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Dual Antiplatelet Therapy for 12 or 30 Months After Drug-Eluting StentsThe DAPT Study

BackgroundStudies suggesting an increased risk of stent thrombosis with drug-eluting stent (DES) prompted the US Food and Drug Administration (FDA) to convene a meeting of its Circulatory System Device Advisory Panel in December 2006, to examine DES safety.

Cessation of DAPT with Aspirin and Thienopyridine is associated with an increased risk of stent thrombosis.

BackgroundThe American College of Cardiology & The American Heart Association guidelines recommend 12 months of DAPT after DES. The European Society of Cardiology recommends DAPT for 6 months or less following DES.

The FDA requested a trial to evaluate the optimal duration of DAPT.

BackgroundThe DAPT study was performed through a private-public collaboration involving the FDA, stent and pharmaceutical manufacturers, and Harvard Clinical Research Institute.

MethodsProspective, international (11 countries), multicenter (452 sites), randomized, double-blind trial

Subjects: Adults (> 18 yrs.) enrolled within 72 hours of stent placement and prescribed 12 months of open-label Thienopyridine plus aspirin

MethodsEligibility: Patients without major adverse cardiovascular and cerebrovascular events (MACCE), repeat revascularization, or moderate/severe bleeding demonstrating adherence to Thienopyridine during the 12 month open label period

Excluded: Warfarin or similar anticoagulant, planned surgery requiring antiplatelet discontinuation, having both DES and bare-metal stent (BMS) during index procedure, stent diameter 4.0mm

Note: Patient who received BMS were not included in this analysis

MethodsPatients were randomly assigned 1:1Continued Clopidogrel 75mg daily or Prasugrel 10mg daily for 18 months (n=5020)Placebo for 18 months (n=4941)

All patients continued Aspirin 75-162mg daily

Primary efficacy endpointsCumulative incidence of definite or probable stent thrombosisMACCE (composite of death, myocardial infarction or stroke)

MethodsPrimary safety endpointModerate or severe bleedingAfter the 30 month randomization treatment period ended, patients continued taking Aspirin alone and were followed for a 3 month observation

DAPT Study Flow

Figure 1: Enrolment, Randomization, and Follow-up. Patients were enrolled within 72 hours after stent placement. They were followed for 12 months while they received open-label treatment with Thienopyridine plus aspirin and were then randomly assigned to receive Thienopyridine therapy or placebo (each in addition to aspirin) for an additional 18 months. The randomized treatment period ended at 30 months; thereafter, patients continued taking aspirin only and were followed for another 3 months. Although the number of patients with available data on clinical follow-up is reported in each group, the co-primary efficacy end points were analysed with the last available follow-up information in the intention-to-treat population, which included all patients who underwent randomization. GUSTO denotes Global Utilization of Streptokinase and Tissue Plasminogen Activator for Occluded Arteries.

Drugs and DES Types at RandomizationThienopyridine (n=5020)Placebo(n=4941)Thienopyridine (%):

ClopidogrelPrasugrel65.234.865.434.6DES Type (%):

Xienca/Promus (Everolimus)TAXUS (Paclitaxel)Endeavor (Zotarolimus)Cypher (Sirolimus)>1 type46.726.912.811.52.147.726.612.610.92.1

Primary Efficacy Endpoints

Bleeding End Point during Month 12 to Month 30.

Stent Thrombosis & MACCEGroups+_TotalIncidencePlacebo6654276494113.46%Thienopyridine464455650209.24%Total112988329961

Risk with placebo treatment = 0.13Risk with Thienopyridine = 0.09Absolute Reduction Risk = 0.04Number Needed To Treat = 25- for every 25 patients treated 1 patient will see a benefitRelative Risk = 0.69- RR1 therefore the event is more likely to occur in the Thienopyridine group than in the placebo groupRelative Risk Reduction = - 0.6- there is an approximately 60% increase risk of bleeding in the Thienopyridine group as opposed to the placebo group

Groups+_TotalIncidencePlacebo210443946490.05%Thienopyridine382432847100.08%Total59287679359

Efficacy Outcomes at 12-33 MonthsThienopyridine (n=5020)Placebo(n=4941)Stratified Hazard RatioStratified log-rank P valueStent Thrombosis (%):

Definite Probable0.7

0.60.11.4

1.30.20.45

0.420.85