Update on Clinical Trials of Antiplatelet Therapy for Cerebrovascular Diseases

2000 ◽  
Vol 10 (Suppl. 5) ◽  
pp. 34-40 ◽  
Author(s):  
Deepak L. Bhatt ◽  
Samir R. Kapadia ◽  
Jay S. Yadav ◽  
Eric J. Topol
Keyword(s):  
Clinical Trials ◽  
Antiplatelet Therapy ◽  
Cerebrovascular Diseases

scholarly journals ANTIPLATELET THERAPY OF ACUTE CORONARY SYNDROME: CURRENT CAPAB ILITIES

The Clinician ◽  
2018 ◽  
Vol 12 (1) ◽  
pp. 10-16
Author(s):  
E. V. Konstantinova ◽  
М. Yu. Gilyarov ◽  
N. А. Shostak ◽  
D. A. Anichkov
Keyword(s):  
Clinical Trials ◽  
Acute Coronary Syndrome ◽  
Antiplatelet Therapy ◽  
Statistical Power ◽  
Randomized Clinical Trials ◽  
Dual Antiplatelet Therapy ◽  
Coronary Intervention ◽  
Careful Analysis ◽  
Level Of Evidence ◽  
Coronary Syndrome

Dual antiplatelet therapy (acetylsalicylic acid and platelet P2Y12 receptor antagonist) is a standard component of treatment of any type of acute coronary syndrome, independently of perfusion and the chosen treatment strategy. Due to certain limitations of clopidogrel as the 2nd component of dual antiplatelet therapy in patients with acute coronary syndrome and percutaneous coronary intervention, the possibility of using prasugrel or ticagrelor should be considered first. Their effectiveness is higher than clopidogrel’s, as was demonstrated in large clinical trials. As a result, prasugrel and ticagrelor were included in all major international and Russian guidelines on treatment of this category of patients with the same class and level of evidence. Currently, there’re no data from any finished large randomized clinical trials of sufficient statistical power directly comparing the effectiveness and safety of prasugrel and ticagrelor. Therefore, careful analysis of the accumulated data on the safety and effectiveness of each drug including meta-analyses and registries is necessary for providing the best care for every individual patient.

scholarly journals Pathophysiological features of chronic cerebrovascular diseases and possibilities of complex neuroprotective therapy

2019 ◽  
pp. 24-30
Author(s):  
E. V. Kostenko ◽  
L. V. Petrova
Keyword(s):  
Clinical Trials ◽  
Cerebrovascular Diseases ◽  
Brain Cells ◽  
Pharmacological Effects ◽  
Good Tolerability ◽  
Wide Range ◽  
Neuroprotective Therapy

The article discusses the principles of neuroprotective therapy as a pathogenetically justified direction in chronic cerebrovascular diseases (CVD). The results of numerous clinical trials demonstrated efficacy, safety, a wide range of pharmacological effects and good tolerability of the powerful antioxidant Idebenone (Neyromet), as well as domestic cytoprotector, Choline alphosceratus of (Cerepro®), affecting the basic pathophysiological processes of the ischemic cascade at CVD. The role of rational multimodal pharmacotherapy of CVD, which provides the necessary energy for the processes of neuroprotection and neuroplasticity of brain cells, is emphasized.

scholarly journals Factor V Leiden and the Risk of Bleeding in Patients With Acute Coronary Syndromes Treated With Antiplatelet Therapy: Pooled Analysis of 3 Randomized Clinical Trials

2021 ◽  
Author(s):  
Bakhtawar K. Mahmoodi ◽  
Niclas Eriksson ◽  
Stephanie Ross ◽  
Daniel M. F. Claassens ◽  
Folkert W. Asselbergs ◽  
...  
Keyword(s):  
Clinical Trials ◽  
Antiplatelet Therapy ◽  
Lower Risk ◽  
Acute Coronary Syndromes ◽  
Randomized Clinical Trials ◽  
Factor V Leiden ◽  
Minor Bleeding ◽  
Factor V ◽  
Risk Of Bleeding ◽  
Coronary Syndromes

