PT170 Mid-Term On-Clopidogrel Platelet Reactivity (PR) and Long-Term Adverse Events in Patients on Prolonged Dual Antiplatelet Therapy (DAPT)

Introduction: The relationship of low “on-treatment” platelet reactivity to longitudinal risks of major bleeding following acute coronary syndromes (ACS) has not been clearly delineated. Methods: We analyzed 2428 patients with non-ST-elevation ACS (NSTE ACS) from the TRILOGY ACS trial who were managed without revascularization and had platelet reactivity measurements (P2Y12 reaction units [PRUs]) collected in a platelet function substudy. Patients received aspirin + prasugrel (10 mg/d; 5 mg/d for those ≥75 y or <75 y and <60 kg) or clopidogrel (75 mg/d). Non-CABG severe/moderate GUSTO bleeding and non-CABG TIMI major/minor bleeding were ascertained through 30 months. Contal’s method was used to investigate whether a PRU cut point could distinguish high vs low bleeding risk. Multivariable Cox proportional hazard models were used to evaluate the association between PRU and time to first bleed. Results: Through 30 months, there were 27 GUSTO severe/moderate bleeds and 37 TIMI major/minor bleeds, with gastrointestinal bleeding the most common. Baseline characteristics were stratified by tertiles of PRU values at 5 d, and significant differences were seen across tertiles (Table). Unadjusted bleeding rates appeared highest among those in the lowest PRU tertile but no reliable PRU cut point was found that significantly distinguished bleeding risk. Unadjusted analyses showed continuous measures of PRUs were not associated with GUSTO (HR=1.00, 95% CI: 0.96-1.04) or TIMI bleeding (HR=1.03, 95% CI: 0.99-1.06). This relationship did not change after multivariable adjustment. Conclusions: Among NSTE-ACS patients managed without revascularization and receiving dual antiplatelet therapy, PRU values were not significantly associated with long-term bleeding risk. The relatively small number of bleeding events accrued limited study power, but these results suggest that low “on-treatment” platelet reactivity does not independently predict post-ACS bleeding risk.

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Prasugrel effectively reduces the platelet reactivity units in patients with genetically metabolic dysfunction of cytochrome P450 2C19 who are treated with long-term dual antiplatelet therapy after undergoing drug-eluting stent implantation

Heart and Vessels ◽

10.1007/s00380-019-01499-7 ◽

2019 ◽

Vol 35 (3) ◽

pp. 312-322 ◽

Cited By ~ 3

Author(s):

Junichiro Shimamatsu ◽

Ken-ichiro Sasaki ◽

Yoshio Katsuki ◽

Tomohiro Kawasaki ◽

Yoshinobu Murasato ◽

...

Keyword(s):

Cytochrome P450 ◽

Antiplatelet Therapy ◽

Stent Implantation ◽

Dual Antiplatelet Therapy ◽

Platelet Reactivity ◽

Late Phase ◽

Coronary Stent ◽

Cyp2c19 Polymorphism ◽

Coronary Stent Implantation

Abstract Dual antiplatelet therapy (DAPT) with aspirin and P2Y12 inhibitor is administered following percutaneous coronary intervention (PCI) with coronary stent implantation. Several studies have reported the effects of switching between P2Y12 inhibitors on platelet reactivity (P2Y12 reaction units: PRU), from acute to late phase after PCI. However, the effect of switching at very late phase is unknown. This study examined the effect on PRU in Japanese coronary heart disease patients with long-term DAPT (aspirin + clopidogrel) when switching from clopidogrel to prasugrel. Ninety-six patients were enrolled in this study. The median DAPT duration at enrollment was 1824.0 days. Twenty-three patients with PRU ≥ 208 at enrollment were randomly assigned into either continuing to receive clopidogrel (Continued Group; n = 11) or switching to prasugrel (Switched Group; n = 12). The primary endpoint was the rate of patients who achieved PRU < 208 at the end of 12 weeks of treatment, which was significantly higher in Switched Group relative to Continued Group (90.0% vs. 36.4%; P = 0.024). The secondary endpoint was the PRU at week 12 in groups subdivided according to cytochrome P450 (CYP) 2C19 genotypes. At week 12, extensive metabolizers (EM Group) had 202.3 ± 60.0 and 174.5 ± 22.3 in Continued Group and Switched Group (P = 0.591), respectively; intermediate and poor metabolizers (non-EM Group) had 229.4 ± 36.9 and 148.4 ± 48.4 in Continued Group and Switched Group (P = 0.002), respectively. The PRU for non-EM Group was significantly reduced in Switched Group. Thus, for patients with long-term DAPT (aspirin + clopidogrel) after PCI with coronary stent implantation, switching from clopidogrel to prasugrel resulted in a stable reduction in PRU, regardless of CYP2C19 polymorphism.

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Anticoagulation in addition to dual antiplatelet therapy has no impact on long-term follow-up after endovascular treatment of (sub)acute lower limb ischemia

VASA ◽

10.1024/0301-1526/a000786 ◽

2019 ◽

Vol 48 (4) ◽

pp. 321-329

Author(s):

Mariya Kronlage ◽

Erwin Blessing ◽

Oliver J. Müller ◽

Britta Heilmeier ◽

Hugo A. Katus ◽

...

Keyword(s):

Endovascular Treatment ◽

Antiplatelet Therapy ◽

Dual Antiplatelet Therapy ◽

Limb Ischemia ◽

Bleeding Complications ◽

Severe Bleeding ◽

Short Term ◽

Long Term Follow Up

Summary. Background: To assess the impact of short- vs. long-term anticoagulation in addition to standard dual antiplatelet therapy (DAPT) upon endovascular treatment of (sub)acute thrombembolic occlusions of the lower extremity. Patient and methods: Retrospective analysis was conducted on 202 patients with a thrombembolic occlusion of lower extremities, followed by crirical limb ischemia that received endovascular treatment including thrombolysis, mechanical thrombectomy, or a combination of both between 2006 and 2015 at a single center. Following antithrombotic regimes were compared: 1) dual antiplatelet therapy, DAPT for 4 weeks (aspirin 100 mg/d and clopidogrel 75 mg/d) upon intervention, followed by a lifelong single antiplatelet therapy; 2) DAPT plus short term anticoagulation for 4 weeks, followed by a lifelong single antiplatelet therapy; 3) DAPT plus long term anticoagulation for > 4 weeks, followed by a lifelong anticoagulation. Results: Endovascular treatment was associated with high immediate revascularization (> 98 %), as well as overall and amputation-free survival rates (> 85 %), independent from the chosen anticoagulation regime in a two-year follow up, p > 0.05. Anticoagulation in addition to standard antiplatelet therapy had no significant effect on patency or freedom from target lesion revascularization (TLR) 24 months upon index procedure for both thrombotic and embolic occlusions. Severe bleeding complications occurred more often in the long-term anticoagulation group (9.3 % vs. 5.6 % (short-term group) and 6.5 % (DAPT group), p > 0.05). Conclusions: Our observational study demonstrates that the choice of an antithrombotic regime had no impact on the long-term follow-up after endovascular treatment of acute thrombembolic limb ischemia whereas prolonged anticoagulation was associated with a nominal increase in severe bleeding complications.

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