prasugrel-hydrochloride and Coronary-Stenosis

Third-generation P2Y12 antagonists (prasugrel and ticagrelor) are recommended in guidelines on ST-segment elevation myocardial infarction. Mechanisms translating their more potent antiplatelet activity into improved clinical outcomes versus the second-generation P2Y12 antagonist clopidogrel are unclear. The aim of this post hoc analysis of the Complete Versus Lesion-Only PRImary PCI Trial-CMR (CvLPRIT-CMR) substudy was to assess whether prasugrel and ticagrelor were associated with reduced infarct size compared with clopidogrel in patients undergoing primary percutaneous coronary intervention.. CvLPRIT-CMR was a multicenter, prospective, randomized, open-label, blinded end point trial in 203 ST-segment elevation myocardial infarction patients with multivessel disease undergoing primary percutaneous coronary intervention with either infarct-related artery-only or complete revascularization. P2Y12 inhibitors were administered according to local guidelines. The primary end point of infarct size on cardiovascular magnetic resonance was not significantly different between the randomized groups. P2Y12 antagonist administration was not randomized. Patients receiving clopidogrel (n=70) compared with those treated with either prasugrel or ticagrelor (n=133) were older (67.8±12 versus 61.5±10 years, P<0.001), more frequently had hypertension (49% versus 29%, P=0.007), and tended to have longer symptom-to-revascularization time (234 versus 177 minutes, P=0.05). Infarct size (median 16.1% [quartiles 1-3, 10.5-27.7%] versus 12.1% [quartiles 1-3, 4.8-20.7%] of left ventricular mass, P=0.013) and microvascular obstruction incidence (65.7% versus 48.9%, P=0.022) were significantly greater in patients receiving clopidogrel. Infarct size remained significantly different after adjustment for important covariates using both generalized linear models (P=0.048) and propensity score matching (P=0.025).. In this analysis of CvLPRIT-CMR, third-generation P2Y12 antagonists were associated with smaller infarct size and lower microvascular obstruction incidence versus the second-generation P2Y12 antagonist clopidogrel for ST-segment elevation myocardial infarction.. URL: http://www.isrctn.com/ISRCTN70913605.

Topics: Adenosine; Aged; Clopidogrel; Coronary Angiography; Coronary Stenosis; Drug Administration Schedule; Female; Humans; Magnetic Resonance Angiography; Male; Microvessels; Middle Aged; Myocardial Revascularization; Organ Size; Percutaneous Coronary Intervention; Platelet Aggregation Inhibitors; Prasugrel Hydrochloride; Prospective Studies; Purinergic P2Y Receptor Antagonists; ST Elevation Myocardial Infarction; Ticagrelor; Ticlopidine; Time Factors; Treatment Outcome

Whether prasugrel plus bivalirudin is a superior strategy to unfractionated heparin plus clopidogrel in patients with ST-segment elevation myocardial infarction (STEMI) undergoing primary percutaneous coronary intervention (PCI) has never been assessed in specifically designed randomized trials.. The Bavarian Reperfusion Alternatives Evaluation (BRAVE) 4 study is an investigator-initiated, randomized, open-label, multicentre trial, designed to test the hypothesis that in STEMI patients with planned primary PCI a strategy based on prasugrel plus bivalirudin is superior to a strategy based on clopidogrel plus heparin in terms of net clinical outcome. Owing to slow recruitment, the trial was stopped prematurely after enrolment of 548 of 1240 planned patients. At 30 days, the primary composite endpoint of death, myocardial infarction, unplanned revascularization of the infarct related artery, stent thrombosis, stroke, or bleeding was observed in 42 patients (15.6%) randomized to prasugrel plus bivalirudin and 40 patients (14.5%) randomized to clopidogrel plus heparin [relative risk, 1.09; one-sided 97.5% confidence interval (CI) 0-1.79, P = 0.680]. The composite ischaemic endpoint of death, myocardial infarction, unplanned revascularization of the infarct-related artery, stent thrombosis, or stroke occurred in 13 patients (4.8%) in the prasugrel plus bivalirudin group and 15 patients (5.5%) in the clopidogrel plus heparin group (relative risk, 0.89; 95% CI 0.40-1.96, P = 0.894). Bleeding according to the HORIZONS-AMI definition was observed in 38 patients (14.1%) in the prasugrel plus bivalirudin group and 33 patients (12.0%) in the clopidogrel plus heparin group (relative risk, 1.18; 95% CI 0.74-1.88, P = 0.543). Results were consistent across various subgroups of patients.. In this randomized trial of STEMI patients, we were unable to demonstrate significant differences in net clinical outcome between prasugrel plus bivalirudin and clopidogrel plus heparin. Neither the composite of ischaemic complications nor bleeding were favourably affected by prasugrel plus bivalirudin compared with a regimen of clopidogrel plus unfractionated heparin. However, the results must be interpreted in view of the premature termination of the trial.. Unique identifier NCT00976092 (www.clinicaltrials.gov).

