prasugrel-hydrochloride and Myocardial-Ischemia

Aspirin was established more than a quarter century ago as an evidence-based therapy to reduce recurrent cardiovascular events in patients with coronary artery disease based on limited data by contemporary standards. Indeed it is unclear how regulatory agencies would define the optimal dose or duration of aspirin therapy if assessed in the current era. Subsequent clinical investigation has focused on the addition of antithrombotic agents on top of baseline aspirin therapy in the acute and chronic setting to reduce patient's risk of further ischemic events, at the cost of increased bleeding complications. The current armamentarium of potent and predictable antiplatelet and antithrombotic agents has ushered in a new era where clinicians and scientists are contemplating withdrawal of previously established agents to minimize bleeding risk while sustaining efficacy; indeed, subtraction may lead to the next advance in the treatment of acute and chronic ischemic vascular disease.

Topics: Adenosine; Antithrombins; Aspirin; Clopidogrel; Drug Therapy, Combination; Evidence-Based Medicine; Factor Xa Inhibitors; Hemorrhage; History, 20th Century; History, 21st Century; History, Ancient; Humans; Myocardial Ischemia; Platelet Aggregation Inhibitors; Prasugrel Hydrochloride; Purinergic P2Y Receptor Antagonists; Secondary Prevention; Ticagrelor; Ticlopidine

Acute coronary syndromes (ACS) encompass a broad spectrum of clinical presentations based on underlying pathology that results in myocardial ischemia and/or infarction. Despite advancements in invasive management and secondary preventive therapies, recurrent atherothrombotic coronary events remain a prevalent cause of death and recurrent cardiac events after ACS and, in those who survive, the root of long-standing cardiac comorbidities. Antiplatelet drug therapy has proven beneficial in the reduction of these events, and novel antiplatelet agents have resulted in significant improvement in clinical outcomes over the last decade. However, the balance of optimal platelet inhibition with minimal bleeding complications remains a clinical challenge. This review focuses on more recent advances in antiplatelet therapies used in the treatment of ACS.

Topics: Acute Coronary Syndrome; Animals; Coronary Artery Disease; Hemorrhage; Humans; Myocardial Ischemia; Piperazines; Platelet Aggregation Inhibitors; Prasugrel Hydrochloride; Thiophenes

Antiplatelet treatment is a cornerstone for patients with acute coronary syndromes treated invasively or conservatively to reduce the risk of early and late occurring ischemic complications and to improve survival. Compared to clopidogrel, the novel antiplatelet agents prasugrel and ticagrelor provide faster and more consistent inhibition of platelet aggregation and result in substantially improved clinical outcome in patients with acute coronary syndromes but also an increased bleeding risk. Therefore, balancing the rope between safety and efficacy of treatment is crucial for optimizing outcome. An understanding of the similarities but also differences in pharmacological effect, clinical trial design, and outcome is crucial for understanding which patient populations benefit the most from novel antiplatelet treatments. This review provides recommendations for their optimal use.

Topics: Acute Coronary Syndrome; Adenosine; Hemorrhage; Humans; Myocardial Ischemia; Patient Selection; Piperazines; Platelet Aggregation Inhibitors; Prasugrel Hydrochloride; Purinergic P2Y Receptor Antagonists; Thiophenes; Ticagrelor

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

Even among biomarker-negative patients undergoing elective percutaneous coronary intervention (PCI), periprocedural thrombotic and bleeding complications can lead to increased morbidity and mortality. Whether stronger platelet inhibition by an intensified oral loading strategy (ILS) before PCI impacts on outcomes among these patients in contemporary practice remains unclear.. This multicenter, randomized, assessor-blinded trial tested the hypothesis that in elective PCI prasugrel 60 mg (ILS) is superior to standard loading strategy with clopidogrel 600 mg regarding a composite primary end point of all-cause death, any myocardial infarction, definite/probable stent thrombosis, stroke, or urgent vessel revascularization. After PCI, all patients were on clopidogrel 75 mg/day and aspirin. The trial was terminated prematurely because of slower-than-expected recruitment and funding discontinuation.. Of 781 patients included in the final analysis, 382 were assigned to ILS and 399 to standard loading strategy. At 30 days, the primary end point occurred in 66 patients (17.3%) assigned to ILS and 74 patients (18.6%) assigned to standard loading strategy (odds ratio, 0.92 [95% CI, 0.63-1.32];. In biomarker-negative stable and unstable angina patients undergoing elective PCI, the trial did not find a conclusive difference in efficacy or safety. This observation should be interpreted in the context of wide CIs and premature termination of the trial. Registration: URL: https://www.clinicaltrials.gov. Unique identifier: NCT02548611.

Topics: Administration, Oral; Aged; Clopidogrel; Coronary Thrombosis; Drug Administration Schedule; Early Termination of Clinical Trials; Female; Hemorrhage; Humans; Male; Middle Aged; Myocardial Ischemia; Percutaneous Coronary Intervention; Platelet Aggregation Inhibitors; Prasugrel Hydrochloride; Prospective Studies; Purinergic P2Y Receptor Antagonists; Recurrence; Risk Assessment; Risk Factors; Stents; Stroke; Time Factors; Treatment Outcome

A unique dose of prasugrel has been approved exclusively for Japanese patients, but real-world data for prasugrel at that dose in patients with ischemic heart disease (IHD) are limited. Therefore, large-scale, real-world data are needed. Methods and Results: A 2-year observational study of Japanese patients with IHD undergoing percutaneous coronary intervention and being treated with prasugrel to evaluate safety and effectiveness. This report is an interim analysis of data from case report forms (CRFs) after 3 months. CRFs were collected from 4,270 patients, 4,157 of whom were eligible for the safety and effectiveness analysis sets (mean age, 68.3 years; male, 76.5%). The median treatment period was 112 days, and 92.3% of patients continued treatment with prasugrel. The incidence of non-coronary artery bypass grafting-related bleeding adverse events (AEs) was 3.1%, of which Thrombolysis in Myocardial Infarction (TIMI) major and minor bleeding accounted for 0.5% and 0.6%, respectively. The most common bleeding AEs were gastrointestinal disorders, which accounted for 43.2% of the sum of "TIMI major and minor bleeding AEs". The incidence of major adverse cardiovascular events (MACE) was 1.0%, and the cumulative incidence of MACE was 1.4%. The incidence of stent thrombosis was 0.2%.. Interim study results indicated that prasugrel was safe and effective during the early phase of treatment in Japanese patients with IHD in real-world clinical settings.

