Real World Evidence of Bempedoic Acid on Efficacy and Safety in Patients with Uncontrolled LDL-c and at High Risk of CVD
Issue: 2023 - Volume 12 [Issue 4]
Kauvery Hospital, Chennai, Tamil Nadu, India.
HCG Hospital, Ahmedabad, Gujarat, India.
Medica Superspecialty Hospital, Kolkata, West Bengal, India.
King George's Medical University, Lucknow, Uttar Pradesh, India.
Amit B. Kinare
Samadhan Heart Centre, Jabalpur, Madhya Pradesh, India.
Ashwani Kumar Sharma
Fortis Escort Hospital, Jaipur, Rajasthan, India.
M. S. Aditya
Yashoda Hospital, Secunderabad, Telangana, India.
Ram Anil Raj
Bhagwan Mahavir Jain Hospital, Bangalore, Karnataka, India.
Akhter Amin Raina
Sub District Hospital, Seer Hamdan, Anantnag, Jammu & Kashmir, India.
Jaynil Hospital, Vadodara, Gujarat, India.
Murshidabad Medical College, Behrampore, West Bengal, India.
Dipak Suresh Bathe
Lifeline Medical, Durgapur, West Bengal, India.
Zydus Lifesciences Limited, Mumbai, Maharashtra, India.
Kunal Jhaveri *
Zydus Lifesciences Limited, Mumbai, Maharashtra, India.
*Author to whom correspondence should be addressed.
Background and Objective: Cardiovascular disease (CVD) is a significant cause of morbidity and mortality worldwide, with high-risk patients requiring effective management to reduce their risk of cardiovascular events. Bempedoic acid is a novel therapeutic agent recently approved as an add-on therapy to statins in patients with uncontrolled LDL-c. Bempedoic acid inhibits cholesterol synthesis in the liver, which ultimately reduces the risk of cardiovascular events. Therefore, the present study aims to assess the efficacy and safety of bempedoic acid in patients with uncontrolled LDL-c (Previously on moderate or high-intensity statins) with a high risk of CVD in real-world settings.
Methods: This is a multicenter, retrospective, observational study on the data of high-risk-CVD patients collected from Bempedoic Acid on Efficacy and Safety in patients (BEST) Registry. The clinical data of 140 patients who were already on statin therapy and were receiving Bempedoic acid at a dose of 180 mg, along with measurements of the level of LDL-c, HbA1c, HDL, TG, TC, PPPG, FPG, AST, ALT, serum creatinine was taken into consideration. The primary outcome includes a change in LDL-c level, and secondary outcomes involve a change in the level of HbA1c, HDL, TG, TC, PPPG, FPG, AST, ALT, and serum creatinine at week 12 and 24. Adverse events were reported at both time points.
Results: A total of 140 patients were included in the present study with a mean age of 51.8 ± 9.2 years and had primary confirmed diagnosis of dyslipidemia with uncontrolled LDL-c. The mean levels of LDL-c decreased from the mean baseline value of 142.67 ± 46.49 mg/dL, to 106.78 ±33.92 mg/d; a statistically significant reduction by 23.23% (p < 0.01) at week 12. Similarly, at week 24, the mean LDL-c value reduced to 90.39 ± 38.89 mg/dL. A 33.38 % decrease was observed (p < 0.01). Other parameters such as non-HDL, FPG, PPPG, AST and serum creatinine also showed statistically significant reduction at week 12 and week 24.
Conclusion: The present study demonstrates that bempedoic acid is an effective add-on medication in lowering LDL-c levels in high-risk CVD patients with uncontrolled LDL-c.
Keywords: ACL inhibitor, Bempedoic Acid (BA), Cardiovascular Diseases (CVDs), dyslipidemia, Low-Density Lipoprotein Cholesterol (LDL-c)
How to Cite
Cardiovascular diseases (CVDs) by World Health Organization (WHO).
Available: https://www.who.int/health-topics/cardiovascular-diseases. Accessed on April 30, 2023.
