prasugrel-hydrochloride and Ischemic-Attack--Transient

The efficacy and safety of different antiplatelet regimes for prevention of stroke in patients at high risk were investigated in a systematic review and meta-analysis.. We searched the Cochrane Central Register of Controlled Trials, MEDLINE, and Web of Science. Twenty-two studies comprising 173 371 patients were included.. In the overall population, dual antiplatelet therapy (DAPT) with aspirin and clopidogrel in comparison to aspirin monotherapy reduced the relative risk of total stroke by 20% (risk ratio [RR], 0.80; 95% confidence interval [CI], 0.73-0.88; P<0.0001; I(2)=28%) and of ischemic stroke or transient ischemic attack by 23% (RR, 0.77; 95% CI, 0.69-0.85; P<0.0001; I(2)=18%) without increasing the risk of intracranial hemorrhage. In the secondary prevention cohort, DAPT with aspirin and clopidogrel also reduced the relative risk of total stroke by 24% as compared with aspirin alone (RR, 0.76; 95% CI, 0.68-0.86; P<0.0001; I(2)=0%). DAPT with prasugrel or ticagrelor and aspirin versus DAPT with clopidogrel and aspirin was not associated with a risk reduction of stroke.. DAPT with clopidogrel and aspirin compared with aspirin effectively reduces the risk of total and ischemic stroke in the overall cohort consisting of patients with cardiovascular disease without increase in intracranial hemorrhage, as well as decreases the risk of a recurrent total stroke in patients with a previous stroke/transient ischemic attack. Our meta-analysis suggests that DAPT including low-dose aspirin (75-100 mg) and clopidogrel (75 mg) should be further investigated as a strategy to reduce recurrent strokes.. http://www.crd.york.ac.uk/prospero. Unique identifier: CRD42011001596.

Topics: Adenosine; Aged; Aspirin; Cerebral Hemorrhage; Cerebrovascular Disorders; Clopidogrel; Cohort Studies; Data Interpretation, Statistical; Drug Therapy, Combination; Female; Humans; Ischemic Attack, Transient; Male; Middle Aged; Piperazines; Platelet Aggregation Inhibitors; Population; Prasugrel Hydrochloride; Randomized Controlled Trials as Topic; Receptors, Purinergic P2; Secondary Prevention; Stroke; Thiophenes; Ticagrelor; Ticlopidine; Vascular Diseases

The new definition and risk stratification for transient ischemic attack (TIA) have clear implications for the urgency of evaluation and treatment. The optimal antithrombotic treatment for TIA is being intensively studied. New guidelines for prevention of non-cardioembolic stroke in patients with stroke or TIA recommend the use of antiplatelet agents rather than oral anticoagulation. New antiplatelet drugs are being used in cardiovascular patients, and their role in cerebrovascular patients is being studied. The impact of genetic CYP2C19 polymorphisms is becoming clarified in cardiovascular patients and it is likely these polymorphisms will affect the management of cerebrovascular patients. The results of trials of clopidogrel plus aspirin in patients with lacunar strokes and acute TIAs are forthcoming. The results of CLOSURE I, a study of a patent foramen ovale device closure trial for cryptogenic stroke or TIA, showed no differences in stroke or TIA at 2 years.

Topics: Adenosine; Aryl Hydrocarbon Hydroxylases; Brain Ischemia; Cilostazol; Clinical Trials as Topic; Clopidogrel; Cytochrome P-450 CYP2C19; Cytochrome P-450 Enzyme System; Fibrinolytic Agents; Foramen Ovale, Patent; Genotype; Humans; Ischemic Attack, Transient; Piperazines; Platelet Aggregation Inhibitors; Polymorphism, Genetic; Prasugrel Hydrochloride; Risk Assessment; Risk Factors; Stroke; Tetrazoles; Thiophenes; Ticagrelor; Ticlopidine