Topics: Aged; Drug Evaluation; Female; Heart Diseases; Hemorrhage; Humans; Japan; Male; Middle Aged; Myocardial Ischemia; Prasugrel Hydrochloride; Product Surveillance, Postmarketing; Treatment Outcome

Topics: Clopidogrel; Drug Therapy, Combination; Drug-Eluting Stents; Female; Follow-Up Studies; Humans; Male; Middle Aged; Myocardial Ischemia; Myocardial Revascularization; Piperazines; Platelet Aggregation Inhibitors; Postoperative Care; Prasugrel Hydrochloride; Prospective Studies; Purinergic P2Y Receptor Antagonists; Thiophenes; Ticlopidine; Time Factors; Treatment Outcome

Dual antiplatelet therapy is recommended after coronary stenting to prevent thrombotic complications, yet the benefits and risks of treatment beyond 1 year are uncertain.. Patients were enrolled after they had undergone a coronary stent procedure in which a drug-eluting stent was placed. After 12 months of treatment with a thienopyridine drug (clopidogrel or prasugrel) and aspirin, patients were randomly assigned to continue receiving thienopyridine treatment or to receive placebo for another 18 months; all patients continued receiving aspirin. The coprimary efficacy end points were stent thrombosis and major adverse cardiovascular and cerebrovascular events (a composite of death, myocardial infarction, or stroke) during the period from 12 to 30 months. The primary safety end point was moderate or severe bleeding.. A total of 9961 patients were randomly assigned to continue thienopyridine treatment or to receive placebo. Continued treatment with thienopyridine, as compared with placebo, reduced the rates of stent thrombosis (0.4% vs. 1.4%; hazard ratio, 0.29 [95% confidence interval {CI}, 0.17 to 0.48]; P<0.001) and major adverse cardiovascular and cerebrovascular events (4.3% vs. 5.9%; hazard ratio, 0.71 [95% CI, 0.59 to 0.85]; P<0.001). The rate of myocardial infarction was lower with thienopyridine treatment than with placebo (2.1% vs. 4.1%; hazard ratio, 0.47; P<0.001). The rate of death from any cause was 2.0% in the group that continued thienopyridine therapy and 1.5% in the placebo group (hazard ratio, 1.36 [95% CI, 1.00 to 1.85]; P=0.05). The rate of moderate or severe bleeding was increased with continued thienopyridine treatment (2.5% vs. 1.6%, P=0.001). An elevated risk of stent thrombosis and myocardial infarction was observed in both groups during the 3 months after discontinuation of thienopyridine treatment.. Dual antiplatelet therapy beyond 1 year after placement of a drug-eluting stent, as compared with aspirin therapy alone, significantly reduced the risks of stent thrombosis and major adverse cardiovascular and cerebrovascular events but was associated with an increased risk of bleeding. (Funded by a consortium of eight device and drug manufacturers and others; DAPT ClinicalTrials.gov number, NCT00977938.).

Topics: Aged; Aspirin; Clopidogrel; Drug Administration Schedule; Drug Therapy, Combination; Drug-Eluting Stents; Female; Hemorrhage; Humans; Incidence; Male; Middle Aged; Myocardial Ischemia; Piperazines; Platelet Aggregation Inhibitors; Prasugrel Hydrochloride; Thiophenes; Thrombosis; Ticlopidine; Time Factors

Elderly patients are at high risk for both ischemic and bleeding events. Platelet monitoring offers the opportunity to individualized antiplatelet therapy to optimize the therapeutic risk/benefit ratio.. The ANTARCTIC study is designed to demonstrate the superiority of a strategy of platelet function monitoring with dose and drug adjustment in patients initially on prasugrel 5 mg as compared with a more conventional strategy using prasugrel 5 mg without monitoring and without adjustment (Conventional Treatment Arm) to reduce the primary end point evaluated 1 year after stent percutaneous coronary intervention in elderly patients presenting with an acute coronary syndrome (ACS). ANTARCTIC is a multicenter, prospective, open-label study with 2 parallel arms. A total of 852 elderly patients (≥ 75 years) undergoing stent percutaneous coronary intervention for ACS are to be enrolled. The primary end point is the time to first occurrence of cardiovascular death, myocardial infarction, stroke, definite stent thrombosis, urgent revascularization, and bleeding complications (Bleeding Academic Research Consortium definition 2, 3, or 5). Platelet function analyses will be performed 14 days after randomization and repeated 14 days later in patients who require a change in treatment.. ANTARCTIC is a nationwide, prospective, open-label study testing a strategy of platelet function monitoring with dose and drug adjustment to reduce ischemic and bleeding complications in elderly ACS patients undergoing coronary stenting.

Topics: Acute Coronary Syndrome; Aged; Aged, 80 and over; Dose-Response Relationship, Drug; Drug Monitoring; Hemorrhage; Humans; Myocardial Ischemia; Percutaneous Coronary Intervention; Piperazines; Platelet Function Tests; Prasugrel Hydrochloride; Purinergic P2Y Receptor Antagonists; Stents; Thiophenes; Treatment Outcome

High on-treatment platelet reactivity (HTPR) is associated with adverse outcomes. We aim to compare the novel thienopyridine prasugrel versus double-dose clopidogrel in patients with HTPR and explore the interaction between CYP2C19 genotype and both drugs.. Consecutive stable patients undergoing percutaneous coronary intervention were screened with the Multiplate Analyzer P2Y12 assay, defining HTPR as area under the curve >450. Those with HTPR were randomized to prasugrel (10 mg/day) or high-dose clopidogrel (150 mg/day) for 2 weeks and then crossed-over to, respectively, clopidogrel and prasugrel, repeating the P2Y12 assay at the end of each cycle. Clinical follow-up (until 3 months) and CYP2C19 genotyping was performed in all patients. The primary end point was platelet reactivity after 14 days of prasugrel versus high-dose clopidogrel. Thirty-two patients were randomized to prasugrel and then high-dose clopidogrel or to high-dose clopidogrel followed by prasugrel. Prasugrel was associated with a significantly lower platelet reactivity than high-dose clopidogrel was (325.8 versus 478.5 area under the curve, P=0.028). No patient treated with prasugrel exhibited HTPR, whereas 9 (28.1%) receiving high-dose clopidogrel still had prevalence of HTPR (P=0.001). Similar findings were obtained changing cutoffs or considering platelet reactivity as a continuous variable. Genotyping showed the same efficacy between high-dose clopidogrel and prasugrel in the 18 (56.3%) CYP2C19*2 noncarriers (HTPR in 12.5% versus 0, P=0.274), whereas it was significantly worse in the 14 (43.7%) carriers (HTPR in 43.7% versus 0, P=0.003).. HTPR is successfully abolished by therapy with prasugrel irrespective of CYP2C19 genotype. Conversely, high-dose clopidogrel can address HTPR only in CYP2C19*2 noncarriers.. URL: http://www.clinicaltrials.gov. Unique identifier: NCT01465828.

Topics: Aged; Area Under Curve; Aryl Hydrocarbon Hydroxylases; Blood Platelets; Chi-Square Distribution; Clopidogrel; Coronary Artery Disease; Cross-Over Studies; Cytochrome P-450 CYP2C19; Drug Substitution; Female; Genotype; Humans; Male; Middle Aged; Myocardial Ischemia; Percutaneous Coronary Intervention; Phenotype; Piperazines; Platelet Aggregation Inhibitors; Platelet Function Tests; Prasugrel Hydrochloride; Prospective Studies; Purinergic P2Y Receptor Antagonists; Receptors, Purinergic P2Y12; Rome; Thiophenes; Ticlopidine; Treatment Outcome

