2023-05-03 02:03:34
In secondary prevention, a variety of treatments allows adequate control of the vascular risk of patients, including those who do not respond to or tolerate statins.
Silently and insidiously, vascular atherosclerosis establishes itself in the arterial tree for decades until, not infrequently, it ends up causing coronary, cerebrovascular, or peripheral vascular disease. Cardiovascular disease is the leading cause of death worldwide, and uncontrolled levels of LDL cholesterol (LDL-c) are well identified among its risk factors.
A study carried out by the Center for Cardiovascular Diseases Network Biomedical Research (CiberCV) revealed that of the more than 120,000 deaths from cardiovascular disease that occur each year in our country, a quarter have high cholesterol as the main cause.
Patients who have had one CV event are at increased risk of suffering another; Those with other risk factors, such as diabetes or hypertension, and with hereditary disorders, such as familial hypercholesterolemia or familial combined hyperlipidemia, are also included as susceptible to secondary prevention. There are tools, along with the essential and well-known guidelines for a healthy lifestyle, to stop or minimize the danger associated with high LDL-c levels and atherosclerotic vascular disease.
Pharmacological treatments developed in recent years offer more opportunities for those whose lipid levels are not well controlled. Because, and this is a cry among specialists, the control of patients in secondary prevention is not enough.
Carlos Guijarro, president-elect of the Spanish Arteriosclerosis Society (SEA), and head of the Vascular Risk consultation at the Fundación Alcorcón University Hospital, in Madrid, provides a figure: “In Europe, more than two thirds of patients in secondary prevention are not achieving the benefit that they could receive from the treatments”, as shown by the Santorini study, published in the online edition of The Lancet Regional Health – Europe.
For Estíbaliz Jarauta, coordinator of the SEA Secondary Prevention group and Cyber Cardiovascular (CV) researcher at the Aragon Health Research Institute, “it is a problem that has been confirmed in study after study. The clinical guidelines give us clear objectives, but when it comes to achieving them in real life, this is not the case”. Among the reasons given are therapeutic inertia on the part of physicians and lack of adherence to patient treatments.
Added to this is the fact that “historically we have not properly evaluated cholesterol levels on patient admission,” adds Carlos Guijarro, as well as the influence of a drug prescription system more focused on controlling spending than on of health results: “A good assessment of vascular risk can mean stopping prescribing unnecessary drugs in certain patients and intensifying treatment in others,” points out the professor of Medicine at the Rey Juan Carlos University, in Madrid.
therapeutic steps
Among the tools available, the internist recalls that statins are in the first therapeutic step, “drugs whose widespread use has shown great efficacy, although, in some patients, they are associated with certain side effects, especially myalgias and headaches.” Jarauta points out that these and other symptoms can be “quite disabling” for some people. “They are side effects that, however, are not reflected or quantified in tests, but many refer to them and abandon the medication for that reason.”
When statins fall short in reducing LDL-C, they can be combined with ezetimibe, which is also indicated in patients who do not tolerate them.
And without abandoning the oral therapeutic arsenal, bempedoic acid has recently been incorporated, a prodrug that is activated at the liver level, through the long-chain acyl-coA synthetase 1 enzyme, and whose therapeutic niche is found in those patients who do not reach LDL-C reduction levels with oral treatments or who are intolerant to statins, but who are not yet considered candidates for the injectable molecules that make up the next step. The activating enzyme is not present in the muscle, so this drug does not produce metabolic effects that can be associated with muscle damage.
In the latter, there are proprotein convertase subtilisin/kexin type 9 (iPCSK9) inhibitors, subcutaneously administered drugs that by themselves reduce LDL cholesterol by 60%, and associated with statins, lower it by up to 70-80%. %. “They are treatments for hospital use, fortnightly, or even monthly; with them we know for sure that there is compliance”, says Estíbaliz Jarauta. Within the pathway of action against PCSK9 there is also inclisiran, an interfering micro-RNA that silences the synthesis of the PCSK9 protein in hepatocytes and thus prevents the uptake of c-LDL. “The great advantage is that its effect persists for several months, so that after the first dose and a second one three months later, one injection every six months is enough.”
