Five Studies: Triple-antiplatelet therapy superior to dual-antiplatelet treatment

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WASHINGTON—Triple-antiplatelet therapy for patients undergoing PCI with drug-eluting stents achieves greater platelet inhibition than conventional dual-antiplatelet therapy, based on the results of five research studies and a clinical registry first-report presentation highlighted on Monday at the 20th annual Transcatheter Cardiovascular Therapeutics (TCT) scientific symposium.

A collection of investigations completed in South Korea examined the use of antiplatelet therapies in a variety of PCI patients, including diabetics and patients with 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 (Pletal from Otsuka America Pharmaceutical from Rockville, Md.) in triple-antiplatelet therapy.

The trial, "Additive Cilostazol to dual-antiplatelet Therapy Achieves Greater Inhibition of Platelet Aggregation Compared with High Maintenance-Dose Clopidogrel in Patients with Acute MI," 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 150 mg/d during sub-acute phases in patients with acute MI (AMI). The researchers randomly assigned AMI patients undergoing uneventful coronary stenting (90 patients) 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. They evaluated platelet functions by conventional aggregometry and the VerifyNow P2Y12 assay before discharge and after 30 days MD therapy.

“triple-antiplatelet therapy achieves greater platelet inhibition when compared with high maintenance dose clopidogrel (150 mg/d) in AMI patients undergoing coronary stenting,” according to lead researcher Young-Hoon Jeong, MD, from the Gyeongsang National University Hospital in Jinju, South Korea.

In another trial—“Triple Versus dual-antiplatelet Therapy in Diabetic Patients with AMI Undergoing PCI in the Era of the DES"—a total of 2,074 diabetic patients with AMI, who underwent PCI with DES received either dual (aspirin plus clopidogrel in 1,220 patients) or triple-antiplatelet therapy (aspirin, plus clopidogrel and cilostazol in 854 patients). The researchers compared the bleeding complications and clinical outcomes at seven days, one month and eight months between the two groups. The triple group was associated with significantly lower incidence of death and major adverse cardiac events (MACE) up to eight months compared with the dual group. The incidence of myocardial re-infarction, revascularization and TIMI major bleeding were similar in the two groups throughout eight months of clinical follow-up.

Kang-Yin Chen, MD, who led the research team from Korea University Guro Hospital and Chonnam National University Hospital in Seoul, South 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.”

The randomized, multicenter, prospective study—“A Randomized Comparison of triple-antiplatelet Therapy with dual-antiplatelet Therapy After DES Implantation in Diabetes Patients: Two-Year Clinical Outcomes of DECLARE Diabetes Trial”—compared triple-antiplatelet therapy (aspirin, clopidogrel and cilostazol) with dual-antiplatelet therapy (aspirin and clopidogrel) for six months in patients with diabetes receiving DES. The investigators showed that six-months restenosis and nine-month target lesion revascularization in the triple group was significantly lower. At two years, triple therapy showed sustained reduction of target lesion revascularization compared to the standard group (4.5 versus 10 percent). The incidence of MACE including death, MI and target lesion revascularization tended to be lower in the triple group (5.5 vs.10.5 percent) than in the standard group.

Lead study author Seung-Whan Lee, MD, of the Asan Medical Center at University of Ulsan College of Medicine in Seoul, South Korea, concluded that, "triple-antiplatelet therapy after DES implantation is effective in reducing two-year target lesion revascularization compared to dual-antiplatelet therapy, which suggests that triple-antiplatelet therapy has durable effectiveness on the performance of DES.”

The randomized, multicenter prospective study, “A Randomized Comparison of triple-antiplatelet Therapy with dual-antiplatelet Therapy After DES Implantation in Long Coronary Lesions: Two-Year Clinical Outcomes of DECLARE-LONG Trial,” which examined the specific impact of cilostazol in triple-antiplatelet therapy on the performance of DES. The investigation compared triple-antiplatelet therapy (aspirin, clopidogrel and cilostazol in 250 patients) with dual-antiplatelet therapy (aspirin and clopidogrel in 250 patients) for six months in patients with long coronary lesions receiving DES. Researchers evaluated long-term clinical outcomes (death, MI and target lesion revascularization) at two years.

Lead investigator Jae-Hwan Lee, MD, of Chungnam National University Hospital in Daejeon, South Korea, noted, "Our study found that triple therapy significantly reduced the two-year target lesion revascularization compared to the standard group. The incidence of MACE was also significantly reduced (4 vs. 8.4 percent) in the triple versus the standard group. The results showed that triple-antiplatelet therapy after DES implantation is superior in reducing two-year risk of target lesion revascularization and major adverse cardiac events in long coronary lesions compared to dual-antiplatelet therapy. The finding suggests that adding cilostazol to the dual-antiplatelet regimen provides improved efficacy of DES in lesions of patients at high risk of restenosis."

Another study—“Triple versus dual-antiplatelet Therapy in Patients with Acute STEMI Undergoing Primary PCI”—examined whether triple-antiplatelet strategy is superior or similar to the dual-antiplatelet strategy in patients with acute 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, according to researchers. The patients in the triple group received additional cilostazol for one 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 eight month follow-up. Both groups had similar incidences of in-hospital major bleeding, revascularization and recurrent myocardial infarction.

Lead researcher Kang-Yin Chen, MD, of Korea University Guro Hospital in Seoul, South Korea, concluded that, "The triple-antiplatelet therapy for one 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."

Each of these studies led the researchers to the overwhelming conclusion “that triple-antiplatelet therapy for PCI patients receiving DES was superior to conventional dual-antiplatelet therapy.”