The relationship of platelet function testing measurements with outcomes in patients with acute coronary syndromes (ACS) initially managed medically without revascularization is unknown.. To characterize the differences and evaluate clinical outcomes associated with platelet reactivity among patients with ACS treated with clopidogrel or prasugrel.. Patients with medically managed unstable angina or non-ST-segment elevation myocardial infarction were enrolled in the TRILOGY ACS trial (2008 to 2011) comparing clopidogrel vs prasugrel. Of 9326 participants, 27.5% were included in a platelet function substudy: 1286 treated with prasugrel and 1278 treated with clopidogrel.. Aspirin with either prasugrel (10 or 5 mg/d) or clopidogrel (75 mg/d); those 75 years or older and younger than 75 years but who weighed less than 60 kg received a 5-mg prasugrel maintenance dose.. Platelet reactivity, measured in P2Y12 reaction units (PRUs), was performed at baseline, at 2 hours, and at 1, 3, 6, 12, 18, 24, and 30 months after randomization. The primary efficacy end point was a composite of cardiovascular death, myocardial infarction, or stroke through 30 months.. Among participants younger than 75 years and weighing 60 kg or more, the median PRU values at 30 days were 64 (interquartile range [IQR], 33-128) in the prasugrel group vs 200 (IQR, 141-260) in the clopidogrel group (P < .001), a difference that persisted through all subsequent time points. For participants younger than 75 years and weighing less than 60 kg, the median 30-day PRU values were 139 (IQR, 86-203) for the prasugrel group vs 209 (IQR, 148-283) for the clopidogrel group (P < .001), and for participants 75 years or older, the median PRU values were 164 (IQR, 105-216) for the prasugrel group vs 222 (IQR, 148-268) for the clopidogrel group (P < .001). At 30 months the rate of the primary efficacy end point was 17.2% (160 events) in the prasugrel group vs 18.9% (180 events) in the clopidogrel group (P = .29). There were no significant differences in the continuous distributions of 30-day PRU values for participants with a primary efficacy end point event after 30 days (n = 214) compared with participants without an event (n = 1794; P = .07) and no significant relationship between the occurence of the primary efficacy end point and continuous PRU values (adjusted hazard ratio [HR] for increase of 60 PRUs, 1.03; 95% CI, 0.96-1.11; P = .44). Similar findings were observed with 30-day PRU cut points used to define high on-treatment platelet reactivity-PRU more than 208 (adjusted HR, 1.16; 95% CI, 0.89-1.52, P = .28) and PRU more than 230 (adjusted HR, 1.20; 95% CI, 0.90-1.61; P = .21).. Among patients with ACS without ST-segment elevation and initially managed without revascularization, prasugrel was associated with lower platelet reactivity than clopidogrel, irrespective of age, weight, and dose. Among those in the platelet substudy, no significant differences existed between prasugrel vs clopidogrel in the occurence of the primary efficacy end point through 30 months and no significant association existed between platelet reactivity and occurrence of ischemic outcomes.. clinicaltrials.gov Identifier: NCT00699998.

Topics: Acute Coronary Syndrome; Age Factors; Aged; Angina, Unstable; Aspirin; Body Weight; Clopidogrel; Female; Humans; Male; Myocardial Infarction; Myocardial Ischemia; Piperazines; Platelet Activation; Platelet Aggregation Inhibitors; Platelet Function Tests; Prasugrel Hydrochloride; Stroke; Thiophenes; Ticlopidine; Treatment Outcome

Currently, no data are available on the direct comparison between the Absorb everolimus-eluting bioresorbable vascular scaffold (Absorb BVS) and conventional metallic drug-eluting stents.. The ABSORB II study is a randomized, active-controlled, single-blinded, multicenter clinical trial aiming to compare the second-generation Absorb BVS with the XIENCE everolimus-eluting metallic stent. Approximately 501 subjects will be enrolled on a 2:1 randomization basis (Absorb BVS/XIENCE stent) in approximately 40 investigational sites across Europe and New Zealand. Treated lesions will be up to 2 de novo native coronary artery lesions, each located in different major epicardial vessels, all with an angiographic maximal luminal diameter between 2.25 and 3.8 mm as estimated by online quantitative coronary angiography (QCA) and a lesion length of ≤48 mm. Clinical follow-up is planned at 30 and 180 days and at 1, 2, and 3 years. All subjects will undergo coronary angiography, intravascular ultrasound (IVUS) and IVUS-virtual histology at baseline (pre-device and post-device implantation) and at 2-year angiographic follow-up. The primary end point is superiority of the Absorb BVS vs XIENCE stent in terms of vasomotor reactivity of the treated segment at 2 years, defined as the QCA quantified change in the mean lumen diameter prenitrate and postnitrate administration. The coprimary end point is the noninferiority (reflex to superiority) of the QCA-derived minimum lumen diameter at 2 years postnitrate minus minimum lumen diameter postprocedure postnitrate by QCA. In addition, all subjects allocated to the Absorb BVS group will undergo multislice computed tomography imaging at 3 years.. The ABSORB II randomized controlled trial (ClinicalTrials.gov NCT01425281) is designed to compare the safety, efficacy, and performance of Absorb BVS against the XIENCE everolimus-eluting stent in the treatment of de novo native coronary artery lesions.

Topics: Absorbable Implants; Adult; Aged; Aspirin; Coronary Angiography; Coronary Artery Disease; Coronary Thrombosis; Drug-Eluting Stents; Europe; Everolimus; Female; Follow-Up Studies; Humans; Immunosuppressive Agents; Male; Middle Aged; Myocardial Ischemia; New Zealand; Piperazines; Platelet Aggregation Inhibitors; Prasugrel Hydrochloride; Research Design; Sample Size; Single-Blind Method; Sirolimus; Spectroscopy, Near-Infrared; Thiophenes; Tissue Scaffolds; Tomography, X-Ray Computed; Ultrasonography, Interventional

The salt linked to the clopidogrel molecule in generic preparations is suspected to affect its clinical efficacy. There is a lack of information about inhibition of platelet reactivity by generic preparations.. To compare the effect of original clopidogrel (clopidogrel bisulphate [Plavix(®)]), generic clopidogrel preparations (clopidogrel hydrochloride [Clopidogrel-Mepha(®)]; clopidogrel besylate [Clopidogrel Sandoz(®)]) and prasugrel (Efient(®)) on platelet reactivity in patients with coronary artery disease.. Patients with coronary artery disease treated with stents received, in a random sequence, original clopidogrel bisulphate, clopidogrel hydrochloride and clopidogrel besylate. Platelet function was assessed with the Multiplate analyser after an initial loading dose (600 mg) and at day 10 after each treatment period. Prasugrel was given for another 10 days. An adenosine diphosphate (ADP) test value<46 antiaggregation units (U) was defined as therapeutic platelet inhibition.. Sixty patients (mean age 69 ± 10 years; 50 men) were randomized. Original clopidogrel bisulphate, clopidogrel hydrochloride and clopidogrel besylate provided similar inhibition of platelet reactivity with values of 31 ± 25, 33 ± 28 and 28 ± 23 U, respectively (P not significant). Prasugrel provided better inhibition of platelet function (10 ± 11 vs. 31 ± 25 U for clopidogrel bisulphate; P<0.001). An ADP test value>46 U was measured in 11 patients (18%) with clopidogrel bisulphate, 13 (22%) with clopidogrel besylate and 13 (22%) with clopidogrel hydrochloride compared with only one (2%) with prasugrel.. Generic clopidogrel preparations provided similar inhibition of platelet reactivity to original clopidogrel bisulphate, although prasugrel was more efficient.

