Daily Archives: January 15, 2025
Meta-Analysis: Beta-Blockers Show No Mortality Reduction in Myocardial Infarction with Preserved Ejection Fraction
15 Jan, 2025 | 13:06h | UTCBackground: Beta-blockers have been a cornerstone of care following myocardial infarction (MI), primarily benefiting patients with reduced left ventricular ejection fraction (LVEF). However, the evidence supporting their routine use in patients with a preserved LVEF remains inconsistent, especially in the context of current revascularization strategies and guideline-directed medical therapy.
Objective: This systematic review and meta-analysis aimed to determine whether beta-blockers confer mortality or cardiovascular event benefits among patients with MI and a preserved LVEF in the contemporary reperfusion era.
Methods: Researchers conducted a PRISMA-compliant search of PubMed and EMBASE, identifying randomized controlled trials (RCTs) that compared long-term beta-blocker therapy versus no beta-blocker therapy in patients with MI and LVEF ≥40%. Three RCTs (total n = 9512) were included. The primary outcome was a composite of all-cause mortality and recurrent MI. Secondary outcomes included all-cause mortality, cardiovascular mortality, MI, and stroke. Risk ratios (RRs) with 95% confidence intervals (CIs) were pooled using a random-effects model. Heterogeneity was assessed via I² statistics. Risk of bias was evaluated with the Cochrane RoB 2.0 tool, and the quality of evidence was reviewed according to GRADE recommendations.
Results: Across the three RCTs, beta-blockers did not significantly reduce the composite of all-cause mortality and MI (RR 0.97, 95% CI: 0.84–1.12; p = 0.671; I² = 0%). Secondary endpoints also showed no significant effect: all-cause mortality (RR 0.96, 95% CI: 0.79–1.17), cardiovascular mortality (RR 1.22, 95% CI: 0.87–1.72), recurrent MI (RR 0.97, 95% CI: 0.78–1.19), and stroke (RR 0.96, 95% CI: 0.66–1.38). Sensitivity analyses, including leave-one-out approaches, yielded consistent findings. There was minimal heterogeneity overall, suggesting stable results. Although one trial strictly excluded patients with LVEF <50%, others allowed mildly reduced LVEF (40–50%), highlighting variability in definitions of “preserved” function.
Conclusions: In contemporary patients with MI and preserved LVEF, beta-blockers did not lower overall mortality, recurrent MI, or stroke. These data suggest that, under current revascularization practices and adjunctive therapies, beta-blockers may not offer the same advantage observed in earlier trials among individuals without significant systolic dysfunction.
Implications for Practice: Clinicians managing MI in patients with preserved LVEF should carefully weigh potential side effects and the absence of clear mortality benefit when deciding on beta-blocker therapy. While widely prescribed, beta-blockers may not improve outcomes for this subgroup in modern practice. Guidelines that currently reflect broad beta-blocker use may need refinement to account for these latest findings.
Study Strengths and Limitations: Major strengths include a focus on contemporary, randomized evidence and rigorous risk-of-bias assessment. The analysis is limited by the small number of RCTs, variable definitions of “preserved” ejection fraction, and a predominantly male study population. Underrepresentation of women and patients with borderline LVEF reduces generalizability to broader clinical cohorts.
Future Research: Ongoing RCTs (such as REBOOT-CNIC, BETAMI, and DANBLOCK) will provide further insight into the impact of beta-blockers in patients with normal or mildly reduced LVEF, particularly regarding safety profiles (e.g., bradyarrhythmias, hypotension, respiratory exacerbations) and subgroup analyses by sex. These data may inform more nuanced guideline recommendations.
