Role of genetic polymorphisms in clopidogrel response variability: a systematic review.

INTRODUCTION: Clopidogrel is a P2Y12 inhibitor that has become a mainstay treatment following percutaneous intervention with drug-eluting stent placement to decrease restenosis and its potential complications, including sudden cardiac death and ischaemic strokes in patients with significant vascular disease. AREAS COVERED: As a prodrug, the metabolism and efficacy of clopidogrel are contingent on the presence of wild-type CYP450 (CYP2C19) alleles. Genetic polymorphisms and variants are well known to impair its ability to prevent major adverse cardiovascular events in these patients, with inadequate response rates as high as 30% in previous publications. Patterns of allelic frequencies are expected to exhibit similarities between individuals of the same ancestry, ethnic group or geographic region. Accordingly, we seek to further elucidate worldwide prevalence rates for genetic polymorphisms in the CYP2C19-dependent metabolism of clopidogrel and review the potential of personalised CYP2C19 genotyping in clinical practice to mitigate this high treatment resistance and its associated burden on patients. EXPERTS' COMMENTARY: Our findings support the consideration of genotyping before initiation of therapy to guide adequate dosage or substitutions of other P2Y12 inhibitors to promote personalised, precision medicine and to prevent adverse events when these therapies may inevitably fail in patients with variants of the CYP450 (CYP2C19) system.

The Effect of Admission During the Weekend On In-Hospital Outcomes for Patients With Peripartum Cardiomyopathy.

Background Previous studies have shown that patients with heart failure (HF) and cardiogenic shock (CS) have worse outcomes when admitted over the weekend. Since peripartum cardiomyopathy (PPCM) is a cause of CS and persisting HF, it is reasonable to extrapolate that admission over the weekend would also have deleterious effects on PPCM outcomes. However, the impact of weekend admission has not been specifically evaluated in patients with PPCM. Methods We analyzed the National Inpatient Sample (NIS) from 2016 to 2019. The International Classification of Diseases, tenth revision (ICD-10) codes were used to identify all admissions with a primary diagnosis of PPCM. The sample was divided into weekday and weekend groups. We performed a multivariate regression analysis to estimate the effect of weekend admission on specified outcomes. Results A total of 6,120 admissions met the selection criteria, and 25.3% (n=1,550) were admitted over the weekend. The mean age was 31.3 ± 6.4 years. There were no significant differences in baseline characteristics between study groups. After multivariate analysis, weekend admission for PPCM was not associated with in-hospital mortality, ventricular arrhythmias, sudden cardiac arrest, thromboembolic events, cardiovascular implantable electronic device placement, and mechanical circulatory support insertion. Conclusion In conclusion, although HF and CS have been associated with worse outcomes when admitted over the weekend, we did not find weekend admission for PPCM to be independently associated with worse clinical outcomes after multivariate analysis. These findings could reflect improvement in the coordination of care over the weekend, improvement in physician handoff, and increased utilization of shock teams.