Intended for healthcare professionals

Fillers POEM

Two-drug hypertension regimen increases CVD mortality

BMJ 2005; 330 doi: (Published 17 March 2005) Cite this as: BMJ 2005;330:0-g

The best-proven two-drug hypertension regime in primary care

The Filler POEM on WHI best hypertension HBP regime requires comment.

The quoted WHI WOMENS’ HEALTH INITIATIVE HBP study (Wasserteil- Smoller ea 2004) was merely an analysis of antihypertensive drugs used in 19 000 women - and gave no specific drug, dose or brand statistics.

So like the ~100 major antihypertensive drug randomised controlled trials RCTs in ~500 000 patients on Pubmed, WHI cannot be quoted as definite evidence favouring any combination, or drug to accompany lowdose LD (co)thiazide.

THIAZIDE PLUS RESERPINE: The exception may arguably be low-dose LD reserpine: in well over 16 000 patients for up to a mean of 7years, LD reserpine plus LD thiazide shone whether as first line or last-ditch add-on (the six Veterans’ randomized controled trials RCTs – 3000 patients- in 30 years; the two 1997 German reserpine RCTs – 400 patients; and observational studies - HDPF 1979 of 11000 patients, and recently SHEP (Kostis ea 1995) and ALLHAT (Barzilay J 2004).

The ~hundred major anti-HBP trials already reported on Pubmed confirm without exception that in general it is not the drugs used sensibly, but the level to which blood pressure is smoothly and tolerably lowered longterm, that matters to cardiovascular outcomes.

But unlike methyldopa, hydralazine, alpha-, angiotensin- or beta- blockers, experience and Pubmed search shows that
*serious adverse effect (SAE) of appropriate thiazide is vanishingly rare (Biron ea CMAJ 1991: interstitial pneumonitis -average onset time 44minutes from first dose of thiazide in 30 reported cases, of whom 90% were women);
*no SAEs have apparently been attributed to amlodipine;
* while reserpine in fact protects against serious allergy (Mekori ea Cell Immunol.1989).

By now after about fifty years, tens of millions of patients must have received (co)thiazide, and somewhat fewer reserpine; so in sensible combination dose (the VA study 1982) they are well proven to be among the most safe effective and widely used drugs ever for chronic disease – including hypertension.

The British National Formulary/ National Health Service and the World Health Organization Essential Drug Unit do not explain on what scientific evidence they (unlike eg the USA and RSA Hypertension Guidelines) dropped lowdose reserpine from their listings ie their approved drugs.

Perhaps the BMJ or it's readers can tell us?

The preliminary ie unpublished ASCOT HBP press releases deserve separate comment.

(the scores of major hypertension studies are freely available on Pubmed word search so are not listed here. It will shortly be tabulated in the public domain on

Competing interests: None declared

Competing interests: No competing interests

21 March 2005
Neil D Burman
Research Internist
Monism HealthSpan Research Foundation, PO Box 44285, Cape Town 7735, RSA