The Experts below are selected from a list of 309 Experts worldwide ranked by ideXlab platform

Michael G. Hennerici - One of the best experts on this subject based on the ideXlab platform.

  • Paracetamol, ibuprofen, and recurrent major cardiovascular and major bleeding events in 19 120 patients with recent ischemic stroke
    Stroke, 2016
    Co-Authors: Jaime Gonzalez-valcarcel, Marie-germaine Bousser, Ángel Chamorro, Marc Fisher, Ian Ford, Michael G. Hennerici, Kim M. Fox, Leila Sissani, Julien Labreuche, Heinrich Mattle
    Abstract:

    Background and Purpose—The presumed safety of paracetamol in high–cardiovascular risk patients has been questioned. We determined whether paracetamol or ibuprofen use is associated with major cardiovascular events (MACE) or major bleeding in 19 120 patients with recent ischemic stroke or transient ischemic attack of mainly atherothrombotic origin included in 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) trial. Methods—We performed 2 nested case–control analysis (2153 cases with MACE during trial follow-up and 4306 controls matched on Essen stroke risk score; 809 cases with major bleeding matched with 1616 controls) and a separate time-varying analysis. Results—12.3% were prescribed paracetamol and 2.5% ibuprofen. Median duration of treatment was 14 (interquartile range 5–145) days for paracetamol and 9 (5–30) days for ibuprofen. Paracetamol, but not ibuprofen, was associate...

  • Thromboxane prostaglandin receptor antagonist and carotid atherosclerosis progression in patients with cerebrovascular disease of ischemic origin: a randomized controlled trial.
    Stroke, 2014
    Co-Authors: Michiel L. Bots, Ian Ford, Suzanne M. Lloyd, Stephane Laurent, Pierre Jean Touboul, Michael G. Hennerici
    Abstract:

    Background and Purpose—Thromboxane prostaglandin receptors have been implicated to be involved in the atherosclerotic process. We assessed whether Terutroban, a thromboxane prostaglandin receptor antagonist, affects the progression of atherosclerosis, as measured by common carotid intima-media thickness and carotid plaques. Methods—A substudy was performed among 1141 participants of the aspirin-controlled Prevention of Cerebrovascular and Cardiovascular Events of Ischemic Origin with Terutroban in Patients with a History of Ischemic Stroke or Transient Ischemic Attack (PERFORM) trial. Common carotid intima-media thickness and carotid plaque occurrence was measured during a 3-year period. Results—Baseline characteristics did not differ between Terutroban (n=592) and aspirin (n=549) treated patients and were similar as in the main study. Mean study and treatment duration were similar (28 and 25 months, respectively). In the Terutroban group, the annualized rate of change in common carotid intima-media thick...

  • Heart rate is a prognostic risk factor for myocardial infarction: A post hoc analysis in the PERFORM (Prevention of cerebrovascular and cardiovascular Events of ischemic origin with Terutroban in patients with a history oF ischemic strOke or tRansien
    International journal of cardiology, 2013
    Co-Authors: Kim Fox, Marie-germaine Bousser, Pierre Amarenco, Ángel Chamorro, Marc Fisher, Ian Ford, Michael G. Hennerici, Heinrich Mattle, Peter M. Rothwell
    Abstract:

    Abstract Background 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. Methods We compared fatal or nonfatal MI using adjusted Cox proportional hazards models for PERFORM patients with baseline heart rate Results Heart rate ≥70bpm 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 ≥70bpm 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 P P 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 P P P =0.057). Conclusion Elevated heart rate ≥70bpm places patients with a noncardioembolic cerebral ischemic event at increased risk for MI.

  • Terutroban versus aspirin in patients with cerebral ischaemic events (PERFORM): a randomised, double-blind, parallel-group trial
    Lancet (London England), 2011
    Co-Authors: Marie-germaine Bousser, Pierre Amarenco, Ángel Chamorro, Marc Fisher, Ian Ford, Kim Fox, Michael G. Hennerici, Heinrich Mattle, Peter M. Rothwell, Agnes De Cordoue
    Abstract:

    Summary Background 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. Methods 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. Findings 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. Interpretation 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. Funding Servier, France.

