New Medicines for Heart Failure treatment.
When I retired as a cardiologist I thought I knew everything about cardiovascular disease and its treatment. Now, ten years later, I have to admit I know almost nothing. New developments come nearly every year. And some are very promising.
So I had to study very hard to bring my knowledge up to date to make this presentation for you.
At the end of my last article, I left you in 2010 with the adagium of treatment for heart failure: ACE inhibitor (or ARB), beta-blocker and diuretics (furosemide and/or Aldactone).
These drugs have improved the clinical situation of the patients dramatically. Patients can be stabilized for a longer period, but stable is never forever.
The prognosis of heart failure is still not as good as we would like, with a 50% mortality in 5 years. Most cancer patients do better and often with complete cure. We can’t cure heart failure, except for the lucky few that can have a heart transplant, so the battle goes on.
The pharmaceutical companies search furiously for new medicines (also because it is big business – in my opinion they should do the same for other diseases as well.)
The first new approach was to develop medicines that influence other steps in the RAAS system that I mentioned last time. Why do they search for new medicines in that very important RAAS enzyme reaction cascade? Well, there are many steps in that system and the effect of blocking an enzyme reaction at any level is widening of the blood vessels and opening of more blood vessels, regulation of the blood pressure and lessening the amount of water in the body.
The ACE inhibitors and ARB’s and Aldactone all interfere with the A‘s in the RAAS cascade. (RAAS means Renin-Angiotensin-Aldosterone System, but it is not necessary that you remember this!)
A drug called Aliskiren was developed that works on the R of the cascade. Aliskiren worked, but it is not used widely, because it has too many side effects.
A second drug, Sacubitril, was developed. This medicine blocks an enzyme called neprisylin, part of a branch on the RAAS-tree. This is a very potent medicine in lowering blood pressure. It has been on the market since 2015. It is combined with valsartan (an ARB drug) and together the group name is ARNI.
The valsartan/sacubitril combination is sold as Entresto. The switch from ACE or ARB to Entresto must be guided by frequent blood pressure controls in the first weeks.
With that, we leave the kidney-heart axis of the RAAS system. The SGLT2 inhibitors are next to be considered, notably dapagliflozin, a drug developed for diabetes mellitus type II (DM II).
Why all these tongue breaking names? Maybe it is to make the doctor look to be more intelligent, but alas not so in my case: I always put the vowels in the wrong place, getting red-faced because I then feel silly.
Anyway, to make it easy, let’s call this one ‘Dapa’. Dapa works for DM II because it stops the reabsorption of glucose in the kidney, so making the urine sweet. At the same time it also blocks reabsorption of water – like with furosemide – and that’s why it’s effective in heart failure.
Two birds with one stone: improving diabetes and heart failure at the same time. But it also works without having diabetes. The FDA approval for Dapa in heart failure came only very recently and it will change the medication of many people.
In my first article about heart failure I mentioned the disappointing result of medicine that make the heart work harder. We call those drugs ‘inotropes’.
But never say never in medicine – remember how the thinking against using beta-blockers in heart failure was reversed. And now we maybe have to say the same about inotropes.
The truth of today is the lie of tomorrow and vice versa because yes, there is also a new inotrope ,with yet another tongue-breaking name – omecamtiv mecarbil.
This drug adds power to each heart beat. When a heart muscle cell is stretched it responds by contracting. As it is stretched more it contracts stronger but at the cost of a lot of energy.
Omecamtiv mecarbil works by making the heart muscle cell contract strongly but without having to use extra energy. The medicine acts like 4 helping hands pulling on a rope attached to each heart muscle cell to do all the work.
The study results are very promising and I think this new drug will be approved soon.
My final article in this series on heart failure is about mechanical solutions for heart failure.
I leave you with one quick tip. Many people ask how much fluid can I drink. (There should be no alcohol by the way, because that’s bad for the failing heart.)
To work out how much you should drink, you need a measuring cup of at least 1 litre. After you wake up in the morning you pee out. After that you start counting how much you pee in the measuring cup. Write it down on a paper and throw a way your pee. Add the amount of pee every time you go to the toilet. Also during the night and your first pee the next morning. The total amount you pee in that period is what you can drink plus 500cc (for compensation of your sweat loss).
I think this presentation has been a little bit tough. Congratulations if you have managed to read this far. Please give us any feed back that you have.
Ben van Zoelen,retired cardiologist, member of the advisory group of Bewell family care clinic in Hua Hin.