Objective: The study of ABCB1 and CYP3A4/3A5 gene polymorphism genes is promising in terms of their influence on prothrombin time variability, the residual equilibrium concentration of direct oral anticoagulants (DOACs) in patients with atrial fibrillation and the development of new personalized approaches to anticoagulation therapy in these patients. The aim of the study is to evaluate the effect of ABCB1 (rs1045642) C>T; ABCB1 (rs4148738) C>T and CYP3A5 (rs776746) A>G, CYP3A4*22(rs35599367) C>T gene polymorphisms on prothrombin time level and residual equilibrium concentration of rivaroxaban in patients with atrial fibrillation.

Methods: In total 86 patients (42 men and 44 female), aged 67.24 +/- 1.01 years with atrial fibrillation were enrolled in the study. HPLC mass spectrometry analysis was used to determine rivaroxaban residual equilibrium concentration. Prothrombin time data were obtained from patient records.

Results: The residual equilibrium concentration of rivaroxaban in patients with ABCB1 rs4148738 CT genotype is significantly higher than in patients with ABCB1 rs4148738 CC (P = 0.039). The analysis of the combination of genotypes did not find a statistically significant role of combinations of alleles of several polymorphic markers in increasing the risk of hemorrhagic complications when taking rivaroxaban.

Conclusion: Patients with ABCB1 rs4148738 CT genotype have a statistically significantly higher residual equilibrium concentration of rivaroxaban in blood than patients with ABCB1 rs4148738 CC genotype, which should be considered when assessing the risk of hemorrhagic complications and risk of drug-drug interactions. Further studies of the effect of rivaroxaban pharmacogenetics on the safety profile and efficacy of therapy are needed.

Essential Med Notes is a clinical complement and resource for medical trainees. This 37th edition features substantial content revisions to the main text, figures, graphics, and evidence-based medicine boxes of all 31 chapters across the 3 volumes - Primary, Medicine, and Surgery.

Medicine:
- Cardiology and Cardiac Surgery
- Endocrinology
- Gastroenterology
- Geriatric Medicine
- Hematology
- Infectious Diseases
- Nephrology
- Neurology
- Respirology
- Rheumatology

Coronavirus disease-2019 (COVID-19) has emerged as a pandemic affecting millions of adults. Severe acute respiratory syndrome coronavirus-2019 (SARS-CoV-2), the causative virus of COVID-19, infects host cells through angiotensin-converting enzyme 2 (ACE2). Preclinical models suggest that ACE2 upregulation confers protective effects in acute lung injury. In addition, renin-angiotensin aldosterone system inhibitors reduce adverse atherosclerotic cardiovascular disease, heart failure, and chronic kidney disease outcomes, but may increase ACE2 levels. We review current knowledge of the role of ACE2 in cardiovascular physiology and SARS-CoV-2 virology, as well as clinical data to inform the management of patients with or at risk for COVID-19 who require renin-angiotensin-aldosterone system inhibitor therapy.

Coronavirus disease-2019 (COVID-19) has emerged as a pandemic affecting millions of adults. Severe acute respiratory syndrome coronavirus-2019 (SARS-CoV-2), the causative virus of COVID-19, infects host cells through angiotensin-converting enzyme 2 (ACE2). Preclinical models suggest that ACE2 upregulation confers protective effects in acute lung injury. In addition, renin-angiotensin aldosterone system inhibitors reduce adverse atherosclerotic cardiovascular disease, heart failure, and chronic kidney disease outcomes, but may increase ACE2 levels. We review current knowledge of the role of ACE2 in cardiovascular physiology and SARS-CoV-2 virology, as well as clinical data to inform the management of patients with or at risk for COVID-19 who require renin-angiotensin-aldosterone system inhibitor therapy.

Le Traité de la Société Française de Cardiologie « Cardiologie et maladies vasculaires » rend compte des progrès considérables de la prise en charge des affections cardiovasculaires au cours des dernières années. Sa préparation a nécessité une synthèse actualisée de chacun des domaines de cette discipline particulièrement riche en évolutions tant en physiopathologie, en explorations qu'en traitements pharmacologiques, interventionnels et chirurgicaux.

La première de ces évolutions tient aux progrès techniques. En dix ans, chacun des domaines de la cardiologie a vu ses méthodes diagnostiques et thérapeutiques faire des pas gigantesques. L'imagerie de coupe scanner et IRM, le strain en échocardiographie, les holters implantables, la cartographie en électrophysiologie endocavitaire, la FFR, les stents coronaires de nouvelle génération, les endoprothèses vasculaires, l'approche interventionnelle neuro-vasculaire, les endoprothèses valvulaires percutanées, les anticoagulants oraux directs, les inhibiteurs plaquettaires de nouvelle génération sont entrés dans la pratique quotidienne.

La seconde grande évolution concerne les stratégies de recours à ces explorations et ces traitements, dont témoigne la vitesse de renouvellement des recommandations de la Société européenne de cardiologie, endossées en aval par la Société française de cardiologie. Toutes ont changé. On n'explore et on ne traite plus de la même manière la maladie coronaire, la plupart des arythmies, les atteintes cardiaques des affections médicales, l'insuffisance cardiaque, l'hypertension artérielle.

Ce sont tous ces changements qui sont à l'origine de la parution de « Cardiologie et maladies vasculaires », le Traité de cardiologie et de Maladies vasculaires de la Société française de cardiologie.

Ce traité est présenté sous une forme combinée, couplant un ouvrage exhaustif publié sous forme numérique complété de suppléments iconographiques et de vidéos, et une version papier principalement focalisée sur les aspects thérapeutiques et novateurs.

