Addition of Bempedoic Acid to Statin–Ezetimibe versus Statin Titration in Patients with High Cardiovascular Risk: A Single-Centre Prospective Study
Open accessAbstract
Reducing levels of low-density lipoprotein cholesterol (LDL-C) below recommended thresholds is a core component of cardiovascular prevention strategies. We hypothesized that the addition of bempedoic acid to patients already on statin–ezetimibe therapy was more effective than titrating the statin dose in reducing LDL-C. The study enrolled 120 patients at high cardiovascular risk and with LDL-C above 70 mg/dL. They were randomly divided into two groups: the bempedoic acid (BA) group, taking bempedoic acid in addition to statin plus ezitimibe, and the statin titration (ST) group, including patients who doubled the dose of statin. At 12 weeks, the BA group presented a more significant decrease in LDL-C compared to the ST group (−22.9% vs. 7.5% p 0.002). The total cholesterol decreased significantly in the BA group compared to ST (−14.8% vs.−4.7%; p 0.013) No significant between-group changes in HDL and triglycerides occurred. At 12 weeks, the number of patients who reached LDL-C lower than 70 mg/dL was 38 (63%) in the BA group versus 22 (37%) in the ST group (between groups, p 0.034). In the BA group, the LDL-lowering effect of bempedoic acid was similar between patients taking atorvastatin and rosuvastatin. No side effects occurred during the follow up period. In conclusion, the addition of bempedoic acid to statin–ezetimibe combined treatment was more effective than doubling the dose of statin in reducing LDL-C levels and increased the number of patients reaching the LDL-C goal.
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One open, pragmatic randomized trial with two parallel arms assessed bempedoic acid versus statin titration.
“Most real-world studies evaluated outcomes in relation to patients’ baseline values following initiation of bempedoic acid (with or without ezetimibe and other LLTs); with one open, pragmatic randomized trial with two parallel arms that assessed bempedoic acid versus statin titration [44].”
From Systematic literature review on the real-world effectiveness and safety of bempedoic acid (2026) · cites this paper as [44]
Section 2.2 (Study Design; page unavailable) describes an open randomized trial with two parallel arms comparing bempedoic acid with statin titration. Our copy does not describe the trial as pragmatic, so that qualifier is not verified. (LLM, conf=0.86)
Experimental — accuracy not yet measuredIn the same primary prevention population, 37% of patients randomized to statin titration alone achieved an LDL-C target of <70 mg/dL at 3 months (baseline LDL-C = 87.5 mg/dL).
“When used as primary prevention in patients with hypercholesterolemia receiving high-intensity statins plus ezetimibe, 63% of those randomized to bempedoic acid achieved an LDL-C target of <70 mg/dL at 3 months (baseline LDL-C = 89.9 mg/dL), compared with 37% of patients randomized to statin titration alone (baseline LDL-C = 87.5 mg/dL).”
From Systematic literature review on the real-world effectiveness and safety of bempedoic acid (2026) · cites this paper as [44]
The Results report that 22 patients (37%) in the statin-titration group reached LDL-C below 70 mg/dL at 12 weeks, equivalent to approximately three months. The Methods identify this as a randomized primary-prevention population already receiving a high-intensity statin plus ezetimibe. The available passages give an overall baseline LDL-C of 88.7 mg/dL but do not verify the claimed 87.5 mg/dL baseline for the statin-titration group. Page numbers were not available in our copy. (LLM, conf=0.86)
Experimental — accuracy not yet measuredIn primary prevention patients with hypercholesterolemia receiving high-intensity statins plus ezetimibe, 63% of those randomized to bempedoic acid achieved an LDL-C target of <70 mg/dL at 3 months (baseline LDL-C = 89.9 mg/dL).
“When used as primary prevention in patients with hypercholesterolemia receiving high-intensity statins plus ezetimibe, 63% of those randomized to bempedoic acid achieved an LDL-C target of <70 mg/dL at 3 months (baseline LDL-C = 89.9 mg/dL), compared with 37% of patients randomized to statin titration alone (baseline LDL-C = 87.5 mg/dL).”
From Systematic literature review on the real-world effectiveness and safety of bempedoic acid (2026) · cites this paper as [44]
The Population section describes primary-prevention patients with hypercholesterolemia taking a high-intensity statin plus ezetimibe. The Results report that 38 of 60 patients (63%) assigned bempedoic acid reached LDL-C below 70 mg/dL at 12 weeks. Our copy gives a baseline LDL-C of 88.7 mg/dL for the entire cohort, but does not establish the claimed 89.9 mg/dL baseline for the bempedoic-acid group. (LLM, conf=0.84)
Experimental — accuracy not yet measuredIn a pragmatic clinical trial in primary prevention patients with hypercholesterolemia on high-intensity statins and ezetimibe for at least 3 months, bempedoic acid achieved a 22.9% LDL-C reduction at 3 months compared with 8% with statin titration alone (p=0.002).
