prasugrel-hydrochloride and Coronary-Restenosis

Prasugrel is a third-generation thienopyridine that achieves potent platelet inhibition with less pharmacological variability than other thienopyridines. However, clinical experience suggests that prasugrel may be associated with a higher risk of de novo and recurrent bleeding events compared with clopidogrel in Japanese patients undergoing percutaneous coronary intervention (PCI). In this review, we evaluate the risk of bleeding in Japanese patients treated with prasugrel at the doses (loading/maintenance doses: 20/3.75 mg) adjusted for Japanese patients, evaluate the risk factors for bleeding in Japanese patients, and examine whether patients with a bleeding event are at increased risk of recurrent bleeding. This review covers published data and new analyses of the PRASFIT (PRASugrel compared with clopidogrel For Japanese patIenTs) trials of patients undergoing PCI for acute coronary syndrome or elective reasons. The bleeding risk with prasugrel was similar to that observed with the standard dose of clopidogrel (300/75 mg), including when bleeding events were re-classified using the Bleeding Academic Research Consortium criteria. The pharmacodynamics of prasugrel was not associated with the risk of bleeding events. The main risk factors for bleeding events were female sex, low body weight, advanced age, and presence of diabetes mellitus. Use of a radial puncture site was associated with a lower risk of bleeding during PCI than a femoral puncture site. Finally, the frequency and severity of recurrent bleeding events during continued treatment were similar between prasugrel and clopidogrel. In summary, this review provides important insights into the risk and types of bleeding events in prasugrel-treated patients.Trial registration numbers: JapicCTI-101339 and JapicCTI-111550.

Topics: Acute Coronary Syndrome; Coronary Restenosis; Hemorrhage; Humans; Incidence; Japan; Percutaneous Coronary Intervention; Platelet Aggregation Inhibitors; Postoperative Hemorrhage; Prasugrel Hydrochloride; Recurrence; Risk Factors

New P2Y12 inhibitors can be classified as oral (prasugrel and ticagrelor) and intravenous drugs (cangrelor and elinogrel). These P2Y12 inhibitors might be superior to clopidogrel for reducing ischemic events in patients with coronary artery disease (CAD). We performed a meta-analysis of randomized trials that compared new oral or intravenous P2Y12 inhibitors with clopidogrel to determine their efficacy and safety in patients.. Twelve randomized, placebo-controlled studies and two subgroup analyses of included studies on ST-segment elevation myocardial infarction (STEMI) were included. The database consisted of 82,784 patients, with 43,875 (53%) on new oral P2Y12 inhibitors and 38909 (47%) on intravenous P2Y12 inhibitors compared with clopidogrel. The primary efficacy endpoint was major adverse cardiac events (MACEs). The primary safety endpoint was thrombolysis in myocardial infarction (TIMI) major bleeding. New oral P2Y12 inhibitors significantly decreased MACEs (odds ratio: 0.85, p<0.0001 for the whole cohort; OR: 0.77, p=0.04 for STEMI) and all-cause death (OR: 0.88, p=0.04 for the whole cohort; OR: 0.77, p=0.01 for STEMI). Among new intravenous P2Y12 inhibitors, only cangrelor significantly decreased the risk of MACEs. An increase in TIMI major bleeding was observed only by prasugrel among the new P2Y12 inhibitors.. New oral P2Y12 inhibitors reduce ischemic events, but there is no obvious increase in major bleeding in patients with CAD, and the risk/benefit ratio is particularly favorable for STEMI patients. Moreover, only cangrelor is beneficial for ischemic events in patients on new intravenous P2Y12 inhibitors.

