Do We Need More Drugs For Hypertension?
By Prof. B. M. Hegde
17 May, 2016
The question of therapy in medicine comes after the diagnosis. The most difficult diagnosis in medicine is the diagnosis of hypertension. Since this label encompasses many maladies, both known (secondary hypertension), and the unknown, the office recording of blood pressure alone will not suffice to warrant treatment with drugs right away. The old dictum that the “war is too serious a matter to be left to the generals alone” could be applied here very aptly thus: ”Hypertension is too complicated a matter to be decided on the spot by doctors alone, without due concern for the human being’s total environment”. If one makes the correct diagnosis therapy becomes very simple. We have enough and more drugs already. Search for newer drugs at this point in time is not worthwhile. We need more research into the aetio-pathogenesis of this enigma and that might give us better clues to the management. In fact, even the very well controlled hypertensives on drug treatment did have significantly increased mortality, in the long run compared to their normotensive counterparts. There is more to it than meets the eye in this business of drug treatment of elevated blood pressure!
Many a time, the numbers he records might alarm the practitioner himself and, he could draw wrong conclusions, in the first place. If only the doctor could sit back, take a couple of deep breaths, and then listen carefully to the patient’s woes, trying to soothe his frayed nerves; the next recording of the pressure could even have come down so much that the patient could not possibly be labeled hypertensive at that time! This scenario is not rare as many would want to believe.
Even after repeated checking of blood pressures over a period of three months, to make a diagnosis of mild-moderate hypertension, in the famous Australasian study, half the patients became normotensive on placebo alone, over a period of next three more months. All that could have changed their diagnosis, would be the tender loving care of the research team. A recent meta-alaysis of the six major journals reporting anti-hypertensive treatment studies, revealed that all of them had flaws in the method of checking blood pressure.
The gravity of the diagnostic dilemma must be clearer to the reader by now. To add to the doctors’ problems is the fact that hypertension, per se, is not a disease. It is, at best, a risk factor for future degenerative diseases, like stroke, heart attack, renal failure, and retinal diseases. Here we are on a very wet wicket. Predicting the future in a dynamic system, like the human body is an impossibility, unless we have the total knowledge of the initial state of the organism. The latter is impossible at the present time. Man consists of his phenotype (of which we know something, viz. blood pressure level etc.), his genotype (of which we know nothing at the moment), and his mind or consciousness (which has been found to play the most decisive role in disease). This was brought home to us in a clear way in the MRC study of mild hypertension treatment. To save one person from a possible future stroke, one has to treat eight hundred and fifty people unnecessarily all their lives. If one could imagine the drug side effects in those 850 people, one would quickly understand the doctor’s dilemma.
However, when the drug companies promote the drugs in a simplified fashion, the gullible doctor falls a prey to the falsehoods and mysteries. He/she starts prescribing drugs at the first contact. Elsewhere in this issue the details of drugless management of hypertension have been detailed. For the more discerning “scientific minded” doctor the dilemma is no less. There are more than six major guidelines in the world about the rules of the game of drug therapy of hypertension. If all of them are compiled together in a super computer, they will have covered only 31% of all hypertensives. Remaining 69% of hypertensives are not covered in this exercise. Put differently, majority (69%) of hypertension patients would not fit into the scientific standards of management! Here we have an evidence-burdened scenario, instead of the much touted evidence-based logic.
In addition, the vested interests are trying to even refute the guidelines of their own countries, on the plea that “seven trusted specialists” there do not follow the guidelines in their practice!
Outwith all these concerns, is the problem of pharmaco-economics in our country. We have been repeatedly stressing the importance of poverty as the basis of human ills. Hypertension is no exception here, even in the advanced countries. A study in the UK showed that the highest incidence of vascular diseases was seen in the lowest socio-economic groups! The present pre-occupation with newer drugs as first line anti-hypertensive drugs would ruin any economy, if the exchequer is to foot the bill. It is estimated that in the USA, about 50-60 million white-coat hypertensives are being treated with ACE inhibitors and Calcium channel blockers, at a phenomenal cost of 8.4 billion dollars. (Roughly three times the annual budget of India). To cap it we have the scenario where these newer drugs are yet to prove their merit in long term clinical trials.
The stress in drug treatment has been the step-care mode of drug therapy where one starts with one drug in small doses, building the dose gradually; adding the next drug to get cumulative power to lower the pressure. We would like to call this as the step-up therapy. We have been stressing, since the early seventies, about the need to step- down therapy, wherein the doctor starts cutting down the drugs and the dosage, once he achieves the desired blood pressure levels. About 50% of the patients remain normo-tensives on that regime and a small percentage would need no more drugs. This could be assessed by trial and error, without detriment to the patient’s well being. As and when the pressure starts moving up, drugs could be reintroduced. Even intermittent treatment with drugs has been shown to be good enough for mild hypertensives. Whereas we introduced it in the seventies, it is now accepted in the West, as well.
Drugs for Treatment:
To do or not to do is the real dilemma in anti-hypertensive drug therapy. As has been already pointed out, all the guidelines, of which there are six organized ones, have differing advices. That makes life that much more difficult for the practising doctor. I have been in this business for well over three decades. My best advice would be to follow the following rules for the time being, till further knowledge comes in. We have the latest Joint National Committee recommendations, JNC VI of the USA, which matches most of the following suggestions:
* Diuretics and beta-blockers should be the first choice when drugs are indicated, unless there are positive indications for other drugs, or the first line drugs are contra-indicated.
* Routine treatment with drugs is recommended by the American JNC for people with sustained blood pressures above 140/90 mm.Hg, but the British recommendations put the cut off at the pressure of 160/100. Your best bet is to take a via media. Watch people in that grey zone between 140/90 and 160/100 without drugs, but with life style modifications; which are now known to be very effective.