Topics: Aged; Anticoagulants; Clopidogrel; Coronary Angiography; Coronary Stenosis; Drug Therapy, Combination; Early Termination of Clinical Trials; Heparin; Hirudins; Humans; Kaplan-Meier Estimate; Male; Middle Aged; Myocardial Infarction; Peptide Fragments; Piperazines; Platelet Aggregation Inhibitors; Prasugrel Hydrochloride; Recombinant Proteins; Thiophenes; Ticlopidine; Treatment Outcome

The use of prasugrel and ticagrelor as part of dual antiplatelet therapy is increasing in patients after percutaneous coronary intervention (PCI). Accordingly, we aimed to evaluate their prescription patterns in the National Cardiovascular Data Registry (NCDR) Practice Innovation and Clinical Excellence (PINNACLE) registry. We analyzed patients enrolled in NCDR PINNACLE registry from January 2013 to March 2015 who underwent PCI with drug-eluting stent and were prescribed dual antiplatelet therapy. All patients received aspirin. The primary study outcome was a 3-level variable denoting the second antiplatelet agent prescribed: (1) clopidogrel, (2) prasugrel, or (3) ticagrelor. Baseline characteristics were compared among the 3 groups. Odds ratios and 95% credible intervals were calculated from a nested hierarchical Bayesian logistic regression models to identify independent predictors of prescription of antiplatelet medications, incorporating practice and provider as random effects. Our study cohort consisted of 26,710 patients during our study period January 2013 to March 2015. Seventy nine percent of patients were prescribed clopidogrel, 12% prasugrel, and 11% ticagrelor. Patients aged ≥75 years, women, history of tobacco use, Peripheral Arterial Disease (PAD), hypertension, diabetes, previous vascular complication, heart failure, and stroke/transient ischemic attack were more likely to be on clopidogrel than prasugrel or ticagrelor. The relative percentages of ticagrelor and prasugrel were higher in patients with history of myocardial infarction, compared with those without myocardial infarction. In summary, our study highlights the prescription patterns associated with prescription of antiplatelet agents after PCI. We found that both ticagrelor and prasugrel were mostly prescribed per the current practice guidelines, thus reflecting appropriate guideline adherence by practices in NCDR PINNACLE registry.

Topics: Aged; Bayes Theorem; Clopidogrel; Cohort Studies; Combined Modality Therapy; Coronary Angiography; Coronary Stenosis; Drug Utilization; Drug-Eluting Stents; Female; Humans; Logistic Models; Male; Middle Aged; Percutaneous Coronary Intervention; Platelet Aggregation Inhibitors; Prasugrel Hydrochloride; Prescriptions; Registries; Retrospective Studies; Severity of Illness Index; Survival Analysis; Ticagrelor; Treatment Outcome; United States

Patients are generally required to stop antiplatelet therapy prior to elective invasive procedures. Some patients receive dual antiplatelet therapy for recent vascular procedures such as drug-eluting coronary stenting, and early discontinuation of antiplatelet agents could lead to a significant risk of stent thrombosis. Most bronchoscopic procedures are performed on patients using Aspirin but not on those using Clopidogrel or Prasugrel. In this report, we describe a unique case of a patient with a recent placement of drug-eluting stents, who required endobronchial biopsies for evaluation of lung cancer recurrence. The procedure was performed successfully and safely with no complications.

