Assessing the Optimal Level of Platelet Inhibition with GPIIb/IIIa Inhibitors in Patients Undergoing Coronary Intervention. Rationale and Design of the GOLD Study

Journal of Thrombosis and Thrombolysis -     

What is the role for improved long-term antiplatelet therapy after percutaneous coronary intervention?

Background

Coronary stent placement has replaced balloon angioplasty as the percutaneous coronary intervention (PCI) method of choice, primarily because of its lower restenosis rate. Compared with aspirin (ASA) monotherapy or ASA plus warfarin, the ticlopidine and ASA combination is superior in reducing thrombotic events after stenting. Clopidogrel plus ASA appears to be at least as effective as ticlopidine and ASA. Intravenous glycoprotein IIb/IIIa inhibitors effectively prevent periprocedural thrombotic complications, but their short duration of action and parenteral dosing don’t allow for long-term protection. This review aimed to answer how long after PCI with a stent patients are at risk for recurrent thrombotic events and what the optimal way to prevent them is.

Results

Classically, ASA has been prescribed indefinitely, whereas adenosine diphosphate receptor antagonists have been discontinued after 2 to 4 weeks. However, the Clopidogrel in Unstable Angina to Prevent Recurrent Events (CURE) trial found that long-term dual antiplatelet therapy with clopidogrel and ASA was more effective than ASA alone in preventing major cardiovascular events in patients with acute coronary syndrome, including those treated with PCI.

Conclusion

Results from additional ongoing studies are needed to clarify the role of long-term dual oral antiplatelet therapy in preventing ischemic events in patients who have undergone PCI.     

Influence of treatment duration with a 600-mg dose of clopidogrel before percutaneous coronary revascularization

OBJECTIVES: We examined clinical outcomes in the Intracoronary Stenting and Antithrombotic Regimen-Rapid Early Action for Coronary Treatment (ISAR-REACT) trial based on the duration of pretreatment with a 600-mg loading dose of clopidogrel. BACKGROUND: The influence of the treatment duration with a 600-mg dose of clopidogrel before percutaneous coronary revascularization on early outcomes remains uncertain. METHODS: Among 2,159 patients with coronary disease who underwent percutaneous coronary intervention (PCI) in the ISAR-REACT trial, we examined clinical outcomes relative to the duration of pretreatment with a 600-mg dose of clopidogrel: (2 to 3 h, 3 to 6 h, 6 to 12 h, or >12 h). Patients were randomly assigned to adjunctive therapy with abciximab or placebo at the beginning of the study. The primary end point was a composite of death, myocardial infarction, or urgent revascularization within 30 days after randomization. RESULTS: No significant differences were observed between patient groups regarding the duration of pretreatment, irrespective of assignment to abciximab or placebo (p = 0.27 for interaction among abciximab/clopidogrel and placebo/clopidogrel treatment at each time interval). Occurrence of major bleeding also did not differ according to time of initial clopidogrel dosing. CONCLUSIONS: For low-to-intermediate risk patients treated with a 600-mg loading dose of clopidogrel before PCI, incremental clinical benefit within the first 30 days from durations of pretreatment >2 to 3 h was not evident.     

Antiplatelet therapy in prevention of cardio- and venous thromboembolic events

The contribution of platelets in the pathophysiology of low-shear thrombosis—specifically, in atrial fibrillation (AF) and venous thromboembolic events (VTE)—remains less clear than for arterial thrombosis. AF itself appears to lead to platelet activation, offering a potential target for aspirin and other antiplatelet agents. Randomized trial results suggest a small benefit of aspirin over placebo, and of dual antiplatelet therapy (aspirin plus clopidogrel) over aspirin alone, for prevention of cardioembolic events in AF. Antiplatelet therapy thus can represent an option for patients with AF who are unsuitable for therapy with warfarin or novel oral anticoagulant agents. For VTE, the rationale for antiplatelet therapy reflects the venous response to disrupted blood flow—interactions among monocytes, neutrophil extracellular traps, and platelets. Early randomized trials generally showed poorer performance of aspirin relative to heparins and danaparoid sodium in prevention of VTE. However, results from large placebo- and dalteparin-controlled randomized trials have spurred changes in the most recent practice guidelines—aspirin is now recommended after major orthopedic surgery for patients who cannot receive other antithrombotic therapies.     

The influence of peripheral arterial disease on outcomes: a pooled analysis of mortality in eight large randomized percutaneous coronary intervention trials.

OBJECTIVES: We aimed to evaluate clinical outcomes among peripheral arterial disease (PAD) patients following percutaneous coronary intervention (PCI). BACKGROUND: A significant proportion of patients with coronary artery disease undergoing PCI have concomitant PAD, which may be associated with worse outcomes. METHODS: We performed a pooled analysis of 8 randomized PCI trials. We included multicenter PCI trials that compared antiplatelet therapies (EPIC, EPILOG, EPISTENT, RAPPORT, CAPTURE, IMPACT-II, TARGET, and CREDO) and had baseline PAD status recorded. Multivariable analyses were performed with stepwise logistic regression for 7- and 30-day outcomes and Cox regression for 6-month and 1-year events. RESULTS: In our pooled analysis of 19,867 patients undergoing PCI, 1,602 (8.1%) were previously diagnosed with PAD. Patients with PAD had higher incidences of 7-day death (1.0% vs. 0.4%; p < 0.001) or myocardial infarction (MI) (6.8% vs. 5.6%; p = 0.047), 30-day death (1.7% vs. 0.7%; p < 0.001) or MI (7.4% vs. 6.1%; p = 0.05), 6-month death (4.2% vs. 1.5%; p < 0.001) or MI (9.1%, vs. 7.7%; p = 0.048), and 1-year death (5.0% vs. 2.1%; p < 0.001). There was a trend toward higher major bleeding risk with PAD (4.8% vs. 3.9%; p = 0.06). With multivariable analyses, PAD remains a significant predictor of mortality at 30 days (hazard ratio [HR] 1.67, 95% confidence interval [CI] 1.03 to 2.70; p = 0.039), 6 months (HR 1.76, 95% CI 1.31 to 2.37; p < 0.001), and 1 year (HR 1.46, 95% CI 1.08 to 1.96; p = 0.013). CONCLUSIONS: The presence of PAD is associated with higher rates of post-PCI death and MI, and is an independent predictor of short- and long-term mortality.