Topics: Acute Coronary Syndrome; Angioplasty, Balloon, Coronary; Cardiovascular Diseases; Clopidogrel; Double-Blind Method; Hemorrhage; Humans; Ischemic Attack, Transient; Piperazines; Platelet Aggregation Inhibitors; Prasugrel Hydrochloride; Prospective Studies; Secondary Prevention; Stents; Stroke; Thiophenes; Ticlopidine; Treatment Outcome

A patient undergoes intracranial stent insertion for stent-assisted coiling of a basilar tip aneurysm and left middle cerebral artery aneurysm. A flow diverting stent is also placed across an anterior communicating artery aneurysm. Prior to the procedure, the patient takes dual antiplatelet medications, being aspirin and clopidogrel. Because of the concern regarding in-stent thrombus and thromboembolic complications related to intracranial stenting and the high rate of clopidogrel resistance, preoperative platelet function testing (PFT) was undertaken to ensure platelet inhibition. In this case, PFT was performed on a platelet function analyser which demonstrated platelet inhibition. Ten days following the procedure, the patient represented with thromboembolic stroke. Repeat PFT performed with whole blood impedance aggregometry and despite full medication compliance demonstrated clopidogrel resistance. Clopidogrel was then ceased and prasugrel commenced. This case demonstrates the importance of appropriate platelet inhibition in patients with intracranial stents and the controversy surrounding PFT.

Topics: Aged; Aspirin; Clopidogrel; Diagnosis, Differential; Drug Resistance; Humans; Intracranial Aneurysm; Ischemic Attack, Transient; Magnetic Resonance Imaging; Male; Platelet Aggregation Inhibitors; Platelet Function Tests; Prasugrel Hydrochloride; Preoperative Care; Stents; Stroke; Thromboembolism; Treatment Outcome; Withholding Treatment

(1) For patients with acute coronary syndromes who have undergone percutaneous angioplasty and stenting, the best-assessed treatment for preventing relapses is a combination of aspirin and clopidogrel; (2) Prasugrel, an antiplatelet drug belonging the same chemical class as clopidogrel, is authorized in the EU for use in this indication; (3) Clinical evaluation is based on a randomized double-blind trial comparing prasugrel + aspirin versus clopidogrel + aspirin in 13 608 patients with acute coronary syndromes, half of whom were treated for at least 15 months. Prasugrel did not reduce overall mortality (about 3%) or the incidence of non-fatal stroke after 15 months (1% of patients). The only advantage reported with prasugrel was a significant reduction in the risk of non-fatal myocardial infarction (7.3% versus 9.5%); (4) In this trial, bleeding events, excluding those related to revascularisation procedures, were more frequent in the prasugrel group than in the clopidogrel group (2.4% versus 1.8%). Haemorrhages associated with revascularisation were also significantly more numerous with prasugrel (11.3% and 3.6%); (5) Subgroup analyses suggest that the risk-benefit balance of prasugrel is unfavourable in patients weighing less than 60 kg, patients over 75 years of age, and patients with a history of transient ischaemic attack or stroke; (6) The trial comparing prasugrel versus clopidogrel, as well as some animal studies, raise the possibility that prasugrel might increase the risk of cancer. In the main trial, prasugrel caused fewer cases of neutropenia than clopidogrel, but more cases of respiratory failure, hypotension and atrial flutter were observed; (7) In practice, for secondary prevention in patients with acute coronary syndromes treated with angioplasty and stenting, the risk-benefit balance of prasugrel, used in combination with aspirin, appears to be no better than that of clopidogrel + aspirin.

Topics: Acute Coronary Syndrome; Angioplasty, Balloon, Coronary; Aspirin; Cardiovascular Diseases; Clopidogrel; Double-Blind Method; Drug Therapy, Combination; Drug-Eluting Stents; Europe; Hemorrhage; Humans; Ischemic Attack, Transient; Myocardial Infarction; Neoplasms; Piperazines; Platelet Aggregation Inhibitors; Prasugrel Hydrochloride; Purinergic P2 Receptor Antagonists; Randomized Controlled Trials as Topic; Receptors, Purinergic P2; Recurrence; Stents; Stroke; Thiophenes; Ticlopidine; Treatment Outcome