Akram, Amina

ABSTRACT Introduction Right ventricular pacing (RVP) has long been the standard therapy for bradyarrhythmias but may induce ventricular dyssynchrony and adverse cardiac remodeling. Physiologic pacing strategies that preserve the native conduction system, particularly left bundle branch area pacing (LBBAP), have emerged as promising alternatives. This study aimed to evaluate the comparative efficacy and safety of LBBAP versus RVP through an updated meta‐analysis. Methods Following PRISMA guidelines, we systematically searched PubMed, Cochrane CENTRAL, and ClinicalTrials.gov for relevant studies published through June 2025. Studies comparing LBBAP and RVP in patients undergoing pacemaker implantation were included. Pooled estimates were calculated using random‐effects models. Results A total of 40 studies comprising 8290 patients were included. LBBAP was associated with significantly shorter QRS duration compared with RVP (30 studies, n = 5510; MD −35.56 ms, 95% CI −41.88 to −29.24; p < 0.0001). Structural remodeling also favored LBBAP, with greater improvement in left ventricular ejection fraction (16 studies, n = 1693; MD +3.77%, 95% CI 2.43–5.12; p < 0.0001) and greater reduction in left ventricular end‐diastolic diameter (13 studies, n = 1666; MD −2.33 mm, 95% CI −3.59 to −1.07; p < 0.0001). Clinically, LBBAP was associated with lower heart failure hospitalization (RR 0.38, 95% CI 0.29–0.52; p < 0.0001) and reduced all‐cause mortality (RR 0.55, 95% CI 0.41–0.72; p < 0.0001), along with greater reduction in NT‐proBNP levels. Conclusion LBBAP provides superior electrical synchrony, improved cardiac remodeling, and favorable clinical outcomes compared with RVP, while maintaining a comparable procedural safety profile.

Background: Inclisiran, a small interfering RNA (siRNA), inhibits hepatic PCSK9 synthesis, leading to significant LDL-C reduction. Previous meta-analyses have addressed short-term efficacy; however, recent long-term data warranted an updated systematic review and meta-analysis to evaluate inclisiran’s lipid-lowering efficacy and safety in hyperlipidemic patients. Methods: A systematic search of PubMed, Embase, Cochrane Library, and ClinicalTrials.gov was conducted from inception to April 2025 to identify randomized controlled trials (RCTs) comparing inclisiran with placebo or standard care in adults with hypercholesterolemia. Primary efficacy outcomes included percentage change in LDL-C, PCSK9, total cholesterol, apolipoprotein B (apo-B), and non-HDL-C. Safety outcomes included adverse events, cardiovascular events, and all-cause mortality. Data were analyzed using a random-effects model following PRISMA guidelines. Risk ratios (RR) and weighted mean differences (WMD) were calculated with 95% confidence intervals. The protocol was registered on PROSPERO (CRD420251059229). Results: Eleven RCTs with 5,601 patients were included; 3,135 received inclisiran and 2,466 received placebo. Inclisiran significantly reduced: LDL-C (WMD –48.99%, 95% CI: –54.29 to –43.69) PCSK9 (WMD –78.52%, 95% CI: –81.52 to –75.51) Total cholesterol (WMD –31.21%, 95% CI: –33.47 to –28.56) Apo-B (WMD –40.09%, 95% CI: –43.43 to –36.75) Non-HDL-C (WMD –35.22%, 95% CI: –41.25 to –29.20) Inclisiran showed no significant impact on all-cause mortality (RR 0.94; p=0.83), cardiovascular mortality (RR 1.19; p=0.60), myocardial infarction (RR 0.85; p=0.60), stroke (RR 0.89; p=0.86), or major adverse cardiovascular events (RR 0.80; p=0.07). Total adverse events were slightly higher with inclisiran (RR 1.06; p=0.02), but serious adverse events were not significantly different (RR 0.90; p=0.36). Injection site reactions were more common with inclisiran (RR 6.45; p<0.001). Conclusion: Inclisiran significantly reduces LDL-C, PCSK9, total cholesterol, apo-B, and non-HDL-C, confirming strong lipid-lowering efficacy. It is generally well tolerated, with a slightly higher incidence of mild injection site reactions but no increase in serious adverse events. Longer-term studies are needed to assess its effect on cardiovascular outcomes.