DRONEDARONE / MULTAQ LAUNCH. 19th Feb. 2011

Last Saturday, I was invited to the launch of a new anti-arrhythmic agent ( there has been so few anti-arrhythmic agents produced since the CAST study ), dronedarone. Sanofi-Aventis, the maker of dronedarone, touted it as an important launch and a paradigm shift. It was a rather low key, muted launch, quite unlike the launch of rimanobant, not so long ago. Yes, the staff were dressed in Greek outfit ( to reflect their landmark study of ATHENA ), the food was good and the speaker, Prof John Camm of UK ( St Georges Hospital, London ), was excellent, as usual. Missing was the fan -fare ( dancing and entertainment ) and wine for the occasion.
Actually, I am in full agreement that drug launches should be for good, pure medical reasons and not a commercial launch like iPhone 3 or iPad.
Anyway, Prof Camm gave a good overall review of Dronedarone, in the management of atrial fibrillation, based primarily on his understanding of ATHENA, which showed that in patients with atrial fibrillation and other coronary risk factors, dronedarone, reduces the primary end-point of mortality and repeat hospitalisation. The p value here was 0.001. This primery end-point however was driven mainly by a mark reduction in repeat hospitalisation ( which to many of us was a rather soft end-point. The mortality reduction, especially cardiac mortality reduction was only modest, and just about made the significance level. I think cardiac mortality reduction p value was 0.02. Whatever it is, I was more intrigued by the fact that dronedarone as an anti-arrhythmic works at all 4 levels of the electric cardiac cycle, as taught to us by Vaungh-Williams. If we had to classify dronedarone using the old Vaungh-Williams classifiaction,, then dronedarone will be a weak class 1, class 2, class 3 and also a weak class 4 ( calcium channel blocker ). Thereby, it will have many other potential uses. Being a weak class 1 agent, it may have ability to reduce ventricular arrhythmias. In fact, the reduction of cardiac mortality in ATHENA was driven mainly by a reduction in sudden cardiac death. Being a class 2 agent, it is a beta blocker of some sort. In fact, as an anti-arrhythmic agent, it has significant Heart Rate lowering effect. The slowing of A.Fib rate was significant. Being a class 4 agent, it does have coronary vasodilatation effects, meaning that it could reduce angina and maybe blood pressure ( through systemic vasodilation like amolodipine ). Interesting, interesting.
I am a little concern about the hepatic toxicity, which were reported, with 2 patients having to undergo liver transplantation. It is also metabolised through the cytochrome P450 system, thereby giving the potential of drug-drug interaction. Of particular importance is the interaction with warfarin, statins and maybe clopidogrel.
Nonetheless, after so many years, we see that anti-arrhythmic agents are still being investigated and being brought to the marketplace. Many of us thought that with the landmark CAST study, showing that anti-arrhythmic agents are potentially pro-arrhythmogenic, anti-arrhythmic agents will be w thing of the past, what with the ICD becoming more popular.
All in all, it was an interseting evening on 19th Feb, very educational and of course, lets see how this new agent for management of atrial fibrillation pan out. Does it have a useful role. Afterall, it does cost about RM 15 a day. It is not cheap. Warfarin and beta-blockers ( the current alternative ) only cost a dollar or so.