New European lipid recommendations adopt an aggressive approach

The new lipid recommendations of the European Society of Cardiology (ESC) / European Atherosclerosis Society (EAS) have adopted an aggressive approach with new lower targets for the reduction of low-density lipoprotein (LDL) compared to those previously observed for most risk categories.

The new guidelines were published on August 31 at the 2019 ESC Congress and simultaneously published online in the European Heart Journal.

"The key strategy in these guidelines is to reduce costs, best of all, and while this has been generally recommended for some time, we claim that it remains valid up to very low levels of LDL," he said. Co-Chair of the Guidelines Working Group, Colin Baigent. FRCP, University of Oxford, UK, commented theheart.org | Medscape Cardiology.

"We wanted a simpler approach than before, and we recommend that LDL be lowered as much as possible, with no lower limit, in high-risk patients."

The recommendations indicate an LDL target of less than 1.4 mmol / L (<55 mg / dL) for very high risk patients and a still lower target of less than 1.0 mmol / L (<40 mg / dL) for the highest patients. patients at risk with several recent events.

Baigent added: "For very high-risk patients (10% risk of death over 10 years), we recommended a target LDL level of 1.4 mmol / L. and at least a 50% reduction. This is much more aggressive than previous recommendations, which targeted 1.8 mmol / L or a reduction of 50%. "

"The difference between" and "and" or "may seem like a subtle change, but it could make a big difference for some patients, for example, if a very high-risk patient has an untreated LDL of 1.5 mmol / L, which is just above the target of 1.4, then the new recommendation that a 50% reduction is needed in addition to the lower threshold of 1.4 would require a much larger reduction in LDL – at 0 75 mmol / L.

"We did it because we know that risk reduction is directly proportional to the magnitude of LDL reduction.If we want a good risk reduction, we need to maximize the reduction of LDL."

New LDL goals among all CV risk categories

For patients at very high risk (cardiovascular risk over 10 years) [CV] deaths> 10%) a reduction of at least 50% in LDL-cholesterol (LDL-C) from baseline and an LDL-C target of less than 1.4 mmol / L (<55 mg / dL) are recommended. In very high-risk patients who present a second vascular event within 2 years (not necessarily of the same type as the first event) during maximally tolerated statin therapy, an LDL-C goal of less than 1.0 mmol / L (<40 mg / dL) may be considered. For high-risk patients (risk of CV death 10% over 10 years), a reduction of LDL-C by 50% or more compared to baseline and a LDL-C target of less than 1.8 mmol / L ( <70 mg / dL) can be considered. For moderate-risk individuals (10% CV death risk over 10 years), an LDL-C goal of less than 2.6 mmol / L (<100 mg / dL) should be considered. For low-risk individuals (CV death risk of less than 1% over 10 years), an LDL-C goal of less than 3.0 mmol / L (<116 mg / dL) may be considered.

"We also recommend that patients be treated aggressively with high dose statins and with the possibility of adding ezetimibe and PCSK9.[p[p[p[prprotein convertase type subtilisin / kexine] inhibitors to achieve these goals. This is another big change from previous guidelines, "said Francois Mach, co-chair of the University Hospital of Geneva, Switzerland.

"We wanted to go beyond what the US did, and we felt the evidence supported a more aggressive approach, although more evidence has been available since the release of the latest US guidelines," Mach said.

"The American approach of" fire and forget "is not good enough," he added. "We need to continue to examine the patient and measure LDL levels to lower them as much as possible – without this approach, patients tend to stop taking their statins."

"The new target of 1.4 mmol / L for very high-risk patients is easy to justify using data from the latest meta-analyzes and clinical trials of high-dose statins and inhibitors of PCSK9, "said Baigent. "The vast majority of patients can reach this level with the high dose statin associated with ezetimibe, which is an inexpensive and safe combination." The PCSK9 inhibitors will only need to be used only in a very small proportion of patients. "

No distinction between primary and secondary prevention

The other major change in the new guidelines is the removal of the distinction between primary prevention and secondary prevention.

"What we have done is to make sure the recommendations are similar for a similar level of risk, whether a patient has ever had an event or not," Baigent explained. "We have not distinguished between primary prevention and secondary prevention, but the risk is calculated in the same way in both contexts.

"While secondary prevention patients are normally at higher risk, a primary-care patient could do so if there are multiple risk factors, and the data show that the benefits of statins do not differ between prevention. primary and secondary prevention per se, it is the level of risk that is important, "he said.

The only exception to this rule is elderly people. "While we have reinforced the recommendation for the use of statins in older people in general, we have made a slightly lower recommendation for primary prevention patients over the age of 75," he noted. .

Focus on the safety of statins

The document contains a new section focusing on the safety of aggressive lowering of LDL and statins. "There are no known adverse effects of very low LDL concentrations," the report says.

