DAPT: Thrombosis Reduced, Bleeding Increased in Everolimus-Eluting Stent Patients

Deborah Brauser

October 14, 2015

SAN FRANCISCO, CA — Continued use of dual antiplatelet therapy (DAPT) with aspirin and a thienopyridine beyond 1 year may reduce stent thrombosis and MI risk but increase bleeding in patients treated with an everolimus-eluting stent (EES) after an ischemic event, suggests new research[1].

Additional analyses from the DAPT trial of a subset of 4703 EES-treated patients showed similar results as the original study with a broader range of stents: those randomly assigned to 18 more months of a thienopyridine plus aspirin (or 30 months total of DAPT) had significantly reduced thrombosis (P=0.04) and MI (P=0.01) compared with those who received placebo plus aspirin after their initial 12 months of DAPT.

However, the continuous-DAPT group also had more moderate and severe bleeding complications (P=0.01).

The results were presented here at TCT 2015 by Dr James B Hermiller Jr (St Vincent Heart Center, Indianapolis, IN) and simultaneously published in JACC: Cardiovascular Interventions.

"I think the major issue is how to balance the bleeding risk, especially because this wasn't a high-risk bleeding group," session comoderator Dr Spencer B King (Emory University, Atlanta, GA) later told heartwire from Medscape, noting that EES has been shown before to have a very low thrombosis rate.

"The main message of all the work on antiplatelet therapy after stenting has to do with trying to find, for the specific patient, a balance between bleeding and thrombosis. And it's different for every patient," said King, who is also editor-in-chief of JACC: Cardiovascular Interventions.

Continuous DAPT Use

The original open-label DAPT study included 25,682 US patients, all of whom received a thienopyridine plus aspirin after receiving a drug-eluting stent (DES) or bare-metal stent. In the DES cohort (which included everolimus-, paclitaxel-, sirolimus-, or zotarolimus-eluting stents) patients had significantly reduced stent thrombosis (hazard ratio [HR] 0.29, P<0.001) and major adverse cardiac or cerebrovascular events ([MACCE] HR 0.71, P<0.001), with increased moderate or severe bleeding (HR 1.61, P=0.001).

Of these participants, 11,308 received an EES. The current ad hoc analysis included the EES patients who were free from MI, stroke, repeat revascularization, and bleeding complications at 12 months. A total of 2345 (75.6% men) were randomly assigned to continue with DAPT for an additional year and a half, while the remaining 2358 (75.8% men) were assigned to placebo plus aspirin during the same time period.

"Assessments of randomized treatment-by-DES type interactions . . . were prespecified to assess consistency of randomized treatment effect across DES types," said Hermiller.

A total of 0.3% of the 30-month/continuous-DAPT group had stent thrombosis vs 0.7% of the 12-month-only group (HR 0.38); 2.11% vs 3.2%, respectively, had an MI (HR 0.63); and 2.5% vs 1.3% had increased bleeding (HR 1.79).

Interestingly, the continuous-use group also had significantly increased all-cause mortality (2.2% vs 1.1%, P=0.02). However, Hermiller reported that this was related to the high number of cancer-related deaths. At the start of the continued-treatment analysis, 10.8% of the continued-thienopyridine group and 10.7% of the placebo group had a history of cancer, which was significantly higher than the 8.7% rate for those receiving other types of drug-eluting stents (P<0.001).

There was no between-group difference for the composite end point of death, MI, or stroke (4.3% vs 4.5%, respectively) or for CV death (1.0% vs 0.8%).

Secondary Prevention?

After the presentation, session moderator King noted that "it's important to know what's going on" with this type of second-generation stent. "What's the message when you're using the most modern stent? What's the recommendation, given this data, for the physician selecting therapy for his or her patient? Should DAPT be given year-to-year, do you keep it going, or do you stop?"

Hermiller answered that with EES, although the risk of MIs and thrombosis is decreased, "the price to be paid is that some people will have bleeding complications." So, it comes down to finding patients who are at high risk for ischemic events but not for bleeding, such as those with ACS and potentially those with diabetes, he said.

"I think that prolonged DAPT becomes really a secondary preventive strategy more than a strategy to treat the stent."

Hermiller noted that additional analysis is scheduled to be presented at a late-breaking clinical trial at the upcoming American Heart Association Scientific Sessions, "including a way to discern who it is you might pick out for long-term DAPT."

"There's no free lunch," King later told heartwire . "If you poison the platelet, you increase bleeding; and if you leave the platelet to do its thing, it will have more thrombosis. We keep struggling for a personalized approach for every patient.

"Since we have a stent with very low stent thrombosis, you probably don't need treatment for 2.5 years and maybe not even a year. Can you use other new stents that will cut that time even shorter? And will that make a difference? We don't know yet," he said.

"But it's quite likely that what we're really talking about here, as Dr Hermiller emphasized, is secondary prevention," added King.

The study was funded by Abbott, Boston Scientific, Cordis, Medtronic, Bristol-Myers Squibb Company/Sanofi Pharmaceutical Partnership, Eli Lilly, Daiichi Sankyo, and the US Department of Health and Human Services. Hermiller reported being a consultant for Abbott Vascular, Boston Scientific, Medtronic, and St Jude Medical. Disclosures for the coauthors are listed in the paper.

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