Mendis S, Puska P, Norrving B, Organization WH, Federation WH, Organization WS. Global atlas on cardiovascular disease prevention and control / edited by: Shanthi Mendis ... [et al.]. World Health Organization; 2011. Published by the World Health Organization in collaboration with the World Heart Federation and the World Stroke Organization.
Pol T, Held C, Westerbergh J, Lindbäck J, Alexander JH, Alings M, et al. Dyslipidemia and Risk of Cardiovascular Events in Patients With Atrial Fibrillation Treated With Oral Anticoagulation Therapy: Insights From the ARISTOTLE (Apixaban for Reduction in Stroke and Other Thromboembolic Events in Atrial Fibrillation) Trial. J Am Heart Assoc. 2018 Feb 6;7(3):e007444.
Carroll MD, Fryar CD, Kit BK. Total and High-density Lipoprotein Cholesterol in Adults: United States, 2011-2014. NCHS Data Brief. 2015 Dec;(226):1–8.
Sadananda SN, Foo JN, Toh MT, Cermakova L, Trigueros-Motos L, Chan T, et al. Targeted next-generation sequencing to diagnose disorders of HDL cholesterol. J Lipid Res. 2015 Oct;56(10):1993–2001.
Schwartz GG, Olsson AG, Abt M, Ballantyne CM, Barter PJ, Brumm J, et al. Effects of Dalcetrapib in Patients with a Recent Acute Coronary Syndrome. N Engl J Med. 2012 Nov 29;367(22):2089–99.
Cannon CP, Braunwald E, McCabe CH, Rader DJ, Rouleau JL, Belder R, et al. Intensive versus Moderate Lipid Lowering with Statins after Acute Coronary Syndromes. N Engl J Med. 2004 Apr 8;350(15):1495–504.
Evolocumab in Patients with Cardiovascular Disease. N Engl J Med. 2017 Aug 24;377(8):785–8.
Amarenco P, Kim JS, Labreuche J, Charles H, Abtan J, Béjot Y, et al. A Comparison of Two LDL Cholesterol Targets after Ischemic Stroke. N Engl J Med. 2020 Jan 2;382(1):9–19.
Ouchi Y, Sasaki J, Arai H, Yokote K, Harada K, Katayama Y, et al. Ezetimibe Lipid-Lowering Trial on Prevention of Atherosclerotic Cardiovascular Disease in 75 or Older (EWTOPIA 75): A Randomized, Controlled Trial. Circulation. 2019 Sep 17;140(12):992–1003.
Grundy SM, Stone NJ, Bailey AL, Beam C, Birtcher KK, Blumenthal RS, et al. 2018 AHA/ACC/AACVPR/AAPA/ABC/ACPM/ADA/AGS/APhA/ASPC/NLA/PCNA Guideline on the Management of Blood Cholesterol: A Report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines. Circulation. 139(25)e1082–e1143. Available:https://www.ahajournals.org/doi/10.1161/CIR.0000000000000625
Ray KK, Ginsberg HN, Davidson MH, Pordy R, Bessac L, Minini P, et al. Reductions in Atherogenic Lipids and Major Cardiovascular Events: A Pooled Analysis of 10 ODYSSEY Trials Comparing Alirocumab With Control. Circulation. 2016 Dec 13;134(24):1931–43.
Wang Q, Liang C. Role of Lipid-Lowering Therapy in Low-Density Lipoprotein Cholesterol Goal Attainment: Focus on Patients With Acute Coronary Syndrome. J Cardiovasc Pharmacol. 2020 Dec;76(6):658–70.
Bytyçi I, Penson PE, Mikhailidis DP, Wong ND, Hernandez AV, Sahebkar A, et al. Prevalence of statin intolerance: a meta-analysis. Eur Heart J. 2022 Sep 7;43(34): 3213–23.
Ray KK, Molemans B, Schoonen WM, Giovas P, Bray S, Kiru G, et al. EU-Wi d e Cross-Section a l Obser v at i o n al Study of Lipid-Modifying Therapy Use in Se c ondary and Pr i mary Care: the DA VINCI study. Eur J Prev Cardiol. 2021 Sep 20;28(11):1279–89.
