A novel way of treating Chronic Heart Failure
Are the current drugs valuable enough to combat heart diseases or would a novel therapy be a more suitable candidate to maintain cardiac function and maybe even reverse the damaged tissues?
The clinical study from Gao et al. centers around a relatively new combination therapy of sacubitril with valsartan, which seems to have promising outcomes.
Methods
From the heart center at People’s Hospital of Liaoning Province 120 patients were separated (according to inclusion and exclusion criteria) in two groups, 60 were assigned to the combination group and 60 to the mono-therapy (valsartan) group. After 8 weeks time, the clinical outcomes and the adverse effects were observed.
Significance
The combination therapy appeared to have better outcomes than the mono-therapy and also the rate of adverse-effects was more than half than that of the valsartan group. You might have never heard of them but high-sensitivity cardiac troponin T (hs-cTnT) and N-terminal pro-brain natriuretic peptide (NT-ProBNP) serum levels are the gold standards for clinical diagnosis of Chronic Heart Failure (CHF). More specifically NT-ProBNP production is up-regulated in the presence of cardiac failure. It is important to mention that these two values decreased considerably after the combination treatment, having better outcomes than valsartan group alone. Moreover, the sacrubitril/valsartan group performed better in lowering left atrial diameter (LAD), left ventricular end diastolic dimension (LVEDD), and improving the left ventricular ejection fraction (LVEF), which are remarkable outcomes! These data can lead to the hypothesis that the combination therapy may have regenerative effects by reducing NT-ProBNP and thus promoting better heart structure.
Limitations
Some factors that may limit this experiment are among others the small number of cases and the short duration of the trial. The age group was chosen to be > 60 years of age and the classification was NYHA Class II-IV which means from slight limitations of physical activity to symptoms at rest. On top of that, the use of sacrubitril/valsartan is an expensive treatment and therefore it might be a burden for a broader clinical use. More specifically this scheme can be 100 times more costly than the standard ACE inhibitor drugs available to date. Lat but not least, this combination is contradicted in pregnancy because valsartan is known for for the birth defects it can cause.
Mechanism of action and the impact of Heart Disease on health expenditure
Sacrubitril effects
This drug is a prodrug that is activated to LBQ657, inhibiting the enzyme neprilysin which is responsible for degrading the atrial and brain natriuretic peptide. While these peptides remain (active) in the circulation, antihypertensive properties are potentiated. As you can see in the figure its usage promotes anti-proliferative effects on the tissues.
Valsatran effects
This agent blocks the action of Angiotensin II (Angiotensin I receptor blocker) and activates Aldosterone. It is an agent that is approved for heart failure patients that are intolerant to ACE inhibitors. Its use also results in a decreased blood pressure, by inhibiting RAAS and also by decreasing the sympathetic tone as shown in the figure below.
Conclusion
CHF is a daunting condition not only for the patient but also for the whole healthcare system. Even though current drugs are helpful to manage most cardiovascular conditions, by 2030 it is estimated that CHF cases will be increased by 50%. Therefore it is of utmost importance to explore new therapeutic agents and new intervention strategies to treat this condition. Therefore, CHF will comprise a major financial burden on healthcare. As you can see in the figure below, the (re)hospitalisation of patients is responsible for 70% of the total cost of the treatment of CHF. The combination of the aforementioned drugs is seemingly promising in reducing hs-cTnT and NT-ProBNP but also in lowering the amount of patients that need to go to the hospital. There is also a possibility that this treatment has regenerative effects on the cardiac tissue. However, the trial’s limitations have to be taken into consideration before introducing this option to the general population as the mainstay for CHF. Is this novel scheme the cure-all we were all waiting for or is it just a slightly improved version of the currently available pharmaceuticals?
