Triple antiplatelet therapy appears superior to dual antiplatelet therapy

October 14, 2008

Results of five research studies and a clinical registry first-report presentation scheduled for the 20th annual Transcatheter Cardiovascular Therapeutics (TCT) scientific symposium, sponsored by the Cardiovascular Research Foundation (CRF), suggest that triple antiplatelet therapy for patients undergoing percutaneous coronary intervention (PCI) with drug-eluting stents achieves greater platelet inhibition than conventional dual antiplatelet therapy.

Antiplatelet agents are medications that block the formation of blood clots by preventing the clumping of platelets.

A collection of investigations completed in Korea examined the use of antiplatelet therapies in a variety of PCI patients including diabetics and patients with ST-segment elevation myocardial infarction (STEMI). The studies measured the overall effectiveness of triple antiplatelet therapy against the more conventional dual drug therapeutic approach and also examined the performance of the drug cilostazol in triple antiplatelet therapy. The overwhelming conclusion of these studies was that triple antiplatelet therapy for PCI patients receiving drug-eluting stents (DES) was superior to conventional dual antiplatelet therapy.

"Additive Cilostazol to Dual Antiplatelet Therapy Achieves Greater Inhibition of Platelet Aggregation Compared with High Maintenance-Dose Clopidogrel in Patients with Acute Myocardial Infarction"
The aim of this study was to compare the impact of platelet inhibition by adjunctive cilostazol to dual antiplatelet therapy (triple antiplatelet therapy) and high-maintenance dose (MD) clopidogrel of 150mg/d during sub-acute phases in patients with acute myocardial infarction (AMI). AMI patients undergoing uneventful coronary stenting (90) were randomly assigned to one of three MD regimens: standard MD group - clopidogrel 75mg/d; high MD group - clopidogrel 150 mg/d; triple group - adjunctive cilostazol 100 mg twice daily to clopidogrel 75 mg/d. Platelet functions were evaluated by conventional aggregometry and the VerifyNow P2Y12 assay before discharge and after 30-days MD therapy. Young-Hoon Jeong, M.D., lead researcher from Gyeongsang National University Hospital in Jinju, Republic of Korea, said, "Triple antiplatelet therapy achieves greater platelet inhibition when compared with high maintenance dose clopidogrel (150 mg/d) in AMI patients undergoing coronary stenting."

"Triple Versus Dual Antiplatelet Therapy in Diabetic Patients with Acute Myocardial Infarction Undergoing Percutaneous Coronary Intervention in the Era of the Drug-Eluting Stent"
In this study, a total of 2,074 diabetic patients with AMI who underwent PCI with DES received either dual (aspirin plus clopidogrel - 1,220 patients) or triple antiplatelet therapy (aspirin, plus clopidogrel and cilostazol - 854 patients). The bleeding complications and clinical outcomes at 7 days, 1 month and 8 months were compared between the two groups. The triple group was associated with significantly lower incidence of death and major adverse cardiac events (MACE) up to 8 months compared with the dual group. The incidence of myocardial re-infarction, revascularization and TIMI major bleeding were similar in these two groups throughout 8 months of clinical follow-up.

Kang-Yin Chen, M.D., who led the research team from Korea University Guro Hospital and Chonnam National University Hospital in Seoul, Republic of Korea, said the study showed: "Triple antiplatelet therapy appears to be superior to the conventional dual antiplatelet therapy in reducing early mortality and major adverse cardiac events without increasing major bleeding in diabetic AMI patients undergoing PCI with DES.

