fresh from HealthSpan Life: NEW PROFITABLE ANTIHYPERTENSIVE COMBINATIONS, OR APPROPRIATE LOW-COST BEST LONG-TERM ANTIHYPERTENSIVE DRUGS, FOR THE UNCOMPLICATED MAJORITY?

It goes without saying that (except in more severe or complicated hypertension)  antihypertensive drugs are only introduced  once bloodpressure is not adequately controlled with appropriate counselling including about  exercise, recreation and weight-normalizing diet,  avoiding all tobacco smoking, sucrose and cooked fats, with appropriate  multivitamin- multimineral supplement and low salt   intake, and prudence with drugs (alcohol,  steroids and nonsteroidal anti-inflammatories)  that can aggravate hypertension .

 

Like Norman Kaplan’s book Clinical Hypertension, Marvin Moser at Yale  in his Clinical Management of Hypertension book 2004,  noted  that combined reserpine + diuretic, like all other antihypertensive combinations,  controls BP <140/90 in 70-75% of patients needing drugs.

 

The Seventh Report (2004) of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure put a thiazide diuretic as initial therapy with reserpine as one of the basic add-on options.

 

The American heart Association has recently published guidelines including that  ” An effective multi-drug regimen to reduce blood pressure is essential. Reports from hypertension speciality clinics indicate that treatment resistance is often in part related to lack of or underuse of diuretics.”

 

A  new review this month   Blood Pressure Control and Pharmacotherapy Patterns in the United States Before and After the Release of the Joint National Committee on the Prevention, Detection, Evaluation, and Treatment of High Blood Pressure (JNC 7)  says “blood pressure control has improved much.. Increase in the use of diuretics in the after-JNC 7 cohort follows the recommendation of thiazide-type diuretics as the preferred initial agent in patients without compelling indications”.

 

Yet vast amounts of money continue to be spent on trials and marketting  touting new patentable combinations without diuretics eg  ACCOMPLISH (Jamerson 2008): benzapril plus amlodipine; ADVANCE (Saito 2008)  nifedipine plus valsartan; COACH (Chrysant 2008) olmesartan plus amlodipine, as safer and better- but without comparing them with the gold standard lowdose reserpine plus lowdose amiloretic.

 

The dozens of reserpine trials for 40years to date (the last were apparently the ALLHAT and SHEP trials), consistently showed that, in low dose,  without exception  (except renal failure) combined with lowdose diuretic  is the best  foundation  treatment of all grades of hypertension  because   BP  control is smooth – reserpine  0.0625 to  0.125mg/d average `<0.1mg/d  is the only drug that works for weeks, lowers pulse by about 7beats/min, and has neutral if not beneficial effect on glucose-insulin-lipid tolerance, anxiety and mood;

and the lowdose thiazide-  eg hydrochlorothiazide 6.25 to 25mg/d average 12,5mg/d –  combined with a lowdose potassium sparer- neutralizes both vasoconstriction, volume expansion and increased cardiac output.

 

In South Africa the average retail cost  of this combination once the BP comes under control and the drug doses are reduced to maintenance is about R5 (ie US$0.5)  a month; without a single significant adverse effect- ie without the  rashes, liver, cough/fatigue /  bronchospasm / heartfailure, oedema, coldness, constipation, depression, sexual problems or  dizziness of methyldopa, clonidine,  betablockers, ACEI, ARBs, calcium antagonists, and more modern drugs.

 

While optimisation of hypertension alone is able to  reduce greatly the complications of heart failure and haemorrhagic stroke, it obviously does nothing for the other invariable concomitants of essential HBP ie glucose/insulin/lipid resistance and overweight  – but  in  the coamiloretic combination , amiloride reverses the adverse metabolic effects of the thiazide, resulting in neutral effect.   (Mammarella 1989, Thomas 1983).

 

 In  Systolic Hypertension in the Elderly trial  SHEP (Kostis 1995; 2005  ) compared to placebo,  a thiazide (chlorthalidone 12,5 – 25mg/d) +- reserpine or atenolol as required to control hypertension lowered all-cause mortality by between 13% and 22%- without worsening diabetes, with even greater reduction in all-cause mortality in diabetic hypertensives- but with far lower mortality on reserpine than atenolol.  In ALLHAT  , not only did reserpine prove superior to clonidine, but the thiazide proved superior to all other classes of antihypertensives.

 

If there is renal failure (which is rarely seen  compared to hypertension in  almost 50% of older fatter people)  the diuretic is  ill-advised, so reserpine can be combined  as appropriate with any of the other drugs.

 

But as this column repeats monthly, with increasing scarcity of fish (oil) in the average diet, everyone should be on some fish oil supplement for its major multisystem benefits including reduction of hypertension, thrombosis, inflammation and insulin resistance;

and for the increasing prevalence of rising  weight, insulin resistance and diabetes, the overweight / insulin resistant of all age should be on metformin to tolerance, at negligible risk but 1/3 reduction in all-cause medical premature deaths and almost halving of all-cause mortality, including by reduction of glucose-insulin-lipid resistance, hypertension, cancer, thrombosis etc.

 

What the ACCOMPLISH paper (Jamerson 2008) appears to studiously ignore is that this trial was done in frankly obese patients (BMI 31kg)- who would be most likely to have insulin glucose resistance IGR – yet the paper does not disclose what their weight or HBA1C did,or what % develloped IGR or  new diabetes. Cases  of resusctitation after cardiac arrest were  something like 14  on Benzapril-amlod vs 7 cases on Benzap-HCT. since these patients were a priori at such high risk, 60% diabetes,  would they not have done far better, lost weight, had far fewer arrests and deaths and heart attacks  from the outset on fish oil and metformin to tolerance?

 

The hypocrisy in most Hypertension guidelines is predictable: they acknowledge that most people need drug combinations; and that  diuretics should be first line in the older ie past 60yrs; but in the younger they piously claim that a diuretic should be avoided due to the increased risk of metabolic adversity. Thus they (ie the Regulators, “experts”, deliberately choose to ignore decades of evidence that lowdose thiazide works best of all drugs, especially when combined with amiloride and reserpine, causing no new  metabolic problems.

 

But if authorities promoted $0.50 a month of  the long-time gold standard  triple combination for hypertension ie  the commercially non- viable  old (lowdose reserpine + amiloretic) trio, the “authorities” would lose their massive income from the new-drug industry.

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One response to “fresh from HealthSpan Life: NEW PROFITABLE ANTIHYPERTENSIVE COMBINATIONS, OR APPROPRIATE LOW-COST BEST LONG-TERM ANTIHYPERTENSIVE DRUGS, FOR THE UNCOMPLICATED MAJORITY?

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