On statins, it says: "While statins rarely cause serious muscle damage (myopathy or rhabdomyolysis in the most severe cases), it is very worrisome to note that statins can usually cause less severe muscle symptoms. often encounters such intolerance ". However, randomized placebo-controlled trials have shown very clearly that true statin intolerance is rare and that it is usually possible to institute a form of statin therapy (eg by modifying the statin or by reducing the dose) in the overwhelming majority of patients ".

"We want to send a strong message to patients and doctors to try to keep patients on statins in the vast majority of cases," Mach said.

Calcium Scores, Lp (a), ApoB for risk stratification

The guidelines also recommend for the first time the use of new tests to help identify high-risk patients. These include both coronary artery calcium (CAC) imaging and biomarker testing.

"Evaluating the CAC score with CT may be helpful in making treatment decisions in people at moderate risk for atherosclerotic cardiovascular disease," notes the paper. "Achieving such a score can facilitate discussions about treatment strategies in patients for whom the goal of LDL-C is not only achieved with an intervention on the mode." of life and the question of whether to initiate a treatment that reduces LDL-C. "

Mach commented: "If patients have a very low calcium score, we can say with certainty that they have a very low risk of cardiovascular disease." This is a new recommendation for Europe which aligns the guidelines on the United States. "

The guidelines also suggest that evaluating the arterial plaque load (carotid or femoral) on ultrasound can also be informative in these circumstances.

In the biomarkers, the guidelines indicate: "ApoB may be a better measure of an individual's exposure to atherosclerotic lipoproteins, so its use may be particularly useful for risk assessment in individuals for which LDL-C measurement underestimates this burden, as in the case of high triglycerides, diabetes mellitus, obesity or very low LDL-C levels. "

He also recommends a single measurement of lipoprotein (a) [Lp(a)] in all individuals. "A spot measurement of Lp (a) can help identify people with very high levels of hereditary Lp (a) who may have a substantial risk of cardiovascular disease in their lifetime," the paper says. "This could also be useful for stratifying the risk of high-risk patients, patients with a family history of premature cardiovascular disease, and for determining treatment strategies in individuals whose estimated risk is at the limit of the risk categories. risk."

The guidelines also include a recommendation based on the recent REDUCE-IT trial on high dose eicosapentaenoic acid (EPA) for patients with high triglyceride (TG) levels.

"We recommend measuring triglycerides and, according to the REDUCE-IT trial, it is reasonable to use high-dose EPA (icosapent ethyl) in high-risk patients with TG levels between 1.5 and 5.6 mmol / L (135-499 mg / dL) despite statin therapy, "said Baigent.

Well received by American experts

The new European directives have been well received by two US experts contacted by theheart.org | Medscape Cardiology.

Steve Nissen, MD, of the Cleveland Clinic in Ohio, said, "These are very thoughtful guidelines.Europeans are more open-minded than Americans with these guidelines."

"I am very satisfied with the" lower is better "message and the recommended goals for LDL The latest US guidelines are more focused on the recommended thresholds for treatment, but the" lower is better "philosophy coincides very precisely with what I believe you are right. "

"Although trials did not impose specific targets on LDL, each trial showed that a reduction in LDLs resulted in better risk reduction, and the European guidelines considered all the data and I think that's the right approach to that, "he added.

Deepak Bhatt, MD, Brigham and Women's Hospital, Boston, Mass., Said, "This guide contains such interesting content, and the editorial board is to be commended for making so many new actionable recommendations. . "

Mr Bhatt agrees with the vast majority of recommendations, "especially the increased use of imaging and biomarkers for low / medium risk patients, and the fact that they are not in the same situation. focus on reducing LDL with multiple treatments in high-risk patients ".

Regarding the imaging recommendations, he stressed that it was a controversial area.

"These guidelines really validate these approaches to stratifying patient risk and personalizing therapies, which is an important conceptual shift," said Bhatt. "I'm sure there will be some who will oppose it because there is no randomized data to support, but in reality, patients want these tests and in many cases, they still get them, so the horse has already come out of the stable.We could also well, try to figure out how we can integrate them into our processing algorithms in a way that complies with the guidelines I really think it will be adopted, "he added.

Bhatt also agreed that the Lp (a) measure would help identify a new cohort of very high risk patients who, at present, are often forgotten. "It will have a big global impact."

Bhatt said that the focus on the safety of statins was also welcome. "They send a positive message that statin intolerance is exaggerated.We can usually treat the statin with the vast majority of patients if we are willing to play with the agent and dose."

The disclosure forms of all the experts involved in the development of these guidelines are available on the ETUC website.

Eur Heart J. Posted online 31 August 2019. Full text

Congress of the European Society of Cardiology (ESC) 2019. Presented 31st August 2019.

For more from theheart.org | Medscape Cardiology, follow us on Twitter and Facebook