Topics: Adenosine Diphosphate; Aged; Aged, 80 and over; Clopidogrel; Cross-Over Studies; Drugs, Generic; Female; Humans; Male; Middle Aged; Myocardial Ischemia; Patient Selection; Percutaneous Coronary Intervention; Piperazines; Platelet Activation; Platelet Aggregation Inhibitors; Prasugrel Hydrochloride; Single-Blind Method; Stents; Therapeutic Equivalency; Thiophenes; Thrombosis; Ticlopidine; Treatment Outcome

Prasugrel was associated with a statistically significant reduction in rates of cardiac ischemic events in patients with ACS who had undergone PCI. Rates of post-PCI death from cardiovascular causes, nonfatal MI, or nonfatal stroke were also significantly reduced with the use of prasugrel versus clopidogrel. Major bleeding was significantly increased with the use of prasugrel versus clopidogrel. Mortality did not differ significantly between the groups.

Topics: Acute Coronary Syndrome; Aspirin; Clopidogrel; Confidence Intervals; Double-Blind Method; Drug Therapy, Combination; Humans; Myocardial Ischemia; Piperazines; Platelet Aggregation Inhibitors; Prasugrel Hydrochloride; Pyridines; Thiophenes; Ticlopidine

Patients with diabetes mellitus (DM) are at high risk for recurrent cardiovascular events after acute coronary syndromes, in part because of increased platelet reactivity. The Trial to Assess Improvement in Therapeutic Outcomes by Optimizing Platelet Inhibition With Prasugrel-Thrombolysis in Myocardial Infarction 38 (TRITON-TIMI 38) showed an overall reduction in ischemic events with more intensive antiplatelet therapy with prasugrel than with clopidogrel but with more bleeding. We compared prasugrel with clopidogrel among subjects with DM in TRITON-TIMI 38.. We classified 13 608 subjects on the basis of preexisting history of DM and further according to insulin use. Prespecified analyses of the primary (cardiovascular death, nonfatal myocardial infarction, or nonfatal stroke) and key secondary end points, including net clinical benefit (death, nonfatal myocardial infarction, nonfatal stroke, and nonfatal TIMI major bleeding) were compared by use of the log-rank test. We found that 3146 subjects had a preexisting history of DM, including 776 receiving insulin. The primary end point was reduced significantly with prasugrel among subjects without DM (9.2% versus 10.6%; hazard ratio [HR], 0.86; P=0.02) and with DM (12.2% versus 17.0%; HR, 0.70; P<0.001, P(interaction)=0.09). A benefit for prasugrel was observed among DM subjects on insulin (14.3% versus 22.2%; HR, 0.63; P=0.009) and those not on insulin (11.5% versus 15.3%; HR, 0.74; P=0.009). Myocardial infarction was reduced with prasugrel by 18% among subjects without DM (7.2% versus 8.7%; HR, 0.82; P=0.006) and by 40% among subjects with DM (8.2% versus 13.2%; HR, 0.60; P<0.001, P(interaction)=0.02). Although TIMI major hemorrhage was increased among subjects without DM on prasugrel (1.6% versus 2.4%; HR, 1.43; P=0.02), the rates were similar among subjects with DM for clopidogrel and prasugrel (2.6% versus 2.5%; HR, 1.06; P=0.81, P(interaction)=0.29). Net clinical benefit with prasugrel was greater for subjects with DM (14.6% versus 19.2%; HR, 0.74; P=0.001) than for subjects without DM (11.5% versus 12.3%; HR, 0.92; P=0.16, P(interaction)=0.05).. Subjects with DM tended to have a greater reduction in ischemic events without an observed increase in TIMI major bleeding and therefore a greater net treatment benefit with prasugrel compared with clopidogrel. These data demonstrate that the more intensive oral antiplatelet therapy provided with prasugrel is of particular benefit to patients with DM.

Topics: Administration, Oral; Aged; Clopidogrel; Coronary Thrombosis; Diabetes Mellitus, Type 1; Diabetes Mellitus, Type 2; Female; Humans; Hypoglycemic Agents; Insulin; Kaplan-Meier Estimate; Male; Middle Aged; Myocardial Infarction; Myocardial Ischemia; Piperazines; Platelet Aggregation Inhibitors; Prasugrel Hydrochloride; Thiophenes; Thrombolytic Therapy; Ticlopidine; Treatment Outcome

We evaluated the relative contributions of the loading and maintenance doses of prasugrel on events in a TRITON-TIMI 38 (TRial to Assess Improvement in Therapeutic Outcomes by Optimizing Platelet InhibitioN with Prasugrel-Thrombolysis In Myocardial Infarction) analysis.. Prasugrel is superior to clopidogrel in preventing ischemic events in patients with an acute coronary syndrome who are undergoing percutaneous coronary intervention, but it is associated with an increased risk of major bleeding.. Landmark analyses for efficacy, safety, and net clinical benefit were performed from randomization to day 3 and from day 3 to the end of the trial.. Significant reductions in ischemic events, including myocardial infarction, stent thrombosis, and urgent target vessel revascularization, were observed with the use of prasugrel both during the first 3 days and from 3 days to the end of the trial. Thrombolysis In Myocardial Infarction major non-coronary artery bypass graft bleeding was similar to clopidogrel during the first 3 days but was significantly greater with the use of prasugrel from 3 days to the end of the study. Net clinical benefit significantly favored prasugrel both early and late in the trial.. Both the loading dose and maintenance dose of prasugrel were superior to clopidogrel for the reduction of ischemic events. This result emphasizes the importance of maintaining high levels of inhibition of platelet aggregation via P2Y(12) receptor inhibition, not only for the prevention of periprocedural ischemic events but also during long-term follow-up. The excess major bleeding observed with the use of prasugrel occurred predominantly during the maintenance phase. Approaches to reduce the relative excess of bleeding with prasugrel should focus on the maintenance dose (e.g., reduction in maintenance dose in previously reported high-risk subgroups, such as the elderly and those patients with low body weight). (A Comparison of CS-747 and Clopidogrel in Acute Coronary Syndrome Subjects Who Are to Undergo Percutaneous Coronary Intervention; NCT00097591).

Topics: Acute Coronary Syndrome; Angina, Unstable; Angioplasty, Balloon, Coronary; Aspirin; Clopidogrel; Combined Modality Therapy; Drug Therapy, Combination; Hemorrhage; Humans; Kaplan-Meier Estimate; Myocardial Infarction; Myocardial Ischemia; Piperazines; Platelet Aggregation Inhibitors; Prasugrel Hydrochloride; Proportional Hazards Models; Purinergic P2 Receptor Antagonists; Stents; Thiophenes; Ticlopidine

Topics: Dose-Response Relationship, Drug; Drug Monitoring; Female; Humans; Male; Middle Aged; Myocardial Ischemia; Outcome and Process Assessment, Health Care; Percutaneous Coronary Intervention; Platelet Aggregation; Platelet Function Tests; Point-of-Care Testing; Prasugrel Hydrochloride; Prospective Studies; Purinergic P2Y Receptor Antagonists; Ticagrelor

