BACKGROUND: Dual antiplatelet therapy with a thienopyridine (ticlopidine or clopidogrel) and aspirin is used to reduce the risk of late stent thrombosis and complications (myocardial infarction [MI] and death) after placement of a drug-eluting stent (DES). OBJECTIVE: This article reviews available clinical efficacy and safety data on antiplatelet therapies for the prevention of stent thrombosis and cardiac events after DES placement. METHODS: MEDLINE, EMBASE, and International Pharmaceutical Abstracts (1966-June 2010) were searched for studies relating to the clinical efficacy and safety of antiplatelet therapy after DES placement using the terms antiplatelet therapy, thienopyridine, aspirin, clopidogrel, cilostazol, prasugrel, ticlopidine, paclitaxel-eluting stent, sirolimus-eluting stent, and drug-eluting stent. The reference lists of the identified articles were reviewed for additional relevant publications. RESULTS: Ten studies were identified that evaluated the efficacy of antiplatelet therapies after DES placement; of these, 5 also assessed safety. In a prospective, observational cohort study, early discontinuation of clopidogrel (within the first 6 months after DES placement) was a major predictor of stent thrombosis (hazard ratio [HR] = 13.74; 95% CI, 4.04-46.68; P < 0.001). In an observational cohort study, early discontinuation of clopidogrel was associated with significantly higher rates of long-term clinical events (death and death or MI) (discontinuation at 6 months: P = 0.004; discontinuation at 12 months: P < 0.001). A multicenter, randomized, double-blind, prospective study found a reduction in the composite end point of death, MI, and target-vessel revascularization within 30 days after DES placement in patients who received a high loading dose of clopidogrel (600 mg) compared with the conventional loading dose (300 mg) (4% vs 12%, respectively; P = 0.041). In a multicenter, randomized, prospective study in patients with long coronary lesions undergoing DES placement, triple antiplatelet therapy (clopidogrel, cilostazol, and aspirin) was associated with significant reductions at 6 months compared with dual antiplatelet therapy (clopidogrel and aspirin) in in-stent late loss (mean [SD], 0.22 [0.48] vs 0.32 [0.51] mm, respectively; P = 0.03) and in-segment late loss (0.34 [0.49] vs 0.51 [0.49] mm; P = 0.001). In a similar study in patients with diabetes mellitus, triple therapy was associated with significant reductions at 6 months in rates of in-segment restenosis (8.0% vs 15.6%; RR = 0.51; 95% CI, 0.27-0.96; P = 0.033), target-lesion revascularization (2.5% vs 7.0%; RR = 0.36; 95% CI, 0.13-0.97; P = 0.034), and major adverse cardiac events (2.8% vs 7.6%; P = 0.016). In a multicenter, retrospective study comparing triple and dual antiplatelet therapy in patients with ST-segment elevation MI undergoing DES placement, triple therapy was associated with significant reductions at 8 months compared with dual therapy in rates of cardiac deaths (2.0% vs 3.2%; P = 0.019), total deaths (3.1% vs 4.9%; P = 0.006), and total major adverse cardiac events (7.6% vs 9.3%; P = 0.049). Overall, use of triple therapy was not associated with an increased risk of major or minor bleeding events compared with dual therapy. In a multicenter, randomized, double-blind, prospective study in patients with acute coronary syndrome (ACS) who underwent DES placement and received the combination of prasugrel or clopidogrel and aspirin, the prasugrel regimen was associated with significant reductions in rates of the composite end point of cardiovascular death, nonfatal MI, and nonfatal stroke (HR = 0.82; 95% CI, 0.69-0.97; P = 0.019) and late stent thrombosis (0.42% vs 0.91%, respectively; P = 0.04). However, the combination of prasugrel and aspirin was associated with significant increases compared with clopidogrel and aspirin in rates of total bleeding events (5.0% vs 3.8%; P = 0.002), major bleeding events (2.4% vs 1.8%; P = 0.03), and life-threatening bleeding events (1.4% vs 0.9%; P = 0.01). CONCLUSIONS: The combination of clopidogrel (loading dose, 300-600 mg; maintenance dose, 75 mg/d) and low-dose aspirin (75-162 mg/d) for 12 months is the preferred regimen for the prevention of stent thrombosis and cardiac complications after DES placement. The combination of prasugrel and aspirin may be appropriate in patients with ACS, although it was associated with a significantly increased risk for bleeding. Triple antiplatelet therapy may be beneficial in certain high-risk patients.
