RESERPINE: WHY ARE IT’S BENEFITS FOR HYPERTENSION BEING IGNORED?

It is now a lifetime ago  since the detailed trial report  showing  the major blood-pressure-lowering  benefit of reserpine on it’s own (without any diet/ salt restriction) in moderate hypertension  by Lieutenant-Colonel Inder Singh in the BMJ in 1955 (fulltext on line).

A Cochrane review of reserpine undertaken in 2000 by Manyemba ea from the Goodenough Trust in London was abandoned without explanation last year, but taken up the same day  by the Department of Medicine,  University of British Columbia on the  Blood pressure lowering efficacy of reserpine for primary hypertension.

The University of British Columbia motivation is that

-“Reserpine is an anti-hypertensive drug that was used as a first-line drug in the late 1950’s [Liebowitz 1957, Blackman 1959] and early 1960’s and recently has been used as a  second-line therapy [SHEP 1991, ALLHAT 2002]. The reasons for using it as (ie relegation to) second-line therapy are not very clear, but it is generally believed that the development of newer antihypertensive medications with better side effects profile rendered reserpine less favourable.”

But there is no evidence to support this aggressive but unsubstantiated marketing hype by lobbyists for the New Drug Industry. Such faith in the divine benignity of registered  drugs and drug companies was laid to rest by the ill-advised Women’s Health Initiative, which – without any clinical precedent for safety- subjected some 12000 “asymptomatic” women over the age of 60years to oral  xenohormone (equine estrogen plus/minus progestin)- with increasing adverse effect the older they were.

-”  Thiazides are the first-line treatment due to their proven benefit in terms of morbidity and mortality [Wright 1999, ALLHAT 2002]. However, other drugs such as ACE (angiotensin converting enzyme) inhibitors, ARBs  (angiotensin II receptor blockers), beta blockers, and calcium channel blockers, have been used as first-line treatments as well. The evidence for these drugs is not as convincing as that for thiazides”.

-“Why it is important to do this review? : More recent studies have shown that reserpine doses of 0.1-0.25 mg daily are effective in reducing blood pressure as monotherapy and doses as low as 0.05 mg daily maybe effective when combined with a diuretic [Vet Admin 1982]. It is rational then to evaluate the efficacy of these new regimens before undermining reserpine’s potential benefit especially when considering its convenient dosage schedule and low cost compared to the newer more expensive alternatives. Reserpine remains to be used in some countries as an antihypertensive drug.”

-“More data about the efficacy of various doses of reserpine in reducing blood pressure is therefore needed to guide future clinical practice and research. The goal of this systematic review is to evaluate the dose related efficacy of reserpine, compared to placebo or no treatment, in reducing blood pressure.”

As this column has regularly reviewed the past two years, the evidence and experience is overwhelming that once-daily (or even 3 times a week) lowdose reserpine plus lowdose co-amilozide is the best initial treatment – costing perhaps US$6/year-  for all grades of essential hypertension- starting with one or even two tablets of tablet of each briefly initially; and  if necessary a 4th (modern) appropriate antihypertensive drug added in rare emergency circumstances. The only exception might be  moderate-to-severe kidney failure, when the co-amilozide would be replaced by furosemide.

And of course management of hypertension includes addressing the risk factors for all the degenerative diseases of aging-

*exercise;   *stress reduction;   *less salt and (cooked) fat intake;

*reversing overweight  and insulin excess (if necessary with permanent metformin) to prevent diabetes;

*supplementing fish oil, magnesium and other appropriate micronutrients  eg vitamins and biologicals including i.a.  coQ10, carnitine, arginine and  appropriate non-oral HRT;

* avoidance of smoking, and excess of alcohol, caffeine, corticosteroid and sex hormones.

But after the results of German trials and the SHEP and ALLHAT trials a decade ago confirmed reserpine and thiazides (especially co-amilozide)   separately to be as good as if not better than newer drugs, no drug company will dare  risk  low-dose reserpine plus (co)thiazide to be tested against any modern patent drug/ combination.

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