DAPT Trial: Extended Post-PCI Dual Antiplatelet Therapy Best in Patients With, Without ACS

Marlene Busko

March 24, 2015

SAN DIEGO, CA — Compared with stopping dual antiplatelet therapy (DAPT) at 12 months, extending therapy to 30 months reduced the risk of stent thrombosis and MI but also increased the risk of mild to moderate bleeding in patients who had a coronary stent implanted—whether this followed an initial MI or stable angina—in a new study[1].

Thus, "continuation of dual antiplatelet therapy for 30 months should be strongly considered in both ACS and non-ACS patients who have tolerated 1 year of treatment," Dr Robert W Yeh (Massachusetts General Hospital, Boston) summarized, presenting this analysis from the Dual Antiplatelet Therapy (DAPT) study at a featured clinical-research session here at the American College of Cardiology 2015 Scientific Sessions. The study was simultaneously published in the Journal of the American College of Cardiology.

"I am certainly strongly considering placing patients on continued dual antiplatelet therapy at 1 year; if they've taken that first year of therapy without any evidence of bleeding complications and there are no reasons to anticipate problems. . . . I would continue treating these patients [with dual therapy], whether or not they had been treated initially for ACS," Yeh said.

"After 1 year, if someone's tolerating dual antiplatelet therapy, it seems like there is greater benefit and less risk [to continue] . . . and ACS by itself is a marker of a higher-risk patient, despite a younger age and a lower burden of comorbidities," session comoderator Dr John D Carroll (University of Colorado, Denver) noted, in a comment to heartwire from Medscape. "The push is going to be individualizing therapy and modifying it as you go on, if patients have either ischemic or bleeding events."

Do Stented MI Patients Benefit More From DAPT?

As previously reported by heartwire , DAPT compared continuing thienopyridine therapy for 30 months as opposed to stopping it after 12 months in patients who were already taking aspirin after coronary stenting. About two-thirds of the study patients had received clopidogrel, and one-third had received prasugrel (Effient, Lilly/Daiichi-Sankyo). Patients who had ischemia or bleeding during the first 12 months were excluded from the 12–30-month study.

The co–primary end points were stent thrombosis and major adverse cardiovascular or cerebrovascular events (MACCE), a composite of death, MI, or stroke. The primary safety end point was GUSTO moderate or severe bleeding.

Yeh and colleagues hypothesized that patients who presented with an initial MI might derive greater benefit from continued dual antiplatelet therapy, since they were at greater risk of stent thrombosis and subsequent MI.

A total of 3576 patients (30.7%) had presented with an MI, and they were randomized to thienopyridine or placebo, both with aspirin; the 8072 patients without an initial MI were similarly randomized to a second antiplatelet agent or placebo.

Patients with an initial MI were younger (mean age 57.8 vs 62.9), more likely to be men, and smoke;they were less likely to have type 2 diabetes or hypertension. About half had presented with non-STEMI (53%) and the rest had STEMI (46.9%).

Most patients (86%) had received a sirolimus-eluting stent (Cypher, Cordis), zotarolimus-eluting stent (Endeavor, Medtronic), paclitaxel-eluting stent (T axus, Boston Scientific), or everolimus-eluting stent (Xience, Abbott Vascular or Promus, Boston Scientific), and the rest (14%) had received a bare-metal stent. The patients received an average of 1.5 stents.

The relative reduction of stent thrombosis associated with continued clopidogrel or prasugrel use was similar for patients with and without an initial MI, but dual antiplatelet therapy was associated with a greater reduction of MACCE in patients with an initial MI. Continued thienopyridine use was associated with reduced MI but increased bleeding.

Outcomes at 12 to 30 Months After Stent Implantation

Outcome, initial presentation DAPT group (%) Placebo group (%) HR (95%CI) P
Stent thrombosis
MI 0.5 1.9 0.27(0.13–0.57) <0.001
No MI 0.4 1.1 0.33 (0.18– 0.60) <0.001
MACCE
MI 3.9 6.8 0.56 (0.42–0.76) <0.001
No MI 4.4 5.3 0.83 (0.68– 1.02) 0.08
Bleeding*
MI 1.9 0.8 2.38 (1.27– 4.43) 0.005
No MI 2.6 1.7 1.53 (1.12– 2.08) 0.007
MI
MI 2.2 5.2 0.42 (0.29– 0.62) <0.001
No MI 2.1 3.5 0.60 (0.45– 0.79) <0.001
Death
MI 1.4 1.6 0.87 (0.50– 1.50) 0.61
No MI 2.1 1.5 1.43 (1.02–2.00) 0.04
*Bleeding=moderate to severe GUSTO bleeding
MACCE=major adverse cardiovascular or cerebrovascular events (the composite of death, MI, or stroke)

"Continued thienopyridine therapy over an 18-month treatment period was associated with an absolute risk reduction of 2.9% for myocardial infarction and 1.4% for stent thrombosis and an absolute risk increase of 1.1% for moderate or severe bleeding . . . among patients with MI," Yeh and colleagues summarize.

Since other studies have shown that ischemic events have a greater impact on quality of life than mild or moderate bleeding events, "our results suggest that among acute-MI patients undergoing PCI, there is a strong benefit for continuing thienopyridine therapy beyond 12 months after presentation . . . [and] even among patients without MI . . . [among patients] able to tolerate the first year of dual antiplatelet therapy," they add. The benefits appeared to be similar with clopidogrel or prasugrel and paclitaxel- or non–paclitaxel-eluting stents.

"We have an [National Institutes of Health] NIH grant to develop a clinical tool that might help identify patients for whom it's exceedingly necessary to continue [the dual antiplatelet therapy] and the population of patients for whom it would be safer to discontinue," Yeh said.

The study was sponsored by Harvard Clinical Research Institute and funded by Abbott, Boston Scientific, Cordis, Medtronic, Bristol-Myers Squibb/Sanofi Pharmaceuticals Partnership, Eli Lilly, Daiichi Sankyo, and the US Department of Health and Human Services. Dr Yeh is on the advisory board of Abbott Vascular and received consulting fees from Gilead Sciences and Merck. Disclosures for the coauthors are listed in the article.

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