Search results for "Platelet Aggregation Inhibitor"

Picotamide, a combined inhibitor of thromboxane A2 synthase and receptor, reduces 2-year mortality in diabetics with peripheral arterial disease: the…

2004

Aims Patients with diabetes are at excessive risk of mortality and cardiovascular morbidity. Previous studies suggest that aspirin may be less effective in diabetic patients. In this multi-centre, randomized, double blind trial picotamide, a dual inhibitor of thromboxane A2 synthase and receptor, was compared with aspirin for the prevention of mortality and major cardiovascular events in diabetics with peripheral arterial disease (PAD). Methods and results A total of 1209 adults aged 40–75 years with type 2 diabetes and PAD were randomized to receive picotamide (600 mg bid) or aspirin (320 mg od) for 24 months. The cumulative incidence of the 2 years overall mortality was significantly lowe…

Platelet aggregation, ATP release and cytoplasmic Ca2+ movement: the effects of cloricromene.

1994

A placebo-controlled, double-blind, randomized, cross-over study was performed in 24 healthy volunteers. 12 volunteers received Cloricromene (100mg gastroresistant capsules twice a day) for 7 days, the other volunteers received identical placebo capsules. Subsequently, after a 7-day wash-out period, at day 15, each subject received the other treatment. Blood samples were taken on days 1 and 15 (1st day of each treatment) as well as on days 7 and 21 (7th day of each treatment) before the morning drug administration and 2 and 4 hours later. Platelet aggregation and ATP secretion were studied in whole blood (WB) using ADP and collagen as stimulating agents. Ca2+ fluxes were studied in aequorin…

PHOSPHODIESTERASE INHIBITORS PIROXIMONE AND ENOXIMONE INHIBIT PLATELET AGGREGATION IN VIVO AND IN VITRO

1997

The phosphodiesterase type III inhibitors piroximone (PIR) and enoximone (ENO) exert positive inotropic and vasodilating effects in patients with severe heart failure. PIR and ENO raise cyclic AMP levels in cardiac and vascular smooth muscle cells. Platelet activity is also regulated by intracellular levels of cyclic AMP. In this study we have investigated the effects of PIR and ENO on platelet activity in vivo and in vitro. PIR and ENO inhibited ADP induced platelet aggregation in a time- and concentration-dependent manner with IC50-values of 67 +/- 14 mumol/l and 129 +/- 6 mumol/l, respectively. Coincubation of PIR with the adenylate cyclase activator iloprost resulted in a synergistic po…

Effects of endotoxin on neurally-mediated gastric acid secretion in the rat.

1998

Abstract The effects of a peripheral administration of E. coli endotoxin on neurally-mediated gastric acid secretion and the role of endogenous opioids or PAF receptors in endotoxin effects have been evaluated in the continuously perfused stomach of the anaesthetized rat. Gastric acid secretion stimulated by distension (20 cm H2O) was reduced dose-dependently by single intravenous bolus injection of endotoxin (0.1–10 μg kg−1). Doses of 5 μg kg−1 induced a peak reduction of distension-stimulated acid output and significantly reduced the secretory response induced by an intravenous bolus of 2-deoxy-d-glucose (150 mg kg−1). This dose of endotoxin did not significantly modify mean systemic arte…

Synergistic Platelet Inhibitory Effect of the Phosphodiesterase Inhibitor Piroximone and Iloprost

1992

Platelet activity is regulated through synthesis and degradation of the intracellular second messengers cAMP or cGMP. The antiplatelet effect of the phosphodiesterase (PDE) III inhibitor Piroximone (PIR) was studied in vitro in platelet rich plasma. ADP induced aggregation was inhibited by PIR with an IC50 of 67 +/- 43 microM. The inhibitory effect was time and dose dependent. The antiaggregatory effects in vivo were studied in anaesthetised rats. Reduction of platelet count following injection of 100 micrograms/kg bw collagen was measured after bolus injection of PIR and vehicle. Piroximone bolus 2 mg/kg bw resulted in a 50% inhibition of platelet aggregation in rats. Cyclic AMP levels in …

2014

Introduction Particularly in the setting of acute coronary syndromes, the interplay between vascular and platelet function has been postulated to have direct clinical implications. The present trial is designed to test the effect of clopidogrel, prasugrel and ticagrelor on multiple parameters of vascular function, platelet aggregation, oxidative and inflammatory stress before and up to 4 weeks after coronary artery stenting. Methods and analysis The study is designed as a three-arm, parallel design, randomised, investigator-blinded study. Patients with unstable angina or non-ST elevation myocardial infarction undergoing coronary intervention with a drug-eluting stent will be randomised to r…

Insights from Experiences on Antiplatelet Drugs in Stroke Prevention: A Review

2020

Reduction of hazard risk of cerebral ischemic event (stroke, transient ischemic attack (TIA)) represents the hard point to be achieved from primary or secondary preventive strategy in the best clinical practice. However, results from clinical trials, recommendations, guidelines, systematic review, expert opinions, and meta-analysis debated on the optimal pharmacotherapy to achieve the objective. Aspirin and a number of antiplatelet agents, alone or in combination, have been considered from large trials focused on stroke prevention. The present review summarizes, discusses results from trials, and focuses on the benefits or disadvantages originating from antiplatelet drugs. Sections of the r…

Temporal quantitative phosphoproteomics of ADP stimulation reveals novel central nodes in platelet activation and inhibition

2017

Adenosine diphosphate (ADP) enhances platelet activation by virtually any other stimulant to complete aggregation. It binds specifically to the G-protein-coupled membrane receptors P2Y1 and P2Y12, stimulating intracellular signaling cascades, leading to integrin aIIbb3 activation, a process antagonized by endothelial prostacyclin. P2Y12 inhibitors are among the most successful antiplatelet drugs, however, show remarkable variability in efficacy. We reasoned whether a more detailed molecular understanding of ADP-induced protein phosphorylation could identify (1) critical hubs in platelet signaling toward aggregation and (2) novel molecular targets for antiplatelet treatment strategies. We ap…

Low-dose rivaroxaban and aspirin among patients with peripheral artery disease: a meta-analysis of the COMPASS and VOYAGER trials.

2021

Abstract Aims Peripheral artery disease (PAD) patients suffer a high risk of major cardiovascular (CV) events, with athero-thrombo-embolism as the underlying pathophysiologic mechanism. Recently, two large randomized clinical trials evaluated the efficacy and safety of low-dose rivaroxaban twice daily plus aspirin in stable PAD outpatients and those immediately after peripheral revascularization. We sought to determine if the effects of low-dose rivaroxaban and aspirin compared to aspirin alone are consistent across this broad spectrum of PAD patients. Methods and results We conducted a random-effects meta-analysis of the COMPASS and VOYAGER randomized trials among 11 560 PAD patients (4996…

The pleiotropic effects of antiplatelet therapies

2019

Percutaneous coronary intervention is the most often used method for coronary revascularization. Stenting restores blood perfusion to ischemic areas, but it also causes mechanical disruption of the atheromatous plaque and the nearby endothelium, stimulating the activation of platelets. In a similar way, platelets are activated by thrombin exposure in the setting of plaque rupture. The interaction between platelets, oxidative stress and inflammation is an important factor determining the extent and severity of vascular dysfunction observed in these settings. Platelets activated by the vessel trauma release inflammatory and mitogenic mediators into the vascular microenvironment, activating le…