Cardiovascular diseases need to develop new drugs

Cardiovascular disease is the world’s leading cause of death. According to the statistics of the World Health Organization, nearly 18 million people die of CVD every year, accounting for more than 30% of the total deaths in the world. CVD mortality and incidence rate are high, but drug development is not satisfactory.

in terms of the number of new drugs approved by the food and Drug Administration of the United States from 2012 to 2019, CVD new drugs account for less than 10% of all indications, which is far lower than that of tumor drugs. It is a major global public health problem to be solved urgently.

recently, on the eve of the annual meeting of European Society of Cardiology in 2020, Bayer held an online meeting. A number of cardiovascular experts from Britain, Singapore and Germany conducted in-depth discussions on the current treatment status of cardiovascular field, and discussed the development direction of CVD management and treatment in the future based on the results of several recent important clinical studies.

according to Carolyn Lam, a professor at the school of medicine at the National University of Singapore, there are about 60 million people suffering from heart failure around the world, and one fifth of the elderly are at risk of heart failure. The quality of life and prognosis of patients are seriously affected. After five years of illness, 50% of patients may die, and the results are similar to many cancers, but they have not received enough attention.

the early symptoms and signs of heart failure are mainly dyspnea and fatigue, which are relatively hidden; most patients with heart failure can not be diagnosed as soon as possible, and their condition is not detected in the early stage of the disease, until they finally appear in the hospital due to decompensated heart failure.

although we provide patients with conventional treatment drugs for heart failure according to the existing guidelines, the patients still have symptoms and signs of disease progression, and need to strengthen treatment including emergency medical treatment, intravenous injection, hospitalization, etc., and once patients begin to show a certain deterioration of heart failure, more and more heart failure deterioration may occur, showing a downward trend, Eventually there was heart failure and death.

in response, Carolyn Lam called for more attention to heart failure. She pointed out that water-soluble guanylate cyclase is essential for the regulation of vascular and cardiac function. Because of the impairment of nitric oxide production and activity in patients with heart failure, guanylate cyclase can not be fully activated, which often leads to abnormal cardiac and vascular functions.

vericiguat is a kind of soluble guanylate cyclase direct stimulant which is in the research and development stage and only needs to be taken orally once a day. It can activate guanylate cyclase which cannot be fully activated due to impaired nitric oxide production and activity in patients with heart failure, and repair cardiac and vascular dysfunction. The results showed that the combined endpoint of cardiovascular death and heart failure was significantly reduced by 10%, and the absolute risk was reduced to 4.2/100 patient years.

Carolyn Lam said that vericiguat could be an important new approach based on the treatment recommended by conventional guidelines. This is because vericiguat can effectively restore the function of special pathway no SGC cGMP, which is a new field that has not been touched before.

the formation of red and white thrombi plays an important role in coronary artery disease and peripheral artery disease. White thrombosis is mainly caused by platelets, while red thrombosis is caused by blood coagulation. In fact, these two pathways are closely related. Platelet aggregation strongly stimulates thrombin production, leading to blood coagulation. Thrombin is a potent activator of platelet aggregation.

“in the past, we expected that the combination of two different types of antithrombotic drugs could achieve targeted efficacy, but previous studies suggested that neither vitamin K antagonist alone nor some new oral anticoagulants combined with aspirin did not reduce the risk of cardiovascular events.” At the meeting, Professor Rupert bauersach of Frankfurt University in Germany made in-depth interpretation and comparison of the experimental design and results of two recent clinical studies compass and Voyager pad. They found that very low dose of rivaroxaban can reduce the risk of cardiovascular disease, but it does not increase the risk of bleeding.

the subjects of compass study were patients with stable atherosclerotic cardiovascular disease who received rivaroxaban + aspirin, rivaroxaban or aspirin respectively.

the results showed that compared with aspirin alone, rivaroxaban + aspirin significantly reduced the incidence of composite endpoint by 24%, significantly reduced the risk of cardiovascular death and stroke by 22% and 42%, reduced the risk of heart attack and all-cause death by 14% and 18%, respectively, while there was no significant difference between the two groups in intracranial hemorrhage or fatal hemorrhage. Due to the significant benefits, the study was terminated early.

Based on the results of compass phase III study, rivaroxaban 2.5 mg bid combined with aspirin has also been recommended by many latest guidelines. It is the only oral anticoagulant of non vitamin K antagonist approved to be used in patients with chronic CAD or pad with high risk of ischemic events to reduce the risk of major cardiovascular events.

Voyager studied peripheral arterial disease patients undergoing lower extremity revascularization due to ischemic symptoms. It was found that rivaroxaban combined with aspirin could reduce the risk of major composite endpoint events by 15%, reduce the risk of acute limb ischemia by 33%, and significantly reduce the risk of future revascularization and hospitalization by 12% and 28%, respectively.

recently, China drug administration has approved the combination of rivaroxaban tablets and aspirin for patients with chronic coronary artery disease or peripheral artery disease to reduce the risk of major cardiovascular events.

Professor George Bakris of Chicago Medical School in Illinois, USA, pointed out that diabetes mellitus is one of the important causes of renal failure. Patients’ renal function damage is often asymptomatic. When detected, renal function often has irreversible decline. Controlling blood pressure and blood glucose and slowing down inflammatory reaction are important measures to delay renal function decline.

finerenone, a non steroidal selective mineralocorticoid receptor antagonist in the research and development stage, has been shown to reduce the harmful effects of excessive activation of the salt cortical hormone receptor – kidney and heart damage.

finerenone is a new type of non steroidal selective mineralocorticoid receptor antagonist in the research and development stage. It has been proved that it can reduce the adverse effects caused by excessive activation of salt cortical hormone receptor. Its cardiorenal benefit is mainly based on the results of phase III fidelio-dkd clinical study.

the finerenone phase III trial included 13000 chronic kidney disease patients with type 2 diabetes mellitus. Among them, 5700 diabetic nephropathy patients were enrolled in the finerenone phase III trial. The efficacy and safety of finerenone in reducing renal failure and progression of kidney disease were evaluated, reaching the primary efficacy end point.

the fidelio-dkd study is part of the largest phase III clinical trial project to date in patients with chronic kidney disease with type 2 diabetes mellitus. A total of 13000 patients with different disease severity were recruited. The study evaluated the efficacy and safety of finerenone in chronic kidney disease patients with type 2 diabetes on the basis of standard treatment.

the results showed that finerenone could delay the progression of chronic kidney disease. On the basis of standard treatment, finerenone significantly reduced the primary and secondary composite endpoints compared with placebo.

at the meeting, George Bakris accurately analyzed the physiological and pathological changes of DKD, emphasized that “protecting renal function is very important, the earlier the protection, the better the outcome”. On this basis, combined with the new drug finerenone and the latest progress of fidelio-dkd clinical research, he provided a special solution for DKD. Focus