Effect of cilostazol on optimized standard antiplatelet therapy in a patient with a cytochrome P450 2C19 *2/*2 genotype.

Department of Medicine, Teikyo University School of Medicine, 2-11-1 Kaga, Itabashi-ku, Tokyo, Japan.
Cardiovascular intervention and therapeutics 01/2011; 26(1):79-82. DOI: 10.1007/s12928-010-0036-x
Source: PubMed

ABSTRACT A 54-year-old man with acute coronary syndrome underwent primary percutaneous coronary intervention (PCI) to implant a bare metal stent. Three weeks later, a subclinical in-stent thrombus was found at staged PCI despite dual antiplatelet therapy with aspirin and clopidogrel. Platelet function tests revealed high post-treatment platelet reactivity, indicating an inadequate response to clopidogrel. The patient's cytochrome P450 2C19 genotype was *2/*2. Cilostazol at 200 mg/day was initiated in addition. Three months later, platelet inhibition was enhanced, and no thrombus was detectable by coronary angiography. Our experience suggests that triple antiplatelet therapy with cilostazol as well as aspirin and clopidogrel could prevent stent thrombosis with improved clopidogrel responsiveness.

  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Traditionally, stent thrombosis has been regarded as a complication of percutaneous coronary interventions during the first 30 postprocedural days. However, delayed endothelialization associated with the implantation of drug-eluting stents may extend the risk of thrombosis beyond 30 days. Data are limited regarding the risks and the impact of this phenomenon outside clinical trials. To evaluate the incidence, predictors, and clinical outcome of stent thrombosis after implantation of sirolimus-eluting and paclitaxel-eluting stents in routine clinical practice. Prospective observational cohort study conducted at 1 academic hospital and 2 community hospitals in Germany and Italy. A total of 2229 consecutive patients underwent successful implantation of sirolimus-eluting (1062 patients, 1996 lesions, 2272 stents) or paclitaxel-eluting (1167 patients, 1801 lesions, 2223 stents) stents between April 2002 and January 2004. Implantation of a drug-eluting stent (sirolimus or paclitaxel). All patients were pretreated with ticlopidine or clopidogrel and aspirin. Aspirin was continued indefinitely and clopidogrel or ticlopidine for at least 3 months after sirolimus-eluting and for at least 6 months after paclitaxel-eluting stent implantation. Subacute thrombosis (from procedure end through 30 days), late thrombosis (>30 days), and cumulative stent thrombosis. At 9-month follow-up, 29 patients (1.3%) had stent thrombosis (9 [0.8%] with sirolimus and 20 [1.7%] with paclitaxel; P = .09). Fourteen patients had subacute thrombosis (0.6%) and 15 patients had late thrombosis (0.7%). Among these 29 patients, 13 died (case fatality rate, 45%). Independent predictors of stent thrombosis were premature antiplatelet therapy discontinuation (hazard ratio [HR], 89.78; 95% CI, 29.90-269.60; P<.001), renal failure (HR, 6.49; 95% CI, 2.60-16.15; P<.001), bifurcation lesions (HR, 6.42; 95% CI, 2.93-14.07; P<.001), diabetes (HR, 3.71; 95% CI, 1.74-7.89; P = .001), and a lower ejection fraction (HR, 1.09; 95% CI, 1.05-1.36; P<.001 for each 10% decrease). The cumulative incidence of stent thrombosis 9 months after successful drug-eluting stent implantation in consecutive "real-world" patients was substantially higher than the rate reported in clinical trials. Premature antiplatelet therapy discontinuation, renal failure, bifurcation lesions, diabetes, and low ejection fraction were identified as predictors of thrombotic events.
    JAMA The Journal of the American Medical Association 05/2005; 293(17):2126-30. DOI:10.1001/jama.293.17.2126 · 30.39 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: We compared intravascular ultrasound findings of drug-eluting stent (DES)-treated lesions that developed thrombosis versus in-stent restenosis (ISR). Stent underexpansion is a predictor of both DES thrombosis and ISR. However, all underexpanded DES may not be equal. Intravascular ultrasound findings from 20 definite DES thrombosis patients (representing all definite thromboses from 1,407 consecutive DES patients undergoing intravascular ultrasound imaging) were compared with 50 risk-factor-balanced ISR patients with no evidence of stent thrombosis and 50 risk-factor-balanced "no-event" patients with neither thrombosis nor ISR. Minimum stent area (3.9 +/- 1.0 mm(2) vs. 5.0 +/- 1.7 mm(2), p = 0.008), mean stent area (5.3 +/- 1.0 mm(2) vs. 7.2 +/- 2.0 mm(2), p = 0.001), and both focal (55.4 +/- 13.2% vs. 74.9 +/- 19.9%, p < 0.001) and diffuse stent expansion (77.4 +/- 19.3% vs. 109.5 +/- 23.1%, p < 0.001) were significantly smaller in the stent thrombosis group versus ISR and in both groups versus the "no-event" group. Minimum stent area <4.0 mm(2) (65% vs. 32%, p = 0.01) or <5.0 mm(2) (85% vs. 52%, p = 0.01) was more common in the stent thrombosis versus the ISR group and in both groups vs. "no-event" patients; and the relative length of the stent area <5 mm(2) was greatest in the stent thrombosis group (36.6 +/- 37.7%), intermediate in the ISR group (22.8 +/- 35.6%), and least in the "no-event" group (10.9 +/- 26.4%), p = 0.04. In the stent thrombosis group, the minimum stent area site occurred in the proximal stent segment in 50% versus 24% in the ISR group (p = 0.03). There were no differences in edge dissection, stent fracture, or stent-vessel-wall malapposition among the groups. The DES-treated lesions that develop thrombosis or restenosis are often underexpanded, but underexpansion associated with thrombosis is more severe, diffuse, and proximal in location.
    JACC. Cardiovascular Interventions 05/2009; 2(5):428-34. DOI:10.1016/j.jcin.2009.01.011 · 7.44 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Stent thrombosis remains a major pitfall of stent implantation in contemporary percutaneous coronary intervention, leading to high rates of death and nonfatal myocardial infarction (MI). Recently, the emergence of drug-eluting stents (DES) has raised concerns regarding the occurrence of late and very late stent thrombosis. Last year, a standardized definition of stent thrombosis was established to provide consistency in the reporting of this complication and to enable accurate and reliable data to be described for both types of stents: bare metal and drug eluting. Subsequent to the publication of this new definition, many updated data have been reported in the literature. On the other hand, antiplatelet therapy response variability is a recent concept and its real place in the pathogenesis of stent thrombosis is yet to be determined. In this article, we review the definition of and predictors for stent thrombosis focusing on DES use and variability in response to antiplatelet therapy, prognosis and treatment.
    Archives of Cardiovascular Diseases 11/2008; 101(11-12):769-77. DOI:10.1016/j.acvd.2008.10.006 · 1.66 Impact Factor