BACKGROUND: Dual antiplatelet therapy with a thienopyridine (ticlopidine or clopidogrel) and aspirin is used to reduce the risk of late stent thrombosis and complications (myocardial infarction [MI] and death) after placement of a drug-eluting stent (DES). OBJECTIVE: This article reviews available clinical efficacy and safety data on antiplatelet therapies for the prevention of stent thrombosis and cardiac events after DES placement. METHODS: MEDLINE, EMBASE, and International Pharmaceutical Abstracts (1966-June 2010) were searched for studies relating to the clinical efficacy and safety of antiplatelet therapy after DES placement using the terms antiplatelet therapy, thienopyridine, aspirin, clopidogrel, cilostazol, prasugrel, ticlopidine, paclitaxel-eluting stent, sirolimus-eluting stent, and drug-eluting stent. The reference lists of the identified articles were reviewed for additional relevant publications. RESULTS: Ten studies were identified that evaluated the efficacy of antiplatelet therapies after DES placement; of these, 5 also assessed safety. In a prospective, observational cohort study, early discontinuation of clopidogrel (within the first 6 months after DES placement) was a major predictor of stent thrombosis (hazard ratio [HR] = 13.74; 95% CI, 4.04-46.68; P < 0.001). In an observational cohort study, early discontinuation of clopidogrel was associated with significantly higher rates of long-term clinical events (death and death or MI) (discontinuation at 6 months: P = 0.004; discontinuation at 12 months: P < 0.001). A multicenter, randomized, double-blind, prospective study found a reduction in the composite end point of death, MI, and target-vessel revascularization within 30 days after DES placement in patients who received a high loading dose of clopidogrel (600 mg) compared with the conventional loading dose (300 mg) (4% vs 12%, respectively; P = 0.041). In a multicenter, randomized, prospective study in patients with long coronary lesions undergoing DES placement, triple antiplatelet therapy (clopidogrel, cilostazol, and aspirin) was associated with significant reductions at 6 months compared with dual antiplatelet therapy (clopidogrel and aspirin) in in-stent late loss (mean [SD], 0.22 [0.48] vs 0.32 [0.51] mm, respectively; P = 0.03) and in-segment late loss (0.34 [0.49] vs 0.51 [0.49] mm; P = 0.001). In a similar study in patients with diabetes mellitus, triple therapy was associated with significant reductions at 6 months in rates of in-segment restenosis (8.0% vs 15.6%; RR = 0.51; 95% CI, 0.27-0.96; P = 0.033), target-lesion revascularization (2.5% vs 7.0%; RR = 0.36; 95% CI, 0.13-0.97; P = 0.034), and major adverse cardiac events (2.8% vs 7.6%; P = 0.016). In a multicenter, retrospective study comparing triple and dual antiplatelet therapy in patients with ST-segment elevation MI undergoing DES placement, triple therapy was associated with significant reductions at 8 months compared with dual therapy in rates of cardiac deaths (2.0% vs 3.2%; P = 0.019), total deaths (3.1% vs 4.9%; P = 0.006), and total major adverse cardiac events (7.6% vs 9.3%; P = 0.049). Overall, use of triple therapy was not associated with an increased risk of major or minor bleeding events compared with dual therapy. In a multicenter, randomized, double-blind, prospective study in patients with acute coronary syndrome (ACS) who underwent DES placement and received the combination of prasugrel or clopidogrel and aspirin, the prasugrel regimen was associated with significant reductions in rates of the composite end point of cardiovascular death, nonfatal MI, and nonfatal stroke (HR = 0.82; 95% CI, 0.69-0.97; P = 0.019) and late stent thrombosis (0.42% vs 0.91%, respectively; P = 0.04). However, the combination of prasugrel and aspirin was associated with significant increases compared with clopidogrel and aspirin in rates of total bleeding events (5.0% vs 3.8%; P = 0.002), major bleeding events (2.4% vs 1.8%; P = 0.03), and life-threatening bleeding events (1.4% vs 0.9%; P = 0.01). CONCLUSIONS: The combination of clopidogrel (loading dose, 300-600 mg; maintenance dose, 75 mg/d) and low-dose aspirin (75-162 mg/d) for 12 months is the preferred regimen for the prevention of stent thrombosis and cardiac complications after DES placement. The combination of prasugrel and aspirin may be appropriate in patients with ACS, although it was associated with a significantly increased risk for bleeding. Triple antiplatelet therapy may be beneficial in certain high-risk patients.