Several studies have demonstrated the safety and feasibility of short (3-6 months) and very short duration (< 2 months) dual antiplatelet therapy (DAPT) in patients with a durable-polymer drug-eluting stent (DP-DES). However, the clinical importance of using very short duration DAPT has yet to be established in patients with a biodegradable polymer drug-eluting stent (BP-DES). The aim of this REIWA registry (multicenter and prospective registry; investigation of clinical outcomes of patients treated with short duration dual antiplatelet therapy after implantation of biodresorbable-polymer drug-eluting stent: a multicenter, prospective registry from Iwate medical university affiliated hospitals) is to determine the safety and feasibility of using 1-month DAPT followed by P2Y12 inhibitor monotherapy in patients after BP-DES implantation. This study is an observational, prospective, multicenter registry encompassing the entire local medical region of Iwate Prefecture (northern area of mainland Japan). A total of 1200 patients who underwent successful PCI with a novel thin strut BP-DES (Synergy, Ultimaster or Orsiro) and are considered to be appropriate patients for very short DAPT, are registered and subsequently administered 1-month DAPT followed by P2Y12 inhibitor monotherapy (clopidogrel 75 mg/day or prasugrel 3.75 mg/day). The primary endpoint was a composite of cardiovascular and bleeding events, which included cardiovascular death, spontaneous myocardial infarction, definite stent thrombosis, ischemic or hemorrhagic stroke, or TIMI major or minor bleeding at 12 months. The REIWA registry (UMIN000037321) will demonstrate both the safety and feasibility of using 1-month DAPT in patients with BP-DES. Furthermore, results of this study will also be able to provide supportive evidence for P2Y12 inhibitor monotherapy after 1-month DAPT following BP-DES implantation.

Topics: Absorbable Implants; Clopidogrel; Coronary Artery Disease; Drug Administration Schedule; Drug Therapy, Combination; Drug-Eluting Stents; Female; Humans; Male; Middle Aged; Myocardial Ischemia; Observational Studies as Topic; Percutaneous Coronary Intervention; Platelet Aggregation Inhibitors; Polymers; Prasugrel Hydrochloride; Prospective Studies; Registries; Time Factors; Treatment Outcome

PRASFIT-Practice II is a postmarketing observational study conducted in 4,155 Japanese patients with ischemic heart disease (IHD) who received long-term prasugrel. The data were used to assess the utility of Academic Research Consortium for High Bleeding Risk (ARC-HBR) criteria.Methods and Results:Patients in PRASFIT-practice II were clinically followed for 2 years. The primary endpoint was the cumulative incidence of major adverse cardiovascular events (MACE) and Thrombolysis in Myocardial Infarction (TIMI) major/minor bleeding. Patients were divided into 2 groups based on ARC-HBR criteria (HBR (40.1% of patients) and non-HBR (59.9%)) and the effect of HBR on the primary endpoint was assessed. The median duration of dual antiplatelet therapy with prasugrel was 391.0 days. At 2 years, the cumulative incidence of MACE was 3.3%, and of TIMI major/minor bleeding was 2.7%. At 1 year, MACE and TIMI major/minor bleeding in the HBR group (4.0% and 3.4%, respectively) were higher than that in the non-HBR group (1.3% for both). Landmark analysis at 3 months and 1 year showed that the higher risk of MACE or TIMI major/minor bleeding in the HBR group persisted through 2 years.. The results of this study confirmed the safety and effectiveness of long-term treatment with prasugrel, and demonstrated that the ARC-HBR criteria for bleeding risk are applicable in Japanese IHD patients treated with prasugrel.

Topics: Follow-Up Studies; Hemorrhage; Humans; Japan; Myocardial Infarction; Myocardial Ischemia; Percutaneous Coronary Intervention; Platelet Aggregation Inhibitors; Prasugrel Hydrochloride; Product Surveillance, Postmarketing; Treatment Outcome

Although the effectiveness and safety of prasugrel for the prevention of cardiovascular events in patients with ischemic heart disease (IHD) undergoing percutaneous coronary intervention (PCI) have been demonstrated, long-term real-world data of Japanese unique doses are insufficient. Therefore, we report the results of an analysis of 1-year follow-up data from a postmarketing observational study (PRASFIT-Practice II).Methods and Results:The safety and effectiveness analysis sets included 4,155 IHD patients receiving prasugrel (loading dose/maintenance dose, 20/3.75 mg) as dual antiplatelet therapy (DAPT) with aspirin. At 360 days (after treatment start), 62.2% continued DAPT. Cumulative incidences of major adverse cardiovascular events and stent thrombosis were 1.6% and 0.2%, respectively. Cumulative incidences of Thrombolysis In Myocardial Infarction (TIMI) major bleeding and TIMI major or minor bleeding were 1.0% and 2.0%, respectively. Risk factors for TIMI major or minor bleeding in the first 30 days of treatment were age ≥80 years, anemia, female sex, and liver disease, and from day 31 to the end of month 12, hypertension and peptic ulcer.. The 1-year follow-up results showed long-term effectiveness and safety of prasugrel at dosages approved in Japan for the treatment of IHD patients undergoing PCI.

Topics: Aged; Aged, 80 and over; Anemia; Aspirin; Female; Follow-Up Studies; Hemorrhage; Humans; Incidence; Japan; Male; Myocardial Ischemia; Peptic Ulcer; Platelet Aggregation Inhibitors; Prasugrel Hydrochloride; Product Surveillance, Postmarketing; Prospective Studies; Risk Factors; Thrombolytic Therapy

Balancing ischemic and bleeding risk is an evolving framework.. Our objectives were to simulate changes in risks for adverse events and event-driven costs with use of ticagrelor or prasugrel versus clopidogrel according to varying levels of ischemic and bleeding risk. Using the validated PARIS risk functions, we estimated 1-year ischemic (myocardial infarction or stent thrombosis) and bleeding (Bleeding Academic Research Consortium types 3 or 5) event rates among PARIS study participants who underwent percutaneous coronary intervention with drug-eluting stent implantation for an acute coronary syndrome and were discharged with aspirin and clopidogrel (n=1497). Simulated changes in adverse events with ticagrelor or prasugrel were calculated by applying treatment effects from randomized trials for a 1-year time horizon. Event costs were estimated using National Inpatient Sample data. Net costs were calculated between antiplatelet therapy groups according to level of ischemic and bleeding risk. After weighting events for quality-of-life impact, we calculated event rates and costs for risk-tailored treatment versus clopidogrel under multiple drug pricing assumptions. One-year rates (per 1000 person-years) for ischemic events were 12.6, 24.1, and 66.1, respectively, among those at low (n=630), intermediate (n=536), and high (n=331) ischemic risk. Analogous bleeding rates were 11.0, 23.9, and 66.2, respectively, among low (n=728), intermediate (n=634), and high (n=135) bleeding risk patients. Mean per event costs were $22 174 (ischemic) and $12 203 (bleeding). When risks for ischemia matched or exceeded bleeding, simulated utility-weighted event rates favored ticagrelor/prasugrel, whereas clopidogrel reduced utility-weighted events when bleeding exceeded ischemic risk. One-year costs were sensitive to drug pricing assumptions, and risk-tailored treatment with either agent progressed from cost incurring to cost saving with increasing generic market share.. Tailoring antiplatelet therapy intensity to patient risk may improve health utility and could produce cost savings in the first year after percutaneous coronary intervention.. URL: https://www.clinicaltrials.gov . Unique identifier: NCT00998127.