Topics: Acute Coronary Syndrome; Adenosine; Adenosine Monophosphate; Administration, Oral; Clopidogrel; Coronary Artery Disease; Coronary Restenosis; Fibrinolytic Agents; Hemorrhage; Humans; Injections, Intravenous; Multicenter Studies as Topic; Myocardial Infarction; Piperazines; Prasugrel Hydrochloride; Purinergic P2Y Receptor Antagonists; Quinazolinones; Randomized Controlled Trials as Topic; Stents; Stroke; Sulfonamides; Thiophenes; Thrombolytic Therapy; Ticagrelor; Ticlopidine

Topics: Angioplasty, Balloon, Coronary; Clopidogrel; Coronary Restenosis; Humans; Piperazines; Platelet Aggregation Inhibitors; Prasugrel Hydrochloride; Thiophenes; Ticlopidine

Topics: Adenosine; Angioplasty, Balloon, Coronary; Clinical Trials as Topic; Clopidogrel; Coronary Angiography; Coronary Disease; Coronary Occlusion; Coronary Restenosis; Drug-Eluting Stents; Foramen Ovale, Patent; Hospital Mortality; Humans; Myocardial Infarction; Piperazines; Platelet Aggregation Inhibitors; Platelet Glycoprotein GPIIb-IIIa Complex; Prasugrel Hydrochloride; Purinergic P2 Receptor Antagonists; Radiology, Interventional; Thiophenes; Thrombolytic Therapy; Ticagrelor; Ticlopidine; Treatment Outcome

The efficacy with aspirin and clopidogrel treatment has been demonstrated in various clinical trials. Laboratory evaluation of platelet response in recent studies revealed that a distinctive response variability and nonresponsiveness/resistance in selected patients were associated with these antiplatelet agents. Moreover, some studies have correlated this nonresponsiveness/resistance phenomenon to the occurrence of thrombotic events. At this time there are no uniformly established methods to quantify exvivo platelet reactivity after clopidogrel and aspirin treatment of the extent of platelet inhibition by clopidogrel and aspirin. Therefore, specific treatment recommendations for patients exhibiting high platelet reactivity or poor platelet inhibition during clopidogrel or aspirin therapy are not established. A higher aspirin dose and strict compliance to therapy may overcome the occurrence of "aspirin resistance" in selected patients. A higher clopidogrel dose may be considered in patients exhibiting clopidogrel nonresponsiveness.

Topics: Adenosine; Adenosine Monophosphate; Angioplasty, Balloon, Coronary; Aspirin; Clinical Trials as Topic; Clopidogrel; Coronary Restenosis; Drug Resistance; Humans; Membrane Proteins; Myocardial Ischemia; Piperazines; Platelet Aggregation Inhibitors; Prasugrel Hydrochloride; Purinergic P2 Receptor Antagonists; Receptors, Purinergic P2Y12; Thiophenes; Ticagrelor; Ticlopidine

In the BAsel Stent Kosten Effektivitäts Trial PROspective Validation Examination (BASKET-PROVE), drug-eluting stents (DESs) had similar 2-year rates of death and myocardial infarction but lower rates of target vessel revascularization and major adverse cardiac events compared with bare-metal stents (BMSs). However, comparative clinical effects of newest-generation DES with biodegradable polymers vs second-generation DES or newest-generation BMS with biocompatible coatings, all combined with a prasugrel-based antiplatelet therapy, on 2-year outcomes are not known.. In BASKET-PROVE II, 2,400 patients with de novo lesions in native vessels ≥3 mm in diameter are randomized 1:1:1 to receive a conventional DES, a DES with a biodegradable polymer, or a BMS with biocompatible coating. In addition to aspirin, stable patients with BMS will receive prasugrel for 1 month, whereas all others will receive prasugrel for 12 months. The primary end point will be combined cardiac death, nonfatal myocardial infarction, and target vessel revascularization up to 2 years. Secondary end points include stent thrombosis and major bleeding. The primary aim is to test (1) the noninferiority of a biodegradable-polymer DES to a conventional DES and (2) the superiority of both DESs to BMS. A secondary aim is to compare the outcomes with those of BASKET-PROVE regarding the effects of prasugrel-based vs clopidogrel-based antiplatelet therapy.. By the end of 2010, 878 patients (37% of those planned) were enrolled.. This study will test the comparative long-term safety and efficacy of newest-generation stents on the background of contemporary antiplatelet therapy in a large all-comer population undergoing large native coronary artery stenting.