  • Terutroban versus aspirin in patients with cerebral ischaemic events (PERFORM): a randomised, double-blind, parallel-group trial
    'Elsevier BV', 2011
    Co-Authors: Marie-germaine Bousser, Pierre Amarenco, Ángel Chamorro, Marc Fisher, Ian Ford, Michael G. Hennerici, Heinrich Mattle, Peter M. Rothwell, Kim M. Fox, Agnes De Cordoue
    Abstract:

    Background: 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. Methods: 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. Findings: 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. Interpretation: 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. Funding: Servier, France. © 2011 Elsevier Ltd

Ian Ford - One of the best experts on this subject based on the ideXlab platform.

  • Paracetamol, ibuprofen, and recurrent major cardiovascular and major bleeding events in 19 120 patients with recent ischemic stroke
    Stroke, 2016
    Co-Authors: Jaime Gonzalez-valcarcel, Marie-germaine Bousser, Ángel Chamorro, Marc Fisher, Ian Ford, Michael G. Hennerici, Kim M. Fox, Leila Sissani, Julien Labreuche, Heinrich Mattle
    Abstract:

    Background and Purpose—The presumed safety of paracetamol in high–cardiovascular risk patients has been questioned. We determined whether paracetamol or ibuprofen use is associated with major cardiovascular events (MACE) or major bleeding in 19 120 patients with recent ischemic stroke or transient ischemic attack of mainly atherothrombotic origin included in 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) trial. Methods—We performed 2 nested case–control analysis (2153 cases with MACE during trial follow-up and 4306 controls matched on Essen stroke risk score; 809 cases with major bleeding matched with 1616 controls) and a separate time-varying analysis. Results—12.3% were prescribed paracetamol and 2.5% ibuprofen. Median duration of treatment was 14 (interquartile range 5–145) days for paracetamol and 9 (5–30) days for ibuprofen. Paracetamol, but not ibuprofen, was associate...

  • Thromboxane prostaglandin receptor antagonist and carotid atherosclerosis progression in patients with cerebrovascular disease of ischemic origin: a randomized controlled trial.
    Stroke, 2014
    Co-Authors: Michiel L. Bots, Ian Ford, Suzanne M. Lloyd, Stephane Laurent, Pierre Jean Touboul, Michael G. Hennerici
    Abstract:

    Background and Purpose—Thromboxane prostaglandin receptors have been implicated to be involved in the atherosclerotic process. We assessed whether Terutroban, a thromboxane prostaglandin receptor antagonist, affects the progression of atherosclerosis, as measured by common carotid intima-media thickness and carotid plaques. Methods—A substudy was performed among 1141 participants of the aspirin-controlled Prevention of Cerebrovascular and Cardiovascular Events of Ischemic Origin with Terutroban in Patients with a History of Ischemic Stroke or Transient Ischemic Attack (PERFORM) trial. Common carotid intima-media thickness and carotid plaque occurrence was measured during a 3-year period. Results—Baseline characteristics did not differ between Terutroban (n=592) and aspirin (n=549) treated patients and were similar as in the main study. Mean study and treatment duration were similar (28 and 25 months, respectively). In the Terutroban group, the annualized rate of change in common carotid intima-media thick...

  • Atherogenic Dyslipidemia and Residual Cardiovascular Risk in Statin-Treated Patients
    Stroke, 2014
    Co-Authors: Gaia Sirimarco, Marie-germaine Bousser, Pierre Amarenco, Ángel Chamorro, Peter M. Rothwell, Kim M. Fox, Julien Labreuche, Eric Bruckert, Larry B. Goldstein, Ian Ford
    Abstract:

