prasugrel-hydrochloride and Acute-Disease

Although some studies have examined platelet reactivity (PR) during prasugrel treatment, little is known about PR during the early treatment period and its clinical significance in Japan.. We investigated the early and medium-term efficacy and safety of prasugrel in patients with acute myocardial infarction (AMI) undergoing primary percutaneous coronary intervention (PCI). Seventy-eight patients were enrolled and PR was measured (in P2Y. In 44 patients, serial measurement revealed that PR was significantly higher at 2h after administration of the 20-mg loading dose of prasugrel than on the morning of the second day at 17.6±6.6h after administration (191.6±75.5 vs. 138.5±68.9PRU). During the 8-month follow-up period, bleeding events occurred in 18 patients (23.1%) (GUSTO minor: 15 patients). Multivariate regression analysis identified oral anticoagulant use as a significant predictor of bleeding events during admission [odds ratio (OR): 4.214, 95% confidence interval (CI): 1.005-17.669, p=0.049]. Administration of prasugrel via a nasogastric tube was a significant predictor of high on-treatment platelet reactivity (HTPR) (PRU≥230) (OR: 43.100, 95% CI: 4.517-411.251, p=0.001). In addition, HTPR was a significant predictor of major adverse cardiac events (cardiovascular death, non-fatal myocardial infarction, stent thrombosis, stroke, and sustained ventricular tachycardia) during the 8-month follow-up period (OR: 4.911, 95% CI: 1.164-20.722, p=0.030).. It is feasible to treat AMI patients with prasugrel. HTPR is a significant independent risk factor for adverse events in AMI patients receiving prasugrel after primary PCI.

Topics: Acute Disease; Aged; Blood Platelets; Female; Hemorrhage; Humans; Male; Middle Aged; Myocardial Infarction; Odds Ratio; Percutaneous Coronary Intervention; Platelet Aggregation Inhibitors; Platelet Function Tests; Prasugrel Hydrochloride; Prospective Studies; Risk Factors; Treatment Outcome

The purpose of this study was to investigate outcomes of patients treated with prasugrel or clopidogrel after percutaneous coronary intervention (PCI) in a nationwide acute coronary syndrome (ACS) registry.. Prasugrel was found to be superior to clopidogrel in a randomized trial of ACS patients undergoing PCI. However, little is known about its efficacy in everyday practice.. All ACS patients enrolled in the Acute Myocardial Infarction in Switzerland (AMIS)-Plus registry undergoing PCI and being treated with a thienopyridine P2Y12 inhibitor between January 2010-December 2013 were included in this analysis. Patients were stratified according to treatment with prasugrel or clopidogrel and outcomes were compared using propensity score matching. The primary endpoint was a composite of death, recurrent infarction and stroke at hospital discharge.. Out of 7621 patients, 2891 received prasugrel (38%) and 4730 received clopidogrel (62%). Independent predictors of in-hospital mortality were age, Killip class >2, STEMI, Charlson comorbidity index >1, and resuscitation prior to admission. After propensity score matching (2301 patients per group), the primary endpoint was significantly lower in prasugrel-treated patients (3.0% vs 4.3%; p=0.022) while bleeding events were more frequent (4.1% vs 3.0%; p=0.048). In-hospital mortality was significantly reduced (1.8% vs 3.1%; p=0.004), but no significant differences were observed in rates of recurrent infarction (0.8% vs 0.7%; p=1.00) or stroke (0.5% vs 0.6%; p=0.85). In a predefined subset of matched patients with one-year follow-up (n=1226), mortality between discharge and one year was not significantly reduced in prasugrel-treated patients (1.3% vs 1.9%, p=0.38).. In everyday practice in Switzerland, prasugrel is predominantly used in younger patients with STEMI undergoing primary PCI. A propensity score-matched analysis suggests a mortality benefit from prasugrel compared with clopidogrel in these patients.

