Protease-activated receptors (PARs) are transmembrane proteins which rank among G-protein-coupled receptors. So far, four PARs (PAR1-4) have been described. They are activated by a protease cleavage at the N-terminal part of the receptor. Through the cleavage a new N-terminus appears which acts as a ligand activating the receptor. A peptide of the same amino acid sequence as the new N-terminus can activate the receptor without its cleavage. Some non-specific proteases can cleave PAR receptors at different sites, which results in changes in cell signaling. Higher activities of PARs have been observed under various pathological conditions, such as thrombosis, atherosclerosis, inflammations or neurodegeneration. Specific modulators of PAR signaling are a promising class of compounds with a wide therapeutic potential. First PAR inhibitors were based mainly on the amino acid sequence in the activating peptides. Recently, new, low-molecularweight, very specific and effective inhibitors have been developed. One of them, vorapaxar, passed the clinical tests and was introduced to the market.

• MeSH
• kardiovaskulární nemoci farmakoterapie   MeSH
• kinasa 1 receptorů spřažených s G-proteiny * MeSH
• lidé MeSH
• neurodegenerativní nemoci farmakoterapie   MeSH
• peptidy MeSH
• receptor PAR-1 * antagonisté a inhibitory   MeSH
• receptory thrombinu * antagonisté a inhibitory   MeSH
• thrombin MeSH
• trypsin MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• práce podpořená grantem MeSH

• Klíčová slova
• Prasugrel, Kangrelor, Vorapaxar,
• MeSH
• adenosin analogy a deriváty   MeSH
• adenosinmonofosfát analogy a deriváty   MeSH
• akutní koronární syndrom farmakoterapie   MeSH
• hodnocení léčiv statistika a číselné údaje   MeSH
• inhibitory agregace trombocytů * farmakologie   škodlivé účinky   terapeutické užití   MeSH
• intrakraniální krvácení chemicky indukované   MeSH
• klinické zkoušky jako téma statistika a číselné údaje   MeSH
• laktony terapeutické užití   MeSH
• lidé MeSH
• piperaziny terapeutické užití   MeSH
• purinergní receptory P2Y - antagonisté farmakologie   škodlivé účinky   terapeutické užití   MeSH
• pyridiny terapeutické užití   MeSH
• receptor PAR-1 antagonisté a inhibitory   MeSH
• receptory thrombinu antagonisté a inhibitory   MeSH
• thiofeny terapeutické užití   MeSH
• ticagrelor MeSH
• trombóza farmakoterapie   MeSH
• Check Tag
• lidé MeSH

The therapeutic potential of vorapaxar in patients with non-ST-segment elevation acute coronary syndrome undergoing percutaneous coronary intervention (PCI) is unknown. This prespecified analysis of a postrandomization subgroup evaluated the effects of vorapaxar compared with placebo among Thrombin Receptor Antagonist for Clinical Event Reduction in Acute Coronary Syndrome (TRACER) participants undergoing PCI, focusing on the implanted stent type (drug-eluting stent [DES] vs bare-metal stent [BMS]). Among 12,944 recruited patients, 7,479 (57.8%) underwent PCI during index hospitalization, and 3,060 (40.9%) of those patients received exclusively BMS, whereas 4,015 (53.7%) received DES. The median (twenty-fifth, seventy-fifth percentiles) duration of thienopyridine therapy was 133 days (47, 246) with BMS and 221 days (88, 341) with DES. At 2 years among patients undergoing PCI, the primary (cardiovascular death, myocardial infarction, stroke, recurrent ischemia with rehospitalization, or urgent coronary revascularization) and secondary (cardiovascular death, myocardial infarction, or stroke) end points did not differ between vorapaxar and placebo groups, which was consistent with the treatment effect observed in the overall study population (p value for interaction = 0.540). However, the treatment effect trended greater (p value for interaction = 0.069) and the risk for bleeding in patients taking vorapaxar versus placebo appeared attenuated in BMS-only recipients. After adjustment for confounders, the interaction was no longer significant (p value = 0.301). The covariate that mostly explained the stent-type-by-treatment interaction was the duration of clopidogrel therapy. In conclusion, among patients with PCI, the effect of vorapaxar is consistent with the overall TRACER results. Patients who received a BMS underwent shorter courses of clopidogrel therapy and displayed trends toward greater ischemic benefit from vorapaxar and lesser bleeding risk, compared with patients who received a DES.