Topics: Angioplasty, Balloon, Coronary; Aspirin; Biopsy, Needle; Bronchoscopy; Carcinoma, Squamous Cell; Coronary Restenosis; Coronary Stenosis; Drug-Eluting Stents; Follow-Up Studies; Humans; Lung Neoplasms; Male; Middle Aged; Monitoring, Physiologic; Neoplasm Recurrence, Local; Patient Safety; Platelet Aggregation Inhibitors; Pneumonectomy; Prasugrel Hydrochloride; Radiography; Risk Assessment; Treatment Outcome

There was an excess of new solid neoplasms (112 vs. 69), and cancer deaths (24 vs. 15) after prasugrel in the TRITON (Trial to Assess Improvement in Therapeutic Outcomes by Optimizing Platelet Inhibition). These cancers usually occur after 4 months following prasugrel, and women are especially at risk. The hypothesis has been offered that prasugrel, but not aspirin or clopidogrel, causes indirect modulation of tumor growth, and/or enhanced metastatic dissemination due to instability of platelet-tumor cell aggregates via the inability to keep cancer locally within the platelet thrombi due to excessive chronic platelet inhibition.. A 70-year old female diabetic patient underwent drug-eluting stent implantation. The patient received a loading dose of prasugrel (60 mg), followed by prasugrel 10 mg/daily as well as aspirin (81 mg/daily). After 4 months on dual antiplatelet therapy she expectorated blood when coughing. A lung X-ray and CT scan revealed numerous lung nodules later diagnosed as unclassified pleomorphic and spindle cell malignant solid neoplasm. The patient died following multiple brain metastasis.. Female gender, duration of prasugrel exposure, rare unclassified neoplasm pathology type and a tumor of a highly metastatic and aggressive nature in the index patient should be regarded with caution. The effects of novel antiplatelet agents on the onset of cancer should be tested in future mega-trials.

Topics: Aged; Aspirin; Brain Neoplasms; Carcinoma; Clinical Trials, Phase III as Topic; Clopidogrel; Colonic Neoplasms; Coronary Stenosis; Diabetes Mellitus, Type 1; Diabetic Cardiomyopathies; Drug Therapy, Combination; Drug-Eluting Stents; Fatal Outcome; Female; Humans; Lung Neoplasms; Piperazines; Platelet Aggregation Inhibitors; Prasugrel Hydrochloride; Purinergic P2Y Receptor Antagonists; Randomized Controlled Trials as Topic; Risk Factors; Thiophenes; Ticlopidine; Time Factors

This study sought to determine angiographic and clinical outcomes among patients with acute coronary syndrome (ACS) presenting with isolated anterior ST-segment depression on 12-lead electrocardiogram (ECG).. In patients with ACS, anterior ST-segment depression on 12-lead ECG may represent plaque rupture with: 1) acute thrombotic occlusion with elevation of cardiac biomarkers (+Tn); 2) a patent artery with +Tn; or 3) a patent artery with -Tn.. The TRITON-TIMI 38 (Trial to Assess Improvement in Therapeutic Outcomes by Optimizing Platelet Inhibition with Prasugrel-Thrombolysis In Myocardial Infarction 38) enrolled 13,608 ACS patients. Those with isolated anterior (leads V(1) to V(4)) ST-segment depression were analyzed. Angiograms and ECGs were interpreted by local investigators.. There were 1,198 (8.8%) patients with isolated anterior ST-segment depression. Of those, 314 (26.2%) had an occluded culprit artery (TIMI flow grade 0/1) and +Tn, 641 (53.5%) had a patent culprit artery (TIMI flow grade 2/3) and +Tn, and 243 (20.3%) had TIMI flow grade 2/3 and -Tn. Among patients with an occluded artery, the culprit artery was most often the left circumflex artery (48.4%). The 30-day incidence of the composite of death and MI was significantly higher among patients with an occluded artery (8.6%) than among those with a patent culprit artery and either +Tn (6.3%) or -Tn (2.9%) (3-way p = 0.006). Among patients with an occluded artery, the median time from ECG to percutaneous coronary intervention was 29.4 h (interquartile range 26.1 to 44.1 h).. Among ACS patients presenting with isolated anterior ST-segment depression, over one-quarter had an occluded culprit artery and elevated cardiac biomarkers. These patients had significantly worse clinical outcomes, and few underwent urgent angiography.

