THIAZIDES - Key to the Problem of Hypertension

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THIAZIDES - Key to the
Problem of Hypertension

Lt. Gen. Prof. Emeritus Mahmud Ahmad Akhtar

Hypertension is a global problem. In Pakistan it has assumed epidemic proportions. The 8th Joint National Committee(2014) of USA has issued an “evidence based guide line” for the management of hypertension. The guideline is based on extensive and intensive studies of randomized, controlled clinical trails meta-analysis, analysis and literature review by expert panels from the various disciplines of medical sciences.


Lt. Gen. Mahmud Ahmad Akhtar

The following are the recommendations

In the adult general population below 60 yrs the committee recommended initiation of treatment to lower systolic blood pressure below 140 mm of Hg and diastolic below 90 mm of Hg. In the age group 60 and above they recommended initiation of treatment to lower systolic blood pressure below 150 mm of Hg and diastolic blood pressure below 90 mm of Hg. For patients of hypertension with kidney diseases and diabetes-mellitus JNC 8 recommended systolic blood pressure to be kept below 140 mm of Hg and diastolic blood pressure below 90 mm of Hg for all adult age groups. The panel found moderate evidence to support initial or add-on anti-hypertensive therapy with an angio-tensin converting enzyme inhibitor or A2 receptor blocker in persons with chronic kidney disease to improve kidney outcomes.
Each of the four drug classes recommended by the panel i.e. Thiazides, ACE1, AR2 and Calcium channel blocker (CCB) produced comparable effects on overall mortality, cardiovascular, cerebrovascular and kidney outcomes with the exception of heart failure outcomes where the thiazides had the advantage over the other groups. The panel recognized the importance that improved heart failure outcome was an important finding that should be considered when selecting a drug for initial treatment of hypertension - heart failure is a serious complication of hypertension.

What should the treatment strategy be in Pakistan?

Thiazide diuretics (in low doses) have earlier been recommended as first line treatment for hypertension in the USA, European and many other countries. On the basis of its cost-effective advantage, I have been advocating the use of thiazides for the last four decades, in my book Rational Therapeutics (1st edition 1990) and in other publications.
In addition to advantage of the thiazides over other anti-hypertensive drugs of greater prevention of heart failure, their profound advantage is their cost-effectiveness for treating a life-long disease. This factor has enormous significance for countries like Pakistan, of which 50 percent population i.e. 90-100 million live below the poverty line, meaning thereby that they cannot afford even two meals a day (also having high prevalence of malnutrition and anaemia) and also a very large percentage of population belonging to the lower middle and middle middle class which cannot afford treatment for a life-long disease.
The Govts in Pakistan have abdicated themselves of their duty to provide healthcare and education to the common poor people of Pakistan. There is an elite system in Pakistan i.e. the Govt of the elite for the elites by the elite. Pro-elitist and anti common man policies are practiced. A large amount of budget is spent on the luxurious living style of the rulers of Pakistan who are amongst the richest people of the world while the large majority of the Pakistanis are deprived of the basic necessities of life including the health care. The health budgets of the Govts in Pakistan are very meager and those too are not managed properly. Hypertensive patients quite often develop complications needing more expenditure. Virchow aptly said “medicine is a social science- politics is medicine on a large scale”.

Cost of treatment (Pharmo-economics)

As an example of the cost of treatment of a hypertensive patient treated with hydro-chlorthiazide, 12-1/2 mg to 25 mg per day, would be from Rs 8.50 to 17 per month, yearly being Rs 100 to 200 which would be even less for hospitals making bulk purchases. While the cost of treatment of a patient with lisinopril ACE1) would be Rs 300 to Rs 600 per month (local coy) to 600 to 1200 (multinational), likewise the cost of treatment with A2 R and CCBs is much higher compared to thiazides. If we calculate the cost of life-long treatment of the hypertensive population of the country the difference between the cost of thiazides and that of other drugs is astronomical. Keeping in view the interest of patients and the larger interest of the country, it is logical and ethical to treat hypertensive patients with thiazides unless there are compelling reasons to use other group of drugs. If hypertension is not controlled with thiazides then add other cost effective drugs like amlodopine a calcium channel blocker which costs about Rs two a day by a national pharmaceutical company while other brands of calcium channel blockers cost Rs 10- 30 a day.
It is pertinent to note that the efficacy and effectiveness of any anti-hypertensive drug can be evaluated by the patient or by the treating doctor by just monitoring blood pressure. Therefore there is no problem with the assessment of the quality of the drug. Unfortunately due to the prevalence of high level of corrupt practices in the country many doctors and the Govt institutions use expensive brands, not only harming the patients financially but also damaging the country because the profits in foreign exchange is siphoned off to the foreign countries.