Topics: Acute Coronary Syndrome; Acute Disease; Aged; Aged, 80 and over; Clopidogrel; Female; Humans; Male; Middle Aged; Myocardial Infarction; Percutaneous Coronary Intervention; Platelet Aggregation Inhibitors; Prasugrel Hydrochloride; Purinergic P2Y Receptor Antagonists; Registries; Switzerland; Ticlopidine; Treatment Outcome

Dual antiplatelet therapy with aspirin and clopidogrel is standard for prevention of thrombotic complications of percutaneous coronary intervention (PCI). Prasugrel is a thienopyridine that is more potent, more rapid in onset, and more consistent in inhibition of platelets than clopidogrel. TRITON-TIMI 38 is designed to compare prasugrel with clopidogrel in moderate to high-risk patients with acute coronary syndrome (ACS).. TRITON-TIMI 38 is a phase 3, randomized, double-blind, parallel-group, multinational, clinical trial. Approximately 13,000 patients with moderate to high-risk ACS undergoing PCI (9500 unstable angina/non-ST-segment elevation myocardial infarction [MI], 3500 ST-segment elevation MI) will be randomized to prasugrel 60 mg loading dose followed by 10 mg daily or clopidogrel 300 mg loading dose followed by 75 mg daily for up to 15 months. The primary end point is the time of the first event of cardiovascular death, MI, or stroke. Analyses will be performed first in the unstable angina/non-ST-segment elevation MI cohort and, conditionally, on the whole ACS population. Major safety end points include TIMI major and minor bleeding unrelated to coronary artery bypass graft surgery.. TRITON-TIMI 38 is a phase 3 comparison of prasugrel versus clopidogrel in patients with moderate to high-risk ACS undergoing PCI. In addition, it is the first large-scale clinical events trial to assess whether a thienopyridine regimen that achieves a higher level of inhibition of platelet aggregation than the standard therapy results in an improvement in clinical outcomes.

Topics: Acute Disease; Aged; Angioplasty, Balloon, Coronary; Clopidogrel; Coronary Disease; Dose-Response Relationship, Drug; Double-Blind Method; Follow-Up Studies; Humans; Myocardial Infarction; Piperazines; Platelet Aggregation Inhibitors; Prasugrel Hydrochloride; Research Design; Syndrome; Thiophenes; Thrombolytic Therapy; Thrombosis; Ticlopidine; Treatment Outcome

Despite dual antiplatelet treatment, major ischemic events are common following ST elevation myocardial infarction (STEMI). We aimed to assess high platelet reactivity on aspirin (HPR-aspirin) and its association with P2Y12i (HPR-P2Y12i) during the acute phase of STEMI.. We included all consecutive patients admitted for STEMI treated by primary angioplasty in our center for 1year. All patients received a loading dose followed by a maintenance dose of aspirin (75mg/day) and prasugrel (ticagrelor or clopidogrel if contraindicated). Platelet reactivity was assessed 4±1days and 75±15days after admission using light transmission aggregometry with arachidonic acid (LTA-AA-HPR-aspirin) and VASP (HPR-P2Y12i) to define HPR as well as serum Thromboxane-B2 and LTA-ADP. Major cardiac and cerebrovascular events were recorded for 1year.. We included 106 patients - mean age was 61y.o., 76% were male and 20% had diabetes. STEMI was anterior in 52% and LV ejection fraction at discharge was 51±9%. 50% of patients were treated with prasugrel and 34% with ticagrelor. At day 4 after STEMI, HPR-aspirin was found in 26% patients and HPR-P2Y12i in 7%. HPR- both aspirin and P2Y12i was found in 4%. Diabetes and age were predictors of HPR-aspirin. HPR-aspirin was persistent 75days later in 36% patients. At 1year, 7.9% patients had experienced major adverse cardiovascular and cerebrovascular events (MACCE). HPR-aspirin and HPR on both aspirin and P2Y12i were significantly associated with MACCE.. HPR-aspirin is frequent just after STEMI and associated with MACCE especially when associated with HPR-P2Y12i.

Topics: Acute Disease; Adenosine; Aspirin; Blood Platelets; Brain Ischemia; Cardiovascular Diseases; Clopidogrel; Female; Humans; Male; Middle Aged; Platelet Aggregation; Platelet Aggregation Inhibitors; Platelet Function Tests; Prasugrel Hydrochloride; Prospective Studies; Purinergic P2Y Receptor Antagonists; ST Elevation Myocardial Infarction; Survival Analysis; Ticagrelor; Ticlopidine