Topics: Coronary Angiography; Coronary Artery Disease; Coronary Restenosis; Denmark; Drug-Eluting Stents; Female; Follow-Up Studies; Germany; Humans; Incidence; Male; Middle Aged; Myocardial Infarction; Piperazines; Prasugrel Hydrochloride; Prospective Studies; Prosthesis Design; Purinergic P2Y Receptor Antagonists; Survival Rate; Switzerland; Thiophenes; Treatment Outcome

Observational studies of new coronary stents are necessary to assess performance in a variety of complex patient and lesion types. Furthermore, the optimal dose and duration of thienopyridine treatment is unclear, particularly in patients with complex clinical conditions. The TAXUS Libertē Post-Approval Study is designed to provide 5-year data on the TAXUS Liberté paclitaxel-eluting stent with concomitant prasugrel therapy in routine clinical practice and to contribute data to the DAPT study.. The TAXUS Libertē Post-Approval Study is a prospective, multicenter, observational study. Enrollment of approximately 4,200 patients receiving ≥1 TAXUS Liberté stents is planned. All patients without a contraindication will be prescribed prasugrel plus aspirin for 1 year. The 12-month primary end point of cardiac death or myocardial infarction in on-label stent patients will be compared with historical TAXUS Express stent data from the TAXUS ATLAS and TAXUS ARRIVE studies. Secondary clinical end points include stent thrombosis, all-cause death, stroke, revascularization, and bleeding in all patients. In addition, this study will be the first to evaluate prasugrel use in a routine practice setting (including 5 and 10 mg daily doses) and will contribute data to the DAPT Study, comparing 12 versus 30 months of dual antiplatelet therapy after drug-eluting stent placement.. The TAXUS Libertē Post-Approval Study will be the first to provide long-term real-world data on use of the TAXUS Liberté Stent with prasugrel treatment. The study is currently enrolling, and primary end point data are expected in mid 2013.

Topics: Aged; Cardiology; Coronary Angiography; Coronary Artery Disease; Coronary Restenosis; Device Approval; Drug-Eluting Stents; Equipment Design; Female; Follow-Up Studies; Humans; Male; Piperazines; Prasugrel Hydrochloride; Prospective Studies; Purinergic P2Y Receptor Antagonists; Thiophenes; Time Factors; Treatment Outcome

The type of periprocedural antithrombotic regimen that is the safest and most effective in percutaneous coronary intervention (PCI) patients on oral anticoagulant (OAC) therapy has not been fully investigated. We aimed to retrospectively investigate the in-hospital bleeding outcomes of patients receiving OAC and antiplatelet therapies during PCI using Japanese nationwide multicenter registry data. A total of 26,938 patients who underwent PCI with OAC and antiplatelet therapies between 2016 and 2017 were included. We investigated in-hospital bleeding requiring blood transfusion, mortality, and stent thrombosis according to the antithrombotic regimens used at the time of PCI: OAC + single antiplatelet therapy (double therapy) and OAC + dual antiplatelet therapy (triple therapy). The antiplatelet agents included aspirin, clopidogrel, and prasugrel. The OAC agents included warfarin and direct OACs. Adjusting the dose of OAC or intermitting OAC before PCI was at each operator's discretion. In the study population [mean age (SD), 73.5 (9.5) years; women, 21.5%], the double therapy and triple therapy groups comprised 5546 (20.6%) and 21,392 (79.4%) patients, respectively. Bleeding requiring transfusion was not significantly different between the groups [adjusted odds ratio (aOR), 0.700; 95% confidence interval (CI), 0.420-1.160; P = 0.165] (triple therapy as a reference). Mortality was not significantly different (aOR, 1.370; 95% CI, 0.790-2.360; P = 0.258). Stent thrombosis was significantly different between the groups (aOR, 3.310; 95% CI, 1.040-10.500; P = 0.042) (triple therapy as a reference). In conclusion, for patients on OAC therapy who underwent PCI, periprocedural triple therapy may be safe with respect to in-hospital bleeding risks. However, further investigations are warranted to establish the safety and efficacy of periprocedural triple therapy.