    Background and Purpose— Treatment with statins reduces the rate of cardiovascular events in high-risk patients, but residual risk persists. At least part of that risk may be attributable to atherogenic dyslipidemia characterized by low high-density lipoprotein cholesterol (≤40 mg/dL) and high triglycerides (triglycerides ≥150 mg/dL). Methods— We studied subjects with stroke or transient ischemic attack in 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; n=19 100) and Stroke Prevention by Aggressive Reduction in Cholesterol Levels (SPARCL; n=4731) trials who were treated with a statin and who had high-density lipoprotein cholesterol and triglycerides measurements 3 months after randomization (n=10 498 and 2900, respectively). The primary outcome measure for this exploratory analysis was the occurrence of major cardiovascular events (nonfatal myocardial infarction, nonfatal stroke, or cardiovascular death). We also performed a time-varying analysis to account for all available high-density lipoprotein cholesterol and triglyceride measurements. Results— A total of 10% of subjects in PERFORM and 9% in SPARCL had atherogenic dyslipidemia after ≥3 months on start statin therapy. After a follow-up of 2.3 years (PERFORM) and 4.9 years (SPARCL), a major cardiovascular event occurred in 1123 and 485 patients in the 2 trials, respectively. The risk of major cardiovascular events was higher in subjects with versus those without atherogenic dyslipidemia in both PERFORM (hazard ratio, 1.36; 95% confidence interval, 1.14–1.63) and SPARCL (hazard ratio, 1.40; 95% confidence interval, 1.06–1.85). The association was attenuated after multivariable adjustment (hazard ratio, 1.23; 95% confidence interval, 1.03–1.48 in PERFORM and hazard ratio, 1.24; 95% confidence interval, 0.93–1.65 in SPARCL). Time-varying analysis confirmed these findings. Conclusions— The presence of atherogenic dyslipidemia was associated with higher residual cardiovascular risk in PERFORM and SPARCL subjects with stroke or transient ischemic attack receiving statin therapy. Specific therapeutic interventions should now be trialed to address this residual risk.

  • Heart rate is a prognostic risk factor for myocardial infarction: A post hoc analysis in the PERFORM (Prevention of cerebrovascular and cardiovascular Events of ischemic origin with Terutroban in patients with a history oF ischemic strOke or tRansien
    International journal of cardiology, 2013
    Co-Authors: Kim Fox, Marie-germaine Bousser, Pierre Amarenco, Ángel Chamorro, Marc Fisher, Ian Ford, Michael G. Hennerici, Heinrich Mattle, Peter M. Rothwell
    Abstract:

    Abstract Background 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. Methods We compared fatal or nonfatal MI using adjusted Cox proportional hazards models for PERFORM patients with baseline heart rate Results Heart rate ≥70bpm 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 ≥70bpm 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 P P 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 P P P =0.057). Conclusion Elevated heart rate ≥70bpm places patients with a noncardioembolic cerebral ischemic event at increased risk for MI.

  • Terutroban versus aspirin in patients with cerebral ischaemic events (PERFORM): a randomised, double-blind, parallel-group trial
    Lancet (London England), 2011
    Co-Authors: Marie-germaine Bousser, Pierre Amarenco, Ángel Chamorro, Marc Fisher, Ian Ford, Kim Fox, Michael G. Hennerici, Heinrich Mattle, Peter M. Rothwell, Agnes De Cordoue
    Abstract:

    Summary Background 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. Methods 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. Findings 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. Interpretation 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. Funding Servier, France.

Paolo Gelosa - One of the best experts on this subject based on the ideXlab platform.

  • Terutroban a thromboxane prostaglandin endoperoxide receptor antagonist prevents hypertensive vascular hypertrophy and fibrosis
    American Journal of Physiology-heart and Circulatory Physiology, 2011
    Co-Authors: Paolo Gelosa, Alice Pignieri, Laura Castiglioni, Vanessa Blancguillemaud, Gulnur Sevin, Silvia Budelli, Laurence Lerond, Elena Tremoli, Luigi Sironi
    Abstract:

    Thromboxane A(2) and other eicosanoids such as isoprostanes contribute to vascular proliferation and atherosclerosis by binding to the thromboxane/prostaglandin endoperoxide receptors. The effects of Terutroban, a thromboxane/prostaglandin endoperoxide receptor antagonist, on aorta remodeling were evaluated in spontaneously hypertensive stroke-prone rats (SHRSPs), a model of severe hypertension, endothelial dysfunction, vascular inflammation, and cerebrovascular diseases. Male SHRSPs were allocated to three groups receiving a standard diet (n = 5) or a high-sodium permissive diet plus vehicle (n = 6) or plus Terutroban (30 mg · kg(-1) · day(-1); n = 6). After 6 wk of dietary treatment, all of the animals were injected with bromodeoxyuridine and simultaneously euthanized for aorta collection. The aortic media thickness-to-lumen ratio significantly (P < 0.0001) increased in the salt-loaded rats compared with the rats fed a standard diet, whereas Terutroban treatment completely prevented media thickening (P < 0.001). When compared with vehicle, Terutroban was also effective in preventing cell proliferation in the media, as indicated by the reduced number of bromodeoxyuridine-positive (P < 0.0001) and proliferating cell nuclear antigen-positive cells (P < 0.0001). Severe fibrosis characterized by a significant accumulation of collagen and fibronectin in the vascular wall was observed in the vehicle-treated rats (P < 0.01) but was completely prevented by Terutroban (P < 0.001). The latter also inhibited heat shock protein-47 (P < 0.01) and TGF-1β expression (P < 0.001), which were significantly increased by the high-salt diet. In conclusion, Terutroban prevents the development of aorta hyperplasia and has beneficial effects on fibrotic processes by affecting TGF-β and heat shock protein-47 expression in SHRSPs. These findings provide mechanistic data supporting the beneficial effects of Terutroban in preventing or retarding atherogenesis.