• MeSH
• akutní koronární syndrom farmakoterapie   patofyziologie   chirurgie   MeSH
• dospělí MeSH
• dvojitá slepá metoda MeSH
• elektrokardiografie * MeSH
• incidence MeSH
• injekce intravenózní MeSH
• koronární angioplastika metody   MeSH
• laktony aplikace a dávkování   MeSH
• lidé středního věku MeSH
• lidé MeSH
• míra přežití trendy   MeSH
• následné studie MeSH
• pooperační komplikace epidemiologie   MeSH
• prospektivní studie MeSH
• pyridiny aplikace a dávkování   MeSH
• receptory thrombinu antagonisté a inhibitory   MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• stenty uvolňující léky * MeSH
• výsledek terapie MeSH
• vztah mezi dávkou a účinkem léčiva MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• klinické zkoušky, fáze III MeSH
• multicentrická studie MeSH
• práce podpořená grantem MeSH
• randomizované kontrolované studie MeSH
• Geografické názvy
• Austrálie MeSH
• Evropa MeSH
• Spojené státy americké MeSH

There are only few areas of cardiology that have witnessed such dramatic innovations as that occurring in the treatment and prophylaxis of thrombotic events. Antithrombotic (i.e., antiplatelet and anticoagulation) therapy plays a pivotal role in the prophylaxis of the pandemic of cardiovascular disease. Given the host of triggers activating primary hemostasis, various therapeutic strategies are currently available. The current approach, monotherapy or dual therapy or, possibly, combination therapy with antiplatelet and anticoagulant agents is selected based on the risk of a thrombotic event, dominant disease, and the risk of bleeding.The main problem associated with the current therapeutic strategy was not an insufficient effect, but major inter-individual variability of effect resulting in therapy failure or an unacceptable risk of bleeding documented in a non-negligible proportion of patients. Hence there is a drive for devising new antiplatelet strategies and innovation in (already) established classes of drugs.Milestones in the evolution of antiplatelet therapy included the advent of new, more effective and/or safer antiplatelet agents inhibiting platelet activation. The new irreversible P2Y12 receptor antagonist prasurgel and reversible P2Y12 receptor antagonist ticagrelor have been approved for clinical use. There has also been major progress in the development of thrombin protease-activated receptor 1 (PAR-1) antagonists (vorapaxar, atopaxar) or serotonin receptor blockers (sarpogrelat). Another promising therapeutic strategy is targeted at platelet stabilization through increased cyclic adenosine monophosphate (cAMP) activity by platelet phosphodiesterase-3 inhibition (cilostazol). Further, new insights into the bioavailability of acetylsalicylic acid under specific conditions have been reported regarding the class of agents inhibiting thromboxane A2-mediated activation.

• MeSH
• antagonisté serotoninu farmakologie   terapeutické užití   MeSH
• antikoagulancia farmakologie   terapeutické užití   MeSH
• Aspirin farmakologie   terapeutické užití   MeSH
• embolie a trombóza * etiologie   farmakoterapie   MeSH
• inhibitory agregace trombocytů * farmakologie   terapeutické užití   MeSH
• lidé MeSH
• purinergní receptory P2Y - antagonisté farmakologie   terapeutické užití   MeSH
• receptor PAR-1 antagonisté a inhibitory   MeSH
• receptory thrombinu antagonisté a inhibitory   MeSH
• thromboxan A2 antagonisté a inhibitory   MeSH
• trombocytový glykoproteinový komplex IIb-IIIa antagonisté a inhibitory   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• přehledy MeSH

• Klíčová slova
• prasugrel, vorapaxar, atopaxar,
• MeSH
• akutní koronární syndrom farmakoterapie   MeSH
• Aspirin farmakologie   terapeutické užití   MeSH
• hodnocení léčiv MeSH
• inhibitory agregace trombocytů * farmakologie   terapeutické užití   MeSH
• kardiovaskulární nemoci * farmakoterapie   prevence a kontrola   MeSH
• klinické zkoušky jako téma MeSH
• klopidogrel MeSH
• kombinovaná farmakoterapie MeSH
• lidé MeSH
• purinergní receptory P2Y - antagonisté farmakologie   terapeutické užití   MeSH
• receptor PAR-1 antagonisté a inhibitory   terapeutické užití   MeSH
• receptory thrombinu antagonisté a inhibitory   MeSH
• thienopyridiny farmakologie   terapeutické užití   MeSH
• tiklopidin MeSH
• výsledek terapie MeSH
• Check Tag
• lidé MeSH

• MeSH
• akutní koronární syndrom farmakoterapie   mortalita   MeSH
• amiodaron analogy a deriváty   aplikace a dávkování   škodlivé účinky   MeSH
• ateroskleróza farmakoterapie   MeSH
• chemoprofylaxe ekonomika   metody   MeSH
• dyslipidemie farmakoterapie   MeSH
• faktor Xa antagonisté a inhibitory   aplikace a dávkování   škodlivé účinky   MeSH
• fibrilace síní farmakoterapie   MeSH
• HDL-cholesterol nedostatek   MeSH
• infarkt myokardu prevence a kontrola   MeSH
• kardiovaskulární nemoci epidemiologie   farmakoterapie   MeSH
• kongresy jako téma MeSH
• lidé MeSH
• náklady na léky MeSH
• niacin aplikace a dávkování   MeSH
• placeba terapeutické užití   MeSH
• receptory thrombinu antagonisté a inhibitory   terapeutické užití   MeSH
• rizikové faktory MeSH
• sekundární prevence ekonomika   metody   MeSH
• statiny aplikace a dávkování   MeSH
• výsledek terapie MeSH
• zdravotní pojištění MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• abstrakty MeSH
• klinické zkoušky MeSH
• randomizované kontrolované studie jako téma MeSH