The question over who should use cholesterol reducing medication is a hotly debated topic among physicians. Researchers at Inova just published an analysis in the current edition of the Journal of the American Medical Association (JAMA) providing foundational findings that will help change the understanding of when and how to use intensive lipid-lowering therapy to reap the highest clinical benefit.
“Establishing a basis for personalization of lipid lowering therapy is a fundamental change,” according to Eliano Navarese, MD, PhD and Director of International Research for Inova Thrombosis Research and Drug Development Center, who serves as first author of the JAMA article. “This analysis is the first time to show there are thresholds of benefit.”
Using current guidelines, it is estimated anywhere from 17-27 million Americans would benefit from the use of low-density lipoprotein cholesterol (LDL-C) medications. The newest version of these medications, known as PCSK9 inhibitors, provides the most intensive, and most expensive, therapy.
“Patients are being treated with more potent and expensive drugs yet the return of benefit has not been fully measured,” according to Paul Gurbel, MD who is Director of the Inova Thrombosis Research and Drug Development Center and a contributor on the analysis design and JAMA article. “This analysis changes the understanding of lipid-lowering therapies and provides a more clear quantification particularly for intensive LDL-C therapies.”
In findings released at last month’s American College of Cardiology Scientific Session it was verified that the newest most intensive therapies provided cholesterol reduction but did not demonstrate a consistent benefit related to mortality. This JAMA article begins to explain that variability and provides evidence to guide the most efficient use of these expensive medications. The central finding being whether a mortality benefit is realized depends on the baseline cholesterol.
“With the cost of these drugs at $14,000 for a single patient over the course of a year, there is a need for an intelligent re-distribution of this therapy,” Navarese indicated.
Through a meta-analysis of 270,000 patients across 34 clinical trials, the findings suggest the greatest benefit from the most intensive LDL-C lowering drugs occur for patients with higher baseline LDL-C levels. Specifically, only for patients whose baseline LDL-C levels are 100 mg/dL or greater. It is only in those patients that a reduction in mortality is demonstrated. Further the analysis showed progressively greater risk reductions with higher baseline LDL-C levels.
Both physicians anticipate the cost-effectiveness implications of the article’s findings to influence guidelines for use of intensive lipid-lowering therapy and to impact when and how community-based cardiologists prescribe these medications.
“Our findings analyzed a point not previously addressed. This work will certainly influence future study design,” according to Gurbel. “These findings reinforce that the more intensive therapies are very effective in the right patient. The focus of past studies was on lowering cholesterol. Now, it has been shown we need to account for baseline LDL in the analysis in demonstrating mortality benefit.”
Ten researchers contributed to the JAMA article and analysis. Four are from Inova Heart and Vascular Institute. The second author of the study is Jennifer Robinson, MD, MPH from the Prevention Intervention Center, Departments of Epidemiology and Medicine, at University of Iowa. Other contributors represent Systematic Investigation and Research on Interventions and Outcomes (SIRIO) MEDICINE Cardiovascular Research Network; Nicolaus Copernicus University, Bydgoszcz, Poland; Memorial University Hospital, Bydgoszcz, Poland; Catholic University Medical School, Rome, Italy; and University of Alberta, Edmonton, Alberta, Canada.