Triple Antiplatelet Therapy with Cilostazol Increases Tachycardia, Arrhythmias

San Francisco, CA—Administration of cilostazol on top of standard dual antiplatelet therapy increases 24-hour average heart rate and premature ventricular contractions (PVCs) after drug-eluting stent (DES) implantation, according to data presented at TCT 2013.

Beom-June Kwon, MD, PhD, of the Catholic University of Korea, Bucheon, South Korea, and colleagues conducted a randomized, prospective trial comparing triple therapy including the phosphodiesterase inhibitor cilostazol (Pletal; Otsuka Pharmaceutical), aspirin and clopidogrel (n=113) with dual therapy (aspirin and clopidogrel; n=114) in patients receiving DES. The groups had similar baseline characteristics.

Triple therapy raises heart rate

At 6 months, the primary endpoints of  24-hour heart rate, 24-hour heart rate increase of at least 5 beats per minute (bpm), and incidence of 24-hour heart rate of at least 70 bpm  assessed by 24-hour Holter ECG monitoring were all higher with triple therapy (Table).

Table. Heart Rate Metrics at 6 Months

The researchers identified two strong predictors of 24-hour heart increase of at least 5 bpm: use of cilostazol (OR 3.10; 95% CI 1.08-8.89) and baseline 24-hour heart rate of less than 70 bpm (OR 4.60; 95% CI 1.16-13.14).

In addition, 24-hour counts of PVCs were higher in patients on triple compared with dual therapy (472 ± 1,497 beats vs. 86 ± 209 beats; P=.016).

Caution warranted in some patients

“Adjunctive cilostazol [in addition to] standard [dual antiplatelet therapy] in patients with long lesions and type 2 diabetes mellitus after DES implantation is associated with a better clinical outcome due to a decreased rate of repeat revascularization,” Dr. Kwon told TCT Daily. “However, some randomized controlled trials showed that cilostazol had no effect on clinically driven target lesion revascularization as well as major cardiovascular events in real-world, all-comer patients.”

Moreover, research has shown that resting heart rate is a potent predictor of major adverse cardiovascular events both in the general population and in patients with cardiovascular disease, Dr. Kwon noted. Prior to this study, data were limited regarding whether cilostazol might induce tachycardia and tachyarrhythmias after DES implantation, as well as on the safety of the drug, especially among patients with 24-hour ambulatory Holter monitoring during both rest and exercise.

“Based on these findings, it is reasonable to believe that cilostazol in addition to [dual antiplatelet therapy] may contribute to positive chronotropic effect and pro-arrhythmic action such as PVCs after DES implantation,” Dr. Kwon said. “[Therefore,] some caution should be exercised [with regard to] use of cilostazol in patients with tachycardia or a large number of PVCs when planning DES implantation.”