Topics: Aged; Aspirin; Clopidogrel; Coronary Artery Disease; Coronary Restenosis; Dual Anti-Platelet Therapy; Factor Xa Inhibitors; Female; Hemorrhage; Humans; Japan; Male; Percutaneous Coronary Intervention; Platelet Aggregation Inhibitors; Postoperative Complications; Prasugrel Hydrochloride; Registries; Retrospective Studies; Warfarin

Topics: Acute Coronary Syndrome; Clopidogrel; Coronary Restenosis; Coronary Vessels; Hemodynamics; Humans; Percutaneous Coronary Intervention; Platelet Aggregation Inhibitors; Prasugrel Hydrochloride; Purinergic P2Y Receptor Antagonists; Secondary Prevention; Spectroscopy, Near-Infrared; Switzerland; Ticagrelor; Tomography, Optical Coherence; Treatment Outcome; Ultrasonography, Interventional

Prasugrel and ticagrelor both reduce ischaemic endpoints in high-risk acute coronary syndromes, compared with clopidogrel. However, comparative outcomes of these two newer drugs in the context of primary percutaneous coronary intervention (PCI) for ST-elevation myocardial infarction (STEMI) remains unclear. We sought to examine this question using the British Cardiovascular Interventional Society national database in patients undergoing primary PCI for STEMI.. Data from January 2007 to December 2014 were used to compare use of P2Y12 antiplatelet drugs in primary PCI in >89 000 patients. Statistical modelling, involving propensity matching, multivariate logistic regression (MLR) and proportional hazards modelling, was used to study the association of different antiplatelet drug use with all-cause mortality.. In our main MLR analysis, prasugrel was associated with significantly lower mortality than clopidogrel at both 30 days (OR 0.87, 95% CI 0.78 to 0.97, P=0.014) and 1 year (OR 0.89, 95% CI 0.82 to 0.97, P=0.011) post PCI. Ticagrelor was not associated with any significant differences in mortality compared with clopidogrel at either 30 days (OR 1.07, 95% CI 0.95 to 1.21, P=0.237) or 1 year (OR 1.058, 95% CI 0.96 to 1.16, P=0.247). Finally, ticagrelor was associated with significantly higher mortality than prasugrel at both time points (30 days OR 1.22, 95% CI 1.03 to 1.44, P=0.020; 1 year OR 1.19 95% CI 1.04 to 1.35, P=0.01).. In a cohort of over 89 000 patients undergoing primary PCI for STEMI in the UK, prasugrel is associated with a lower 30-day and 1-year mortality than clopidogrel and ticagrelor. Given that an adequately powered comparative randomised trial is unlikely to be performed, these data may have implications for routine care.

Topics: Aged; Clopidogrel; Coronary Restenosis; Dose-Response Relationship, Drug; Female; Follow-Up Studies; Humans; Incidence; Male; Middle Aged; Percutaneous Coronary Intervention; Platelet Aggregation Inhibitors; Postoperative Care; Prasugrel Hydrochloride; Retrospective Studies; ST Elevation Myocardial Infarction; Survival Rate; Ticagrelor; United Kingdom

