Triple Antiplatelet Therapy Improves Outcomes after PCI
Adding cilostazol to aspirin and clopidogrel did not appear to increase the risk of hemorrhage or major bleeding.
Triple antiplatelet therapy with aspirin, clopidogrel, and cilostazol improved short-term outcomes compared with standard dual antiplatelet therapy in patients who underwent percutaneous coronary intervention (PCI), according to two studies from Northern Hospital in Shenyang, China.
“The triple therapy was also associated with a more potent inhibition of platelet function, especially in patients with acute coronary syndromes,” explained Yaling Han, MD, Department of Cardiology, Northern Hospital.
Short-term outcomes
In one study, 3,135 consecutive patients who underwent successful PCI received either dual antiplatelet therapy (n = 2,032) or triple antiplatelet therapy (n = 1,103). Dual antiplatelet therapy consisted of 100 mg aspirin plus 75 mg clopidogrel per day. Triple antiplatelet therapy added 200 mg cilostazol to the daily regimen.
The primary endpoint was the rate of major adverse cardiac events (MACE), defined as the composite of death, myocardial infarction (MI), or target lesion revascularization (TLR) within 30 days.
The 30-day rate of MACE was 1.3% with triple antiplatelet therapy and 2.6% with dual antiplatelet therapy (P < .01). The incidences of MI and TLR were similar between the two groups. The incidence of death was significantly lower in patients who received triple antiplatelet therapy: 0.4% vs. 1.6% (P < .05).
Rates of hemorrhage and major bleeding were not statistically different between groups. The incidence of sub-acute thrombosis was 0.7% with triple antiplatelet therapy and 1.0% with dual antiplatelet therapy (P = NS).
Platelet functions
The second study evaluated 120 patients who underwent successful PCI. Sixty received dual antiplatelet therapy; the remaining patients received triple antiplatelet therapy. Patients began aspirin and clopidogrel at least two days before PCI and cilostazol directly afterward.
Immediately and five days after PCI, Han and colleagues measured PAC-1 and CD62p expression and maximum platelet aggregation rate (MPAR) induced by 5 and 20 µmol/L adenosine diphosphate (ADP). Baseline values were comparable between the two groups.
Within five days, decreases in PAC-1 and CD62p expression were greater in patients who received triple antiplatelet therapy. The decrease in PAC-1 expression was 12.1 ± 12.3% vs. 2.2 ± 15.2% with dual antiplatelet therapy (P < .05) (Figure). The decrease in CD62p expression was 5.1 ± 11.3% vs. 1.1 ± 5.0% with dual antiplatelet therapy (P < .05). Changes in MPAR were similar between the two groups.
Subgroup analysis for patients with acute coronary syndromes showed that changes of PAC-1 (11.6 ± 12.7% vs. 1.3 ± 15.7%), CD62p (5.6 ± 12.1% vs. 1.3 ± 4.4%) and MPAR induced by 20 μmol/L ADP (11.0 ± 11.1% vs. 5.2 ± 13.3%) or by 5 μmol/L ADP (8.7 ± 10.4% vs. 2.9 ± 13.1%) were all greater with triple antiplatelet therapy (P < .05).
At 6-month follow-up, the rate of major adverse cardiac and cerebral events and the rate of hemorrhage were statistically similar between the two groups.
“The results suggest that the novel triple antiplatelet regimen should be promising in reducing ischemic events in selected post-PCI patients,” Han said, adding that questions still remain about long-term outcomes, bleeding complications, tolerance, and cost-effective ratio.
To evaluate long-term outcomes, Han and colleagues are conducting a single-center, randomized, controlled clinical trial in about 1,200 patients with acute coronary syndromes and undergoing coronary stenting.
The researchers plan to observe clinical outcomes for up to three years.