Nexletol (Bempedoic Acid) Prescribing Information.
Niman S, Rana K, Reid J, Sheikh-Ali M, Lewis T, Choksi RR, et al. A Review of the Efficacy and Tolerability of Bempedoic Acid in the Treatment of Hypercholesterolemia. Am J Cardiovasc Drugs. 2020 Dec;20(6): 535–48.
Pinkosky SL, Filippov S, Srivastava RAK, Hanselman JC, Bradshaw CD, Hurley TR, et al. AMP-activated protein kinase and ATP-citrate lyase are two distinct molecular targets for ETC-1002, a novel small molecule regulator of lipid and carbohydrate metabolism. J Lipid Res. 2013 Jan;54(1): 134–51.
Ballantyne CM, Bays H, Catapano AL, Goldberg A, Ray KK, Saseen JJ. Role of Bempedoic Acid in Clinical Practice. Cardiovasc Drugs Ther. 2021 Aug;35(4): 853–64.
Mortensen MB, Nordestgaard BG. 2019 vs. 2016 ESC/EAS statin guidelines for primary prevention of atherosclerotic cardiovascular disease. Eur Heart J. 2020 Aug 14;41(31): 3005–15.
Laufs U, Banach M, Mancini GBJ, Gaudet D, Bloedon LT, Sterling LR, et al. Efficacy and Safety of Bempedoic Acid in Patients With Hypercholesterolemia and Statin Intolerance. J Am Heart Assoc. 2019 Apr 2;8(7):e011662.
Agarwala A, Quispe R, Goldberg AC, Michos ED. Bempedoic Acid for Heterozygous Familial Hypercholes-terolemia: From Bench to Bedside. Drug Des Devel Ther. 2021;15:1955–63.
Goldberg AC, Leiter LA, Stroes ESG, Baum SJ, Hanselman JC, Bloedon LT, et al. Effect of Bempedoic Acid vs Placebo Added to Maximally Tolerated Statins on Low-Density Lipoprotein Cholesterol in Patients at High Risk for Cardiovascular Disease: The CLEAR Wisdom Randomized Clinical Trial. JAMA. 2019 Nov 12;322(18):1780–8.
Ballantyne CM, Banach M, Bays HE, Catapano AL, Laufs U, Stroes ESG, et al. Long-Term Safety and Efficacy of Bempedoic Acid in Patients With Atherosclerotic Cardiovascular Disease and/or Heterozygous Familial Hypercholesterolemia (from the CLEAR Harmony Open-Label Extension Study). Am J Cardiol. 2022 Jul 1;174:1–11.
Ballantyne CM, Banach M, Mancini GBJ, Lepor NE, Hanselman JC, Zhao X, et al. Efficacy and safety of bempedoic acid added to ezetimibe in statin-intolerant patients with hypercholesterolemia: A randomized, placebo-controlled study. Atherosclerosis. 2018 Oct;277:195–203.
Nissen SE, Lincoff AM, Brennan D, Ray KK, Mason D, Kastelein JJP, et al. Bempedoic Acid and Cardiovascular Outcomes in Statin-Intolerant Patients. N Engl J Med. 2023 Apr 13;388(15):1353–64.
Ballantyne CM, Laufs U, Ray KK, Leiter LA, Bays HE, Goldberg AC, et al. Bempedoic acid plus ezetimibe fixed-dose combination in patients with hypercholesterolemia and high CVD risk treated with maximally tolerated statin therapy. Eur J Prev Cardiol. 2020 Apr;27(6):593–603.
Leiter LA, Banach M, Catapano AL, Duell PB, Gotto AM, Laufs U, et al. Bempedoic acid in patients with type 2 diabetes mellitus, prediabetes, and normoglycaemia: A post hoc analysis of efficacy and glycaemic control using pooled data from phase 3 clinical trials. Diabetes Obes Metab. 2022 May;24(5): 868–80.