Previously, we showed preventive effects of prasugrel, a P2Y12 antagonist, in a non-human primate model of thrombotic middle cerebral artery occlusion (MCAO); however, it remains unclear if P2Y12 inhibition after MCAO reduces cerebral injury and dysfunction. Here we investigated the effects of R-138727, the major active metabolite of prasugrel, on ex vivo platelet aggregation at 5min, 15min, 60min, and 24h after administration to non-human primates (n=3). A single intravenous dose of R-138727 (0.03-0.3mg/kg) resulted in significant and sustained dose-related effects on platelets for up to 24h. R-138727 was administered 1h after MCAO induction, and its effects on thrombosis, cerebral infarction, and neurological deficits were determined (n=8-10). R-138727 (0.3mg/kg) significantly increased total patency rate of the MCA (P=0.0211). Although there was no effect on the patency rate before R-138727 dosing (P=0.3975), it increased 1h after dosing (P=0.0114). R-138727 significantly reduced total ischaemic infarction volumes (P=0.0147), including those of basal ganglia (P=0.0028), white matter (P=0.0393), and haemorrhagic infarction (P=0.0235). Additionally, treatment with R-138727 reduced overall neurological deficits (P=0.0019), including the subcategories of consciousness (P=0.0042), sensory system (P=0.0045), motor system (P=0.0079) and musculoskeletal coordination (P=0.0082). These findings support the possible utility of P2Y12 inhibition during early-onset MCAO to limit the progression and degree of cerebral ischaemia and infarction and also associated neurological deficits.

Topics: Acute Disease; Animals; Brain; Brain Infarction; Cell Adhesion Molecules; Cerebrovascular Circulation; Infarction, Middle Cerebral Artery; Macaca fascicularis; Male; Microfilament Proteins; Phosphoproteins; Phosphorylation; Piperazines; Platelet Aggregation; Prasugrel Hydrochloride; Receptors, Purinergic P2Y12

Morphine is recommended in patients with ST-segment-elevation myocardial infarction, including those undergoing primary percutaneous coronary intervention. Suboptimal antiplatelet effect during and after primary percutaneous coronary intervention is associated with increased thrombotic complications. It was hypothesized a potential drug-drug interaction between morphine and antiplatelet agents. We sought to assess platelet inhibition after a loading dose of the currently recommended antiplatelet agents in ST-segment-elevation myocardial infarction patients according to morphine use.. Three hundred patients undergoing primary percutaneous coronary intervention receiving either prasugrel (n = 95) or ticagrelor (n = 205) loading dose had platelet reactivity assessed by VerifyNow 1, 2, and 4 hours after loading dose. Patients treated with morphine (n = 95; 32%) had a higher incidence of vomit (15% versus 2%; P = 0.001). P2Y12 reactivity units 2 hours after the loading dose was 187 (153-221) and 133 (102-165) in patient with and without morphine (P < 0.001); the difference persisted after excluding patients with vomit (P < 0.0001). High residual platelet reactivity (P2Y12 reactivity units ≥ 208) at 2 hours was found in 53% and 29% patients with and without morphine (P < 0.001) and without difference between prasugrel and ticagrelor patients. The independent predictors of high residual platelet reactivity at 2 hours were morphine use (odds ratio, 2.91 [1.71-4.97]; P < 0.0001) and age (odds ratio, 1.03 [1.01-1.05]; P = 0.010). Morphine remained associated with high residual platelet reactivity after propensity score adjustment (c-statistic, 0.68; 95% confidence interval, 0.66-0.70; P = 0.879 for Hosmer-Lemeshow test).. In patients with ST-segment-elevation myocardial infarction, morphine use is associated with a delayed onset of action of the oral antiplatelet agents. This association persisted after adjusting for the propensity to receive morphine and after excluding patients with vomit.

Topics: Acute Disease; Adenosine; Age Factors; Aged; Analgesics, Opioid; Drug Interactions; Electrocardiography; Female; Humans; Male; Middle Aged; Morphine; Myocardial Infarction; Percutaneous Coronary Intervention; Piperazines; Platelet Activation; Platelet Aggregation Inhibitors; Platelet Function Tests; Prasugrel Hydrochloride; Thiophenes; Ticagrelor

