ANGPTL3 Targeting Monoclonal Antibodies Lead to Robust Reductions in LDL-C, Triglycerides, ApoB, and Non-HDL-C in Dyslipidemic Patients: A Meta-Analysis of 5 Randomized Controlled Trials
Abstract Body (Do not enter title and authors here): 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.
Daid, Simranpreet Singh
( Roger William Medical center
, Providence
, Rhode Island
, United States
)
Sharma, Anubhuti
( Mayo Clinic
, Scottsdale
, Arizona
, United States
)
Sharma, Arundhati
( Mayo clinic
, Sayre
, Pennsylvania
, United States
)
Pannu, Sagal
( University of Oklahoma
, Oklahoma City
, Oklahoma
, United States
)
Asnani, Heena
( Roger Williams Medical Center
, Providence
, Rhode Island
, United States
)
Bhanushali, Karan
( Roger Williams Medical Center
, Providence
, Rhode Island
, United States
)
Choudhary, Khushal
( Roger Williams Medical Center
, North Providence
, Rhode Island
, United States
)
Sharma, Saurabh
( Guthrie Robert Packer Hospital
, Sayre
, Pennsylvania
, United States
)
Author Disclosures:
Simranpreet Singh Daid:DO NOT have relevant financial relationships
| Anubhuti Sharma:DO NOT have relevant financial relationships
| Arundhati Sharma:DO NOT have relevant financial relationships
| Sagal Pannu:DO NOT have relevant financial relationships
| Heena Asnani:No Answer
| Karan Bhanushali:DO NOT have relevant financial relationships
| Khushal Choudhary:DO NOT have relevant financial relationships
| Saurabh Sharma:DO NOT have relevant financial relationships