Tuesday, August 07, 2007

New Drug In the Treatment of Heart Failure

Over the weekend, I was invited to Bangkok to hear Dr R Ferari speak to us about Ivabradine, the first in a group of anti heart failure drugs which are what we call I-f channel blockers. we were briefed that the sinus node (SA node) of humans have I-f channels, which when blocked, can slow the heart rate, without affecting myocardial contractility. We all know so well, from our physiology days, that when cardiac output falls, the heart either increases stroke volume or heart rate. After all, cardiac output is determined by stroke volume, multiplied by heart rate (CO=SVxHR). This is probably the most basic of all cardiac physiology equations

Therefore, the rise in heart rate in a patient with heart failure, is actually a cry for help. It is also true that this increased heart rate will use up more myocardial cell energy, in a situation in heart failure where the myocardial cells are energy deficient (oxygen deficient, especially in patients with ischemic cardiomyopathy). The question that we are all asking is, is blocking this rise in heart rate, good for the patient? If you block a cry for help, you will in fact deny help for the victim.

Yet, if you block the rise in heart rate, you may infact save energy (particularly in ischemic cardiomyopathy). Which is the more important? Will blocking this heart rate, improve or deprove cardiac output? Well, Servier, the maker of this new drug called Ivabradine, contents that the latter is more important, thereby saying that Ivabradine is good for my heart failure patients, and that it should improve cardiac output. They have in fact gone on to run two large scale RCT to prove this. The "BEAUTIFUL" study, has just completed recruiting 20,000 patients with ischemic cardiomyopathy. There will be a standard treatment arm and the Ivabradine arm (where ivabradine is given on top of standard CCF therapy). If we wait 2 years, in 2008, we will be able to see if the treatment arm shows lesser cardiac death, and repeat CCF hospital admissions. Which such a large cohort, I am sure that the trial will be quite definitive.

The other study is the "SHIFT" study, where Ivabradine is given to patients with depressed LV systolic function, to see if these patients did better. This study is just starting and we may get some results in 2012 or thereabouts. We wish Servier every succes and hope that this new group of drugs (some call it B-Blocker with less cardiac effects) will indeed be benefiacial to our patients. I have always found that the increase heart rate in CCF is a compensation, and that blocking it could cause problems. If the patients can compensate with increase in stoke volume, fine, otherwise, it could be disastrous. Anyway Servier has rightly subjected it to clinical testing. We shall know in a year or so. I also believe that is servier is right, very soon we shall also see the production of other "me too" drugs by other pharmaceuticals. This is a cheap way of knowing the answer, perhaps sooner. As they say "Imitation is the best form of flattery" . Then we will all know that blocking the I-f channel is good for our patients.

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