Efficacy and outcomes of bempedoic acid versus placebo in patients with hypercholesterolemia: an updated systematic review and meta-analysis of randomized controlled trials.

Introduction: Bempedoic acid (BA) has shown varied efficacy in managing hyperlipidemia. We conducted the most extensive up-to-date meta-analysis, the first to include recent studies by Nissen et al., which boast the largest sample size. Methods: Literature search was done on Medline, EMBASE, and Cochrane Library. The primary endpoint was a change in low-density lipoprotein-cholesterol (LDL-C) levels, while secondary endpoints encompassed changes in lipid parameters, clinical endpoints, and safety endpoints. The least-square mean (LSM) percent change was utilized for lipid changes, with statistical significance set at P < 0.05. Results: This analysis included 12 randomized control trials with 22,249 participants. BA exhibited a substantial reduction in LDL-C levels [LSM % change, -24.34; 95% confidence interval (CI), -27.80 to -20.88; P < 0.0001], total cholesterol levels (LSM % change, -16.62; 95% CI, -21.70 to -11.54; P < 0.00001) and high-density lipoprotein-cholesterol (HDL-C) levels (LSM % change, -4.22; 95% CI, -5.51 to -2.92; P < 0.00001) compared to the placebo. Conclusions: BA significantly lowers LDL-C, total cholesterol, HDL-C, non-HDL-C, high sensitivity C reactive protein, and apolipoprotein levels.

The Presence of Chronic Total Occlusion in Noninfarct-Related Arteries Is Associated With Higher Mortality and Worse Patient Outcomes Following Percutaneous Coronary Intervention for STEMI: A Systematic Review, Meta-Analysis and Meta-Regression.

Reperfusion therapy with percutaneous coronary intervention improves outcomes in patients with ST-elevation myocardial infarction. We conducted a meta-analysis to assess the impact of chronic total occlusion (CTO) in noninfarct-related artery on the outcomes of these patients. Comprehensive searches were performed using PubMed, Google Scholar, and EMBASE. The primary endpoint was the 30-day mortality rate, with secondary endpoints including all-cause mortality, repeat myocardial infarction, and stroke. Forest plots were created for the pooled analysis of the results, with statistical significance set at P < 0.05. A total of 19 studies were included in this meta-analysis, with 23,989 patients (3589 in CTO group and 20,400 in no-CTO group). The presence of CTO was associated with significantly higher odds of 30-day mortality [18.38% vs 5.74%; relative risk (RR), 3.69; 95% confidence intervals (CI), 2.68-5.07; P < 0.00001], all-cause mortality (31.00% vs 13.40%; RR, 2.79; 95% CI, 2.31-3.37; P < 0.00001), cardiovascular-related deaths (12.61% vs 4.1%; RR, 2.61; 95% CI, 1.99-3.44; P < 0.00001), and major adverse cardiovascular events (13.64% vs 9.88%; RR, 2.08; 95% CI, 1.52-2.86; P < 0.00001) than the non-CTO group. No significant differences in repeated myocardial infarction or stroke were observed between the CTO and non-CTO groups. Our findings underscore the need for further research on the benefits and risks of performing staged or simultaneous percutaneous coronary intervention for CTO in the noninfarct-related artery in patients with ST-elevation myocardial infarction.

Efficacy and outcomes of Bempedoic acid versus placebo in patients with statin-intolerance: A pilot systematic review and meta-analysis of randomized controlled trials.

INTRODUCTION: Bempedoic acid (BA) has shown significant progress in reducing cholesterol levels and is relatively free from the many side effects encountered with the use of other hyperlipidemic drugs such as statins. However, its efficacy in patients with statin intolerance is controversial with inconsistent results among studies. MATERIALS AND METHODS: An electronic literature search was performed using various databases such as Medline, Google Scholar, and the International Registry of Clinical Trials. The primary endpoint was the change in LDL-C levels. The secondary endpoints included changes in HDL-C, non-HDL-C, triglycerides (TG), clinical outcomes such as MACE, all-cause mortality (ACM), cardiovascular mortality, myocardial infarction (MI), and additional safety outcomes. The least-square mean (LSM) percent change for assessing changes in lipid parameter levels from the baseline and the risk ratio (RR) were used for the evaluation of binary endpoints, with statistical significance set at p<0.05. Random-effects meta-analyses were performed for all the outcomes. RESULTS: Our analysis included 5 randomized controlled trials (RCTs) with a total of 18,848 participants. BA showed a significant reduction in LDL-C [LSM difference in %: -25.24; 95 % CI: -30.79 to -19.69; p < 0.00001], total cholesterol [LSM difference in %:-21.28; 95 % CI:-30.58 to-11.98; p < 0.00001], non-HDL-C [LSM difference in %: -23.27; 95 % Cl: -29.80 to -16.73 p < 0.00001], and HDL-C [LSM difference in %:-3.37, 95 % CI:-3.73 to-3.01, p < 0.00001] compared to placebo. In terms of clinical efficacy, BA was associated with a lower risk of coronary revascularization [RR:0.81; 95 % CI:0.66 to 0.99; p = 0.04], hospitalization for unstable angina [RR:0.67; 95 % CI:0.50 to 0.88; p = 0.005], and myocardial infarction [RR:0.76; 95 % CI:0.66 to 0.88;p = 0.0004]. No significant difference was observed in MACE [RR:0.81; p = 0.15], ACM [RR:0.86; p = 0.46], cardiovascular-related mortality [RR:0.79; p = 0.44], and stroke [RR:0.83; p = 0.08] between the two groups. In terms of safety efficacy, the risk for myalgia was significantly lower in BA-treated patients than in placebo [RR:0.80; p = 0.0002], while the risk for gout [RR:1.46; p < 0.0001] and hyperuricemia [RR:1.93; p < 0.00001] was higher for BA than for placebo. The risks for other adverse effects, such as neurocognitive disorder, nasopharyngitis urinary tract infection, upper respiratory infection, muscular disorder, and worsening hyperglycemia/DM were comparable between the two groups. CONCLUSION: Our analysis demonstrated that BA significantly reduced the levels of LDL-C, total cholesterol, non-HDL-C, HDL-C, ApoB, and hs-CRP compared with the placebo group. Additionally, patients who received BA had a lower likelihood of coronary revascularization and hospitalization due to unstable angina, MI, and myalgia. Further large-scale RCTs are required to generate more robust evidence.

The role of renal denervation in cardiology and beyond: An updated comprehensive review and future directives.

Renal denervation (RDN) is a minimally invasive intervention performed by denervation of the nervous fibers in the renal plexus, which decreases sympathetic activity. These sympathetic nerves influence various physiological functions that regulate blood pressure (BP), including intravascular volume, electrolyte composition, and vascular tone. Although proven effective in some trials, controversial trials, such as the Controlled Trial of Renal Denervation for Resistant Hypertension (SYMPLICITY-HTN3), have demonstrated contradictory results for the effectiveness of RDN in resistant hypertension (HTN). In the treatment of HTN, individuals with primary HTN are expected to experience greater benefits compared to those with secondary HTN due to the diverse underlying causes of secondary HTN. Beyond its application for HTN, RDN has also found utility in addressing cardiac arrhythmias, such as atrial fibrillation, and managing cases of heart failure. Non-cardiogenic applications of RDN include reducing the intensity of obstructive sleep apnea (OSA), overcoming insulin resistance, and in chronic kidney disease (CKD) patients. This article aims to provide a comprehensive review of RDN and its uses in cardiology and beyond, along with providing future directions and perspectives.