Considerable advances have been carried out since the 1990s. But recently, the therapeutic arsenal has further enriched against hypertension, diabetes or heart failure.
One of the greatest successes of medicine in the last fifty years is, undoubtedly, the phenomenal decrease in mortality by heart disease. It owes a lot to the considerable advances carried out in the field of drug treatments. “We have at our disposal many classes of molecules in many pathologies or risk factors which, in the 1990s, brought robust evidence of their effectiveness To protect the heart », explains Dr. François Montastruc, pharmacologist at the Toulouse University hospital.
Antihypertensive, statins, antidiabetics, antithrombotics … Many of these drugs have been the subject of clinical trials conducted on thousands of patients who, for example, confirmed the interest of statins to protect the heart and arteries. Others have proven that antidiabetics lower blood sugar levels, but above all decreased the number of cardiovascular complications.
Spectacular reversals
These clinical studies were also the source of spectacular reversals. Thus for a long time, beta-blockers, a class of antihypertensivers who were contraindicated in heart failure, became one of the pillars of its management. “In the past fifty years, cardiology has undoubtedly been the darling child of drug development. But we still have many challenges to take up. If we take the only example of hypertension, we only have one in four patients under treatment whose tension is controlled ”, Recalls Professor ATUL PATHAK, pharmacologist and head of the cardiology department at the Princess-Grace hospital center in Monaco.
Over the past fifty years, cardiology has undoubtedly been the darling child of drug development. But we still have many challenges to take up
Pr ATUL PATHAK, pharmacologist and head of the cardiology department at the Princess-Grace Hospital Center in Monaco
Research in this area is therefore still very active. Even if for new drugs, it is more difficult to make a place for yourself, while there is already a well -supplied therapeutic arsenal that has proven itself. “In the field of hypertension, the revolution will undoubtedly come from these molecules which are called interferent RNAs. These injectable drugs control after a single administration hypertension as effectively as two to three antihypertensors already known, for a period of up to six months ”, explains Professor ATUL PATHAK.
Les «Anti- Pcsk9»
Interferent RNAs are small molecules that will interfere with others, messengers, and thus block the production of pathological proteins. Note that it is not in any case of gene therapies, because DNA remains untouched. Their development concerned first of all rare diseases, linked to the expression of harmful proteins such as amyloidosis. But today, they are developing in many diseases to target the organ that produces a pathogenic protein, to block a deleterious path while extending the duration of action.
In hypertension, the drug, administered as subcutaneous every six months, inhibits the production of angiotensinogen, a liver protein involved in the regulation of blood pressure. It thus prevents the constriction of blood vessels, a mechanism which contributes to the rise in blood pressure.
-Interferent RNAs are also developed in the treatment of hypercholesterolemia. In this case, they hinder production by the RNA liver involved in the synthesis of the PCSK9 protein, which regulates the number of LDL-cholesterol receptors (bad cholesterol). “In doing so, they will therefore increase the elimination of bad cholesterol”, explains Professor ATUL PATHAK.
With the arrival of these cardioprotective molecules, we can think that tomorrow, diabetes and obesity will also become diseases of the cardiologist
Pr ATUL PATHAK, pharmacologist and head of the cardiology department at the Princess-Grace Hospital Center in Monaco
This PCSK9 protein is also the target of another class of drugs: monoclonal antibodies. Called “anti-PCSK9” they also neutralize the action of the protein “Chaperonne” PCSK9. All these drugs therefore lower cholesterol in a drastic way. “However, they must still prove it, as did statins, that they are beneficial on cardiovascular risk and mortality in less specific indications”, underlines Dr. François Montastruc. Especially since these drugs are particularly expensive. Especially if they are compared to statins, generic drugs that return to a few cents per day.
GLP-1’s analogues
Type 2 diabetes, a risk factor well known for the heart, has also benefited, in recent years, from the arrival of new classes of drugs, GLP-1 or incretinomimetic analogues. This complicated name means that these molecules produce the same effects as the incretins, hormones produced naturally by the intestine which stimulates insulin secretion in response to the increase in blood sugar levels.
These drugs act on the drop in blood sugar, but also on the prevention of cardiovascular risk in obesity subjects. This explains their success, in particular the Ozempic (semaglutide) which requires a single injection per week. The care of obesity is revolutionized, and it is not over. “With the arrival of these cardioprotective molecules, we can think that tomorrow, diabetes and obesity will also become diseases of the cardiologist”, predicts Professor Pathak.
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Les gliflozines
Less famous than GLP-1’s analogues, a class of medication, SGLT2 or Gliflozines inhibitors, initially developed in diabetes are essential in heart failure. “They promote the elimination of sugar and water by the kidneys. And while they are moderately useful in diabetes, they have shown effectiveness, first in diabetic cardiac insufficients, then in all those struck by this pathology regardless of the type of heart failure “, Tells Dr. François Montastruc.
In France, these drugs put on the market in 2020 are now prescribed at more than 870,000 people, according to a study published by the Dr. Montastruc team in the scientific journal Therapies, who looked at the health insurance database. These molecules prove to be particularly protective on the renal and cardiac level. “In our study, we have found a decrease in the number of hospitalizations for heart failure in France since the marketing of these drugs, but clinical benefit in common practice must be confirmed by other real life studies, and by a decrease in mortality which must be confirmed by other studies”, explains Dr. Paul Gautier, cardiologist, principal author of this work.