Topics: Acute Coronary Syndrome; Aged; Aged, 80 and over; Clinical Decision-Making; Clopidogrel; Coronary Thrombosis; Cost Savings; Cost-Benefit Analysis; Drug Costs; Drug-Eluting Stents; Europe; Female; Hemorrhage; Humans; Male; Middle Aged; Myocardial Ischemia; Percutaneous Coronary Intervention; Platelet Aggregation Inhibitors; Prasugrel Hydrochloride; Registries; Risk Assessment; Risk Factors; Ticagrelor; Time Factors; Treatment Outcome; United States

Topics: Clopidogrel; Cross-Sectional Studies; Databases, Factual; Drug Utilization; Humans; Myocardial Ischemia; Off-Label Use; Percutaneous Coronary Intervention; Platelet Aggregation Inhibitors; Practice Patterns, Physicians'; Prasugrel Hydrochloride; Purinergic P2Y Receptor Antagonists; Ticagrelor; Time Factors; Treatment Outcome; United States

Aim of the present study was to investigate the frequency and predictors of premature discontinuation or switch of ADP receptor blockers and its association with serious adverse events. For this purpose 571 consecutive ACS patients receiving ticagrelor (n = 258, 45%) or prasugrel (n = 313, 55%) undergoing PCI were enrolled in this prospective, observational, multicenter ATLANTIS-SWITCH substudy. Predictors of premature discontinuation or switch of antiplatelet therapy and their association with major adverse cardiovascular events and TIMI bleeding events were evaluated. Premature stop/switch was found in 72 (12.6%) patients: 34 (5.9%) stopped and 38 (6.7%) switched the ADP blocker. Ticagrelor treated patients were significantly more likely to stop/switch therapy as compared to prasugrel (15.9% vs. 9.2%, p = 0.016). We identified 4 independent predictors for stop/switch of ADP blocker: major surgery, need for oral anticoagulation (OAC), TIMI major bleeding and drug intolerance. TIMI major bleeding was a driver of stop/switch actions and occurred in 4.3% vs 0.2% in patients with vs without stop/switch (p = 0.001). The majority of stop/switch actions (75%) were physicians driven decisions. Importantly, stop/switch of therapy was not associated with increased risk of MACE (p = 0.936). In conclusion premature switch/stop of ADP blockers appears to be safe when mainly driven by physician's decision and clinical indication.

Topics: Acute Coronary Syndrome; Aged; Anticoagulants; Drug Administration Schedule; Drug Substitution; Drug-Eluting Stents; Female; Hemorrhage; Humans; Incidence; Kaplan-Meier Estimate; Male; Middle Aged; Myocardial Ischemia; Platelet Aggregation Inhibitors; Prasugrel Hydrochloride; Prognosis; Prospective Studies; Purinergic P2Y Receptor Antagonists; Registries; Risk Factors; Ticagrelor

Acute coronary syndrome (ACS) guidelines recommend the use of newer P2Y. Retrospective analysis of a multicenter ACS registry; 3515 consecutive patients were included. The association between risk scores and prescription of newer P2Y. A total of 1021 patients (29%) were treated with prasugrel or ticagrelor. On multivariate analyses, both GRACE (OR per 10 points, 0.89; 95%CI, 0.86-0.92; P < .001) and CRUSADE (OR per 10 points, 0.96; 95%CI, 0.94-0.98; P < .001) risk scores were inversely associated with the use of newer P2Y. New P2Y

Topics: Acute Coronary Syndrome; Adenosine; Aged; Drug Prescriptions; Female; Hemorrhage; Hospitalization; Humans; Male; Myocardial Ischemia; Patient Discharge; Practice Patterns, Physicians'; Prasugrel Hydrochloride; Purinergic P2Y Receptor Antagonists; Registries; Retrospective Studies; Risk Assessment; Ticagrelor

The HEAT-PPCI trial compared bivalirudin and unfractionated heparin in patients undergoing primary percutaneous coronary intervention (PPCI). The aim of this study was to report pre-specified, secondary analyses comparing the effects of P2Y12 inhibiting agents on platelet reactivity and clinical events.. All patients received preprocedural oral antiplatelet therapy. During the early stages of the trial, the P2Y12 inhibitor of choice was prasugrel with some use of clopidogrel. Later, routine therapy switched to ticagrelor. For cases performed during working hours, multiple electrode aggregometry (MEA) was used to assess ADP-induced platelet aggregation at the end of the index procedure. The effect of P2Y12 inhibitors on the primary efficacy (major adverse cardiac events [MACE]) and safety (major bleeding) outcomes was assessed in all patients. Multiple logistic regression was used to adjust for differences in baseline characteristics. With MEA data from 469 patients, prasugrel therapy resulted in significantly greater suppression of ADP-induced platelet aggregation at 40 U (23, 78) (median; interquartile range [IQR]) when compared against ticagrelor 75 U (41, 100.75); p<0.001 or clopidogrel 79 U (56, 96); p<0.001. In the entire study population (N=1,803), prasugrel therapy was associated with significantly fewer MACE (26/497; 5.2%) in comparison to ticagrelor (83/1,123; 7.4%) or clopidogrel (18/183; 9.8%); odds ratio (OR) 0.64, confidence interval (CI): 0.41-0.99, p=0.045. For major bleeding, there were no significant differences among the three groups - clopidogrel (3/183; 1.6%), prasugrel (13/497; 2.6%) and ticagrelor (43/1,123; 3.8%); OR 0.73, CI: 0.39-1.35, p=0.31. Patients treated with clopidogrel had more high-risk features and clopidogrel use was more common as an alternative to prasugrel. After adjustment, there were no significant differences in the rates of MACE (OR 0.70, CI: 0.41-1.21, p=0.20) or major bleeding (OR 0.80, CI: 0.41-1.60, p=0.53).. In HEAT-PPCI, patients who received prasugrel (rather than clopidogrel or ticagrelor) had significantly greater suppression of ADP-induced platelet aggregation at the end of the procedure. After adjustment for differences in baseline characteristics, there were no significant differences in ischaemic or bleeding outcomes among the antiplatelet therapies.

Topics: Anticoagulants; Clopidogrel; Coronary Thrombosis; Hemorrhage; Humans; Myocardial Ischemia; Percutaneous Coronary Intervention; Platelet Aggregation; Platelet Aggregation Inhibitors; Platelet Function Tests; Prasugrel Hydrochloride; Purinergic P2Y Receptor Antagonists; Randomized Controlled Trials as Topic; Risk Factors; Ticagrelor; Time Factors; Treatment Outcome

Dual antiplatelet therapy (DAPT) helps prevent ischemic events after coronary stenting but comes with an increased risk of bleeding. Several risk scores have been proposed for the management of patients receiving DAPT, but no standardized tool exists for the purpose. We sought to compare the performance of the new PRECISE-DAPT (Predicting Bleeding Complication in Patients Undergoing Stent Implantation and Subsequent Dual Antiplatelet Therapy), CRUSADE (Can Rapid Risk Stratification of Unstable Angina Patients Suppress Adverse Outcomes with Early Implementation of the American College of Cardiology/American Heart Association Guidelines), and ACUITY (Acute Catheterization and Urgent Intervention Triage Strategy) scores for the prediction of bleeding in Korean patients receiving DAPT.. Nine hundred and four consecutive patients who underwent stent implantation received DAPT. One-year bleedings were assessed using TIMI (Thrombolysis in Myocardial Infarction), GUSTO (Global Use of Strategies to Open Occluded Arteries), and BARC (Bleeding Academic Research Consortium). Bleeding events occurred in 154 patients (17.0%) by BARC type ≥3a criteria, 119 patients (13.2%) by the TIMI minor or major criteria, and 80 patients (8.8%) by the GUSTO moderate or severe criteria. In the C statistic analysis, CRUSADE, ACUITY, and PRECISE-DAPT scores showed high area under the curve values for 1-year bleeding (area under the curve 0.73, 0.75, and 0.75 for TIMI minor or major bleeding; area under the curve 0.81, 0.79, and 0.82 for GUSTO moderate to severe; and area under the curve 0.79, 0.81, and 0.81 for BARC type ≥3a, respectively). The discriminate ability of PRECISE-DAPT was similar to CRUSADE and ACUITY in bleeding complications. However, the PRECISE-DAPT score was better at reclassifying the risk of 1-year bleeding compared with ACUITY for the 3 bleeding criteria.. The PRECISE-DAPT score is a simple 5-item risk score that represents a standardized tool for the prediction of 1-year bleeding in Korean patients receiving DAPT, regardless of bleeding definition.

