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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.
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Background: Recent guidelines suggest that antiplatelet therapy (APT) is the standard of care in the absence of long-term oral anticoagulation (OAC) indications in patients post-transcatheter aortic valve replacement (TAVR). The superiority of one method over the other remains controversial. Materials and methods: Several databases, including MEDLINE, Google Scholar, and EMBASE, were electronically searched. The primary endpoint was the all-cause mortality (ACM) rate. Secondary endpoints included cardiovascular death, myocardial infarction (MI), stroke/TIA, haemorrhagic stroke, bleeding events, systemic embolism, and valve thrombosis in post-TAVR patients receiving APT and oral anticoagulants (OACs). Forest plots were generated using Review Manager version 5.4, with a p value less than 0.05 indicating statistical significance. Subgroup analysis was performed to explore potential sources of heterogeneity. Results: Twelve studies were selected. No significant differences were observed in APT and OAC group for ACM [risk ratio (RR): 0.67; 95% CI:0.45-1.01; P=0.05], cardiovascular death [RR:0.91; 95% CI:0.73-1.14; P=0.42], MI [RR:1.69; 95% CI:0.43-6.72; P=0.46], Stroke/TIA [RR:0.79; 95% CI:0.58-1.06; P=0.12], ischaemic stroke [RR:0.83; 95% CI:0.50-1.37; P=0.47], haemorrhagic stroke [RR:1.08; 95% CI: 0.23-5.15; P=0.92], major bleeding [RR:0.79; 95% CI:0.51-1.21; P=0.28], minor bleeding [RR:1.09; 95% CI: 0.80-1.47; P=0.58], life-threatening bleeding [RR:0.85; 95% CI:0.55-1.30; P=0.45], any bleeding [RR:0.98; 95% CI:0.83-1.15; P=0.78], and systemic embolism [RR:0.87; 95% CI:0.44-1.70; P=0.68]. The risk of valve thrombosis was higher in patients receiving APT than in those receiving OAC [RR:2.61; 95% CI:1.56-4.36; P =0.0002]. Conclusions: Although the risk of valve thrombosis increased in patients receiving APT, the risk of other endpoints was comparable between the two groups.
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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.
Subject(s)
Hydroxymethylglutaryl-CoA Reductase Inhibitors , Myocardial Infarction , Humans , Hydroxymethylglutaryl-CoA Reductase Inhibitors/adverse effects , Cholesterol, LDL , Myalgia/chemically induced , Myalgia/drug therapy , Randomized Controlled Trials as Topic , Myocardial Infarction/epidemiology , Myocardial Infarction/drug therapy , Angina, UnstableABSTRACT
INTRODUCTION: Hepatocellular carcinoma is a lethal disease and there has been a debate regarding the first-line treatment of its advanced and unresectable form. Observational studies have explored atezolizumab plus bevacizumab versus lenvatinib, yielding mixed results. This systematic review and meta-analysis aim to compare efficacy and safety of both treatment arms. METHODS: A systematic literature review was conducted in accordance with PRISMA guidelines. Randomized control trials, cohort studies, or case-control that included patients above age 60 with unresectable hepatocellular carcinoma confirmed by radiological imaging were included. At least one of the outcomes: overall survival (OS), progression-free survival (PFS), objective response rate (ORR), duration of response, or adverse events was included in the selected studies. RESULTS: Ten cohorts were included in the analysis with a total of 6493 patients. Nine of the included studies had patients with advanced HCC (BCLC-C) or intermediate HCC (BCLC-B) and 1 study included patients with all three stages (BCLC-A, BCLC-B, and BCLC-C). Of these patients, 2524 patients received atezolizumab plus bevacizumab (A + B) combination while 3969 received lenvatinib. The overall survival was better statistically in the A + B group then the lenvatinib group (MD: - 5.06; 95% CI: - 7.79 to - 2.33; p = 0.0003, I2 = 0%). The progression-free survival was significantly improved in A + B arm as well group (MD: - 4.96; 95% CI: - 7.67 to - 2.26; I2 = 0%, p = 0. 0003). There was no significant difference in objective response rate, disease control rate, and frequency of adverse events in either of the group. CONCLUSION: Our study concluded that combination therapy with atezolizumab plus bevacizumab could increase the survival duration without affecting the disease course. Moreover, while the severity of adverse events was greater in the A + B group, their frequency was comparable to the lenvatinib group.