Background Whether factor V Leiden is associated with lower bleeding risk in patients with acute coronary syndromes using (dual) antiplatelet therapy has yet to be investigated. Methods and Results We pooled data from 3 randomized clinical trials, conducted in patients with acute coronary syndromes, with adjudicated bleeding outcomes. Cox regression models were used to obtain overall and cause‐specific hazard ratios (HRs) to account for competing risk of atherothrombotic outcomes (ie, composite of ischemic stroke, myocardial infarction, and cardiovascular death) in each study. Estimates from the individual studies were pooled using fixed effect meta‐analysis. The 3 studies combined included 17 623 patients of whom 969 (5.5%) were either heterozygous or homozygous (n=23) carriers of factor V Leiden. During 1 year of follow‐up, a total of 1289 (7.3%) patients developed major (n=559) or minor bleeding. Factor V Leiden was associated with a lower risk of combined major and minor bleeding (adjusted cause‐specific HR, 0.75; 95% CI, 0.56–1.00; P =0.046; I 2 =0%) but a comparable risk of major bleeding (adjusted cause‐specific HR, 0.93; 95% CI, 0.62–1.39; P =0.73; I 2 =0%). Adjusted pooled cause‐specific HRs for the association of factor V Leiden with atherothrombotic events alone and in combination with bleeding events were 0.75 (95% CI, 0.55–1.02; P =0.06; I 2 =0%) and 0.75 (95% CI, 0.61–0.92; P =0.007; I 2 =0%), respectively. Conclusions Given that the lower risk of bleeding conferred by factor V Leiden was not counterbalanced by a higher risk of atherothrombotic events, these findings warrant future assessment for personalized medicine such as selecting patients for extended or intensive antiplatelet therapy.

Inhibition of the ADP/P2Y12 Pathway Confers Additional Protection against Arterial Thrombosis in PAR-4 Deficient Mice

Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 3933-3933
Author(s):  
Ivo Cornelissen ◽  
Erica De Candia ◽  
Daniel Palmer ◽  
Shaun R Coughlin
Keyword(s):  
Clinical Trials ◽  
Antiplatelet Therapy ◽  
Dual Antiplatelet Therapy ◽  
Thrombus Formation ◽  
Combined Treatment ◽  
Wild Type ◽  
Thrombosis Model ◽  
Platelet Receptor ◽  
The Relationship ◽  
Deficient Mice

Abstract Clopidogrel, a potent anti-thrombotic drug widely used for the secondary prevention of myocardial infarction and ischemic stroke, inhibits the ADP/P2Y12 pathway by inducing irreversible alteration of the platelet receptor P2Y12, ultimately uncoupling ADP from adenylyl cyclase inhibition. Clinical trials have demonstrated additional benefits of dual antiplatelet therapy, such as combined treatment with clopidogrel and aspirin, in the prevention of ischemic cardiovascular disease. We previously established that protease-activated receptor (PAR) signaling is necessary for platelet activation by thrombin and plays an important role in mouse models of hemostasis and thrombosis. Indeed a PAR antagonist is currently being used as an anti-thrombotic agent in clinical trials. In order to evaluate the possible interaction between the thrombin/PAR and ADP/P2Y12 pathways, we orally administered clopidogrel (30mg/kg) or vehicle to PAR-4 null, heterozygous and wild type littermates, and evaluated arterial thrombus formation and bleeding during surgical challenge. In a FeCl3-induced carotid thrombosis model, PAR-4 deficient mice treated with clopidogrel were completely protected from thrombosis compared to their wild type treated littermates. Interestingly, clopidogrel treated PAR-4 heterozygotes showed an intermediate level of protection compared to treated wild type and null mice that was similar to vehicle-treated PAR-4 deficient mice. Additionally, we scored bleeding during the surgical procedure while blinded to genotype and treatment. The bleeding score was increased in clopidogrel treated mice compared to vehicle treated mice and was exacerbated with increasing haplotype deficiency of Par-4. To better define the relationship between these two activation pathways, we generated mice lacking both PAR-4 and P2Y12. All genetic combinations were born at the expected Mendelian distribution. Females lacking both receptors carried offspring to term, but signs of bleeding were observed during parturition. Preliminary data from PAR-4/P2Y12 double null mice, in both the tail bleeding assay and in a FeCl3-induced carotid thrombosis model, is in agreement with the results obtained in clopidogrel treated PAR-4 deficient mice. This study provides useful information to evaluate the efficacy and safety of dual antiplatelet therapy inhibiting the thrombin/PAR and ADP/P2Y12 pathways and explores the relationship between these two critical pro-thrombotic pathways in an in vivo setting.

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