"A Randomized Comparison of Triple Antiplatelet Therapy with Dual Antiplatelet Therapy After Drug-Eluting Stent Implantation in Diabetes Patients: Two-Year Clinical Outcomes of DECLARE Diabetes Trial"
This randomized, multicenter, prospective study compared triple antiplatelet therapy (aspirin, clopidogrel and cilostazol) with dual antiplatelet therapy (aspirin and clopidogrel) for 6 months in patients with diabetes receiving DES. It showed that six-months restenosis and 9-month target lesion revascularization in the triple group was significantly lower. At 2 years, triple therapy showed sustained reduction of target lesion revascularization compared to the standard group (4.5% versus 10.0%). The incidence of MACE including death, myocardial infarction and target lesion revascularization tended to be lower in the triple group (5.5% vs.10.5%) than in the standard group.

Lead study author Seung-Whan Lee, M.D., of Asan Medical Center, University of Ulsan College of Medicine in Seoul, Republic of Korea, concluded that, "Triple antiplatelet therapy after DES implantation is effective in reducing 2 year target lesion revascularization compared to dual antiplatelet therapy, which suggests that triple antiplatelet therapy has durable effectiveness on the performance of drug-eluting stents."

"A Randomized Comparison of Triple Antiplatelet Therapy with Dual Antiplatelet Therapy After Drug-Eluting Stent Implantation in Long Coronary Lesions: Two-Year Clinical Outcomes of DECLARE-LONG Trial"
This study, which also included Seung-Whan Lee, M.D. among its investigators, examined the specific impact of cilostazol in triple antiplatelet therapy on the performance of DES. The investigation was a randomized, multicenter prospective study that compared triple antiplatelet therapy (aspirin, clopidogrel and cilostazol - 250 patients) with dual antiplatelet therapy (aspirin and clopidogrel - 250 patients) for 6 months in patients with long coronary lesions receiving DES. Researchers evaluated long-term clinical outcomes (death, myocardial infarction and target lesion revascularization) at 2 years.

Lead investigator Jae-Hwan Lee, M.D., of Chungnam National University Hospital in Daejeon, Republic of Korea, noted, "Our study found that triple therapy significantly reduced the 2-year target lesion revascularization compared to the standard group. The incidence of MACE was also significantly reduced (4.0% vs. 8.4%) in the triple versus the standard group. The results showed that triple antiplatelet therapy after DES implantation is superior in reducing 2-year risk of target lesion revascularization and major adverse cardiac events in long coronary lesions compared to dual antiplatelet therapy. This finding suggests that adding cilostazol to the dual antiplatelet regimen provides improved efficacy of DES in lesions of patients at high risk of restenosis."

"Triple versus Dual Antiplatelet Therapy in Patients with Acute ST-Segment Elevation Myocardial Infarction Undergoing Primary Percutaneous Coronary Intervention"
This study examined whether triple antiplatelet strategy is superior or similar to the dual antiplatelet strategy in patients with acute ST-segment elevation myocardial infarction (STEMI) undergoing primary PCI. It followed a total of 2,404 STEMI patients undergoing primary PCI who received either dual antiplatelet (1,432) or triple antiplatelet (972) therapy. The patients in the triple group received additional cilostazol for 1 month and then were shifted to dual antiplatelet therapy.

The triple group showed lower total death and lower incidences of all MACE - approximately half - throughout the 8 month follow-up. Both groups had similar incidences of in-hospital major bleeding, revascularization and recurrent myocardial infarction. Lead researcher Kang-Yin Chen, M.D., of Korea University Guro Hospital in Seoul, Republic of Korea, concluded that, "The triple antiplatelet therapy for 1 month appears to be superior to dual antiplatelet therapy, reducing early mortality and MACE without increasing the major bleeding events in STEMI patients undergoing primary PCI."

In addition to these abstracts, Korean researcher Seong-Wook Park, M.D., will summarize early results from "DECREASE: A Prospective Registry Examining the Safety and Efficacy of Triple Antiplatelet Therapy after Drug-Eluting Stent Implantation" during Plenary Session 6: " 'First Report' Randomized Trials and Registries I" on Tuesday, October 14 at 12:45 p.m. in the Main Arena of the Washington Convention Center.

Cardiovascular Research Foundation

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