Cardiovascular & Haematological Disorders - Drug Targets - Online First

Acute coronary syndrome (ACS) is a leading cause of death, and clopidogrel resistance remains a major challenge in its treatment. This study aims to determine the impact of CYP2C19 genetic variants on clopidogrel resistance (CR) and major adverse cardiovascular events (MACEs) in Vietnamese patients undergoing percutaneous coronary intervention (PCI).

We carried out a descriptive cross-sectional study, supplemented by a prospective longitudinal follow-up, on 113 ACS patients undergoing PCI with drug-eluting stent implantation at the Department of Cardiology, Military Hospital 103, from January 2015 to May 2018. We excluded patients with a decreased platelet count (< 100 × 10^9/L), a decreased estimated glomerular filtration rate (< 15 mL/min), ongoing bleeding, coagulation disorders, planned or recent surgery, or a coexisting malignancy. CR was defined as platelet aggregation ≥ 46%. The Amplification Refractory Mutation System (ARMS)-PCR was used to determine the CYP2C19 genotype and phenotype. Causes leading to patient readmission, such as angina, recurrent acute myocardial infarction, stroke, or death within 30 days, were recorded as MACEs.

The rate of CR was 29.9% (33/113 patients), and the incidence of MACEs was 15.9% (18/113 patients). The frequencies of CYP2C192 and CYP2C193 polymorphisms, as well as the PM CYP2C19 phenotype, were higher in the CR and MACE groups compared to those without these characteristics (p = 0.24, 0.006, and < 0.001, respectively). The PM CYP2C19 phenotype was predictive of 30-day MACEs in ACS patients undergoing PCI with stent implantation (p < 0.001).

Our findings demonstrate a strong association between CYP2C19 PM phenotypes and increased risks of both clopidogrel resistance and 30-day MACEs in Vietnamese ACS patients undergoing PCI. These results underscore the clinical significance of CYP2C19 genotyping in optimizing antiplatelet therapy and enhancing outcomes in this patient population.

PM CYP2C19 phenotypes were associated with an increased risk of CR and MACEs in Vietnamese patients undergoing PCI with stent implantation.

Sacubitril/valsartan (SAC/VAL) is a combination medication primarily used to treat heart failure with reduced ejection fraction (HFrEF). This randomized controlled trial (RCT) assessed the impacts of SAC/VAL compared with valsartan (VAL) on left ventricular (LV) remodeling, clinical outcomes, and cardiac function in patients with HFrEF.

A single-blinded run-in phase and a double-blinded treatment phase were conducted at Imam Hospital (Ahvaz, Iran) among 106 patients (SAC/VAL group: n=54; VAL group=52). Patients were randomly assigned to receive a combination of SAC/VAL (up-titrated to the target dosage of 200 mg, twice daily) or VAL (up-titrated to 160 mg, twice daily) for a six-month of intervention. Patients' clinical, demographic, and echocardiographic data were collected before and after the intervention.

After a six-month intervention, statistically significant mean differences were detected in various echocardiographic parameters (e.g., LV end-systolic volume, LV ejection fraction, and LV end-diastolic volume) within each group and between the two groups. Significant mean differences were noted in the six-minute walk test, serum levels of blood urea nitrogen, aspartate aminotransferase, sodium, creatinine, alanine aminotransferase, N-terminal pro–B-type natriuretic peptide, and scores of the Kansas City Cardiomyopathy questionnaire in post-intervention assessments within each group and between the two groups (P <0.05). There was a substantial within-group difference in the frequency of the New York Heart Association (NYHA) functional class from pre- to post-intervention (P <0.05).

This study revealed that SAC/VAL exhibited superior efficacy compared to VAL. However, the follow-up period was relatively short, and the potential risks associated with the prolonged administration of this medication have not been thoroughly evaluated.

This RCT indicated that the combination of SAC/VAL had better therapeutic effects than VAL on LV remodeling, clinical outcomes, and cardiac function in patients with ischemic HFrEF. These findings may help refine treatment priorities for patients with HFrEF and improve the quality of their care.

IRCT20240117060713N1.

Oroxylin A is primarily sourced from the roots of Scutellaria baicalensis, a medicinal plant commonly used in traditional Chinese medicine. It can also be found in other Scutellaria species. The plant's rich bioactive profile makes it a significant source of various flavonoids, including Oroxylin A.

The proposed aim of this study is to investigate in-vitro anti-oxidant activity, toxicity studies and in-vitro cardioprotective activity of Oroxylin-A against Doxorubicin mediated myocardial damage on H9c2.

The total phenolic content was estimated using Folin-Ciocalteu test and in-vitro activity was performed using DPPH assay. Acute toxicity studies were performed according to OECD 423 guidelines. In vitro cardioprotective activity was performed on H9c2 cells and was estimated for the biomarkers.

Oroxylin-A showed good antioxidant activity. No abnormalities were found in animals upon its usage, indicating that Oroxylin-A was safe at 2000 mg/kg. 150ug/ml of Oroxylin-A significantly increased the cell viability up to 99% and also decreased the LDH and ROS generation indicating that Oroxylin-A showed significant cardioprotective activity on H9c2 cells.

This research underscores the potential of Oroxylin A as a candidate for further investigation as a cardioprotective agent. Also, the present study contributes to the growing body of knowledge aimed at identifying natural compounds that may offer protective effects against myocardial damage, providing hope for future therapeutic interventions in the field of cardiovascular medicine.

Stroke is the second leading cause of death and the third leading cause of disability worldwide, with hypertension and diabetes mellitus being its most prominent risk factors. This study aims to assess the utilization trends and clinical outcomes of Alteplase in patients presenting with acute cerebral ischemia and known history of hypertension and/or diabetes, within our local population in Southern Punjab, Pakistan-a region with limited stroke care infrastructure.

This observational study was conducted at the emergency department of a tertiary care hospital. A total of 106 patients presenting with acute cerebral ischemia confirmed via CT scan and/or MRI were enrolled. All patients had a documented history of hypertension (n = 91), diabetes mellitus (n = 27), or both (n = 64). Patients who presented within 4.5 hours of symptom onset and met standard inclusion criteria were administered intravenous Alteplase as per AHA/ASA guidelines. Patients were divided into two groups: Group 1 (received Alteplase, n = 56) and Group 2 (did not receive Alteplase, n = 82). Outcomes were measured using the modified Rankin Scale (mRS) at 3 months post-intervention, with favorable recovery defined as mRS 0-2.

Of the 44 patients who received Alteplase, 66% (n = 37) achieved favorable outcomes (mRS 0-2). In contrast, only 39% (n = 32) of the 62 patients in the non-Alteplase group had favorable recovery. No significant increase in hemorrhagic complications was observed in the Alteplase group.

In patients with acute cerebral ischemia and pre-existing hypertension or diabetes, the timely administration of Alteplase significantly improves functional outcomes. Despite its proven efficacy, access to thrombolytic therapy remains inadequate in public sector hospitals in Southern Punjab. Efforts must be made to expand stroke services and standardize acute stroke care across the region.