* Indian patients respond to very small doses in the beginning. Our experience is that our patients respond to as small a dose as 10-20 mg of propranolol and/or 25 mg of hydrochlorthiazide. Potassium supplements may be needed, if hydrochlorthiazide is used alone. Some of our patients may not respond to a larger doses if used initially, without trying the small dose first!
* Although the JNC VI committee has slightly modified their stand from their own JNC V recommendations, we feel this was done at the behest of vested interests! The above recommendations meet with the approval of JNC V, JNC VI, and also the British recommendations.
* If Calcium Channel-Blockers and/ or ACE inhibitors are to be used as the first line, there must be very compelling reasons; keeping in mind the fact that we are only treating a risk factor, and not a disease and, therefore, our selection of drugs for life long use, in an apparently healthy individual, must be above all suspicion. This can not be said about the latter drugs in the setting of uncomplicated hypertension.
* When in doubt, it is better to take an opinion of the specialist in the field. This should also be done in the following special circumstances.
a) Very young or very old hypertensives detected for the first time.
b) Patients who do not respond to the ideal line of treatment, despite the fact that the patient compliance is good (resistant hypertension)
c) Hypertension with end organ damage.
d) Patients with evidence of coronary artery disease, in addition.
e) Secondary hypertensives.
The compelling reasons for using drugs other than thiazides and beta-blockers, as the first line drugs, are listed below:
* Presence of associated Diabetic Nephropathy.
* Congestive Heart failure.
* Post-myocardial Infarction.
* Systolic hypertension in the elderly.
* Presence of diseases likes Asthma, Benign Prostatic Hypertrophy, and dyslipidaemias.
As has been pointed out earlier, it is safe to keep one’s options to a few well trusted drugs, as otherwise one could get into trouble with prolonged usage of the newer drugs. Labetolol is a good example. This was being advocated for use in pregnancy hypertension at one time, and was freely being used, based on theoretical considerations. Now there are reports to show how this drug could produce foetal changes in the new born babies of mothers, who have been on labetolol during pregnancy.
The main goal of anti-hypertensive therapy is to reduce cardiovascular morbidity and mortality. This has been demonstrated for diuretics and beta-blockers very well. Other drugs should be recommended for initial therapy only if they demonstrate their capacity to do just that, without serious side effects. In that direction a new class of drugs is showing good promise, to be proved by the passage of time. AT1 blockers (Angiotensin II antagonist) could be ideal candidates. Candesartan seems to be the most efficient molecule, as far as potency goes. Other drugs are also being tried. Two important aspects of these drugs are their prolonged action, due to prolonged receptor blockage property with a peak trough ratio of more than 0.9, and the dose response curve, which shows a continuous increase in efficacy between 2mg and16 mg daily.
What does the future hold for us in this field? We have been in for quite a lot of disappointment in this field. The HOT study ( hypertension optimal treatment study) failed to demonstrate a significant difference between the three randomized target blood pressure groups for the majority of cardiovascular events, although it did prove the theoretical hypothesis, that more vigorous treatment could certainly bring down the measured blood pressure to greater extent, in 90% of patients! Linear relationship between blood pressure and benefit does not seem to work in a dynamic system like the human body! This brings me back to my old and firm belief that the step-care treatment, although good for bringing down the box blood pressure, need not necessarily be good for the patient in the long run.
Gussipi Mancia, a great proponent of the step-care treatment, is slowly being converted to our view, which was being criticized by many, of step-down treatment, of using less and less drugs, as the pressures start coming down, to see if one could withdraw the drugs, at least intermittently, to lessen their side effects. “ Greater importance will be given in the future for the non-pharmacological approaches, as well as to baseline blood pressure values, at which drug treatment should be started” writes Mancia, in his recent article in the Journal of Hypertension, entitled Anti-Hypertensive treatment: Past, Present, and Future.14 We are pleased that our stand is being slowly vindicated! Ours was a plea to treat with empathy the human being with raised blood pressure, and not to target the blood pressure level, without any consideration for the human being that is labeled.
Belle Monappa Hegde often abbreviated as B. M. Hegde (born 18 August 1938) is an Indian medical scientist, educationist and author. He is a retired Vice Chancellor of the Manipal University and the head of the Mangalore Chapter of Bharatiya Vidya Bhavan. He has authored several books on medical practice and ethics. He was Professor of Cardiology [Visiting] London University since 1982. He was Emeritus International Advisor to The Royal College of Physicians of London and Edinburgh. He was First Indian examiner for MRCP [UK] examination in the UK from 1988 to 1998. He was MRCPI examiner in Dublin since 2000 till 2009. He served as President of World Academy of Authentic Healing Sciences, Mangalore. He has been a Non Executive & Independent Director of Zydus Wellness Limited since July 29, 2009. Dr. Hegde has 47 years of teaching experience to undergraduates and postgraduates. He has been a professor of Medicine since 1973. Dr. Hegde, an elected fellow of the National Academy of Medical Sciences, has won Dr. B. C. Roy National Award in the category of an Eminent Medical Teacher, Dr. J. C. Bose Award for Life Sciences Research, PRIDE OF INDIA Award from the Pacific Association of Indians in California and many more. Dr. Hegde is Padma Bhushan awardee 2010. He is MBBS, Ph. D. [Hon. Causa], MD, FRCP [London], FRCP [Edinburgh], FRCP [Glasgow], FRCPI [Dublin], FACC [USA] and FAMSHe is also the Editor in Chief of the medical journal, Journal of the Science of Healing Outcomes. He was awarded the Dr. B. C. Roy Award in 1999. In 2010 He was honoured with a Padma Bhushan, one of India's highest civilian awards. Hegde is visiting faculty at many universities. Email: firstname.lastname@example.org