Ask you cardiologist about the PRODIGY Trial? Basically 6 months of Aspirin and Plavix as good as 2 years with less bleeding. The trial is yet to be published, but this will be a big change in cardiology.
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www.cardiosource.com
Trial Summary PRODIGY
Title:
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PROlonging Dual antiplatelet treatment after Grading stent-induced Intimal hyperplasia studY
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Trial Sponsor:
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University of Ferrara (Italy)
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Year Presented:
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2011
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Topic(s):
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General Cardiology, Interventional Cardiology, Prevention/Vascular
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Summary Posted:
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08/30/2011
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Description:
Current guidelines recommend that dual antiplatelet therapy (DAPT) with aspirin and a thienopyridine be continued for a minimum of 12 months following drug-eluting stent (DES) percutaneous coronary intervention (PCI). This recommendation comes from data from numerous observational studies suggesting that early DAPT discontinuation is associated with an increased risk of stent thrombosis. However, randomized controlled data to support this recommendation are lacking. Accordingly, the PRODIGY investigators sought to study if 24 months of DAPT is superior to 6 months of DAPT in all-comers undergoing PCI with both DES and bare-metal stents (BMS).
Hypothesis:
A 24-month duration of aspirin and clopidogrel would be superior to a short course of up to 6 months of aspirin and clopidogrel therapy.
Drugs/Procedures Used:
Patients were randomized in a 1:1:1:1 balanced randomization to receive either Xience V (zotarolimus-eluting stent), Taxus (paclitaxel-eluting stent), Endeavor (everolimus-eluting stent), or BMS, and then further randomized 30 days thereafter to either a short duration of DAPT (≤6 months) or prolonged duration (24 months). Duration <6 months was acceptable in patients with stable coronary artery disease (CAD) undergoing BMS PCI.
Principal Findings:
A total of 2,013 patients were randomized to the four stents, of which 1,970 were then randomized to short DAPT (n = 983) or prolonged DAPT (n = 987) after 1 month. Baseline characteristics were fairly similar between the two arms. About 25% had diabetes mellitus, 4% had history of prior stroke, 26% had prior myocardial infarction (MI), and 18% had undergone prior PCI. Presentation was ST-segment elevation MI (STEMI) in 33%, non-STEMI in 23%, and unstable angina in about 19% of the patients (acute coronary syndrome total 75%).
Multivessel CAD was noted in 66%; 38% underwent multivessel PCI. Left anterior descending artery PCI was performed in 53% of the patients, and left main trunk in 6%. The mean number of treated lesions was 1.5, with a total stent length of about 30 mm per patient. Per randomization, 75% were treated with DES (50% with so-called “second-generation DES”) and 25% with BMS. About 83.1% were on DAPT at 6 months in the short DAPT arm (all discontinuations were in BMS patients) and 98.8% in the prolonged DAPT arm; at 2 years, the respective numbers were 0.3% and 94.7% (p < 0.0001 for all time points).
The primary endpoint of death/MI/cerebrovascular accident (CVA) was similar between the short duration and prolonged duration arms over 720 days of follow-up (10.0% vs. 10.1%, hazard ratio [HR] 0.98, 95% confidence interval [CI] 0.74-1.29; p = 0.91). Individual endpoints including all-cause mortality (6.6% vs. 6.6%, p = 0.98), death or MI (9.6% vs. 8.9%, p = 0.62), cardiovascular (CV) death (3.8% vs. 3.7%, p = 0.98), and CVA (1.4% vs. 2.1%, p = 0.17) were all similar between the two arms. On landmark analysis at 6 months, no difference was noted between the two arms for the primary endpoint (6.4% vs. 7.2, p = 0.53). Stent thrombosis rates were also similar. None of the prespecified subgroups including diabetes, DES versus BMS, single- versus multi-vessel PCI, age, or gender demonstrated any difference.
The key safety endpoint of bleeding (defined as Bleeding Academic Research Consortium [BARC] type II, III, or V) was significantly lower in the short-duration DAPT arm (3.5% vs. 7.4%, HR 0.46, 95% CI 0.1-0.69, p = 0.00018). Thrombolysis In Myocardial Infarction (TIMI) major bleeding (0.6% vs. 1.6%, p = 0.04) and red blood cell transfusions (1.3% vs. 2.6%, p = 0.04) were also lower with short-duration DAPT.
The primary endpoint of death/MI/cerebrovascular accident (CVA) was similar between the short duration and prolonged duration arms over 720 days of follow-up (10.0% vs. 10.1%, hazard ratio [HR] 0.98, 95% confidence interval [CI] 0.74-1.29; p = 0.91). Individual endpoints including all-cause mortality (6.6% vs. 6.6%, p = 0.98), death or MI (9.6% vs. 8.9%, p = 0.62), cardiovascular (CV) death (3.8% vs. 3.7%, p = 0.98), and CVA (1.4% vs. 2.1%, p = 0.17) were all similar between the two arms. On landmark analysis at 6 months, no difference was noted between the two arms for the primary endpoint (6.4% vs. 7.2, p = 0.53). Stent thrombosis rates were also similar. None of the prespecified subgroups including diabetes, DES versus BMS, single- versus multi-vessel PCI, age, or gender demonstrated any difference.
The key safety endpoint of bleeding (defined as Bleeding Academic Research Consortium [BARC] type II, III, or V) was significantly lower in the short-duration DAPT arm (3.5% vs. 7.4%, HR 0.46, 95% CI 0.1-0.69, p = 0.00018). Thrombolysis In Myocardial Infarction (TIMI) major bleeding (0.6% vs. 1.6%, p = 0.04) and red blood cell transfusions (1.3% vs. 2.6%, p = 0.04) were also lower with short-duration DAPT.
Interpretation:
The results of this landmark trial indicate that short duration of DAPT (≤6 months) is similar to prolonged duration of DAPT (24 months) following PCI with either DES or BMS for ischemic endpoints; all bleeding is significantly reduced. This was true for all subgroups studied, including patients with acute coronary syndrome. If confirmed by other ongoing trials, this is likely to revolutionize the management of patients undergoing PCI.
Currently, based on American College of Cardiology and European Society of Cardiology recommendations, patients undergoing PCI, especially those undergoing DES PCI, are kept on DAPT for at least 1 year. However, these recommendations are based on multiple reports suggesting an increased risk of stent thrombosis after DES PCI, with premature DAPT discontinuation being a significant risk factor, without direct evidence from randomized clinical trials designed to specifically compare different durations of DAPT use. Final full publication and longer follow-up are eagerly awaited.
Currently, based on American College of Cardiology and European Society of Cardiology recommendations, patients undergoing PCI, especially those undergoing DES PCI, are kept on DAPT for at least 1 year. However, these recommendations are based on multiple reports suggesting an increased risk of stent thrombosis after DES PCI, with premature DAPT discontinuation being a significant risk factor, without direct evidence from randomized clinical trials designed to specifically compare different durations of DAPT use. Final full publication and longer follow-up are eagerly awaited.
