A randomized trial assessing the effect of coumarins started before coronary angioplasty on restenosis: results of the 6-month angiographic substudy of the Balloon Angioplasty and Anticoagulation Study (BAAS)

Background Thrombus formation during coronary angioplasty may play a role in the restenosis process.Methods The effect of pretreatment with coumarins on 6-month angiographic outcome was studied. In addition, the effect of “optimal” anticoagulation, defined as an international normalized ratio >70% of the follow-up time in the target range, was studied. A total of 261 patients were assigned to aspirin alone (ASA group) and 270 patients to aspirin plus coumarins started 1 week before the procedure (coumarin group).Results The mean international normalized ratio was 2.7 ± 1.2 at the start of the procedure and 3.1 ± 0.5 during follow up. Quantitative coronary analysis was performed on 301 lesions in the ASA group and of 297 lesions in the coumarin group. At 6 months, the minimal luminal diameter was similar in the ASA and coumarin groups. Optimal anticoagulation, however, was an independent predictor of a larger minimal luminal diameter at follow up (P = .01).Conclusion Overall, coumarins do not improve angiographic outcome 6 months after coronary angioplasty. (Am Heart J 2003;145:58-65.)     

Platelet Function Testing and Tailored Antiplatelet Therapy

Dual antiplatelet therapy, consisting of aspirin and a P2Y12 receptor inhibitor, has dramatically reduced the incidence of atherothrombotic events for patients with acute coronary syndrome and those undergoing a percutaneous coronary intervention (PCI). However, the platelet inhibitory effect of clopidogrel, the most commonly used P2Y12 inhibitor, is variable between patients. Patients exhibiting high platelet reactivity (HPR) despite clopidogrel treatment are at higher risk of recurrent atherothrombotic events after PCI. In order to reduce the incidence of HPR, the more potent P2Y12 receptor inhibitors prasugrel and ticagrelor are used. However, these drugs increase the risk of bleeding. As there is evidence of a therapeutic window for platelet inhibition, platelet function tests could be helpful for tailoring antiplatelet therapy based on the patient’s thrombotic and bleeding risk. In the present article, we review the most commonly used platelet function tests and the current evidence for tailoring of antiplatelet therapy in PCI patients.     

High-dose aspirin in addition to daily low-dose aspirin decreases platelet activation in patients before and after percutaneous coronary intervention

BACKGROUND: Activated platelets play a major role in acute vessel closure after coronary angioplasty. Although aspirin is the routine therapy during angioplasty, it only incompletely prevents acute closure. This might be due to suboptimal dosing. OBJECTIVE: First, to study the effect of additional high-dose aspirin on platelet activation during coronary angioplasty. Second, to assess the potential of the new PFA-100 analyzer to evaluate the effect of different doses of aspirin in patients undergoing angioplasty. METHODS: Fifty-one patients on 100 mg aspirin/day for at least 1 month were randomized to continuation of 100 mg aspirin/day only (Group A=24 patients), or to this regime plus a bolus of 1000 mg of aspirin given 1 day before angioplasty (Group B=27 patients). Results were compared with 15 controls. Platelet function was measured before angioplasty by the PFA-100 analyzer; platelet activation was measured by flow cytometry just before and 1 h after angioplasty. RESULTS: At baseline, Group A had significantly more activated platelets than the control group (P<.001). High-dose aspirin in Group B resulted in significantly lower platelet activation as compared with both controls (P<.001) and Group A (P<.001). During angioplasty, the number of activated platelets decreased significantly in Group A (P<.001), while there was no change in Group B (P=.6). The PFA-100 analyzer was unable to detect differences between the two treatment groups. CONCLUSIONS: The addition of high-dose aspirin to daily low-dose aspirin, 1 day before coronary angioplasty, significantly reduced the platelet activation state before and after intervention. The PFA-100 analyzer did not detect differences in the effect of low- versus high-dose aspirin on platelet function.     

Evaluation of Dual Versus Triple Therapy by Landmark Analysis in the RE-DUAL PCI Trial

ObjectivesThe aim of this study was to explore the early versus late benefits and risks of dabigatran dual therapy versus warfarin triple therapy in the RE-DUAL PCI (Randomized Evaluation of Dual Antithrombotic Therapy With Dabigatran Versus Triple Therapy With Warfarin in Patients With Nonvalvular Atrial Fibrillation Undergoing Percutaneous Coronary Intervention) trial.BackgroundPatients with atrial fibrillation who undergo percutaneous coronary intervention are at increased risk for both bleeding and thrombotic events.MethodsA total of 2,725 patients with atrial fibrillation underwent percutaneous coronary intervention and were randomized to receive dabigatran 110 mg, or dabigatran 150 mg plus a P2Y₁₂ inhibitor (and no aspirin), or warfarin plus a P2Y₁₂ inhibitor plus aspirin. Landmark analysis was performed at 30 and 90 days.ResultsThere was a consistent and large reduction in major or clinically relevant nonmajor bleeding in patients randomized to dual therapy during the first 30 days (110 mg: hazard ratio [HR]: 0.45; 95% confidence interval [CI]: 0.31 to 0.66; p < 0.0001; 150 mg: HR: 0.46; 95% CI: 0.30 to 0.72; p = 0.0006) compared with warfarin triple therapy. There was early net clinical benefit in both dabigatran groups versus warfarin (110 mg: HR: 0.65; 95% CI: 0.47 to 0.88; p = 0.0062; 150 mg: HR: 0.54; 95% CI: 0.37 to 0.79; p = 0.0015), due to larger reductions in bleeding than increased thrombotic events for dabigatran 110 mg and bleeding reduction without increased thrombotic risk for dabigatran 150 mg dual therapy versus warfarin triple therapy. After the removal of aspirin in the warfarin group, bleeding remained lower with dabigatran 110 mg and was similar with dabigatran 150 mg versus warfarin.ConclusionsIn RE-DUAL PCI, in which patients in the dual-therapy arms were treated with aspirin for an average of only 1.6 days, there was early net clinical benefit with both doses of dabigatran dual therapy, without an increase in thrombotic events with dabigatran 150 mg. This could be helpful in the subset of patients with elevated risk for both bleeding and thrombotic events.