‘Unlearn concern’ about going too low with LDL
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Key takeaways:
- LDL can be safely reduced to very low levels, even when starting LDL is very high.
- Solutions are needed to close implementation gaps for LDL-lowering therapies.
PHILADELPHIA — LDL is a central component of CV risk reduction and data now show clear benefits of a sustained and substantial reduction, even in the setting of very high baseline LDL, according to a speaker.
LDL should guide clinical decision-making when initiating statin or nonstatin therapies and clinicians should not be concerned about adverse events related to going “too low,” Healio | Cardiology Today Editorial Board Member Seth S. Martin, MD, MHS, FAHA, cardiologist at Johns Hopkins Hospital and professor of medicine at Johns Hopkins University School of Medicine, 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 has persisted about risk for cerebral hemorrhage.
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“There are lingering questions around things like diabetes, hemorrhagic stroke and cataracts,” Martin said. “But the first question should be, is [the LDL] truly low?”
LDL may be overestimated
The Friedewald equation, a commonly used formula that estimates LDL using total cholesterol, triglycerides and HDL, can underestimate LDL, sometimes by large magnitudes, Martin said. Data published by Martin and colleagues demonstrated that, especially if triglyceride levels are greater than 150 mg/dL, the Friedewald estimation commonly classifies LDL as less than 70 mg/dL despite directly measured levels greater than 70 mg/dL. Martin said additional evaluation is warranted for high-risk patients.
A novel method to estimate LDL using an adjustable factor for the triglyceride to VLDL ratio, the Martins/Hopkins equation, may provide 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 low,” Martin said.
Very low LDL level safe
Data from PCSK9 inhibitor trials also support low LDL. The FOURIER trial, 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 nonstatin expert consensus decision pathway 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 editorial, titled ‘Is It Time to Unlearn Concern for Hemorrhagic Stroke?’ As we enter this new era with combination lipid-lowering therapies, we are able to achieve LDL levels that are lower than ever before,” Martin said. “It is really an exciting time to go lower because of these clear benefits without any lower safety limit. This is being adopted by consensus documents and pathways around the world.”
Still, Martin said, creative solutions are needed to help close 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 be celebrating,” Martin said. “We should not be creating undue concern.”
References:
- Martin SS, et al. J Am Coll Cardiol. 2013;doi:10.1016/j.jacc.2013.01.079.
- Michos ED, et al. Circulation. 2019;doi:10.1161/CIRCULATIONAHA.119.044275.
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Martin SS, et al. Session 19 – Dyslipidemia. Presented at: Heart in Diabetes CME Conference; June 9-11, 2023; Philadelphia.
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