Mild therapeutic hypothermia (TH) is standard of care after cardiac arrest of any cause. However, its impact on on-treatment platelet reactivity and clinical outcome in patients with acute myocardial infarction (AMI) complicated by cardiogenic shock and undergoing PCI with P2Y12 receptor inhibitor treatment is less clear.. For the ISAR-SHOCK registry, 145 patients with AMI, cardiogenic shock and primary PCI in two centers (Deutsches Herzzentrum München and Klinikum rechts der Isar, Technical University Munich) between January 2009-May 2012 were analysed. Of these, 64 (44%) patients received TH treatment. The median [IQR] ADP-induced platelet aggregation following thienopyridine loading dose administration (clopidogrel in 95 and prasugrel in 50 patients) did not differ between the two groups (419 [283-684] for TH vs. 355 [207-710] AU x min for non-TH patients, P=0.22). After 30days follow-up, no significant differences were observed between both groups for mortality (42 vs. 44 %, HR: 0.93, 95% CI [0.56-1.53], p=0.77), MI (6 vs. 6%, HR: 0.99 95% CI [0.27-3.7], p=0.99) and TIMI minor bleedings (17 vs. 17%, HR 0.99 95% CI [0.45-2.18], p=0.98). TIMI major bleedings were numerically higher in the TH vs. non-TH cohort (25 % vs. 12 %, HR: 2.1 95% CI [0.95-4.63], p=0.07). Three definite stent thrombosis (ST) were observed in this registry and all STs occurred in the TH group of patients (p=0.09).. Results of this registry suggest that TH does not negatively impact on platelet reactivity in shock patients receiving either clopidogrel or prasugrel. The numerically higher rate of major bleedings and the clustering of STs in the TH cohort warrant further investigation.

Topics: Acute Disease; Aged; Aged, 80 and over; Blood Platelets; Clopidogrel; Female; Humans; Hypothermia, Induced; Male; Middle Aged; Myocardial Infarction; Percutaneous Coronary Intervention; Platelet Aggregation Inhibitors; Platelet Function Tests; Prasugrel Hydrochloride; Purinergic P2Y Receptor Antagonists; Registries; Shock, Cardiogenic; Ticlopidine; Treatment Outcome

Although randomized clinical trials have compared clopidogrel with higher potency ADP receptor inhibitors (ADPris) among patients with myocardial infarction, little is known about the frequency and factors associated with switching between ADPris in clinical practice.. We studied 47 040 patients with myocardial infarction treated with percutaneous coronary intervention, who received either clopidogrel or prasugrel within 24 hours of admission at 361 US hospitals from July 2009 to June 2011 using the merged Acute Coronary Treatment and Intervention Outcomes Network Registry-Get With the Guidelines and CathPCI Registry database. Hierarchical logistic regression modeling was used to determine factors independently associated with in-hospital ADPri switching. Among 40 531 patients treated initially in-hospital with clopidogrel, 2125 (5.2%) were discharged on prasugrel; this frequency steadily increased from 0% to 7% during the study period. Among 6509 patients treated initially in-hospital with prasugrel, 751 (11.5%) were discharged on clopidogrel. The frequency of this switch increased from 6% to 18% during the first 2 quarters of the study period and decreased to 9% by the end. Switching clopidogrel to prasugrel was associated with high-risk angiographic characteristics (thrombotic, long, and bifurcating lesions), reinfarction in-hospital, and private health insurance coverage. Older age, previous cerebrovascular event, in-hospital coronary artery bypass grafting, in-hospital bleeding, and warfarin use at discharge were associated with switching prasugrel to clopidogrel.. Clopidogrel and prasugrel are not uncommonly switched in-hospital in patients with myocardial infarction undergoing percutaneous coronary intervention. In contemporary US practice, in addition to risk for bleeding and recurrent ischemic events, medical drug coverage is a major determinant of ADPri selection.

Topics: Acute Disease; Age Factors; Aged; Clopidogrel; Drug Substitution; Female; Humans; Male; Middle Aged; Myocardial Infarction; Percutaneous Coronary Intervention; Piperazines; Postoperative Complications; Practice Guidelines as Topic; Prasugrel Hydrochloride; Purinergic P2Y Receptor Antagonists; Recurrence; Registries; Risk Factors; Thiophenes; Thrombosis; Ticlopidine; United States

Romiplostim is a thrombopoietin receptor agonist that increases platelet counts and restores platelet function in patients with chronic immune thrombocytopenia (ITP). Increase in platelet count and platelet activation has been associated with increased thromboembolic risk. The present case report describes an interesting case of acute stent thrombosis in a patient with chronic immune thrombocytopenic purpura (ITP) being treated with romiplostim.

Topics: Acute Disease; Aspirin; Chest Pain; Clopidogrel; Eptifibatide; Female; Humans; Middle Aged; Peptides; Piperazines; Platelet Aggregation Inhibitors; Platelet Count; Prasugrel Hydrochloride; Purpura, Thrombocytopenic, Idiopathic; Receptors, Thrombopoietin; Risk Factors; Stents; Thiophenes; Thrombosis; Ticlopidine; Ultrasonography, Interventional