Unlearning the worry of getting too low on LDL

Key points:

• LDL can be safely reduced to very low levels, even when the initial LDL is very high.
• Solutions are needed to fill the gap in the implementation of LDL-lowering therapies.

PHILADELPHIA — LDL is a central component of CV risk reduction, and data now show clear benefits of sustained and substantial reduction, even in the context of very high baseline LDL, according to one panelist.

LDL should guide clinical decision-making when initiating statin and non-statin therapies, and physicians should not be concerned about adverse events related to going “too low,” Healio | Member of the editorial board of Cardiology Today Seth S. Martin, MD, MHS, FAHA, cardiologist at Johns Hopkins Hospital and professor of medicine at Johns Hopkins University School of Medicine, he said during a presentation at the Heart in Diabetes CME conference. Newer therapies such as PCSK9 inhibitors can now lower LDL to levels never seen before; however, debate over the risk of cerebral hemorrhage continued.

“There are lingering questions about things like diabetes, hemorrhagic stroke and cataracts,” Martin said. “But the first question should be, is it [the LDL] really low?”

LDL can be overestimated

Seth S. Martin

The Friedewald equation, a commonly used formula that estimates LDL using total cholesterol, triglycerides and HDL, can underestimate LDL, sometimes by a large amount, Martin said. Published data by Martin and colleagues demonstrated that, especially if triglyceride levels are greater than 150 mg/dL, the Friedewald estimate commonly classifies LDL as less than 70 mg/dL despite measured levels directly above 70 mg/dL. Martin said additional evaluation is needed for high-risk patients.

A new method for estimating LDL using an adjustable factor for the ratio of triglycerides to VLDL, the Martins/Hopkins equation, may provide a more accurate guideline risk classification than the Friedewald equation, Martin said.

“If you use a more accurate LDL equation, you now have more opportunities for prevention; more opportunities to go down,” Martin said.

Safe very low LDL level

Data from PCSK9 inhibitor trials also support low LDL. The FOURIER study, which enrolled patients with established stable atherosclerotic CVD, found that the PCSK9 inhibitor drug evolocumab (Repatha, Amgen), compared with placebo, dramatically reduced LDL to a median of 30 mg/dL. Hemorrhagic stroke events were few and not statistically different between treatment groups, and long-term follow-up — now more than 8 years — also demonstrated safety, Martin said.

The 2022 American College of Cardiology Non-Statin Expert Consensus Decision Trail now states that an LDL of 55 mg/dL is the threshold for people at very high CV risk; an LDL of 70 mg/dL is the threshold for people at high CV risk.

“This led Erin Michos and I to publish an op-ed, titled, “Is It Time to Unlearn Hemorrhagic Stroke Concern?” As we enter this new era of combination lipid-lowering therapies, we are able to achieve lower LDL levels than ever before,” Martin said. lower security This is being adopted by consensus papers and pathways around the world.

However, Martin said, creative solutions are needed to help fill implementation gaps and educate patients about the safety of LDL-lowering therapies.

“If we can get LDL levels down to very low levels, we should celebrate,” Martin said. “We shouldn’t create undue concern.”

References:

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