Topics: Aged; Aspirin; Clopidogrel; Decision Support Techniques; Drug Therapy, Combination; Female; Hemorrhage; Humans; Male; Middle Aged; Myocardial Ischemia; Percutaneous Coronary Intervention; Platelet Aggregation Inhibitors; Prasugrel Hydrochloride; Predictive Value of Tests; Purinergic P2Y Receptor Antagonists; Republic of Korea; Retrospective Studies; Risk Assessment; Risk Factors; Stents; Ticagrelor; Treatment Outcome

Disaggregation as the difference between maximal and final platelet aggregation by light transmission aggregometry indicates the stability of platelet aggregates. We evaluated the extent of disaggregation after platelet stimulation with adenosine diphosphate (ADP), arachidonic acid (AA), collagen, epinephrine, and thrombin receptor-activating peptide (TRAP)-6 in 323 patients on dual antiplatelet therapy with daily aspirin and clopidogrel (group 1), prasugrel (group 2), or ticagrelor (group 3) therapy. All patients in group 1 underwent elective angioplasty and stenting, whereas all patients included in groups 2 and 3 suffered from acute coronary syndromes (STEMI or NSTEMI) and underwent urgent PCI. Significant differences between maximal and final platelet aggregation were observed with all agonists throughout the groups (all p<0.001). Disaggregation was highest using AA (clopidogrel 36.5%; prasugrel/ticagrelor 100%) and ADP (clopidogrel 21.7%; prasugrel/ticagrelor 100%). In contrast, low disaggregation was observed after platelet stimulation with collagen and TRAP-6 in clopidogrel-treated patients, and after platelet stimulation with collagen and epinephrine in prasugrel- and ticagrelor-treated patients. In conclusion, pathways of platelet activation that are not inhibited by standard antiplatelet therapy allow persisting platelet aggregation and may at least in part be responsible for adverse ischemic events.

Topics: Adenosine; Aged; Aspirin; Blood Platelets; Clopidogrel; Drug Monitoring; Drug Resistance; Drug Therapy, Combination; Female; Humans; Male; Middle Aged; Myocardial Ischemia; Percutaneous Coronary Intervention; Platelet Aggregation; Platelet Aggregation Inhibitors; Platelet Function Tests; Prasugrel Hydrochloride; Predictive Value of Tests; Reproducibility of Results; Signal Transduction; Stents; Ticagrelor; Ticlopidine; Treatment Outcome

Several clinical trials have demonstrated the benefits of thienopyridine monotherapy in ischaemic stroke patients. Non-human primate models of ischaemic stroke have been used for various antithrombotic agents; however, to the best of our knowledge, there is no data on the effects of P2Y12 antagonists in models, such as the thrombotic middle cerebral artery occlusion (MCAO) monkey model. Accordingly, it remains unclear what level of inhibition of platelet aggregation (IPA) is required for optimal treatment of ischaemic stroke. In the present study, we investigated the effects of prasugrel, a third-generation thienopyridine antiplatelet drug, on platelet aggregation, thrombus formation and cerebral infarct volume in a non-human primate model. Daily oral administration of prasugrel resulted in significant and stable platelet inhibitory effects on Day 3, with IPA values ranging from 31% to 36% at 0.3mg/kg/day and from 44% to 50% at 1mg/kg/day. These IPA levels encompassed values observed in clinical trials of clopidogrel, and were thus selected for further study. In the thrombotic MCAO model, prasugrel increased MCA patency in a dose-dependent manner and significantly reduced ischaemic infarct volume by approximately 70% at 0.3mg/kg/day and 90% at 1mg/kg/day without increasing haemorrhagic infarction. Prasugrel also significantly reduced neurological deficit scores by 60% at 0.3mg/kg/day and 80% at 1mg/kg/day. In conclusion, prasugrel treatment resulted in effective reduction of ischaemic infarction and an associated improvement in neurological function without increasing haemorrhagic infarction. These data suggest that prasugrel monotherapy would be effective for the prevention of thrombotic stroke.

Topics: Adenosine Diphosphate; Administration, Oral; Animals; Blood Pressure; Disease Models, Animal; Dose-Response Relationship, Drug; Haplorhini; Hemorrhage; Infarction, Middle Cerebral Artery; Macaca fascicularis; Male; Myocardial Ischemia; Platelet Aggregation; Platelet Aggregation Inhibitors; Prasugrel Hydrochloride; Purinergic P2Y Receptor Antagonists; Receptors, Purinergic P2Y12; Stroke; Thrombosis; Time Factors

Topics: Anticoagulants; Aspirin; Drug-Eluting Stents; Female; Humans; Male; Myocardial Ischemia; Piperazines; Prasugrel Hydrochloride; Purinergic P2Y Receptor Antagonists; Thiophenes

This study sought to evaluate whether prasugrel may serve as an alternative to clopidogrel in patients with triple therapy.. Approximately 10% of patients who receive dual antiplatelet therapy after percutaneous coronary intervention have an indication for oral anticoagulation and are thus treated with triple therapy. The standard adenosine diphosphate receptor blocker in this setting is clopidogrel. Data regarding prasugrel as part of triple therapy are not available.. We analyzed a consecutive series of 377 patients who underwent drug-eluting stent implantation and had an indication for oral anticoagulation between February 2009 and December 2011 and were treated with a 6-month regimen of aspirin and oral anticoagulation with either prasugrel or clopidogrel. The primary endpoint was a composite of Thrombolysis In Myocardial Infarction (TIMI) major and minor bleeding at 6 months. The secondary endpoint was a composite of death, myocardial infarction, ischemic stroke, or definite stent thrombosis.. Twenty-one patients (5.6%) received prasugrel instead of clopidogrel. These patients had a higher-risk profile at baseline, and the majority had high platelet reactivity to clopidogrel. TIMI major and minor bleeding occurred significantly more often in the prasugrel compared with the clopidogrel group (6 [28.6%) vs. 24 [6.7%]; unadjusted hazard ratio (HR): 4.6, 95% confidence interval [CI]: 1.9 to 11.4], p < 0.001; adjusted HR: 3.2, 95% CI: 1.1 to 9.1], p = 0.03). There was no significant difference regarding the combined ischemic secondary endpoint (2 [9.5%] vs. 25 [7.0%]; unadjusted HR: 1.4, 95% CI: 0.3 to 6.1], p = 0.61).. These findings suggest that substitution of prasugrel for clopidogrel in patients needing triple therapy increases the risk of bleeding. However, specific randomized trials are needed to define the role of newer adenosine diphosphate receptor antagonists in this setting.

