-- Findings Presented on VASCEPA/VAZKEPA Utility in REDUCE-IT Patient Subgroups by
-- Lp(a) Results Published Simultaneously in the
“These new findings provide additional important evidence about the clinical utility of VASCEPA/VAZKEPA and further demonstrate its value in reducing cardiovascular events in at-risk patients in key subgroups,” said Nabil Abadir, MB. CH.B., Chief Medical Officer and Head of Global Medical Affairs, Amarin. “At Amarin, we’re focused on the continuous generation of science to further advance the medical community’s understanding of the role and value of VASCEPA/VAZKEPA in reducing cardiovascular events in at-risk patients globally, and we are proud to add to the body of research that further demonstrates our commitment to value creation.”
The subgroup analyses and their key findings are outlined below:
Icosapent Ethyl Reduces MACE in Patients with
High Lp(a) concentrations are associated with increased CV event risk, even when LDL-C levels are well-managed. There are no treatments currently approved to reduce residual CV risk on top of contemporary medical therapy in patients with high Lp(a) levels.
In this post hoc analysis of REDUCE-IT, the relationship between continuous baseline Lp(a) concentration and risk of MACE was analyzed in models that also accounted for baseline LDL-C, baseline triglycerides (TG), and double-blind treatment.
REDUCE-IT participants were randomized to receive either 2g twice daily of icosapent ethyl (IPE) or matching placebo and followed for a median 4.9 years. In this subanalysis, there were 7,026 REDUCE-IT patients with baseline Lp(a) data and a median Lp(a) value of 11.6 (Q1-Q3: 5.0-37.4) mg/dL. Results showed that baseline Lp(a) had a strong and significant relationship with MACE irrespective of baseline LDL-C, baseline TGs, and treatment assignment, and that the benefit of IPE was consistent across Lp(a) concentrations. Importantly, the treatment benefit of IPE was evident across subgroups with both high (≥50 mg/dL) and low (<50 mg/dL) Lp(a) concentrations. Specifically, for first MACE, the relative IPE treatment effects for Lp(a) ≥50 mg/dL and <50 mg/dL were HR 0.79 (95% CI 0.64-0.97; P=0.0248) and HR 0.75 (95% CI 0.66-0.84; P<0.0001), respectively. Absolute risk reductions at 5 years with IPE were 6.5% and 5.7% for Lp(a) ≥50 mg/dL and <50 mg/dL, respectively.1
Limitations include that participants in REDUCE-IT were not selected on the basis of their baseline Lp(a) concentration and that not all REDUCE-IT patients had available baseline Lp(a) data.
“In this analysis, IPE showed a clear clinical benefit for patients with both high and low Lp(a) levels. IPE provided a relative risk reduction of 21% among patients with an Lp(a) level of ≥50 mg/dL and 25% for those patients with an Lp(a) level of <50 mg/dL,” said Dr.
The analysis and its findings were published simultaneously online in JACC.
Efficacy of Icosapent Ethyl for Reducing Cardiovascular Outcomes by Baseline Low Density Lipoprotein Cholesterol Level
Elevated low-density lipoprotein cholesterol (LDL-C) is a well-established major CV risk factor supported by clinical evidence showing decreased atherosclerotic disease events when LDL-C is therapeutically lowered. Recent international guidelines recommend lowering LDL-C to <55 mg/dL in those patients who are at very high risk for a future CV event.
In this post hoc analysis, investigators explored REDUCE-IT data to determine if IPE reduces CV outcomes among high-risk CV patients irrespective of baseline LDL-C. Patients were stratified by LDL-C <55 vs ≥55 mg/dL. The primary outcome was a composite of CV death, nonfatal myocardial infarction, nonfatal stroke, coronary revascularization, or unstable angina.
Among statin-treated REDUCE-IT patients with baseline LDL-C data, 1,058 (12.9%) had LDL-C <55 mg/dL and 7,117 (87.1 %) had LDL-C ≥55 mg/dL. The primary outcome rate among patients with LDL-C <55 mg/dL was 16.2% in the IPE group and 22.8% in the placebo group, HR 0.66 (95% CI 0.50-0.87; P=0.003). Findings were consistent in the LDL-C ≥55 mg/dL subgroup, with rates of 17.4% in the IPE group and 21.9% in the placebo group, HR 0.76 (95% CI 0.69-0.85; P<0.0001). No significant interaction by baseline LDL-C was observed.
Limitations are that randomization was not stratified by baseline LDL-C, however, baseline characteristics were similar among the two baseline LDL-C subgroups. REDUCE-IT patients were on statin therapy, but with low rates or unavailability of other lipid therapies such as ezetimibe, proprotein convertase subtilisin-kexin type 9 (PCSK9) inhibitors, or small interfering RNA (siRNA) therapies.
“As we know, LDL-C is a well-established major CV risk factor. These data are important and show that among adults with increased CV risk and elevated TGs, icosapent ethyl clearly reduced the rate of CV outcomes irrespective of baseline LDL-C, including in those with very well controlled LDL-C <55 mg/dL,” said
All analyses highlighted above were funded by Amarin. Dr.
About Amarin
Amarin is an innovative pharmaceutical company leading a new paradigm in cardiovascular disease management. We are committed to increasing the scientific understanding of the cardiovascular risk that persists beyond traditional therapies and advancing the treatment of that risk for patients worldwide. Amarin has offices in
About REDUCE-IT®
REDUCE-IT was a global cardiovascular outcomes study designed to evaluate the effect of VASCEPA in adult patients with LDL-C controlled to between 41-100 mg/dL (median baseline 75 mg/dL) by statin therapy and various cardiovascular risk factors including persistent elevated triglycerides between 135-499 mg/dL (median baseline 216 mg/dL) and either established cardiovascular disease (secondary prevention cohort) or diabetes mellitus and at least one other cardiovascular risk factor (primary prevention cohort).
