Identifying Clinical Predictors of Switching From Direct Oral Anticoagulants to Warfarin

Purpose: Direct oral anticoagulants (DOACs) have been shown to be as effective or superior to warfarin, but warfarin use remains constant. Knowledge regarding the patient population who have switched from a DOAC to warfarin is limited. The objective of this study was to identify clinical predictors which may influence a patient’s likelihood of switching from a DOAC to warfarin for atrial fibrillation (AF) or venous thromboembolism (VTE). Methods: In this single-center, case-control study, patients who switched from a DOAC to warfarin were compared with patients who remained on a DOAC. Baseline demographics were compared between the switch and control groups. Independent factors that increased the likelihood of switching from a DOAC to warfarin were analyzed using logistic regression. Results: A total of 150 patients were included in the control (n = 100) and switch (n = 50) groups. Patients switched from a DOAC to warfarin had more medications at baseline (9 [7, 13] vs 11 [8, 18], P = 0.009). The presence of heart failure (HF) increased the likelihood of switching (odds ratio [OR] = 3.95, confidence interval [CI] = 1.70-9.21, P = 0.002), and for every 10 mL/min increase in creatinine clearance (CrCl), the likelihood of switching decreased ( R = 0.89 [0.80-0.99], P = 0.026). Patients with pulmonary embolism (PE) were less likely to switch from a DOAC to warfarin (OR = 0.20, CI = 0.05-0.86, P = 0.031). Explicitly listed reasons for switching included left ventricular assist device (LVAD) implantation (20%) and valve replacement procedures (20%). Conclusion: Congestive HF was a clinical predictor associated with an increased likelihood of switching from a DOAC to warfarin. Anticoagulation therapy for PE and higher CrCl was associated with a decreased likelihood in switching from DOAC to warfarin.

Concordance Among Methods for Empiric Renal Drug Dosing: Meropenem as a Role Model for Clinical Superiority of Cockroft–Gault or Modification of Diet in Renal Disease

Objective: The objectives of this study are, first, to measure concordance between 5 different renal function estimates (methods) in terms of recommended drug doses, and, subsequently, to establish the potential for significant clinical differences between Cockroft–Gault (CG) and Modification of Diet in Renal Disease (MDRD) equations in dosing a specific medication, namely, meropenem. Design and setting: This study used a Monte Carlo simulation, and this is a computer–based study with no actual patient data. Patients: A total of 1200 and 8701 simulated cases to study the concordance for the 5 methods and the potential clinical significance of discordance between CG and MDRD, respectively, were chosen for the study. Methods: Simulated factors were age, sex, height, weight, serum creatinine, ethnicity, and albumin. We estimated the renal function using 5 formulas (ie, 10 combinations) including CG, MDRD, and Chronic Kidney Disease Epidemiology Collaboration (CKD–EPI). Next, the team evaluated concordance for each combination in dosing 22 drugs. Finally, our researchers reviewed and simulated data from the literature to show how CG versus MDRD use can result in clinically significant differences for meropenem. Results: Pairwise combinations yielded statistically significant differences ( P < .0001) except for CG and MDRD ( P < .5147). In addition, the highest concordance was for MDRD and CKD–EPI. Average discordance is in the range of 25% to 30% with the lowest being between CG and albumin–based estimates. Both CG and MDRD were largely discordant which can reach up to 40% with a drug like meropenem and may be associated with significant adverse outcomes. Conclusions: Both CG and MDRD in our simulation are statistically comparable. Clinically, nonetheless, they are significantly inconsistent in terms of recommended drug dosing. We encourage practical comparisons of outcomes for individual or groups of medications (eg, meropenem and antibiotics) empirically dosed in renal patients on the basis of equations used in distinct populations.

Advances in the Therapy of Bleeding Peptic Ulcer

Peptic ulcer bleeding remains an important medical emergency. Important recent advances are reviewed. These include further support for a more restrictive transfusion strategy aiming for a target haemoglobin of 70-90 g/L. The Glasgow-Blatchford score remains the most useful assessment score for identifying the lowest risk patients suitable for outpatient management and predicting the need for intervention. Newer scores such as the AIMS65 and Progetto Nazionale Emorragia Digestive score (PNED) may be more accurate in predicting mortality. Pre-endoscopy erythromycin improves outcomes and is underused. A new disposable Doppler probe appears to provide more accurate determination of both rebleeding risk and the success of endoscopic therapy than purely visual guidance. Over-the-scope clips and haemostatic powders appear to have some role as endoscopic salvage therapies. Non- H. pylori, non-aspirin/non-steroidal anti-inflammatory drug (NSAID) ulcers contribute to an increasing percentage of bleeding peptic ulcers and are associated with a high rebleeding rate. The optimal management of these ulcers remains to be determined.

Role of Aldosterone Receptor Antagonists in Heart Failure With Preserved Ejection Fraction

Aldosterone receptor antagonists have recently been added to the American College of Cardiology/American Heart Association/Heart Failure Society of America 2017 guideline update for serving a role in the reduction in morbidity in patients with heart failure with preserved ejection fraction and an ejection fraction greater than 45%. This recent addition to the heart failure with preserved ejection fraction recommendations is supported by the findings of the Treatment of Preserved Cardiac Function Heart Failure with an Aldosterone Antagonist study. All trials with spironolactone or eplerenone in the treatment of patients with heart failure with preserved ejection fraction are reviewed for both cardiovascular morbidity and mortality and symptom improvement. Limited positive data exist on the role aldosterone receptor antagonists has on mortality and symptom improvement in patients with heart failure with preserved ejection fraction. Ongoing trials with angiotensin receptor neprilysin inhibitor and sodium-glucose co-transporter 2 inhibitors in patients with heart failure with preserved ejection fraction are reviewed. This review provides the current clinical and scientific data pertaining to the safety and efficacy of aldosterone receptor antagonists in patients with heart failure with preserved ejection fraction.

Direct Oral Anticoagulant Use in Valvular Heart Disease

Direct oral anticoagulants (DOACs) are indicated by the European Medicines Agency and US Food and Drug Administration for stroke prevention in patients with nonvalvular atrial fibrillation (AF). The role of DOACs in patients with AF and concomitant valvular heart disease (VHD) is less clear. Recent subanalyses of randomized controlled trials and meta-analyses have evaluated the role of DOACs in patients with AF and VHD. Patients with native aortic valve disease, tricuspid valve disease, or mitral regurgitation will be the primary focus as these represent the majority of VHD represented in the DOAC AF trials. Limited data exist on the role in patients with rheumatic mitral stenosis, mechanical heart valves, and mitral valve repair. This review provides the current clinical and scientific data pertaining to the safety and efficacy of DOAC use in patients with VHD.