Calcutta Medical Research Institute, Kolkata
Sir, your topic was very-very interesting especially in Indian context, fixed dose combinations in hypertension. We Indians are very-very possessive about using fixed dose combinations other than the West. West, usually, they use monotherapy, single drug. So, what is the thing which encourages our physicians to use this fixed dose combinations sir?
The first thing that I would like to mention you that this fixed dose combination is not a new concept. It started way back in 1960 when the old generation drugs like Zirpine, methyldopa and hydrochlorothiazide all these are available and they were combined together and they were being sold in Indian market and gradually as the newer and newer antihypertensive drugs came forward, the combinations were also being done right from that era until 1980 or 1990 when the ARB and the ACE inhibitors, they came forward, so they were also combined with various other drugs especially the hydrochlorothiazide and calcium channel blockers which came earlier to the ACE inhibitor and ARBs. Now this is now a very-very important thing to be followed that one of the most important aspect of therapy with antihypertensive drug in Indian patients is the cost factor. Now this cost factor really inhibits the patients to go ahead with the therapy adequately and for that reason they might actually fail to take the drugs properly, the number of the drugs that are individually prescribed will not be taken up. So, this kind of things ultimately totally allow the patient to fail in terms of controlling the blood pressure. So, that is called the achieving the target blood pressure becomes a failure. If you combine the drugs,then obviously you find that you are obviating the time, you are obviating the cost and the compliance factor also gets increased and these compliance factors have also been studied in different trials like empire is the latest one which has shown that the compliance increases from 30% to 70%. So if that is so, I think it is very-very essential that in the Indian scenario especially where the cost is a very-very important factor, we should follow the combination therapy.
I think you brought a very important 03:00 point as a compliance, 30 to 70 is a huge jump and I think we should encourage use of those combination in interest of cost and interest of the compliance with it so more and more patient are able to adhere to the therapy. This concept of poly pill which was there before but it could not happen, so what is your take on this Sir?
Again, the concept of poly pill is a greater extension of the fixed dose combination therapy. Now, in case of poly pill, it is not only the hypertension part which is taken care of, in addition to the hypertension, the other disease like metabolic syndrome, dyslipidemia, and coronary artery disease, so they are combinedly taken care of. Now there are certain drugs which have actually come up in the market where they are combining the statins, combining the antihypertensive drug or drugs and along with that aspirin or clopidogrel and along with that some diuretics like hydrochlorothiazide or chlorthalidone are being used or combined and these actually reduce the risk factors, risk factors means it will take care of hypertension or metabolic syndrome or dyslipidemia, but there are certain caveats in the poly pill concept that the trials that have been presented till now, out of them two are very much important, one is the TIPS 1 trial, and TIPS 2 drug, they have shown the reduction in the hypertension level, reduction in the statin level and all these, but they have not yet shown the mortality benefit.So this is a very-very important point which must be kept in mind and to circumvent that the TIPS 3 tier is coming now and that might give actually the result in 2016 or 2017. That might give some indication about the mortality benefits, about the poly pill concept and if it really becomes successful, then my feeling is that it will do a paradigm change in the concept of overall management of cardiovascular diseases and overall reduction in the cardiovascular mortality.
So, what is your approach on starting of dual combination earlier than escalating the mono therapy dose and then failing and then going to the dual combination, which approach do you find more rational?
In our practice, actually the patients come at a later stage with a little bit of more severe group of hypertension. So they are already on certain medication or medications. Now, automatically when they come to us, we go for the stage therapy that is we add some more drugs. So that is the usual case in our case but for all other purposes or other physicians and cardiologists who are getting a naive patient, so for those it is always preferable to start with monotherapy and wait for some time, see whether the target blood pressure is being achieved or not. If it is not achieved, then you start the second line of drug or second group of drug. Now, there is another point which should be kept in mind that while treating the patient if the target blood pressure is not reached by more than 20/10 mmHg, then straight away the recommendations as per the American Heart Association and other societies, they recommend that the combination therapy is a preferable one because that achieves the target blood pressure much faster and thereby reducing the major adverse cardiovascular events.
So, is titration not a big challenge when you are using fixed dose combinations?
Yes, that is a very-very good point; in fact, I always tell the companies that you just try different combinations with different dosage.Though it is a fixed drug combination but it should not be fixed dose combination. There should be some what is called free hand for the doctors to adjust the dose to escalate the dose or to reduce the dose and in that way definitely not only the side effects of the drugs, individual drugs is reduced but also you can achieve better compliance of the patient.
Sir, my last question will be, does fixed dose means only two or you will prefer even three or may be four antihypertensives in the same pill?
Well, it does not only mean two-drug combination. It might be three and sometime it might be four. But automatically whenever the number of drugs becomes more, the problems in the form of side effects also get more. So naturally you must be very much confident that when you are prescribing four drugs all at a time you should not have the side effects, otherwise the compliance factor will be again compromised. To start with, it is better to have two-drug combination and then you can opt for the three-drug combination and at the last when you have given another drug to add to the three or two drug combination you can have that combination of four.
Right, so thanks a lot Sir for sharing your very valuable comments on use of fixed dose combination. I think it makes sense especially in Indian practice because of the cost concerns and compliance to go ahead with the fixed dose. Titration remains a challenge but with more reliable combination with various dosing things, I think that could be handled. Thanks a lot Sir.