Thiazides preparations and their availability

The thiazide preparations, hydrochlorthiazide and bendr-chlorthiazide are included in the WHO model ‘essential drug list’ and also in the “Pakistan National Drug Formulary” 1st prepared in 1989, but never implemented. In Pakistan only one coy manufactures tablets of hydrochlorthiazide which are quite often not available or scarcely available at many places and at many times. The other companies have stopped manufacturing these drugs since decades. Unfortunately Pakistan is the only country in the world where many of the essential drugs are not available while the markets are flooded with irrational and harmful drugs, robbing the people of their health and the country of its meager finances.
The 1976 Drug Act makes it obligatory for the drug companies to manufacture essential drugs otherwise the company would loose the license to produce drugs. The Govt must implement and enforce the law. It is ironic that one of the expensive analogues of thiazides, indipamide is available in abundance. It is the constitutional and moral duty of the Govt to make essential drugs available to the people of Pakistan at all times and everywhere and also supply to the poor people free of cost as is done all over the world.

Education

Medical institutions, specialty organizations like Pakistan Hypertension League, Pakistan Cardiac Society, Nephrology and other associations, should promote the rational use of medications and for hypertension thiazides serve the purpose as these are effective, efficacious, relatively safe, affordable and cost effective. In medical education and practice Pakistan has enormous, therapeutic deficit. In order to ameliorate the situation, units of clinical therapeutics and clinical pharmacology should be set up in all teaching institutions and general hospitals manned by physicians, like units of cardiology, Pulmonology, gastroenterology etc.
These units educate and train the undergraduate and post graduate students in the art and science of clinical application of drugs, in holding clinical trials, conducting research, making guide-lines on the use of drugs, drug policy making, manning drug regulatory bodies, teaching clinical pharmacy, monitoring adverse effects of drugs and drug surveillance, in fact all activities concerned with the clinical uses of drugs as recommended by the WHO committee on clinical pharmacology and therapeutics. All over the world teaching institutions have units of clinical pharmacology and therapeutics.

The Drug Regulation

The drug regulation authority should be manned by high class experts and people of impeccable integrity which is the practice in developed countries. Unfortunately the present Drug Regulatory Authority has only one competent professional of basic pharmacology and has no clinical pharmacologist/therapeutican/ clinical pharmacist - in fact all other members are non academicians, that is the reason for abysmal drug situation in Pakistan. The “Drug Regulatory Authority” should be on the pattern of FDA of USA, Europe, UK and other progressive countries.

Prevention

The most effective strategy to deal with diseases is prevention which has been used successfully by many countries. Prevention is not only better than cure - in fact and in reality it is the only cure.For hypertension, the most effective preventive measure which costs nothing and saves lives is to reduce the consumption of common salt. In UK during the last 10 yrs active measures have been adopted to reduce the consumption of salt by creating awareness, educating the public about the hazards of consumption of excessive salt by the health-care professionals media and celebrities and adopting and implementing active legislative measures. Due to these measures the heart attacks are reduced by 40% and strokes by 42% during this period.
Similarly in Belgium the heart attacks have decreased by eight million and stokes by six million during the last ten years. In many other countries by adopting these measures, the incidence of hypertension and its complications have fallen considerably.
In Pakistan, the consumption of salt is very high. Salt is added to all types of eatables including fruits. Salt should be added to one dish only and that too in small quantities. Excess salt not only causes hypertension but also is directly injurious to the heart, kidneys and blood vessels. There should be an all out massive campaign by the Govt, media, academia and health care professionals against its excessive use.
This simple measure would produce win- win situation. The diet, to reduce the burden of hypertension, should consist of 5-7 portions of vegetables and fruits, grains(complex carbohydrates), beans, lentils, peas, low fat dairy products, oily fish(at least two servings in a week) chicken, nuts and seeds. Mono-saturated and poly-unsaturated fats while red meat and saturated fats should be in low quantities and water in liberal amounts. Healthy sleep is very important.
Regular exercises like muscle stretching, muscle strengthening, aerobics and relaxation are important. Exercises should be a part of life style like food and sleep. Weight should be kept within limits (within normal BMI range). Abdominal waist measurement should be less than 35-1/2 in males and less than 31-1/2 in females. This is most important as increased abdominal fat is a high risk factor. Tension and anxieties should be avoided. Harmony of mind and body should be inculcated. Preventive measures should be adopted at National levels.

Conclusion

In conclusion hypertension is a very common disease in Pakistan and is spreading exponentially. It is a devastating disorder causing heart attacks, strokes, renal failures and peripheral vascular disease leading to high morbidity and mortality. The main strategy to tackle hypertension should be preventive measures. The most effective one being the reduced consumption of salt. Other effective measures are diet consisting of vegetables, fruits, whole grains, pulses, seeds, nuts, oily fish, chicken, mono-saturated and poly-unsaturated fats, low consumption of saturated fats and red meat. Regular exercise to be a part of one’s life style. Thiazide should be the 1st line drug therapy on account of its low cost and high effectiveness. BP should be kept within limits i.e. below 140/90 in adults till age 59 and for age 60 and above, below 150/90.

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