Reference: Sabina M, Shah S, Grimm M, Daher JC, Campillo P, Boozo MB, Al-Abdouh A, Abusnina W, D’Ascenzo F, Bizanti A. Beta-Blockers in Patients with Myocardial Infarction and Preserved Left Ventricular Ejection: A Systematic Review and Meta-Analysis of Randomized Controlled Trials. Journal of Clinical Medicine. 2025;14(1):150. DOI: https://doi.org/10.3390/jcm14010150
RCT: Empagliflozin Lowers Urinary Supersaturation in Nondiabetic Adults With Calcium and Uric Acid Kidney Stones
15 Jan, 2025 | 12:03h | UTCBackground: Kidney stones represent a major health challenge worldwide, with calcium-based (calcium oxalate or phosphate) and uric acid (UA) stones accounting for most cases. Despite multiple preventive measures—including hydration, dietary modification, and, in certain cases, pharmacotherapy—recurrence rates remain high. Recent retrospective analyses suggest sodium-glucose cotransporter 2 (SGLT2) inhibitors may reduce stone episodes in patients with type 2 diabetes. These agents could theoretically lower stone risk by promoting urinary citrate excretion, altering urine pH, and enhancing UA clearance. However, prospective data are lacking in nondiabetic individuals. This phase 2, single-center, double-blind, placebo-controlled, crossover study (SWEETSTONE) explored whether empagliflozin (25 mg daily) modifies urinary relative supersaturation ratios (RSRs)—a validated surrogate of stone risk—in adults without diabetes who have a history of either calcium or UA stones.
Objective: To determine if empagliflozin significantly reduces RSRs for calcium oxalate (CaOx), calcium phosphate (CaP), and UA in nondiabetic adults with recurrent kidney stones and to assess short-term safety.
Methods: A total of 53 participants (28 calcium stone formers, 25 UA stone formers) were randomized to empagliflozin 25 mg once daily or placebo for two weeks, followed by a 2–6-week washout, then crossed over to the alternative treatment. Primary outcomes were changes in RSR CaOx, RSR CaP, and RSR UA. Secondary measures included 24-hour urine pH, citrate, calcium, and UA, as well as key blood parameters. Analyses were performed separately for calcium and UA stone groups using a generalized linear mixed effects model. The per protocol set was used for the main analysis, with additional intention-to-treat assessments for confirmation.
Results: In calcium stone formers, empagliflozin lowered RSR CaP by 36% (95% CI −48% to −21%; p<0.001) compared with placebo but did not significantly change RSR CaOx. Uric acid supersaturation rose modestly, yet nonsignificantly. Among UA stone formers, empagliflozin reduced RSR UA by 30% (95% CI −44% to −12%; p=0.002), with no significant effect on RSR CaOx or RSR CaP. Both groups showed substantial increases in 24-hour urine citrate (60% for calcium stones, 40% for UA stones) and marked reductions in plasma UA levels. Urine calcium rose in some calcium stone formers, but no severe adverse events were reported during the study.
Conclusions: Short-term treatment with empagliflozin produced meaningful decreases in key urinary supersaturation indices among nondiabetic adults with calcium or UA stones, while exhibiting an acceptable safety profile. These favorable laboratory changes offer mechanistic promise but do not establish definitive evidence that long-term stone recurrence is reduced.
Implications for Practice: Although the pronounced improvement in urinary lithogenic profiles is encouraging, it remains unclear whether these shifts will translate into sustained reductions in actual stone formation. Consequently, clinicians should be cautious about recommending off-label SGLT2 inhibition for stone prevention solely on the basis of these short-term biochemical improvements. Larger, longer-duration trials with clinical endpoints (i.e., stone recurrence) are warranted before SGLT2 inhibitors can be broadly endorsed for this indication. In addition, practical considerations—such as cost, insurance coverage, and potential off-target effects—must be weighed in individualized clinical decisions.
Study Strengths and Limitations: Strengths include the randomized crossover design and distinct analyses for calcium and UA stone phenotypes. Nevertheless, the sample size was modest, and the treatment duration too brief to capture definitive impacts on stone recurrence. The predominance of white male participants also limits generalizability to more diverse populations.
Future Research: Extended follow-up is crucial to determine the long-term clinical effectiveness of empagliflozin in preventing stone events. Future work should also explore potential mechanisms in larger cohorts, assess cost-effectiveness in real-world settings, and evaluate whether other SGLT2 inhibitors elicit comparable effects.
Reference: Anderegg MA, Schietzel S, Bargagli M, et al. Empagliflozin in nondiabetic individuals with calcium and uric acid kidney stones: a randomized phase 2 trial. Nature Medicine (2025). DOI: https://doi.org/10.1038/s41591-024-03330-x