Jornal Médico – Antidislipidemic therapies and new targets for LDL cholesterol

Jornal Médico – Antidislipidemic therapies and new targets for LDL cholesterol

Invited to participate as a speaker in “Module 2: New Perspectives in the Treatment of Coronary Heart Disease in 2022” of the updated cycle of the Portuguese Congress of Cardiology 2022, Ricardo Fontes-Carvalho, Director of Cardiology at the Centro Hospitalar de Vila Nova de Gaia / Espinho, discussed on the importance of LDL cholesterol control and the role of various anti-dyslipidemic therapies in patients at very high cardiovascular risk.

“Today, there is very strong evidence of a cause-and-effect relationship between increased LDL cholesterol and the development of atherosclerosis, including meta-analyzes and Mendel’s randomization studies.”

Regarding the management of dyslipidemia, the guidelines of the European Society of Cardiology (ESC) from 2019 “mention that LDL cholesterol is an excellent biomarker and therapeutic target,” said the speaker and reviewer of these guidelines. Due to the results of the evidence, “the guidelines have started to recommend lower and lower LDL cholesterol targets, which vary depending on the cardiovascular risk that the patient has,” he underlined.

However, Ricardo Fontes-Carvalho warned of a “gap between the evidence known from clinical trials and guidelines and the application of this knowledge in clinical practice”, which leads experts to call dyslipidemia “a bad relative of cardiovascular prevention”. In fact, he elaborated, “unlike hypertension and diabetes, it is estimated that only 3% of high-risk patients and 7% of high-risk patients, respectively, have controlled LDL cholesterol levels, according to the study. LATINO, performed in Portugal ”.

As Ricardo Fontes-Carvalho explained about these numbers, “despite the existence of effective therapies and high cardiovascular risk, the vast majority of the population studied were treated with low-intensity therapies.”

As an example of the treatment of dyslipidemia, a clinical case discussion followed, of which the following were highlighted as cardiovascular risk factors: arterial hypertension, type II diabetes, smoking and dyslipidemia, history of ischemic stroke and acute myocardial infarction. The lipid profile shown at admission was as follows:

  • Total cholesterol = 260 mg / dl,
  • HDL cholesterol = 35 mg / dl
  • LDL cholesterol = 199 mg / dl
  • Non-HDL cholesterol = 225 mg / dl

With the participation of the audience, it was concluded that the recommended release therapy is a combination of high-intensity statins with ezetimibe. “However,” as he noted, “in order to achieve the recommended target values ​​of LDL-cholesterol (<55mg / dl) and thus achieve a 87% reduction in the risk of cardiovascular events, an absolute reduction of 144 mg / dl would be needed in relative to the base value. ”

Ricardo Fontes-Carvalho warned in this regard that “although the guidelines recommend starting high-intensity statin therapy, once the LDL-cholesterol target has been defined, they also recommend starting therapy that achieves the recommended target. LDL cholesterol ”.

Therefore, in this case, the therapeutic combination of atorvastatin 40 mg with ezetimibe was chosen, which after eight weeks of treatment was able to effectively reduce cholesterol levels to the following levels:

  • Total cholesterol = 176 mg / dl
  • HDL cholesterol = 39 mg / dl
  • LDL cholesterol = 118 mg / dl
  • Non-HDL cholesterol = 137 mg / dl

“As it turned out,” the cardiologist noted, “despite a significant reduction in LDL cholesterol, it was not possible to reach the recommended target value, which allowed the patient to be treated with PCSK9 inhibitors.”

In this regard, Ricardo Fontes-Carvalho referred to the “Practical Guide to the Use of PCSK9 Inhibitors in Portugal”, which is the result of cooperation between the Portuguese Society of Cardiology, the Portuguese Society of Atherosclerosis, the Portuguese Society of Internal Medicine and the Portuguese Society of Endocrinology, Diabetes and Metabolism.

Looking to the future, new antidislipidemic therapies are also being briefly discussed, with an emphasis on “bempedoic acid 180 mg, which, as an alternative to statins, acts at the level of ATP citrate lyase and is enclosed, inhibiting LDL cholesterol receptor degradation and therefore can significantly reduce LDL cholesterol (40-50%) with only two injections a year ”.

Finally, Ricardo Fontes-Carvalho solidified the concept of “the lower, the sooner and the longer, the better” in relation to LDL cholesterol and the idea that “reducing cholesterol is more important than reducing events.” cardiovascular diseases, implementation and maintenance of access to patient therapies ”.

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