Abstract: Statins have been suggested in previous studies to play a protective role in experimental cerebral aneurysm (CA) models; however, no evidence supports that the application of statins can protect against aneurysm rupture in humans, and the risks of lipid levels and aneurysms remain unknown. Therefore, this meta-analysis aimed to summarize and update the epidemiological evidence to systematically assess the relationships of statin therapy and hyperlipidemia with the incidence, rupture, postrepair mortality, and all-cause mortality of abdominal aortic aneurysm (AAA) and CA. Related studies were initially retrieved from the electronic databases PubMed, Embase, and Cochrane Library from inception to August 4, 2018. Subsequently, 33 studies were enrolled into this meta-analysis, and the maximum adjusted risk ratios (RRs) as well as the corresponding 95% confidence intervals were extracted. Finally, a total of 32 observational studies involving 150,134 participants were enrolled into this meta-analysis. The RRs of statin therapy for AAA incidence, AAA rupture, CA rupture, postrepair mortality, all-cause mortality, and adverse events were 1.83 (0.56-5.98), 0.67 (0.47-0.97), 0.50 (0.18-1.36), 0.60 (0.48-0.74), 0.66 (0.58-0.75), and 0.58 (0.47-0.71), respectively. Besides, the RR of hyperlipidemia for CA rupture was 0.79 (0.67-0.93). Our findings suggested that statin therapy could reduce the risks of AAA rupture, postrepair mortality, all-cause mortality, and adverse events, without inducing the risk of AAA incidence or CA rupture, and that hyperlipidemia was associated with a lower risk of CA rupture.

Background: Radiofrequency ablation (RFA) and antiarrhythmic drugs (AADs) are the main treatments used for atrial fibrillation (AF). In recent years, a number of articles comparing the 2 treatments have begun to emerge. Though, the influence of follow-up time in the meta-analysis was not considered in these articles. However, more recently, large-scale clinical trial articles have included follow-up with the patients up to 5 years after treatment. Therefore, the aim of this study was to assess the impact of variable follow-up times on the recurrence of AF by observing both the short-term and long-term efficacy and safety of catheter ablation and AADs for the treatment of AF.

Methods and Results: The primary investigators of eligible randomized controlled trials were invited to contribute standardized outcome data. Random effect summary estimates were calculated as standardized mean differences and odds ratios with 95% confidence intervals for continuous and binary outcomes. In this study, 9 randomized controlled trials (n = 1542 patients) were included. The rate of recurrence of AF with no limit on follow-up time, >12 months, >18 months, >24 months, >30 months, and approximately 36 months was compared. Furthermore, the gap between the RFA and AAD groups in the recurrence rate of AF was found to decrease inversely to follow-up time. When the follow-up time reached 24 months, the difference between RFA and AAD was relatively stable with an odds ratio of 0.45 (95% confidence interval: 0.32-0.62). Overall, RFA decreased adverse events in the remaining trials; however, AAD performed better in terms of safety and had fewer adverse events with RFA usually causing more serious complications.

Conclusion: RFA is more advantageous in terms of recurrence rate of AF than drug therapy. In addition, the analysis suggests that this effect persists during long-term follow-up; however, these benefits appear to decrease with longer follow-up time. Finally, AAD performed better in terms of safety and had fewer adverse events.

Abstract: Little is known about the dosing and tolerability of sacubitril/valsartan (LCZ696; Entresto, Quebec, Canada) in a nonclinical trial population. This study was conducted to evaluate the use and tolerability of sacubitril/valsartan in patients followed at a multidisciplinary heart failure (HF) clinic. We performed a retrospective chart review of 126 patients with HF, initiated on sacubitril/valsartan, and seen at a specialty HF clinic between August 1, 2015, and August 1, 2017. We defined the target dose of sacubitril/valsartan as 200 mg twice a day. At baseline, median age was 67 years, 77% were men, median ejection fraction was 29%, and 86.5% of patients had symptoms of New York Heart Association class >=II. Within 6 months of being transitioned onto sacubitril/valsartan therapy, 27.2% achieved the target dose of 200 mg twice a day, 40.8% achieved the target dose of 100 mg twice a day, and 32.0% achieved the target dose of 50 mg twice a day. The main reasons for not achieving target dose within 6 months included slower uptitration of therapy than in the trial (n = 41, 54.7%), a decrease in systolic blood pressure (n = 19, 25.3%), not completing blood work (n = 3, 4%), and patient noncompliance (n = 3, 4%). Overall, achievement of sacubitril/valsartan target doses was modest in a tertiary HF clinic, limited by various factors such as side effects and patients' medication noncompliance. Implementation of patient and clinician support pathways may improve uptake, uptitration, and maintenance of evidence-based doses in clinical practice.

Abstract: To date, many questions about the extent and cause of pharmacokinetic (PK) variability of even the most widely studied and prescribed [beta]1-adrenergic receptor blockers, such as metoprolol and bisoprolol, remain unanswered. Given that there are still no published population pharmacokinetic (PopPK) analyses of bisoprolol in routinely treated patients with acute coronary syndrome (ACS), the aim of this study was to determine its PK variability in 71 Serbian patients with ACS. PopPK analysis was conducted using a nonlinear mixed-effects model (NONMEM), version 7.3.0 (Icon Development Solutions). In each patient, the same formulation of bisoprolol was administered once or twice daily at a total daily dose of 0.625-7.5 mg. We separately assessed the effects of 31 covariates on the PKs of bisoprolol, and our results indicated that only 2 covariates could have possible influence on the variability of the clearance of bisoprolol: the mean daily dose of the drug and smoking habits of patients. These findings suggest that possible autoinduction of drug metabolism by higher total daily doses and induction of cytochrome P450 isoform 3A4 (CYP3A4) by cigarette smoke in liver could be the potential causes of increased total clearance of bisoprolol in patients with ACS.