An adapted cardioprotective diet with or without phytosterol and/or krill oil supplement in familial hypercholesterolemia: A pilot study protocol

BACKGROUND AND AIMS: A healthy diet is one of the pillars of familial hypercholesterolemia (FH) treatment. However, the best dietary pattern and indication for specific supplementation have not been established. Our aim is to conduct a pilot study to assess the effect of an adapted cardioprotective diet with or without phytosterol and/or krill oil supplement in participants with a probable or definitive diagnosis of FH, treated with moderate/high potency statins. METHODS: A national, multicenter, factorial, and parallel placebocontrolled randomized clinical trial with a superiority design and 1:1:1:1 allocation rate will be conducted. The participants will undergo whole exome sequencing and be allocated into four treatment groups: 1) a cardioprotective diet adapted for FH (DICAFH) þ phytosterol placebo þ krill oil placebo; 2) DICA-FH þ phytosterol 2 g/day þ krill oil placebo; 3) DICA-FH þ phytosterol placebo þ krill oil 2 g/day; or 4) DICA-FH þ phytosterol 2 g/day þ krill oil 2 g/day. The primary outcomes will be low-density lipoprotein (LDL)-cholesterol and lipoprotein (a) levels and adherence to treatment after a 120-day follow-up. LDL- and high-density lipoprotein (HDL)-cholesterol subclasses, untargeted lipidomics analysis, adverse events, and protocol implementation components will also be assessed. RESULTS: A total of 58 participants were enrolled between May e August 2023. After the end of the follow-up period, the efficacy and feasibility results of this pilot study will form the basis of the design of a large-scale randomized clinical trial. CONCLUSIONS: This study's overall goal is to recommend dietary treatment strategies in the context of FH.

A randomized clinical trial to evaluate the efficacy and safety of rivaroxaban in patients with bioprosthetic mitral valve and atrial fibrillation or flutter: rationale and design of the RIVER trial

Background The efficacy and safety of rivaroxaban in patients with bioprosthetic mitral valves and atrial fibrillation or flutter remain uncertain. Design RIVER was an academic-led, multicenter, open-label, randomized, non-inferiority trial with blinded outcome adjudication that enrolled 1005 patients from 49 sites in Brazil. Patients with a bioprosthetic mitral valve and atrial fibrillation or flutter were randomly assigned (1:1) to rivaroxaban 20 mg once daily (15 mg in those with creatinine clearance <50 mL/min) or dose-adjusted warfarin (target international normalized ratio 2.0-30.); the follow-up period was 12 months. The primary outcome was a composite of all-cause mortality, stroke, transient ischemic attack, major bleeding, valve thrombosis, systemic embolism, or hospitalization for heart failure. Secondary outcomes included individual components of the primary composite outcome, bleeding events, and venous thromboembolism. Summary RIVER represents the largest trial specifically designed to assess the efficacy and safety of a direct oral anticoagulant in patients with bioprosthetic mitral valves and atrial fibrillation or flutter. The results of this trial can inform clinical practice and international guidelines.

Rivaroxaban in patients with atrial fibrillation and a bioprosthetic mitral valve

BACKGROUND The effects of rivaroxaban in patients with atrial fibrillation and a bioprosthetic mitral valve remain uncertain. METHODS In this randomized trial, we compared rivaroxaban (20 mg once daily) with dose adjusted warfarin (target international normalized ratio, 2.0 to 3.0) in patients with atrial fibrillation and a bioprosthetic mitral valve. The primary outcome was a composite of death, major cardiovascular events (stroke, transient ischemic attack, systemic embolism, valve thrombosis, or hospitalization for heart failure), or major bleeding at 12 months. RESULTS A total of 1005 patients were enrolled at 49 sites in Brazil. A primary-outcome event occurred at a mean of 347.5 days in the rivaroxaban group and 340.1 days in the warfarin group (difference calculated as restricted mean survival time, 7.4 days; 95% confidence interval [CI], −1.4 to 16.3; P<0.001 for noninferiority). Death from cardiovascular causes or thromboembolic events occurred in 17 patients (3.4%) in the rivaroxaban group and in 26 (5.1%) in the warfarin group (hazard ratio, 0.65; 95% CI, 0.35 to 1.20). The incidence of stroke was 0.6% in the rivaroxaban group and 2.4% in the warfarin group (hazard ratio, 0.25; 95% CI, 0.07 to 0.88). Major bleeding occurred in 7 patients (1.4%) in the rivaroxaban group and in 13 (2.6%) in the warfarin group (hazard ratio, 0.54; 95% CI, 0.21 to 1.35). The frequency of other serious adverse events was similar in the two groups. CONCLUSIONS In patients with atrial fibrillation and a bioprosthetic mitral valve, rivaroxaban was noninferior to warfarin with respect to the mean time until the primary outcome of death, major cardiovascular events, or major bleeding at 12 months.