Several investigations have been conducted to evaluate the off-target effects of ticagrelor. The aim of the present study was to evaluate the off-target effects of ticagrelor such as neointimal formation and endothelial function after drug-eluting stent implantation in a porcine restenosis model.. A total of 30 pigs were randomly allocated based on the following P2Y. Regarding vasomotor responses to acetylcholine infusion, there were significant vasoconstrictions to maximal acetylcholine infusion in the clopidogrel and prasugrel group compared with those in the ticagrelor group. The mean neointimal area were significantly lower in the ticagrelor group (1.0±0.3 by OCT, 0.9±0.3 by histology), than in the clopidogrel (1.8±0.7, p=0.003, 1.6±0.8, p=0.030) and prasugrel (1.8±0.5, p=0.001, 1.5±0.5, p=0.019) groups. Percentages of moderate to dense peri-strut inflammatory cell infiltration were significantly lower in the ticagrelor group (9.0%) compared with the clopidogrel (17.3%, p<0.001) and prasugrel groups (15.7%, p=0.002). There were no significant differences in all findings between clopidogrel and prasugrel groups.. Compared to clopidogrel and prasugrel, ticagrelor reduced neointimal formation, endothelial dysfunction, and peri-strut inflammation.

Topics: Adenosine; Animals; Clopidogrel; Coronary Restenosis; Drug-Eluting Stents; Endothelium, Vascular; Hyperplasia; Male; Neointima; Prasugrel Hydrochloride; Purinergic P2Y Receptor Antagonists; Random Allocation; Swine; Ticagrelor; Ticlopidine; Tomography, Optical Coherence; Treatment Outcome

Antiplatelet and antithrombotic therapies are systematically considered to prevent restenosis following coronary stent implantation. Currently, patients receiving medicated stents are prescribed to orally take anticoagulants and antiplatelet drugs such as aspirin (ASP) and prasugrel (PRAS). Propolis (PROP) known as a natural organic compound was recently evaluated for its antiplatelet activity, antibiotics and immunomodulatory activities. In this study, antiplatelet drug-coated Co-Cr substrates were prepared with biodegradable poly(d,l-lactide) (PDLLA) containing ASP, PRA, or PROP using electrospray and the blood compatibility of the different substrates was investigated by measuring protein adsorption and platelet adhesion. In addition, the anti-inflammatory properties of the modified Co-Cr surfaces were assessed by measuring IL-8 and IL-6 expression levels in human endothelial cell cultures. Drug-coated surfaces were found to resist the adsorption of fibrinogen when compared to bare Co-Cr or PDLLA-coated Co-Cr. Interestingly, ASP- and PROP-containing substrates not only showed reduced adhesion of platelets and delayed coagulation time, but also drastically reduced the expression level of IL-8 and IL-6. Such results are supported that ASP- or PROP-coated Co-Cr can be potentially used as a stent material to mitigate early stage of restenosis. The developed coating materials might be an interesting alternative to systemic anticoagulant therapies prescribed after stent implantation.

Topics: Anti-Inflammatory Agents; Aspirin; Cells, Cultured; Chromium Alloys; Cobalt; Coronary Restenosis; Drug Liberation; Drug Synergism; Drug-Eluting Stents; Humans; Microscopy, Electron, Scanning; Platelet Activation; Platelet Adhesiveness; Platelet Aggregation Inhibitors; Polyesters; Prasugrel Hydrochloride; Propolis; Sirolimus

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

Topics: Aged; Angioplasty, Balloon, Coronary; Anterior Wall Myocardial Infarction; Clopidogrel; Coronary Restenosis; Drug Resistance; Drug Substitution; Humans; Male; Platelet Aggregation Inhibitors; Platelet Function Tests; Prasugrel Hydrochloride; Stents; Thrombectomy; Ticlopidine; Time Factors; Tomography, Optical Coherence; Treatment Outcome; Vascular Patency

Topics: Adult; Aneurysm, Ruptured; Behcet Syndrome; Cerebral Hemorrhage; Combined Modality Therapy; Coronary Aneurysm; Coronary Restenosis; Drug-Eluting Stents; Humans; Intracranial Aneurysm; Male; Myocardial Ischemia; Piperazines; Platelet Aggregation Inhibitors; Prasugrel Hydrochloride; Rupture, Spontaneous; Stents; Thiophenes

