This article is more than 5 years old. Information may no longer be current.
Triple antiplatelet therapy after PCI with aspirin, clopidogrel and cilostazol
Click Here to Manage Email Alerts
Dual antiplatelet therapy with aspirin and clopidogrel is currently the standard of care to prevent stent thrombosis after percutaneous coronary intervention with bare metal stent or drug-eluting stent placement. Patients continue dual therapy for one year after drug-eluting stent placement vs. one month after bare metal stent placement due to differing risks for late and very late stent thrombosis.
Cilostazol is a potent antiplatelet agent that reduces platelet activity through phosphodiesterase 3 inhibition (a different mechanism of action than aspirin or clopidogrel). Cilostazol is currently FDA approved for the treatment of peripheral arterial disease. It has antiplatelet activity that is estimated to be 10 to 30 times greater than aspirin and reduces smooth muscle cell proliferation and neointimal hyperplasia after tissue injury. Research suggests that its novel mechanism of action may be beneficial in preventing stent thrombosis, especially in cases of aspirin or clopidogrel treatment resistance.
 Patrycja Wilczynska |
 Andrew J. Smith |
A 2005 study by Lee et al was conducted to examine 3,012 patients undergoing PCI with a bare metal stent. In this Korean, retrospective, nonrandomized trial, the primary endpoint (including death, MI, target lesion revascularization and stent thrombosis) was 0.8% in the dual antiplatelet therapy group and 0.3% in the triple antiplatelet therapy group (P=.085). Although a statistically significant difference was not found in the primary endpoint, the 30-day stent thrombosis rate was significantly lower in the triple antiplatelet therapy group (0.1%) when compared with the dual antiplatelet therapy group (0.5%). In addition, the study results showed no differences in the overall number of adverse events, major bleeding episodes, neutropenia or thrombocytopenia between the two study groups (P=.104). The result suggested better outcomes in the triple antiplatelet therapy group despite the fact that this group had more unfavorable anatomical and procedural characteristics compared with the dual antiplatelet therapy group. The researchers concluded that the addition of cilostazol to aspirin and clopidogrel was more effective than dual antiplatelet therapy in preventing early stent thrombosis and was at least as safe as dual antiplatelet therapy.
A prospective, randomized, open-label study by Han et al was conducted to examine 1,212 patients following successful PCI with either a bare metal stent or drug-eluting stent in a single center in China. The results showed that triple antiplatelet therapy — addition of six months of cilostazol to a standard dose of aspirin (indefinitely) and clopidogrel (three to 12 months depending on stent type) — resulted in a 51% lower combined number of cardiac deaths, nonfatal MIs, strokes and target vessel revascularizations in one year post-PCI when compared with standard dual antiplatelet therapy (10.3% vs. 15.1%; P=.011). Incidence of cardiac or ischemic events was significantly reduced in the triple antiplatelet therapy group when compared with the dual antiplatelet therapy group (2.6% vs. 5.1%). The target vessel revascularization after one year was reduced in the triple antiplatelet therapy group, but the difference between the two treatment groups was not statistically significant (7.8% triple therapy vs. 10.4% double therapy). In addition, the researchers did not find significant differences between the two study groups at the one-year follow-up when examining the mortality rate (2.6% triple therapy vs. 4.1% dual therapy), CV–related death (1.7% vs. 3.3%), nonfatal MI (0.3% vs. 0.7%) and stroke (0.7% vs. 1.6%). The analysis of the subgroups in the study suggested that those who benefited the most from triple antiplatelet therapy were women, patients with diabetes, patients with multivessel disease, patients assigned to a stent larger than 30 mm in length and patients who had stenting of a vessel with a diameter less than 2.75 mm. There was not a significant difference in episodes of bleeding between the two study groups, suggesting that triple antiplatelet therapy was at least as safe as dual antiplatelet therapy.
The benefit of triple antiplatelet therapy with addition of cilostazol was also investigated in a 2009 retrospective study from Korea by Chen et al. The researchers evaluated 4,203 patients with STEMI who underwent primary PCI with a drug-eluting stent. After eight months of treatment, when compared with the dual antiplatelet therapy group, the group assigned to cilostazol in addition to dual antiplatelet therapy for at least one month (n=1,634) had reduced cardiac death (adjusted OR=0.52; 95% CI, 0.32-0.84), total death (adjusted OR=0.6; 95% CI, 0.41-0.89) and total major adverse cardiac events (adjusted OR=0.74; 95% CI, 0.58-0.95). The findings supported the safety of triple antiplatelet therapy, as the adverse effect profile of the triple antiplatelet therapy group was not significantly different from that of the dual antiplatelet therapy group (major bleedings: 0.2% in the cilostazol group vs. 0.4% in the dual therapy group). Patients who benefited the most from triple therapy were women, patients aged older than 65 years and patients with diabetes.
Current data suggest that triple antiplatelet therapy is at least as safe as standard dual antiplatelet therapy and may be more beneficial than dual antiplatelet therapy in preventing stent thrombosis, especially in high-risk patients. High-risk patients would include women, patients aged older than 65 years, patients with diabetes and recipients of drug-eluting stents or long stents. However, all available data come from Asian studies and lack external validity. These data need to be validated in more diverse patient populations before global implementation of triple antiplatelet therapy.
Patrycja Wilczynska, PharmD candidate, is from the University of Missouri–Kansas City School of Pharmacy.
Andrew J. Smith, PharmD, BCPS, is a Clinical Assistant Professor, University of Missouri–Kansas City School of Pharmacy, and a Cardiology Clinical Pharmacist, Truman Medical Centers–Hospital Hill, Cardiology Center, Kansas City, Mo.
Rhonda Cooper-DeHoff, PharmD, MS, Associate Professor, University of Florida College of Pharmacy, Gainesville, is Cardiology Today’s Pharmacology Consult column editor and a member of the CHD and Prevention section of the Cardiology Today Editorial Board.
For more information:
- Chen KY. Circulation. 2009;119:3207-3214.
- Han Y. Am Heart J. 2009;157:733-739.
- Lee SW. J Am Coll Cardiol. 2005;46:1833-1837.