In the ‘grey zone’
However, injectables are reserved for those patients considered to be at very high risk, who must maintain their LDL-C levels below 55 mg/dL and start at 100 mg/dL, since their technical data sheet recognizes financing if the patient exceeds that figure despite optimal treatment with statins.
One remains like this Gray zonerecognizes Jarauta, for those who move between that figure but do not drop below 100, or 70 mg/dL, where injectable molecules are not yet indicated, but for whom oral lipid-lowering therapy with statins and ezetimibe is insufficient.
Bempedoic acid was approved last year by the Ministry of Health for the first time under restrictive non-financing conditions, because at that time there were no efficacy studies in cardiovascular prevention.
Now that endorsement is notorious, with the recent publication of the study Clear Outcomes in The New England Journal of Medicine (NEJM), as well as its presentation at the annual meeting of the American Cardiology Association (ACC).
Regarding this recent publication, Carlos Guijarro highlights that it supports, “with the highest quality provided by a randomized, blind, placebo-controlled trial”, the availability of “a new well-tolerated oral molecule that has been shown to reduce cardiovascular complications, and that can administered in patients intolerant to statins”, a population for which “it is important to have an alternative”, he recalls.
The prodrug confirms in this work that “the proportional reduction of cholesterol translates into a benefit in cardiovascular prevention.”
female representation
In addition, the internist points out that the study was carried out “in almost the same number of men as women (48% of the people recruited)”, a noteworthy fact if one takes into account that in historical cardiovascular studies “there is a underrepresentation of women.
It is also worth mentioning that one third of the included patients had high vascular risk, but had not presented a CV event. “They are patients with diabetes (45% of the population studied was diabetic) or arterial hypertension (AHT), or a combination of other risk factors.”They constitute a target population that we all want to reach before the disease occurs. heart attack or stroke”, he qualifies.
The ‘fine line’ of secondary prevention
In this regard, Carlos Guijarro reflects on the scope of what is considered secondary prevention: “The patient who has a heart attack today, yesterday was a high-risk patient who we have not been able to detect and treat adequately,” he says. “It is a pity that having prevention instruments and high-risk patients identified, we skimp on treatment the day before the heart attack and, instead, the next day, we give them eight drugs.” The less damaged the artery is, the better results will be obtained by protecting it, he adds.
The internist considers that the therapeutic objectives established as figures “are a warning about where to go, but that they must be properly assessed: when they are not reached, there is no need to despair, because a patient who started with 200 cholesterol and today He has it at 105, he is much better than before ”.
On the other hand, reaching beyond the objectives is also beneficial for patients. Unlike what happens in the control of blood pressure or blood glucose, where there is a debate on what figures should be stopped to avoid a possible harmful effect for patients, “there are already many studies with statins, ezetimibe, PCSK9 inhibitors and bempedoic acid that indicate that cholesterol lowering has not reached the limit at which we stop offering a benefit. The side effect does not depend on the cholesterol level that is reached, but on other mechanisms of the drug”.
Lower to 40 mg/dL
Hence, now the values for a person who is in secondary prevention are even established at 40 mg/dL, if they have had more than one event in the last two years. “Now we are talking about 40, because we can reach that figure,” says Estíbaliz Jarauta. For her, a key message for primary care is to “be vigilant”, since many patients are unaware of their risk factors.
He comments that in a small study at the Ernest Lluch Hospital in Calatayud, in which “we observed some 320 young patients who had had a CV event (women under 65 and men under 55) and found that a third were diabetics and 80% did not know. An equally striking percentage of ignorance was found among those with dyslipidemia, in 25% of the study”.
In addition, it emphasizes the role of lifestyle and, specifically, diet. “There is increasing evidence that diet plays an essential role in favoring or protecting cardiovascular disease. There is the Predimed study, the reference research in the Mediterranean diet, which shows in high-risk patients that this type of diet, with supplements of olive oil and walnuts, achieves a 30% reduction in events”. Sonia Moreno
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