terutroban and Ischemic-Attack--Transient

One of the leading causes of mortality worldwide is ischemic stroke, which is a major contributor to neurological disability and dementia. Terutroban is a specific thromboxane A2 receptor antagonist with antithrombotic, antivasoconstrictive, and antiatherosclerotic properties, which make it a promising tool for secondary prevention of ischemic stroke.. The Prevention of Cerebrovascular and Cardiovascular Events of Ischemic Origin with Terutroban in Patients with a History of Ischemic Stroke or Transient Ischemic Attack (PERFORM) Study is an international, multicenter, randomized, double-blind, parallel-group study in patients aged > or =55 years who have suffered ischemic strokes (<3 months) or transient ischemic attacks (<8 days), and who are stable at inclusion with no intracranial hemorrhage or nonischemic neurological diseases. Patients are randomly allocated to terutroban (30 mg/day) or aspirin (100 mg/day). The primary efficacy end point is a composite of ischemic stroke (fatal or nonfatal), myocardial infarction (fatal or nonfatal), or other vascular death (excluding hemorrhagic death of any origin). Safety is evaluated by assessing hemorrhagic events. The first patient was randomized in February 2006 and more than 19,000 patients will be included.. The PERFORM Study will explore the benefits of terutroban in secondary prevention of ischemic stroke. The study results are expected in 2011.

Topics: Brain Ischemia; Humans; Ischemic Attack, Transient; Multicenter Studies as Topic; Naphthalenes; Propionates; Randomized Controlled Trials as Topic; Stroke

Elevated resting heart rate is known to be detrimental to morbidity and mortality in cardiovascular disease, though its effect in patients with ischemic stroke is unclear. We analyzed the effect of baseline resting heart rate on myocardial infarction (MI) in patients with a recent noncardioembolic cerebral ischemic event participating in PERFORM.. We compared fatal or nonfatal MI using adjusted Cox proportional hazards models for PERFORM patients with baseline heart rate <70 bpm (n=8178) or ≥70 bpm (n=10,802). In addition, heart rate was analyzed as a continuous variable. Other cerebrovascular and cardiovascular outcomes were also explored.. Heart rate ≥70 bpm was associated with increased relative risk for fatal or nonfatal MI (HR 1.32, 95% CI 1.03-1.69, P=0.029). For every 5-bpm increase in heart rate, there was an increase in relative risk for fatal and nonfatal MI (11.3%, P=0.0002). Heart rate ≥70 bpm was also associated with increased relative risk for a composite of fatal or nonfatal ischemic stroke, fatal or nonfatal MI, or other vascular death (excluding hemorrhagic death) (P<0001); vascular death (P<0001); all-cause mortality (P<0001); and fatal or nonfatal stroke (P=0.04). For every 5-bpm increase in heart rate, there were increases in relative risk for fatal or nonfatal ischemic stroke, fatal or nonfatal MI, or other vascular death (4.7%, P<0.0001), vascular death (11.0%, P<0.0001), all-cause mortality (8.0%, P<0.0001), and fatal and nonfatal stroke (2.4%, P=0.057).. Elevated heart rate ≥70 bpm places patients with a noncardioembolic cerebral ischemic event at increased risk for MI.

Topics: Aged; Female; Heart Rate; Humans; Ischemic Attack, Transient; Male; Middle Aged; Myocardial Infarction; Myocardial Ischemia; Naphthalenes; Prognosis; Propionates; Risk Factors; Stroke

Patients with ischaemic stroke or transient ischaemic attack (TIA) are at high risk of recurrent stroke or other cardiovascular events. We compared the selective thromboxane-prostaglandin receptor antagonist terutroban with aspirin in the prevention of cerebral and cardiovascular ischaemic events in patients with a recent non-cardioembolic cerebral ischaemic event.. This randomised, double-blind, parallel-group trial was undertaken in 802 centres in 46 countries. Patients who had an ischaemic stroke in the previous 3 months or a TIA in the previous 8 days were randomly allocated with a central interactive response system to 30 mg per day terutroban or 100 mg per day aspirin. Patients and investigators were masked to treatment allocation. The primary efficacy endpoint was a composite of fatal or non-fatal ischaemic stroke, fatal or non-fatal myocardial infarction, or other vascular death (excluding haemorrhagic death). We planned a sequential statistical analysis of non-inferiority (margin 1·05) followed by analysis of superiority. Analysis was by intention to treat. The study was stopped prematurely for futility on the basis of the recommendation of the Data Monitoring Committee. This study is registered, number ISRCTN66157730.. 9562 patients were assigned to terutroban (9556 analysed) and 9558 to aspirin (9544 analysed); mean follow-up was 28·3 months (SD 7·7). The primary endpoint occurred in 1091 (11%) patients receiving terutroban and 1062 (11%) receiving aspirin (hazard ratio [HR] 1·02, 95% CI 0·94-1·12). There was no evidence of a difference between terutroban and aspirin for the secondary or tertiary endpoints. We recorded some increase in minor bleedings with terutroban compared with aspirin (1147 [12%] vs 1045 [11%]; HR 1·11, 95% CI 1·02-1·21), but no significant differences in other safety endpoints.. The trial did not meet the predefined criteria for non-inferiority, but showed similar rates of the primary endpoint with terutroban and aspirin, without safety advantages for terutroban. In a worldwide perspective, aspirin remains the gold standard antiplatelet drug for secondary stroke prevention in view of its efficacy, tolerance, and cost.. Servier, France.

