Choudhary, Khushal

Introduction: Hypercholesterolemia drives atherosclerotic cardiovascular disease. Bempedoic acid (BA) lowers low-density-lipoprotein cholesterol (LDL-C) by inhibiting ATP-citrate-lyase, providing a non-statin option for patients who need additional lipid control. Hypothesis: We expected BA to improve atherogenic lipids and major adverse cardiovascular events (MACE) without raising cardiovascular (CV) mortality and with an acceptable safety profile. Aims: To measure the pooled effect of BA on (1) LDL-C, (2) non-HDL-C, (3) high-sensitivity C-reactive protein (hsCRP) and to compare clinical outcomes for (4) MACE, (5) CV mortality, and (6) hyperuricemia versus placebo. Methods: A systematic search of PubMed, Embase, MEDLINE, Google Scholar and ClinicalTrials.gov through 1 April 2025 identified randomized controlled trials (RCTs) of BA versus placebo in adults with hypercholesterolemia. Data were extracted into a spreadsheet, and analyses were performed with RevMan 5.4. Results: 13 RCT's with 22345 patients met the inclusion criteria. BA produced robust lipid and inflammatory improvements. LDL-C fell by 24.3 % (95 % CI −27.8 to −20.9), non-HDL-C by 19.8 % (95 % CI −25.0 to −14.6), and hsCRP by 26.7 % (95 % CI −39.6 to −13.7). These changes translated into a 19 % relative reduction in MACE (RR 0.81, 95 % CI 0.68–0.96), while CV mortality was unchanged (RR 0.87, 95 % CI 0.53–1.43). As anticipated, hyperuricemia risk almost doubled with BA (RR 1.93, 95 % CI 1.75–2.14). Conclusion: BA consistently lowers LDL-C, non-HDL-C and systemic inflammation and reduces MACE without affecting CV mortality. The main safety concern is higher hyperuricemia, which appears manageable with monitoring. These findings support BA as an effective add-on therapy for patients who are statin-intolerant or need further lipid reduction, while highlighting the need for longer trials to assess mortality benefits and long-term safety.

Introduction: Dyslipidemia remains a major driver of cardiovascular disease. Monoclonal antibodies (mAb) that block angiopoietin-like protein 3 (ANGPTL3) lower atherogenic lipids by a mechanism distinct from statins. Earlier evidence centred on the Evinacumab. A new trial now evaluate the investigational antibody SHR-1918. Hypothesis: We hypothesized that treatment with ANGPTL3 mAbs whether evinacumab or SHR-1918 would significantly improve lipid parameters compared to placebo without increasing adverse events. Aims: To Quantify the pooled effect of ANGPTL3 mAbs on low-density lipoprotein cholesterol (LDL-C), Triglycerides, apolipoprotein B (ApoB) and non-high-density lipoprotein cholesterol (non-HDL-C) and Compare efficacy and safety between Evinacumab and SHR-1918 subgroups. Methods: A systematic search of Pubmed, Google Scholar MEDLINE, Embase, and ClinicalTrials.gov untill 1 April 2025 was done and relevant randomised controlled trials (RCT's) comparing ANGPTL3 mAbs with placebo in dyslipidaemic patients were included. Data was extracted on spreadsheet and Data analysis was done in RevMan 5.4. Results: 5 RCT's comprising of 603 patients met inclusion criteria. The pooled analysis showed marked reductions in atherogenic lipids with ANGPTL3 monoclonal antibodies versus placebo, including low-density lipoprotein cholesterol (SMD = –2.73, 95 % CI –4.16 to –1.31, P < 0.001), triglycerides (SMD = –3.54, 95 % CI –4.71 to –2.37, P < 0.001), apolipoprotein B (SMD = –1.98, 95 % CI –2.97 to –1.00, P < 0.001) and non-HDL-C (SMD = –2.89, 95 % CI –4.00 to –1.78, P < 0.001). Sub-group analyses demonstrated directionally consistent lipid lowering for both evinacumab and the newer agent SHR-1918. Adverse-event due to treatment evaluation revealed no significant increase in Adverse events due to treatment (RR = 1.05, 95 % CI 0.87 to 1.27, P = 0.63) or serious events (RR = 1.37, 95 % CI 0.54 to 3.44, P = 0.49), indicating good overall tolerability. Conclusion: monoclonal antibodies targeting ANGPTL3 encompassing both evinacumab and the newer agent SHR-1918 consistently reduced LDL-C, triglycerides, and related lipid markers with a favourable tolerability profile. Further large, long-term studies are needed to fully establish their safety, clinical effectiveness, and potential to improve cardiovascular outcomes.