Did Prasugrel and Ticagrelor Offer the Same Benefit in Patients with Acute Coronary Syndromes after Percutaneous Coronary Interventions Compared to Clopidogrel? Insights from Randomized Clinical Trials, Registries and Meta-analysis.

BACKGROUND: According to ACC/ AHA guidelines, a minimum of 1 year of dual anti- platelet therapy (DAPT) consisting of aspirin and a platelet ADP-receptor antagonist (P2Y12 inhibitor) is recommended for patients presenting acute coronary syndromes (ACS), regardless of which type of revascularization is performed during the acute event. METHODS: The purpose of this presentation was to review the present data either from a direct randomized comparison among the three compounds and also large prospective observational registries and meta-analysis were analyzed in detail. With this aim, we performed an extensive large search from PubMed/Medline Journals identifying studies comparing fashion the new P2Y12 inhibitors in patients with ACS including ST elevation myocardial infarction (STEMI) in direct and indirect manner. RESULTS: Pivotal large randomized clinical trials (RCT) in patients with ACS including STEMI, comparing clopidogrel, a first generation P2Y12 inhibitor against the newer prasugrel and ticagrelor showed major efficacy advantages of the latters although both drugs had more bleeding risk than clopidogrel. Direct comparisons of prasugrel and ticagrelor from large RCT are not yet available, however, several observational registries and metaanalysis reported results from an indirect comparison between both compounds. Major findings and limitations of each of these studies were identified, highlighted and discussed. CONCLUSION: Prasugrel and ticagrelor are both more effective than clopidogrel to prevent adverse cardiac events in patients with ACS. Compared to ticagrelor, prasugrel appears to be more effective in patients with STEMI, although lack of randomized data didn't allow to draw definitive conclusions.

Biventricular structural and functional responses to aortic constriction in a rabbit model of chronic right ventricular pressure overload.

OBJECTIVES: Chronic right ventricular (RV) pressure overload results in pathologic RV hypertrophy and diminished RV function. Although aortic constriction has been shown to improve systolic function in acute RV failure, its effect on RV responses to chronic pressure overload is unknown. METHODS: Adjustable vascular banding devices were placed on the main pulmonary artery and descending aorta. In 5 animals (sham group), neither band was inflated. In 9 animals (PAB group), only the pulmonary arterial band was inflated, with adjustments on a weekly basis to generate systemic or suprasystemic RV pressure at 28 days. In 9 animals, both pulmonary arterial and aortic devices were inflated (PAB + AO group), the pulmonary arterial band as for the PAB group and the aortic band adjusted to increase proximal systolic blood pressure by approximately 20 mm Hg. Effects on the functional performance were assessed 5 weeks after surgery by conductance catheters, followed by histologic and molecular assessment. RESULTS: Contractile performance was significantly improved in the PAB + AO group versus the PAB group for both ventricles. Relative to sham-operated animals, both banding groups showed significant differences in myocardial histologic and molecular responses. Relative to the PAB group, the PAB + AO group showed significantly decreased RV cardiomyocyte diameter, decreased RV collagen content, and reduced RV expression of endothelin receptor type B, matrix metalloproteinase 9, and transforming growth factor ß genes. CONCLUSIONS: Aortic constriction in an experimental model of chronic RV pressure overload not only resulted in improved biventricular systolic function but also improved myocardial remodeling. These data suggest that chronically increased left ventricular afterload leads to a more physiologically hypertrophic response in the pressure-overloaded RV.

Development of a hamster superovulation program and adverse effects of gonadotropins on microfilament formation during oocyte development.

OBJECTIVE: To establish a superovulation procedure for the golden hamster (Mesocricetus auratus) by elucidating gonadotropin effects on oocyte development. DESIGN: Randomized, prospective study. SETTING: University laboratory of embryology and gamete biotechnology. ANIMAL(S): Twelve- to 15-week-old female and sexually mature male hamsters. INTERVENTION(S): Different doses of pregnant mare serum gonadotropin (PMSG) were injected into female hamsters in metestrus, diestrus, or proestrus. The same dose of hCG was injected 56 hours later. MAIN OUTCOME MEASURE(S): Embryo development and oocyte morphology after treatment. RESULT(S): First, 10 IU or 15 IU each of PMSG and hCG was injected into 10 hamsters weighing <110 or 110-130 g, respectively. All hamsters were mated, but none delivered live young after injection. Second, the doses of 15 IU, 7.5 IU, 5 IU, or 0 IU of each gonadotropin were injected into each hamster (regardless of body weight, 5 per each group). Increasing numbers of embryos were retrieved as the dosage was increased (11.2 to 46.6 embryos per hamster), whereas the percentage of two-cell embryos at retrieval was significantly decreased (100% to 3%, P<.05). In subsequent culture, none developed to blastocysts after 15-IU injection, whereas 47%, 55%, and 70% of two-cell embryos developed after 7.5-IU, 5-IU, and 0-IU treatments, respectively. As a result, females injected with 5 IU yielded more blastocysts than did females without injection (67 vs. 39). The number of inner cell mass cells per blastocyst was greatly increased in the control groups compared with the 5-IU and 7.5-IU treatment groups (22 vs. 14.3-14.7 cells per blastocyst). Third, the ultrastructure of oocytes was examined after injecting 5 IU each of PMSG and hCG (regardless of body weight). Superovulation did not affect oocyte maturation, but different patterns in microfilament formation were detected after the treatment. CONCLUSION(S): Female hamsters can be superovulated effectively by injecting equal amounts of PMSG and hCG, 56 hours apart. However, embryo development was adversely affected in a dose-dependent manner at all doses of gonadotropins, and microfilament distribution was affected by such treatment.