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There has been a growing realisation that almost 2 decades of diuretic prescribing in hypertension have not been evidence based. A recent meta-analysis confirmed that low-dose thiazides—hydrochlorothiazide (HCTZ) 25 mg in most of the world—achieve only small falls in ambulatory blood pressure (BP),1 and the 2011 revision of the National Institute for Health and Clinical Excellence's (NICE's) guidance for hypertension concedes lack of outcome data to support HCTZ 25 mg or bendroflumethiazide 2.5 mg.2 NICE does a U-turn on previous UK and all other international guidelines by dropping diuretic from first to third choice in most patients (unless deemed at ‘high risk of heart failure’), and NICE seems to jump out of the frying pan into the fire by recommending formulations which are either not available in the UK (chlortalidone 12.5–25 mg) or have been used in only one outcome trial in hypertension, which was too small to achieve its primary outcome benefit (indapamide 1.25–2.5 mg). How did this mess come about, and what should now be done?
Sodium (Na+) retention causes hypertension; diuretics developed to reverse Na+ retention
The thiazides were developed in the late 1950s as effective diuretics. In the next decade, they entered use as antihypertensive drugs, and over the next 3 decades, numerous outcome trials demonstrated their efficacy, alone and in combination, in preventing strokes and heart failure, being superior to placebo and non-inferior or equivalent to other antihypertensive classes. The doses used in such trials were those shown to be effectively natriuretic, for example, HCTZ 50 mg in the Multiple Risk Factor Intervention Trial (MRFIT), Medical Research Council (mild hypertension and elderly trials) and International Nifedipine GITS Study: Intervention as a Goal in Hypertension Treatment (INSIGHT).3–5 Lower doses were effective in combination with renin–angiotensin system (RAS) blockers, and such combinations are indeed effective natriuretic treatments, as is apparent from their widespread …
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