Ideal Duration of Dual Antiplatelet Therapy May Depend on Stent Type

The optimal duration of dual antiplatelet therapy may depend on the individual stent, with shorter length of treatment preferred with some platforms but not others, according to a subanalysis of the PRODIGY trial published online January 12, 2013, ahead of print in the European Heart Journal.

Specifically, ischemic outcomes were worse with longer dual therapy in patients receiving zotarolimus-eluting (ZES) Endeavor Sprint (Medtronic, Santa Rosa, CA) stents, while patients receiving paclitaxel-eluting (PES) Taxus stents (Boston Scientific, Natick, MA) had less stent thrombosis with longer dual therapy. But patients receiving BMS or everolimus-eluting (EES) Xience V (Abbott Vascular, Santa Clara, CA) stents showed no such differences.

For the main PRODIGY (PROlonging Dual antiplatelet treatment after Grading stent-induced Intimal hyperplasia studY) trial, investigators led by Marco Valgimigli, MD, PhD, of the University of Ferrara (Ferrara, Italy), randomized 2,013 patients with stable CAD or ACS at 3 Italian centers to PCI with ZES, PES, a third-generation thin-strut BMS, or EES. After further randomizing each stent group to receive dual therapy for 6 or 24 months, the researchers found that extending dual antiplatelet therapy beyond 6 months after stenting not only fails to reduce thrombotic events but doubles the risk of major bleeding.

Shorter Dual Therapy Better for ZES

For the subanalysis, Dr. Valgimigli and colleagues assessed device-specific outcomes relative to dual therapy duration.

At 24 months, the primary outcome (death, MI, and stroke) did not differ by length of dual therapy in the BMS (HR 0.89; 95% CI 0.54-1.45; P = 0.64), PES (HR 0.74; 95% CI 0.43-1.25; P = 0.26), or EES (HR 0.63; 95% CI 0.33-1.21; P = 0.17) groups. However, patients receiving ZES showed higher rates with 24-month vs. 6-month dual therapy (table 1).

Table 1. Ischemic Outcomes in ZES Patients with 24-Month vs. 6-Month Dual Therapy

These results were maintained on 6-month landmark analysis of 1,924 patients. Stent thrombosis endpoints were also assessed, showing no differences with regard to stent type and length of dual therapy, with the exception of PES, which showed lower stent thrombosis outcomes in patients receiving 24 months of treatment vs. 6 months (table 2).

Table 2. PES Patients with 24-Month vs. 6-Month Dual Therapy

However, there may have been a lack of power for this analysis, the researchers note.

Using BMS as a reference, ZES, PES, and EES decreased the risk of TLR by 29% (95% CI 12.9-55.5), 63% (95% CI 38.4-87.3), and 69% (95% CI 46.0-93.6), respectively, consistent with the expected stent efficacy profiles from previous research looking at  late loss results for each stent type.

However, the primary endpoint from 6 months onward as well as the 6-month landmark incidence of definite, probable or possible stent thrombosis showed no relationship between duration of dual therapy and actual or expected potency of stent types for inhibition of intimal hyperplasia.

“Our study . . . offers no evidence supporting the association between stent-related late loss and need for prolonged [dual antiplatelet therapy],” the authors conclude. “On the contrary, the results of our explorative yet prespecified analysis suggest that the minimal [dual therapy] duration may be stent-specific and not clearly related to stent potency towards inhibition of intimal hyperplasia.”

Current Guidelines ‘Without Sound Basis’

In a telephone interview with TCTMD, David E. Kandzari, MD, of the Piedmont Heart Institute (Atlanta, GA), called the study “one more piece of the puzzle that contributes to a revised clinical notion that our existing guidelines recommending at least 1 year of antiplatelet therapy and the clinical perception among some clinicians that a DES confers a lifetime commitment to dual therapy are really without a sound basis.”

He added that the overall PRODIGY trial is one of several studies starting to shift opinions in the clinical community toward favoring 6 vs. 12 months of dual therapy after DES implantation. “The reality is it’s probably not just a story around dual antiplatelet therapy alone,” Dr. Kandzari said. “It’s probably better patient selection, better technique, better appropriate coverage of the lesion, stent apposition, expansion, things like that as well [that are producing better outcomes with shorter therapy duration].”

In addition, the stent-based analysis confirms observations made previously in trials such as RESET that shorter dual therapy duration is beneficial with ZES.

“I’ve always firmly believed it would be an oversimplification for us to consider all DES equal,” Dr. Kandzari said. “As clinical trialists, we’ve known that there are differences between drug-eluting stents in designing trials and picking comparator stents that had higher late loss, or higher TLR, or maybe a difference in safety signals, so that’s been a little bit of an unaddressed issue in interventional cardiology.”

He added that “there are different drugs and polymers and there might be different biological reactions to these different products,” making it likely that “not only would efficacy outcomes be different, but safety outcomes might be as well.”

 

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Source:
Valgimigli M, Borghesi M, Tebaldi M, et al. Should duration of dual antiplatelet therapy depend on the type and/or potency of implanted stent? A prespecified analysis from the PROlonging Dual antiplatelet treatment after Grading stent-induced Intimal hyperplasia studY (PRODIGY). Eur Heart J. 2013;Epub ahead of print.

 

Disclosures:

• Dr. Valgimigli reports receiving honoraria for lectures and advisory board services and/or research grants from Abbott Vascular, CID, Cordis, Daiichi Sankyo, Eli Lilly, Iroko, Medtronic, Merck, St. Jude, Terumo, and The Medicines Company.  
• Dr. Kandzari reports no relevant conflicts of interest.

 

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