Topics: Aged; Aspirin; Double-Blind Method; Female; Humans; Ischemic Attack, Transient; Male; Middle Aged; Naphthalenes; Platelet Aggregation Inhibitors; Propionates; Receptors, Thromboxane; Secondary Prevention; Stroke; Treatment Outcome

Ischemic stroke is the leading cause of mortality worldwide and a major contributor to neurological disability and dementia. Terutroban is a specific TP receptor antagonist with antithrombotic, antivasoconstrictive, and antiatherosclerotic properties, which may be of interest for the secondary prevention of ischemic stroke. This article describes the rationale and design of the Prevention of cerebrovascular and cardiovascular Events of ischemic origin with teRutroban in patients with a history oF ischemic strOke or tRansient ischeMic Attack (PERFORM) Study, which aims to demonstrate the superiority of the efficacy of terutroban versus aspirin in secondary prevention of cerebrovascular and cardiovascular events.. The PERFORM Study is a multicenter, randomized, double-blind, parallel-group study being carried out in 802 centers in 46 countries. The study population includes patients aged > or =55 years, having suffered an ischemic stroke (< or =3 months) or a transient ischemic attack (< or =8 days). Participants are randomly allocated to terutroban (30 mg/day) or aspirin (100 mg/day). The primary efficacy endpoint is a composite of ischemic stroke (fatal or nonfatal), myocardial infarction (fatal or nonfatal), or other vascular death (excluding hemorrhagic death of any origin). Safety is being evaluated by assessing hemorrhagic events. Follow-up is expected to last for 2-4 years. Assuming a relative risk reduction of 13%, the expected number of primary events is 2,340. To obtain statistical power of 90%, this requires inclusion of at least 18,000 patients in this event-driven trial. The first patient was randomized in February 2006.. The PERFORM Study will explore the benefits and safety of terutroban in secondary cardiovascular prevention after a cerebral ischemic event.

Topics: Aged; Aged, 80 and over; Aspirin; Cardiovascular Diseases; Dose-Response Relationship, Drug; Double-Blind Method; Endpoint Determination; Female; Humans; International Cooperation; Ischemic Attack, Transient; Male; Middle Aged; Naphthalenes; Platelet Aggregation Inhibitors; Propionates; Receptors, Thromboxane; Stroke; Treatment Outcome

The Prevention of cerebrovascular and cardiovascular Events of ischemic origin with teRutroban in patients with a history oF ischemic strOke or tRansient ischeMic attack (PERFORM) study is an international double-blind, randomized controlled trial designed to investigate the superiority of the specific TP receptor antagonist terutroban (30 mg/day) over aspirin (100 mg/day), in reducing cerebrovascular and cardiovascular events in patients with a recent history of ischemic stroke or transient ischemic attack. Here we describe the baseline characteristics of the population.. Parameters recorded at baseline included vital signs, risk factors, medical history, and concomitant treatments, as well as stroke subtype, stroke-associated disability on the modified Rankin scale, and scores on scales for cognitive function and dependency. Eight hundred and two centers in 46 countries recruited a total of 19,119 patients between February 2006 and April 2008. The population is evenly distributed and is not dominated by any one country or region. The mean +/- SD age was 67.2 +/- 7.9 years, 63% were male, and 83% Caucasian; 83% had hypertension, and about half the population smoked or had quit smoking. Ninety percent of the qualifying events were ischemic stroke, 67% of which were classified as atherothrombotic or likely atherothrombotic (pure or coexisting with another cause). Modified Rankin scale scores showed slight or no disability in 83% of the population, while the scores on the Mini-Mental State Examination, Isaacs' Set Test, Zazzo's Cancellation Test, and the instrumental activities of daily living scale showed a good level of cognitive function and autonomy.. The PERFORM study population is homogeneous in terms of demographic and disease characteristics. With 19,119 patients, the PERFORM study is powered to test the superiority of terutroban over aspirin in the secondary prevention of cerebrovascular and cardiovascular events in patients with a recent history of ischemic stroke or transient ischemic attack.

Topics: Activities of Daily Living; Aged; Aspirin; Cognition; Diabetes Complications; Dose-Response Relationship, Drug; Double-Blind Method; Female; Humans; Hypertension; International Cooperation; Ischemic Attack, Transient; Male; Middle Aged; Naphthalenes; Platelet Aggregation Inhibitors; Propionates; Receptors, Thromboxane; Risk Factors; Secondary Prevention; Severity of Illness Index; Stroke