JACC: Triple-antiplatelet therapy is no better than dual therapy

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Despite a greater reduction of platelet reactivity by the addition of cilostazol to conventional dual-antiplatelet therapy (DAPT), triple-antiplatelet therapy did not show superiority in reducing the composite of adverse cardiovascular outcomes after drug-eluting stent (DES) implantation, according to a study in the Jan. 18 Journal of the American College of Cardiology.

Jung-Won Suh, MD, from Seoul National University Hospital in South Korea, and colleagues noted that between 15 to 30 percent of patients on DAPT have high residual platelet reactivity. Reports have described an association between high post-treatment platelet reactivity and atherothrombotic cardiovascular complications after PCI.

They also wrote that few studies have reported the efficacy of the VerifyNow (Accumetrics) P2Y12 system in predicting clinical outcomes in Asians.

In that regard, researchers from five centers in South Korea enrolled 960 patients who received DES into the CILON-T (Influence of CILostazol-based triple-antiplatelet therapy ON ischemic complication after drug-eluting stenT implantation) trial.

Patients were randomized to receive either DAPT (aspirin and clopidogrel [Plavix, Bristol-Myers Squibb/Sanofi-Aventis]) or triple-antiplatelet therapy (aspirin, clopidogrel and cilostazol [Pletal, Otsuka Pharmaceutical]) for six months.

Cilostazol is a selective phosphodiesterase-3 inhibitor that is commonly used as a vasodilator with antiplatelet activity in patients with peripheral arterial disease.

The primary endpoint was the composite of cardiac death, nonfatal MI, ischemic stroke or target lesion revascularization. Secondary endpoints were P2Y12 reaction unit (PRU) measured with the VerifyNow P2Y12 assay at discharge and at six months after the index procedure. All-cause death, stent thrombosis and each component of the primary endpoint at six months were other secondary endpoints. Analysis was done on an intention-to-treat basis.

At six months of follow-up, there was no difference in the primary endpoint between the two groups (8.5 percent in triple therapy vs. 9.2 percent in DAPT). In addition, there were no differences between the two groups in the secondary endpoints, or any of these events combined. Subgroup analysis according to clinical and angiographic characteristics demonstrated no significant differences in clinical outcomes between the two groups, except in female patients, in whom triple therapy showed a higher rate of adverse cardiac events than DAPT.

In the secondary endpoint analysis, the triple therapy group achieved significantly lower PRU levels than the DAPT group both at discharge (206.6 PRU vs. 232.2 PRU) and at six months (210.7 PRU vs. 255.7 PRU).

Researchers found that lesion length (>28 mm) and PRU level at discharge were predictors of the primary endpoint, but the use of cilostazol was not a predictor.

Suh and colleagues found that a PRU of at least 252.5 was the optimal cutoff value to predict post-discharge six-month atherothrombotic events, providing a sensitivity of 75 percent, specificity of 62 percent, positive predictive value of 3.2 percent and negative predictive value of 99.3 percent. Patients with PPR greater than the cutoff value had significantly higher rates of the primary endpoint and atherothrombotic complications.