REDUCE-IT, conducted over seven years and completed in 2018, followed 8,179 patients at over 400 clinical sites in 11 countries with the largest number of sites located within
About Cardiovascular Risk
Cardiovascular disease is the number one cause of death in the world. In
Controlling bad cholesterol, also known as LDL-C, is one way to reduce a patient’s risk for cardiovascular events, such as heart attack, stroke or death. However, even with the achievement of target LDL-C levels, millions of patients still have significant and persistent risk of cardiovascular events, especially those patients with elevated triglycerides. Statin therapy has been shown to control LDL-C, thereby reducing the risk of cardiovascular events by 25-35%.6 Significant cardiovascular risk remains after statin therapy. People with elevated triglycerides have 35% more cardiovascular events compared to people with normal (in range) triglycerides taking statins.7,8,9
About VASCEPA®/VAZKEPA® (icosapent ethyl) Capsules
VASCEPA (icosapent ethyl) capsules are the first prescription treatment approved by the
Indications and Limitation of Use
VASCEPA is indicated:
- As an adjunct to maximally tolerated statin therapy to reduce the risk of myocardial infarction, stroke, coronary revascularization and unstable angina requiring hospitalization in adult patients with elevated triglyceride (TG) levels (≥ 150 mg/dL) and
- established cardiovascular disease or
- diabetes mellitus and two or more additional risk factors for cardiovascular disease.
- As an adjunct to diet to reduce TG levels in adult patients with severe (≥ 500 mg/dL) hypertriglyceridemia.
The effect of VASCEPA on the risk for pancreatitis in patients with severe hypertriglyceridemia has not been determined.
Important Safety Information
- VASCEPA is contraindicated in patients with known hypersensitivity (e.g., anaphylactic reaction) to VASCEPA or any of its components.
- VASCEPA was associated with an increased risk (3% vs 2%) of atrial fibrillation or atrial flutter requiring hospitalization in a double-blind, placebo-controlled trial. The incidence of atrial fibrillation was greater in patients with a previous history of atrial fibrillation or atrial flutter.
- It is not known whether patients with allergies to fish and/or shellfish are at an increased risk of an allergic reaction to VASCEPA. Patients with such allergies should discontinue VASCEPA if any reactions occur.
- VASCEPA was associated with an increased risk (12% vs 10%) of bleeding in a double-blind, placebo-controlled trial. The incidence of bleeding was greater in patients receiving concomitant antithrombotic medications, such as aspirin, clopidogrel or warfarin.
- Common adverse reactions in the cardiovascular outcomes trial (incidence ≥3% and ≥1% more frequent than placebo): musculoskeletal pain (4% vs 3%), peripheral edema (7% vs 5%), constipation (5% vs 4%), gout (4% vs 3%), and atrial fibrillation (5% vs 4%).
- Common adverse reactions in the hypertriglyceridemia trials (incidence >1% more frequent than placebo): arthralgia (2% vs 1%) and oropharyngeal pain (1% vs 0.3%).
- Adverse events may be reported by calling 1-855-VASCEPA or the FDA at 1-800-FDA-1088.
- Patients receiving VASCEPA and concomitant anticoagulants and/or anti-platelet agents should be monitored for bleeding.
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For further information about the Summary of Product Characteristics (SmPC) for VAZKEPA® in
Globally, prescribing information varies; refer to the individual country product label for complete information.
Forward-Looking Statements
This press release contains forward-looking statements which are made pursuant to the safe harbor provisions of the Private Securities Litigation Reform Act of 1995, including beliefs about the potential for VASCEPA (marketed as VAZKEPA in
Amarin Contact Information
Investor & Media Inquiries:
PR@amarincorp.com
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1 Szarek M, Bhatt DL, Miller M, et al. Lipoprotein(a) blood levels and cardiovascular risk reduction with icosapent ethyl. J Am Coll Cardiol. 2024; epub ahead of print.
2 Bhatt DL, Steg PG, Brinton E, et al., on behalf of the REDUCE-IT Investigators. Rationale and Design of REDUCE‐IT: Reduction of Cardiovascular Events with Icosapent Ethyl–Intervention Trial. Clin Cardiol. 2017;40:138-148.
3 Bhatt DL, Steg PG, Miller M, et al., on behalf of the REDUCE-IT Investigators. Cardiovascular Risk Reduction with Icosapent Ethyl for Hypertriglyceridemia. N Engl J Med. 2019;380:11-22.
4 Bhatt DL, Steg PG, Miller M, et al., on behalf of the REDUCE-IT Investigators. Effects of Icosapent Ethyl on Total Ischemic Events: From REDUCE-IT. J Am Coll Cardiol. 2019;73:2791-2802.
5
6 Ganda OP, Bhatt DL, Mason RP, et al. Unmet need for adjunctive dyslipidemia therapy in hypertriglyceridemia management. J Am Coll Cardiol. 2018;72(3):330-343.
7 Budoff M. Triglycerides and triglyceride-rich lipoproteins in the causal pathway of cardiovascular disease. Am J Cardiol. 2016;118:138-145.
8 Toth PP, Granowitz C, Hull M, et al. High triglycerides are associated with increased cardiovascular events, medical costs, and resource use: A real-world administrative claims analysis of statin-treated patients with high residual cardiovascular risk. J Am Heart Assoc. 2018;7(15):e008740.
9 Nordestgaard BG. Triglyceride-rich lipoproteins and atherosclerotic cardiovascular disease - New insights from epidemiology, genetics, and biology. Circ Res. 2016;118:547-563
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