Topics: Acute Coronary Syndrome; Aged; Angina, Unstable; Angioplasty, Balloon, Coronary; Biomarkers; Chi-Square Distribution; Coronary Angiography; Coronary Stenosis; Creatine Kinase, MB Form; Electrocardiography; Female; Humans; Male; Middle Aged; Myocardial Infarction; Piperazines; Platelet Aggregation Inhibitors; Prasugrel Hydrochloride; Proportional Hazards Models; Randomized Controlled Trials as Topic; Retrospective Studies; Risk Assessment; Risk Factors; Thiophenes; Time Factors; Treatment Outcome; Up-Regulation; Vascular Patency

Therapy with aspirin and/or adenosine diphosphate (ADP) receptor blockers is associated with better outcomes via inhibition of platelet activity, and subsequent reduction of ischemic vascular events. Non-compliance (NC) is a well-recognised hazard limiting the clinical utility of antiplatelet agents, and, probably worsening outcomes. However, comprehensive platelet characteristics of a confirmed NC patient after acute vascular event have never been reported within a major randomised trial with ADP-receptor antagonists. A 48-year-old male patient, well-educated, was among patients enrolled in the platelet sub-study for the JUMBO trial. He received 325 mg of aspirin daily for 9 months, presented with unstable angina for urgent coronary intervention, and was successfully reperfused with two intracoronary stents. The patient was randomised to a 60 mg prasugrel loading dose, and 10 mg of prasugrel daily for 30 days. Platelets were assessed at baseline, 4 and 24 h, and at 30 days after acute coronary event utilising ADP-, and collagen-induced conventional aggregometry, rapid cartridge-based analyser and flow cytometry. Loading with prasugrel resulted in significant inhibition of platelet activity during and after stenting. However, after assessing platelet biomarkers at 30 days, voluntary withdrawal from the antiplatelet agents was suspected. Based on the platelet activity characteristics, NC was later confirmed, and the patient admitted that he stopped taking both prasugrel and aspirin shortly after discharge due to minor bleeding episodes after shaving. Major platelet activity biomarkers of the index NC patient were compared with those from compliant prasugrel-, clopidogrel-treated patients, and healthy controls. The platelet tests uniformly revealed rebound activation by all platelet measures (at least twofold increase) while being especially high for ADP-, and collagen-induced aggregation, platelet/endothelial cell adhesion molecule-1 (PECAM-1), glycoprotein (GP)Ib, GPIIb/IIIa activity, P-selectin, protease activated receptor (PAR)-1 thrombin receptor (activated and intact epitopes), and thrombospondin expression. The clinical benefits of antiplatelet agents are not only denied in NC outpatients, but may put them at additional risk for worsened vascular outcomes due to the rebound platelet activation. Proclaimed 'resistance' to antiplatelet agents may at least in part be a result of NC, especially in the chronic uncontrolled setting. Enforcing compliance wi

Topics: Angina Pectoris; Aspirin; Chronic Disease; Coronary Stenosis; Drug Therapy, Combination; Humans; Male; Middle Aged; Myocardial Ischemia; Piperazines; Platelet Activation; Platelet Aggregation Inhibitors; Prasugrel Hydrochloride; Randomized Controlled Trials as Topic; Thiophenes; Treatment Refusal