Effect of prasugrel versus ticagrelor on coronary microcirculation in patients undergoing pharmacoinvasive strategy - acute and short-term results.

INTRODUCTION: Both ticagrelor and prasugrel are class I recommendations for treatment of ST-elevation myocardial infarction (STEMI) undergoing percutaneous coronary intervention (PCI) [ 1 ]. But clinical outcomes with the two drugs are conflicting which might be due to differential effects on coronary microcirculation. No study to date had compared the effects of prasugrel or ticagrelor on coronary microcirculation in patients undergoing pharmacoinvasive PCI (pPCI). AIM AND OBJECTIVE: To compare the effects of prasugrel and ticagrelor on coronary microcirculation in STEMI patients undergoing pPCI as assessed by Myocardial Blush Grade (MBG). The secondary aim was to assess flow in the infarct-related artery by corrected thrombolysis in myocardial infarction (TIMI) frame count (cTFC) and whether a differential effect if detected on coronary microcirculation translated in improvement in left ventricular ejection fraction assessed at 6 months. MATERIAL AND METHODS: A total of 240 patients with STEMI were evaluated in this open-label randomized control trial who initially underwent thrombolysis and later PCI (from 24 to 48 h) post-successful thrombolysis. The study subjects were randomized to receive either ticagrelor ( n  = 120) or prasugrel ( n  = 120) in 1 : 1 ratio 2 h prior to elective PCI. Patients underwent PCI according to standard protocol and post-procedure cTFC and MBG were compared. Patients were also followed up for 6 months to compare ejection fractions in both groups. We also assessed the effect of the two drugs on bleeding complications during hospitalization and over 6-month follow-up period. RESULTS: There were no significant differences between the two groups with respect to baseline characteristics. Prasugrel administration resulted in higher MBG Grade 3 (50.86% vs 33.89%, P  = 0.012) and lower cTFC (17.14 ±â€…4.08 vs 19.3 ±â€…4.06, P  < 0.01). Improvement in ejection fraction was significantly higher with prasugrel compared to ticagrelor (10.29% ± 15.2 vs 4.66% ± 13.5, P  = 0.003). Bleeding events at 6 months follow-up according to TIMI classification were similar in both the groups (11.86% vs 6.9%, P  = 0.39). CONCLUSION: Prasugrel produces greater improvement in coronary microcirculation than Ticagrelor resulting in improved myocardial salvage in patients of STEMI undergoing pPCI.

Bradyarrhythmias in patients with COVID-19: A case series.

Novel coronavirus disease (COVID-19) can have variety of cardiac manifestations; however, less is known about the prevalence, clinical characteristics and outcomes of bradyarrhythmias in patients with COVID-19. In the present case series of bradyarrhythmia in patients with COVID-19, we report complete heart block requiring intervention in 5 patients and sinus node dysfunction in 2 patients.

Development of a series of novel o-phenylenediamine-based indoleamine 2,3-dioxygenase 1 (IDO1) inhibitors.

A novel series of o-phenylenediamine-based inhibitors of indoleamine 2,3-dioxygenase (IDO) has been identified. IDO is a heme-containing enzyme, overexpressed in the tumor microenvironment of many cancers, which can contribute to the suppression of the host immune system. Synthetic modifications to a previously described diarylether series resulted in an additional degree of molecular diversity which was exploited to afford compounds that demonstrated significant potency in the HeLa human cervical cancer IDO1 assay. .

Palladium-catalyzed aerobic oxidative kinetic resolution of alcohols with an achiral exogenous base.

Substitution of exogenous (-)-sparteine for a more practical achiral base in the aerobic oxidative kinetic resolution of secondary alcohols is described. Carbonate bases are the most effective of those screened and allow for effective kinetic resolution of benzylic, allylic, and aliphatic substrates. The procedure was also successfully extended to the oxidative desymmetrization of meso diols.

Scope of enantioselective palladium(II)-catalyzed aerobic alcohol oxidations with (-)-sparteine.

Evaluation of the substrate scope for Pd(II)/ (-)-sparteine catalyzed aerobic oxidative kinetic resolution of secondary alcohols is disclosed. An improved system is found with use of tert-butyl alcohol solvent in which benzylic and aliphatic alcohols as well as alcohols containing olefins are effectively oxidatively resolved. For substrates that successfully undergo oxidative kinetic resolution, k(rel) values are generally between 10 and 20. Successful scale-up of various substrates to 10-mmol scale is described. Extension to oxidative desymmetrization of 1,3-meso-diols is successful with enantiomeric excesses ranging from 78 to 85%.

Cleavage of Si-Ar bond vs Si-Me bond: a remarkable counterion effect on reactivity.

Formation of distinctly different products from the same alkoxide intermediate indicates a strong dependence of reaction pathways on counterions.