Topics: Aged; Aged, 80 and over; Anticoagulants; Aspirin; Clopidogrel; Cohort Studies; Drug Therapy, Combination; Drug-Eluting Stents; Female; Humans; Male; Middle Aged; Myocardial Ischemia; Patient Selection; Percutaneous Coronary Intervention; Piperazines; Platelet Aggregation Inhibitors; Prasugrel Hydrochloride; Purinergic P2Y Receptor Antagonists; Thiophenes; Ticlopidine; Vitamin K

Identification of factors affecting platelet reactivity (PR) and high PR (HPR) or high platelet inhibition (HPI) rates while on prasugrel maintenance dose (MD) might be helpful in avoiding ischemic or bleeding complications. We retrospectively analyzed all patients (n=233) treated in our institution between April 2010 and November 2012 who had platelet function assessment pre-prasugrel and following prasugrel 10 mg MD for at least 5 days, using the Verify Now P2Y12 platelet function assay. Multiple linear regression and logistic regression models were applied to identify independent factors affecting post-prasugrel PR level, HPR and HPI status. The amount of variance in PR under prasugrel MD that could be explained by the model was 25.9% (adjusted R²), p<0.001. Pre-prasugrel treatment PR, acute coronary syndrome (ACS), prasugrel loading and smoking uniquely accounted for 10.8%, 1.3%, 3.5% and 1.2% of the observed variance, respectively. HPR and HPI were observed in 7.7% and 13.7% of the cases, respectively. On multivariate analysis, pre-prasugrel PR in the upper quartile (>313 PRU) was the only independent factor associated with HPR under prasugrel MD. In contrast, pre-prasugrel PR in the lower quartile (<242 PRU) and prasugrel loading emerged as the only independent predictors of HPI. In patients under different clinical settings receiving prasugrel 10 mg MD a significant amount of the PR variability in response to prasugrel may be explained by pre- treatment PR level, ACS, prasugrel loading and smoking status. A high pre- treatment PR is associated with HPR, while a low pre-treatment PR and prasugrel loading predict HPI.

Topics: Acute Coronary Syndrome; Aged; Blood Platelets; Cohort Studies; Drug Resistance; Female; Heart Diseases; Hemorrhage; Humans; Maintenance Chemotherapy; Male; Middle Aged; Models, Biological; Myocardial Ischemia; Percutaneous Coronary Intervention; Piperazines; Platelet Aggregation; Platelet Aggregation Inhibitors; Postoperative Complications; Prasugrel Hydrochloride; Purinergic P2Y Receptor Antagonists; Retrospective Studies; Smoking; Thiophenes

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

Ischemic heart disease is uncommon during pregnancy, occurring in approximately 1/10,000 pregnancies resulting in live births. However, the increased age and fertility of mothers has suggested that the coexistence of pregnancy and coronary artery disease is likely to increase. A subject of debate is the management of dual antiplatelet therapy among pregnant women. The potential teratogeneous effects, particularly with regards to thienopyridines, on the fetus are not fully established. In addition, the use of dual antiplatelet therapy is associated with an increased risk for bleeding events, raising concerns in the peripartum period with regards to the route of delivery and choice of anesthestic techniques. Limited data and experience is available with clopidogrel, the most commonly used thienopyridine. Prasugrel is third generation thienopyridine recently introduced into clinical practice with ever growing use in the setting of acute coronary syndrome patients undergoing percutaneous coronary interventions. The present manuscript describes the first case report of a pregnancy while on prasugrel therapy.

Topics: Adult; Female; Humans; Live Birth; Myocardial Ischemia; Piperazines; Platelet Aggregation Inhibitors; Prasugrel Hydrochloride; Pregnancy; Pregnancy Complications, Cardiovascular; Purinergic P2Y Receptor Antagonists; Thiophenes

Post-treatment platelet reactivity (PR) is associated with ischemic and bleeding events in patients receiving P2Y12 receptor antagonists.. We aimed to study the relationship between post-treatment PR after a 60-mg loading dose (LD) of prasugrel and 1-year thrombotic and bleeding events.. Patients were prospectively included in this multicenter study if they had a successful percutaneous coronary intervention (PCI) for acute coronary syndrome (ACS) and received prasugrel. The platelet reactivity index (PRI) was measured using the Vasodilator-Stimulated Phosphoprotein index (VASP) after a prasugrel LD. Endpoints included the rate of thrombotic events and bleeding events at 1 year.. Among the 301 patients enrolled, 9 (3%) were lost to follow-up at 1 year. The rates of thrombotic and bleeding events at 1 year were of 7.5% and 6.8%, respectively. Receiver-operating curve (ROC) analysis demonstrated an optimal cut-off value of 53.5% of PRI to predict thrombotic events at 1 year. Using this cut-off value we observed that patients exhibiting high on-treatment platelet reactivity (HTPR) had a higher rate of thrombotic events (22.4% vs. 2.9%; P < 0.001). In parallel the optimal cut-off value of PRI to predict bleeding was 16%. Patients with a PRI ≤ 16% had a higher rate of bleeding events compared with those with a PRI > 16% (15.6% vs. 3.3%; P < 0.001). In multivariate analysis, the PRI predicted both thrombotic and bleeding events (OR: 1.44, 95% confidence interval [CI]: 1.2-1.72; P < 0.001 and OR: 0.75, 95% CI: 0.59-0.96; P = 0.024 [respectively, per 10% increase]).. Platelet reactivity measurement after a prasugrel LD predicts both ischemic and bleeding events at 1 year follow-up for ACS patients undergoing PCI.

Topics: Acute Coronary Syndrome; Blood Platelets; Cell Adhesion Molecules; Coronary Thrombosis; Female; Follow-Up Studies; France; Hemorrhage; Humans; Kaplan-Meier Estimate; Linear Models; Male; Microfilament Proteins; Middle Aged; Multivariate Analysis; Myocardial Ischemia; Odds Ratio; Percutaneous Coronary Intervention; Phosphoproteins; Piperazines; Platelet Aggregation; Platelet Aggregation Inhibitors; Platelet Function Tests; Prasugrel Hydrochloride; Predictive Value of Tests; Proportional Hazards Models; Prospective Studies; Purinergic P2Y Receptor Antagonists; Receptors, Purinergic P2Y12; Risk Assessment; Risk Factors; Thiophenes; Time Factors; Treatment Outcome

Topics: Acute Coronary Syndrome; Clinical Trials, Phase III as Topic; Data Interpretation, Statistical; Humans; Myocardial Ischemia; Piperazines; Prasugrel Hydrochloride; Purinergic P2Y Receptor Antagonists; Risk Factors; Thiophenes

Topics: Acute Coronary Syndrome; Clopidogrel; Double-Blind Method; Humans; Myocardial Ischemia; Piperazines; Platelet Aggregation Inhibitors; Prasugrel Hydrochloride; Randomized Controlled Trials as Topic; Thiophenes; Ticlopidine

Topics: Clopidogrel; Humans; Myocardial Ischemia; Piperazines; Platelet Aggregation Inhibitors; Prasugrel Hydrochloride; Purinergic P2 Receptor Antagonists; Randomized Controlled Trials as Topic; Thiophenes; Ticlopidine; Time Factors

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