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Lowering LDL beyond current targets may further reduce CVD
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Lowering LDL as much as possible via statin and nonstatin therapies resulted in reduced risk for CV events without serious adverse effects, according to an analysis published in JAMA Cardiology.
“These data suggest further lowering of LDL-C beyond the lowest current targets would further reduce cardiovascular risk,” Marc S. Sabatine, MD, MPH, chairman of the TIMI Study Group and the Lewis Dexter, MD, Distinguished Chair in Cardiovascular Medicine at Brigham and Women’s Hospital and professor of medicine at Harvard Medical School, and colleagues wrote.
Sabatine and colleagues analyzed the Cholesterol Treatment Trialists Collaboration data for statin therapies and three randomized trials of nonstatin therapies to determine the magnitude of clinical benefit of further lowering LDL in patients who already had low LDL.
The primary outcome was the RR for major vascular events, defined as CHD death, MI, ischemic stroke or coronary revascularization, for each reduction in LDL of 1 mmol/L (38.7 mg/dL).
For statin therapies, the median LDL in the control arm was 1.7 mmol/L (65.7 mg/dL) and the RR for major vascular events per 1 mmol/L reduction in LDL was 0.78 (95% CI, 0.65-0.94), Sabatine and colleagues wrote.
For the nonstatin therapies evaluated in the IMPROVE-IT, FOURIER and REVEAL trials (n = 50,627), the median LDL in the control arm was 1.6 mmol/L (63 mg/dL) to 1.8 mmol/L (70 mg/dL) and the RR for major vascular events per 1 mmol/L reduction in LDL was 0.79 (95% CI, 0.71-0.87), they wrote.
LDL lowering in these populations was not associated with risk for serious adverse events including myalgias, myositis, elevated aminotransferases, new-onset diabetes, hemorrhagic stroke or cancer, according to the researchers.
“As implied by the findings, there is a strong case for updating the current American Heart Association/American College of Cardiology 2013 guidelines. A revision is currently underway, and new guidelines are anticipated in the near future,” Antonio M. Gotto Jr., MD, DPhil, from Weill Cornell Medicine, wrote in a related editorial. “Whether one calls it a target or a threshold, practicing physicians need some guidance as they venture into achieved levels of LDL-C levels that are as foreign as travel to outer space. I have confidence that the new guidelines will be closer to a global positioning system map rather than just a compass and the stars. Treating physicians should apply informed clinical judgment to each individual patient.” – by Erik Swain
Disclosure: Gotto reports he consults for Kowa, serves on the board of directors for Esperion and serves on the data safety monitoring board for Ionis. Sabatine reports
he receives honoraria for consulting from Alnylam, Amgen, AstraZeneca, Bristol-Myers Squibb. CVS Caremark, Dyrnamix, Esperion, Intarcia, Ionis, Janssen Research and Development, Medicines Company, MedImmune, Merck, MyoKardia and Novartis; and that he is deputy editor of JAMA Cardiology but had no role in any decisions related to the review and publication of the manuscript. Please see the study for a list of the other authors’ relevant financial disclosures.
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