CHICAGO – Clinicians managing patients who have just received drug-eluting coronary stents need to individualize the duration of the antiplatelet therapy they prescribe and stop thinking that a single length of treatment works best for all patients, based on results from a trio of newly reported trials, as well as earlier study findings.
In general, the new findings seemed to show that following percutaneous coronary intervention (PCI) with a stent, patients with a low risk for stent thrombosis, myocardial infarction, or another type of ischemic event, as well as those with a high bleeding risk, fare best when their duration of dual antiplatelet therapy (DAPT) with aspirin plus a thienopyridine ends after 6 months, while patients with a low bleeding risk and a high risk for an ischemic event will usually do better when their DAPT continues well beyond 12 months, for 30 months and possibly longer.
“We now have results from 35,000 patients in randomized trials that addressed the question of duration of DAPT. We need to make up our minds, and it’s probably an individualized decision,” Dr. Gilles Montalescot said at the American Heart Association Scientific Sessions.
Michel L. Zoler/Frontline Medical News
Dr. Gilles Montalescot
“The patients [in the three newly reported studies] were generally doing well, and so we are operating at the edge of competing risks” they face for ischemia and bleeding. “We need individualization of treatment, but what remains to be determined is, how do we make that decision? Who is more at risk for ischemic events and less at risk for bleeding, and who is more at risk for bleeding and less from ischemia?” commented Dr. Elliott M. Antman, professor of medicine and associate dean for clinical and translational research at Harvard University in Boston.
The DAPT trial
Drug-eluting stent recipients at increased risk for bleeding who are good candidates for a briefer, 6-month duration of DAPT include those with a history of a prior bleed, advanced age, pending need for surgery, patients who need anticoagulation treatment such as those with atrial fibrillation, patients with one or more comorbidities that put them at higher bleeding risk such as gastrointestinal disease or a history of stroke, and patients with a “nuisance” bleed, said Dr. Montalescot, a professor of cardiology at the University of Paris and director of the cardiac care unit at Pitié-Salpêtrière Hospital in Paris.
These conclusions emerged from a surge of new data from three studies presented at the meeting that all addressed DAPT duration following PCI.
Perhaps most noteworthy and anticipated were results from the Dual Antiplatelet Therapy study, a randomized trial that had its beginnings in 2006 when cardiologists first became alarmed by the potential risk from stent thrombosis associated with the use of first-generation DES, specifically the original sirolimus-eluting (Cypher) and paclitaxel-eluting (Taxus) models. At the urging of staffers at the Food and Drug Administration, a group of eight stent manufacturing companies and pharmaceutical companies joined together to sponsor the DAPT study, which started with nearly 23,000 patients who received a DES and, after their first year of DAPT treatment, whittled down to 9,961 patients who were eligible for randomization to either stop DAPT after 1 year or continue on DAPT for an additional 18 months (30 months total time on DAPT).
The results showed that this highly selected group of patients – who went through their first year on DAPT with no bleeding event, no ischemic event, and who were willing to be randomized – those assigned to 30 months of DAPT had a 1% absolute and 71% relative reduction in stent thrombosis, compared with patients who stopped DAPT after 12 months, and a 1.6% absolute and 29% relative reduction in their rate of major cardiovascular or cerebrovascular events, statistically significant differences for the study’s two primary endpoints. The reduction in major events was driven mainly by a 2% absolute reduction in the rate of myocardial infarctions, reported Dr. Laura Mauri at the meeting, and in a report simultaneously published online (N. Engl. J. Med. 2014 [doi:10.1056/NEJMoa1409312]).
Dr. Laura Mauri
Counterbalancing this benefit was a statistically significant excess of moderately severe bleeding events among patients on longer-term DAPT, who had a 0.7% absolute increased rate, and a trend toward increased severe bleeds, with a 0.2% absolute increased rate. Patients on longer-term DAPT also showed an unexpected, 0.5% increased rate of both all cause death and noncardiovascular death. Detailed analysis indicated that this seemed to result from a “chance imbalance” in randomization that put an excess of patients with cancer into the 30-month DAPT subgroup, said Dr. Mauri, professor of medicine at Harvard Medical School and an interventional cardiologist at Brigham and Women’s Hospital, both in Boston.