“At 3 months, bempedoic acid achieved a 22.9% LDL-C reduction (baseline LDL-C = 90 mg/dL), compared with an 8% reduction with statin titration alone (baseline LDL-C = 86 mg/dL; between group comparison: p = 0.002) [44].”
From Systematic literature review on the real-world effectiveness and safety of bempedoic acid (2026) · cites this paper as [44]
Split into 2 atoms — 0 confirmed, 2 partially supported, 0 disputed, 0 misattributed, 0 unverifiable. Expand the claim to see per-atom verdicts.
Experimental — accuracy not yet measuredReal-world LDL-C reductions with bempedoic acid in primary prevention populations ranged from 23% to 39%.
“These reductions were reported across both primary (23% to 39%) [24,29,44] and secondary prevention populations (15% to 39%) [25,32,38,39].”
From Systematic literature review on the real-world effectiveness and safety of bempedoic acid (2026) · cites this paper as [44]
The Abstract reports a 22.9% LDL-C reduction with bempedoic acid, consistent with the cited range’s rounded 23% lower end. Materials and Methods (§2.1, Population) excludes patients with prior cardiovascular or cerebrovascular disease, supporting the primary-prevention designation. This paper does not report a 39% LDL-C reduction; its Discussion uses 39% for a cardiovascular mortality risk reduction reported by another study. (LLM, conf=0.88)
Experimental — accuracy not yet measured
LDL-C reductions with bempedoic acid added to statins ranged from 15% to 39%.
“Consistent effects were also seen when bempedoic acid was added to statins (15% to 39%) [25,30,32,38,39,44], and when used in statin intolerant patients (22% to 38%) [24,29,34,35,37,40,41], despite the latter group having higher baseline LDL-C.”
From Systematic literature review on the real-world effectiveness and safety of bempedoic acid (2026) · cites this paper as [44]
The Discussion (page not supplied) reports a 22.9% LDL-C reduction in this study when bempedoic acid was added to statin–ezetimibe therapy, and describes 15–18% reductions in earlier studies adding it to statins. It does not support a 39% LDL-C reduction: the Discussion’s 39% figure concerns cardiovascular mortality, not LDL-C. (LLM, conf=0.87)
Experimental — accuracy not yet measuredThe difference between bempedoic acid and statin titration alone in achieving LDL-C <70 mg/dL was statistically significant (p = 0.034).
“The difference between groups was statistically significant (p = 0.034) [44].”
From Systematic literature review on the real-world effectiveness and safety of bempedoic acid (2026) · cites this paper as [44]
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- Authors
- Marazzi, G., Caminiti, G., Perrone, M., Campolongo, G., Cacciotti, L., Giamundo, D., Iellamo, F., Severino, P., Volterrani, M., & Rosano, G.
- Affiliations
- IRCCS San Raffaele Roma (IT)
- San Raffaele University of Rome (IT)
- University of Rome Tor Vergata (IT)
- Servizio Sanitario Nazionale (IT)
- Cardiology Unit, Madre Giuseppina Vannini Hospital, 00177 Rome, Italy
- Sapienza University of Rome (IT)
- St George's, University of London (GB)
- Corresponding author
- Caminiti, Giuseppe
- Perrone, Marco
- ORCID
- Venue
- Journal of Cardiovascular Development and Disease
- Publisher
- MDPI AG
- Published
- 2024-09-14
- Volume
- 11
- Issue
- 9
- Pages
- 286
- ISSN
- 2308-3425 (ISSN-L)
- PMC
- PMC11432672
- OpenAlex
- W4402818916
- Cited by
- 10
- References
- 29
- Citations by year
- 2026: 7 · 2025: 3
- FWCI
- 4.21
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- Journal of Cardiovascular Development and Disease (publishedVersion, cc-by)
- Preprints.org (acceptedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- St George's Online Research Archive (St George's University of London) (acceptedVersion)
- Cineca Institutional Research Information System (Tor Vergata University) (submittedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- IRIS Research product catalog (Sapienza University of Rome) (submittedVersion, cc-by)
- Funders
- Italian Ministry of Health [Ricerca corrente]
- Topics
- Health Sciences › Medicine › Surgery › Lipoproteins and Cardiovascular Health
- Health Sciences › Medicine › Surgery › Cholesterol and Lipid Metabolism
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Cancer, Lipids, and Metabolism
- Keywords
- bempedoic acid, ezetimibe, LDL cholesterol lowering, high cardiovascular risk, atorvastatin, rosuvastatin, LDL-C goal attainment, hypercholesterolemia, lipid-lowering therapy
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