Dual antiplatelet therapy (DAT) has become standard care for patients undergoing percutaneous coronary intervention (PCI). Following balloon injury and stent placement, the intima at the site is distressed, resulting in the activation of coagulation cascade and platelets. In the case of bare metal stents (BMS), it takes six to eight weeks for the stent surface to be covered with neointima. However, in the case of a drug-eluting stent (DES), the process of healing is delayed and neointima may not form for months or even years. To prevent the formation of platelet thrombi, dual antiplatelet therapy is given as a combination of aspirin and clopidogrel for three months in a case of BMS and for a minimum of one year in a case of DES. A prolonged duration of therapy is often required for a subset of patients who are highly prone to thrombus formation. During most non-cardiac surgeries, dual antiplatelet therapy should be continued if bleeding can be directly controlled and excessive bleeding will have no adverse effect on the outcome of surgery. Prasugrel, another thienopyridine, is more potent and faster acting than clopidogrel, and is therefore of great value in cases of acute coronary syndrome during PCI, particularly in diabetics. Triple drug therapy, by adding cilastozol, is reserved for some selected thrombotic lesions. Ticagrelor and cangrelor are two new antiplatelet agents undergoing various clinical trials. (Cardiol J 2011; 18, 6: 712-717).

Topics: Angioplasty, Balloon, Coronary; Aspirin; Cilostazol; Clopidogrel; Coronary Restenosis; Drug Resistance; Drug Therapy, Combination; Drug-Eluting Stents; Hemorrhage; Humans; Metals; Patient Selection; Piperazines; Platelet Aggregation Inhibitors; Prasugrel Hydrochloride; Prosthesis Design; Risk Assessment; Risk Factors; Stents; Tetrazoles; Thiophenes; Thrombosis; Ticlopidine; Treatment Outcome

Central adjudication of clinical events in randomized controlled trials represents an attractive but still controversial approach since the adjudicated data usually match well with the investigator-reported event rates but increase affiliated costs.. The aim was to assess the timing of clinical event adjudication in the TRITON trial.. A review of the FDA action package for prasugrel was conducted.. Adjudications for deaths and strokes were distributed evenly throughout the study period. Bleeding event adjudications were performed predominantly in the later stages of the study. Adjudications for myocardial infarction and especially stent thrombosis were significantly delayed.. Among all clinical events, only deaths and strokes in TRITON were adjudicated without delays. Late adjudication of myocardial infarction and stent thrombosis are uncommon but at least can be explained by lack or change of event definitions. However, the delays with adjudications of revascularization procedures and especially timely recording of bleeding complications lack reasonable explanation. The regulatory authorities should consider independent audits when there is a major disagreement between centrally adjudicated and site-reported events influencing the results of a major clinical trial.

Topics: Acute Coronary Syndrome; Angioplasty, Balloon, Coronary; Cerebral Infarction; Clopidogrel; Coronary Restenosis; Data Collection; Disease-Free Survival; Hemorrhage; Myocardial Infarction; Observer Variation; Piperazines; Platelet Aggregation Inhibitors; Prasugrel Hydrochloride; Randomized Controlled Trials as Topic; Reproducibility of Results; Research Design; Stents; Thiophenes; Ticlopidine; Treatment Outcome; United States; United States Food and Drug Administration

Topics: Coronary Restenosis; Coronary Thrombosis; Drug Therapy, Combination; Eptifibatide; Fibrinolytic Agents; Humans; Peptides; Piperazines; Platelet Aggregation Inhibitors; Platelet Glycoprotein GPIIb-IIIa Complex; Practice Guidelines as Topic; Prasugrel Hydrochloride; Stents; Thiophenes

Topics: Aged; Angioplasty, Balloon, Coronary; Aryl Hydrocarbon Hydroxylases; Aspirin; Biotransformation; Clopidogrel; Combined Modality Therapy; Coronary Restenosis; Drug Resistance; Genotype; Humans; Male; Middle Aged; Myocardial Infarction; Piperazines; Platelet Aggregation; Platelet Aggregation Inhibitors; Polymorphism, Single Nucleotide; Prasugrel Hydrochloride; Prodrugs; Radiography; Stents; Thiophenes; Ticlopidine