late spontaneous MI in patients with prior PCI,” they wrote. Disclosures Brener reported no relevant conflicts of interest. Several co-authors declared relationships with industry. Cutlip disclosed receiving institutional contract funding from Medtronic, Boston Scientific, and Celonova.