  • Terutroban, a thromboxane/prostaglandin endoperoxide receptor antagonist, prevents hypertensive vascular hypertrophy and fibrosis
    American journal of physiology. Heart and circulatory physiology, 2010
    Co-Authors: Paolo Gelosa, Alice Pignieri, Laura Castiglioni, Vanessa Blanc-guillemaud, Gulnur Sevin, Silvia Budelli, Laurence Lerond, Elena Tremoli, Luigi Sironi
    Abstract:

    Thromboxane A2 and other eicosanoids such as isoprostanes contribute to vascular proliferation and atherosclerosis by binding to the thromboxane/prostaglandin endoperoxide receptors. The effects of...

  • Terutroban a thromboxane prostaglandin endoperoxide receptor antagonist increases survival in stroke prone rats by preventing systemic inflammation and endothelial dysfunction comparison with aspirin and rosuvastatin
    Journal of Pharmacology and Experimental Therapeutics, 2010
    Co-Authors: Paolo Gelosa, R. Ballerio, Cristina Banfi, Elena Nobili, Anita Gianella, Alice Pignieri, Maura Brioschi, Uliano Guerrini, Laura Castiglioni, Vanessa Blancguillemaud
    Abstract:

    This study investigated the efficacy of Terutroban, a specific thromboxane/prostaglandin endoperoxide receptor antagonist, on stroke incidence in spontaneously hypertensive stroke-prone rats (SHRSP). The effects of Terutroban were compared with those of aspirin, another antiplatelet agent, and rosuvastatin, known to exert end-organ protection in SHRSP. Salt-loaded male SHRSP were treated orally once a day with vehicle, Terutroban (30 mg/kg/day), aspirin (60 mg/kg/day), or rosuvastatin (10 mg/kg/day). Compared with vehicle, and regardless of any effect on blood pressure or serum thromboxane B(2) levels, Terutroban significantly increased survival (p < 0.001) as a consequence of a delayed brain lesion occurrence monitored by magnetic resonance imaging (p < 0.001), and a delayed increase of proteinuria (p < 0.001). Terutroban decreased cerebral mRNA transcription of interleukin-1beta, transforming growth factor-beta, and monocyte chemoattractant protein-1 after 6 weeks of dietary treatment. Terutroban also prevented the accumulation of urinary acute-phase proteins at high molecular weight, identified as markers of systemic inflammation, and assessed longitudinally by one-dimensional electrophoresis. Terutroban also has protective effects on the vasculature as suggested by the preservation of endothelial function and endothelial nitric-oxide synthase expression in isolated carotid arteries. These effects are similar to those obtained with rosuvastatin, and superior to those of aspirin. Terutroban increases survival in SHRSP by reducing systemic inflammation as well as preserving endothelial function. These data support clinical development of Terutroban in the prevention of cerebrovascular and cardiovascular complications of atherothrombosis.

  • Terutroban, a Thromboxane/Prostaglandin Endoperoxide Receptor Antagonist, Increases Survival in Stroke-Prone Rats by Preventing Systemic Inflammation and Endothelial Dysfunction: Comparison with Aspirin and Rosuvastatin
    The Journal of pharmacology and experimental therapeutics, 2010
    Co-Authors: Paolo Gelosa, R. Ballerio, Cristina Banfi, Elena Nobili, Anita Gianella, Alice Pignieri, Maura Brioschi, Uliano Guerrini, Laura Castiglioni, Vanessa Blanc-guillemaud
    Abstract:

    This study investigated the efficacy of Terutroban, a specific thromboxane/prostaglandin endoperoxide receptor antagonist, on stroke incidence in spontaneously hypertensive stroke-prone rats (SHRSP). The effects of Terutroban were compared with those of aspirin, another antiplatelet agent, and rosuvastatin, known to exert end-organ protection in SHRSP. Salt-loaded male SHRSP were treated orally once a day with vehicle, Terutroban (30 mg/kg/day), aspirin (60 mg/kg/day), or rosuvastatin (10 mg/kg/day). Compared with vehicle, and regardless of any effect on blood pressure or serum thromboxane B(2) levels, Terutroban significantly increased survival (p < 0.001) as a consequence of a delayed brain lesion occurrence monitored by magnetic resonance imaging (p < 0.001), and a delayed increase of proteinuria (p < 0.001). Terutroban decreased cerebral mRNA transcription of interleukin-1beta, transforming growth factor-beta, and monocyte chemoattractant protein-1 after 6 weeks of dietary treatment. Terutroban also prevented the accumulation of urinary acute-phase proteins at high molecular weight, identified as markers of systemic inflammation, and assessed longitudinally by one-dimensional electrophoresis. Terutroban also has protective effects on the vasculature as suggested by the preservation of endothelial function and endothelial nitric-oxide synthase expression in isolated carotid arteries. These effects are similar to those obtained with rosuvastatin, and superior to those of aspirin. Terutroban increases survival in SHRSP by reducing systemic inflammation as well as preserving endothelial function. These data support clinical development of Terutroban in the prevention of cerebrovascular and cardiovascular complications of atherothrombosis.

  • Terutroban, a Thromboxane/Prostaglandin Endoperoxide receptor antagonist, increases survival in stroke-prone rats by preventing systemic inflammation and endothelial dysfunction. Comparison with aspirin and rosuvastatin
    'American Society for Pharmacology & Experimental Therapeutics (ASPET)', 2010
    Co-Authors: Paolo Gelosa, R. Ballerio, Cristina Banfi, Elena Nobili, Anita Gianella, Alice Pignieri, Maura Brioschi, Uliano Guerrini, Laura Castiglioni, Vanessa Blanc-guillemaud
    Abstract:

    This study investigated the efficacy of Terutroban, a specific thromboxane/prostaglandin endoperoxide receptor antagonist, on stroke incidence in spontaneously hypertensive strokeprone rats (SHRSP). The effects of Terutroban were compared with those of aspirin, another antiplatelet agent, and rosuvastatin, known to exert end-organ protection in SHRSP. Saltloaded male SHRSP were treated orally once a day with vehicle, Terutroban (30 mg/kg/day), aspirin (60 mg/kg/day), or rosuvastatin (10 mg/kg/day). Compared with vehicle, and regardless of any effect on blood pressure or serum thromboxane B2 levels, Terutroban significantly increased survival (p 0.001) as a consequence of a delayed brain lesion occurrence monitored by magnetic resonance imaging (p 0.001), and a delayed increase of proteinuria (p 0.001). Terutroban decreased cerebral mRNA transcription of interleukin-1 , transforming growth factor- , and monocyte chemoattractant protein-1 after 6 weeks of dietary treatment. Terutroban also prevented the accumulation of urinary acute-phase proteins at high molecular weight, identified as markers of systemic inflammation, and assessed longitudinally by one-dimensional electrophoresis. Terutroban also has protective effects on the vasculature as suggested by the preservation of endothelial function and endothelial nitric-oxide synthase expression in isolated carotid arteries. These effects are similar to those obtained with rosuvastatin, and superior to those of aspirin. Terutroban increases survival in SHRSP by reducing systemic inflammation as well as preserving endothelial function. These data support clinical development of Terutroban in the prevention of cerebrovascular and cardiovascular complications of atherothrombosis

Peter M. Rothwell - One of the best experts on this subject based on the ideXlab platform.

  • Atherogenic Dyslipidemia and Residual Cardiovascular Risk in Statin-Treated Patients
    Stroke, 2014
    Co-Authors: Gaia Sirimarco, Marie-germaine Bousser, Pierre Amarenco, Ángel Chamorro, Peter M. Rothwell, Kim M. Fox, Julien Labreuche, Eric Bruckert, Larry B. Goldstein, Ian Ford
    Abstract:

    Background and Purpose— Treatment with statins reduces the rate of cardiovascular events in high-risk patients, but residual risk persists. At least part of that risk may be attributable to atherogenic dyslipidemia characterized by low high-density lipoprotein cholesterol (≤40 mg/dL) and high triglycerides (triglycerides ≥150 mg/dL). Methods— We studied subjects with stroke or transient ischemic attack in 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; n=19 100) and Stroke Prevention by Aggressive Reduction in Cholesterol Levels (SPARCL; n=4731) trials who were treated with a statin and who had high-density lipoprotein cholesterol and triglycerides measurements 3 months after randomization (n=10 498 and 2900, respectively). The primary outcome measure for this exploratory analysis was the occurrence of major cardiovascular events (nonfatal myocardial infarction, nonfatal stroke, or cardiovascular death). We also performed a time-varying analysis to account for all available high-density lipoprotein cholesterol and triglyceride measurements. Results— A total of 10% of subjects in PERFORM and 9% in SPARCL had atherogenic dyslipidemia after ≥3 months on start statin therapy. After a follow-up of 2.3 years (PERFORM) and 4.9 years (SPARCL), a major cardiovascular event occurred in 1123 and 485 patients in the 2 trials, respectively. The risk of major cardiovascular events was higher in subjects with versus those without atherogenic dyslipidemia in both PERFORM (hazard ratio, 1.36; 95% confidence interval, 1.14–1.63) and SPARCL (hazard ratio, 1.40; 95% confidence interval, 1.06–1.85). The association was attenuated after multivariable adjustment (hazard ratio, 1.23; 95% confidence interval, 1.03–1.48 in PERFORM and hazard ratio, 1.24; 95% confidence interval, 0.93–1.65 in SPARCL). Time-varying analysis confirmed these findings. Conclusions— The presence of atherogenic dyslipidemia was associated with higher residual cardiovascular risk in PERFORM and SPARCL subjects with stroke or transient ischemic attack receiving statin therapy. Specific therapeutic interventions should now be trialed to address this residual risk.

  • Heart rate is a prognostic risk factor for myocardial infarction: A post hoc analysis in the PERFORM (Prevention of cerebrovascular and cardiovascular Events of ischemic origin with Terutroban in patients with a history oF ischemic strOke or tRansien
    International journal of cardiology, 2013
    Co-Authors: Kim Fox, Marie-germaine Bousser, Pierre Amarenco, Ángel Chamorro, Marc Fisher, Ian Ford, Michael G. Hennerici, Heinrich Mattle, Peter M. Rothwell
    Abstract:

    Abstract Background 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. Methods We compared fatal or nonfatal MI using adjusted Cox proportional hazards models for PERFORM patients with baseline heart rate Results Heart rate ≥70bpm 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 ≥70bpm 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 P P 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 P P P =0.057). Conclusion Elevated heart rate ≥70bpm places patients with a noncardioembolic cerebral ischemic event at increased risk for MI.

  • Terutroban versus aspirin in patients with cerebral ischaemic events (PERFORM): a randomised, double-blind, parallel-group trial
    Lancet (London England), 2011
    Co-Authors: Marie-germaine Bousser, Pierre Amarenco, Ángel Chamorro, Marc Fisher, Ian Ford, Kim Fox, Michael G. Hennerici, Heinrich Mattle, Peter M. Rothwell, Agnes De Cordoue
    Abstract:

    Summary Background 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. Methods 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. Findings 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. Interpretation 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. Funding Servier, France.

  • Terutroban versus aspirin in patients with cerebral ischaemic events (PERFORM): a randomised, double-blind, parallel-group trial
    'Elsevier BV', 2011
    Co-Authors: Marie-germaine Bousser, Pierre Amarenco, Ángel Chamorro, Marc Fisher, Ian Ford, Michael G. Hennerici, Heinrich Mattle, Peter M. Rothwell, Kim M. Fox, Agnes De Cordoue
    Abstract:

    Background: 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. Methods: 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. Findings: 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. Interpretation: 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. Funding: Servier, France. © 2011 Elsevier Ltd

  • 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: Baseline Characteristics of the Population
    Cerebrovascular diseases (Basel Switzerland), 2009
    Co-Authors: M G Bousser, Pierre Amarenco, Ángel Chamorro, Marc Fisher, Ian Ford, M G Hennerici, Heinrich Mattle, K. M. Fox, Peter M. Rothwell
    Abstract:

    Background: The Prevention of cerebrovascular and cardiovascular Events of ischemic origin with Terutroban in patients with a history oF ischemic strOke or tRansient ischeMic attack

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