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How Low to Go With Lipid-Lowering Therapies in a Cost-effective and Prudent Manner
Rhanderson Cardoso1, Roger S Blumenthal1, Stephen Kopecky2
1Ciccarone Center for the Prevention of Cardiovascular Disease, Division of Cardiology, Department of Medicine, Johns Hopkins Medical Institutions, Baltimore, MD.
Insights
New evidence supports aggressive low-density lipoprotein cholesterol (LDL-C) reduction for cardiovascular risk. This review examines the efficacy, safety, and cost-effectiveness of intensive lipid-lowering therapies and recent guideline recommendations.
Area of Science:
- Cardiovascular Medicine
- Lipidology
- Pharmacotherapy
Background:
- The 2013 ACC/AHA cholesterol guideline focused on statins, finding insufficient evidence for specific LDL-C targets.
- Significant advancements in lipid research have emerged since 2013, particularly regarding LDL-C's role in atherogenesis.
Purpose of the Study:
- To review the relationship between lowering low-density lipoprotein cholesterol (LDL-C) and reducing cardiovascular risk.
- To discuss the efficacy, safety, and cost-effectiveness of intensive lipid-lowering therapies.
- To analyze recent guideline recommendations in light of new clinical trial data.
Main Methods:
- Literature review of pivotal clinical trials and recent guideline publications.
- Analysis of data on LDL-C lowering agents including statins, ezetimibe, evolocumab, and alirocumab.
- Evaluation of cardiovascular outcomes, safety profiles, and cost-effectiveness.
Main Results:
- Clinical trials demonstrate the critical role of LDL-C in atherogenesis and improved outcomes with aggressive LDL-C reduction.
- Novel therapies (ezetimibe, PCSK9 inhibitors) achieve substantial reductions in major adverse cardiovascular events.
- Emerging data necessitate a discussion on the appropriateness and optimal levels for LDL-C targets in primary and secondary prevention.
Conclusions:
- Aggressive LDL-C reduction is strongly supported by recent evidence for cardiovascular risk management.
- The safety, cost-effectiveness, and optimal target levels for very low LDL-C require further consideration.
- Updated guidelines are needed to incorporate the latest findings on lipid-lowering therapies.
Abstract:
The 2013 American College of Cardiology/American Heart Association guideline on the treatment of blood cholesterol was a landmark document guiding health care professionals around the globe on how to administer lipid-lowering therapies. Those guidelines were primarily focused on statin therapy benefit groups. The writing committee found insufficient evidence for specific low-density lipoprotein cholesterol (LDL-C) treatment targets. There have been many important updates in the lipid literature since the publication of that document. Most importantly, clinical trials have provided definitive evidence for the pivotal role of LDL-C in atherogenesis and the improvement in clinical outcomes by means of aggressive LDL-C reduction. Ezetimibe, evolocumab, and alirocumab treatment resulted in substantial reductions in major adverse cardiovascular outcomes. These data encourage a discussion on whether LDL-C targets are warranted in primary and/or secondary prevention, and if so, how low should those targets be. In order to answer such questions, the costs and safety of such therapies, as well as the safety of very low levels of LDL-C need to be addressed. This review discusses the relationship between LDL-C lowering and cardiovascular risk reduction, the efficacy, safety, and cost-effectiveness of high-intensity lipid-lowering therapies, and the recommendations from the most recent lipid guidelines.
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