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PARIS -- LDL cholesterol levels should be driven as low as possible, especially in high-risk patients, according to new European guidelines that tighten down treatment targets.

"[T]here is no longer an 'LDL-C hypothesis', but established facts that increased LDL-C values are causally related to ASCVD [atherosclerotic cardiovascular disease], and that lowering LDL particles and other ApoB-containing lipoproteins as much as possible reduces CV events," the European Society of Cardiology (ESC) and European Atherosclerosis Society guideline stated.

"What's changing is the mindset, the idea that when you get down to 1.8 [70 mg/dL] you still go further, you push it down lower because there's clear evidence you can still benefit even at that low level," said guideline writing committee co-chair Colin Baigent, MD, of Oxford University in England.

Revised recommendations in the document, and slated for presentation at the ESC meeting here, included:

• For secondary prevention in "very-high-risk" patients, cut LDL by at least 50% from baseline and to under 55 mg/dL ()
• For very-high-risk patients on maximally tolerated statin therapy with a second vascular event within 2 years (regardless of type), an LDL goal under 40 mg/dL may be considered
• Primary prevention for people with a risk factor other than familial hypercholesterolemia, at least halve LDL from baseline and reach less than 55 mg/dL
• For patients at high risk, the target was below 50% of baseline and less than 70 mg/dL (previous goal was 100 mg/dL)
• For individuals at moderate risk (calculated 10-year risk of 1% to less than 5%) or young diabetes patients without other risk factors, the goal to consider is under 100 mg/dL (previously 115 mg/dL)
• For those with a 10-year risk score under 1%, an LDL goal under 116 mg/dL should be considered

High and very-high risk was delineated by ASCVD, diabetes, chronic kidney disease, familial hypercholesterolemia, and very high levels of triglycerides or other individual risk factors. Risk stratification using the newly tweaked Systematic Coronary Risk Estimation (SCORE) charts was otherwise recommended.

There's no lower limit for LDL or J-curve effect for efficacy, and "studies of the clinical safety of these very low achieved LDL-C values have proved reassuring," the document added.

As with the 2018 American Heart Association/American College of Cardiology (AHA/ACC) lipid guidelines, ESC upgraded PCSK9 inhibitor use from "may be considered" to "is recommended" for certain high-risk groups.

It also, in parallel with the AHA/ACC, added a recommendation that coronary artery calcium score is reasonable to assess as a cardiovascular risk modifier for asymptomatic individuals at low or moderate risk along with a recommendation to consider icosapent ethyl (Vascepa) for higher risk patients with triglycerides that remain high despite statins.

But unlike the AHA/ACC guideline, ESC suggested considering measurement of Lp(a) at least once for adults to catch inherited levels over 180 mg/dL, which may confer lifetime ASCVD risk on par with heterozygous familial hypercholesterolemia.

"Because it's stable over a lifetime, there's no need to keep redoing it," Baigent noted.

However, he cautioned that the impact of these guidelines really will depend upon the extent to which PCSK9 inhibitors are available to patients.

"Many patients will achieve their goals just using what's already available and cheap," he said. "However, where people do remain at very high risk despite being on a high-dose statin and ezetimibe [Zetia], we think that the evidence supports further reduction in LDL cholesterol, and that can only be achieved currently with PCSK9 inhibitors. We know that they are expensive, we know that there are many parts of Europe they won't be affordable, but we believe that we should reflect the available evidence in the guidelines."

The ESC also released a slate of other guidelines, including those on diabetes and pre-diabetes, acute pulmonary embolism, supraventricular tachycardia, and stable coronary artery disease -- now renamed to chronic coronary syndromes.

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