Diuretics: Hydrochlorothiazide Preserves Bone Density: Large epidemiologic studies, including the Nurses’ Health Study, indicate that people treated with thiazide diuretics have higher bone mineral density (BMD) than those who don’t take them, and an approximately 30% lower risk of hip fracture. In a 3-year DB PC study of 320 healthy, normotensive men and women (aged 60 to 79) to hydrochlorothiazide, either 12.5 or 25 mg/day, led to gains in BMD at the hip of about 0.5% to 0.6% from baseline vs. a decrease of 0.3% for placebo. Spinal BMD was not significantly different. Ann Intern Med. 2000;133:516-26. 

Diuretics: Thiazides Decrease Fractures: In an 8 year follow-up study of 7,891 older adults, those using a thiazide blood pressure medication for more than 1 year were 54% less likely to sustain a hip fracture. There were no clear dose-response trends. Protective effects, caused by reducing calcium excretion, disappear about 4 months after such drugs were stopped. Bruno H. Ch. Stricker, Erasmus MC in Rotterdam, Ann Intern Med 2003;139:476-482.

Chlorthalidone Small Benefit in Elderly: In the Systolic Hypertension in the Elderly Program (n = 4,732) who were randomized to stepped-care therapy with 12.5 to 25.0 mg/day of chlorthalidone or matching placebo, if blood pressure remained above the goal, atenolol or matching placebo was added. At a mean follow-up of 14.3 years, cardiovascular (CV) mortality rate was significantly lower in the chlorthalidone group (19%) than in the placebo group (22%; adjusted hazard ratio [HR] 0.854). Diabetes at baseline (n = 799) was associated with increased CV mortality rate (HR 1.659) and total mortality rate (HR 1.510). Diabetes that developed during the trial among subjects on placebo (n = 169) was also associated with increased CV adverse outcome (HR 1.562) and total mortality rate (HR 1.348). However, diabetes that developed among subjects during diuretic therapy (n = 258) did not have significant associations with CV mortality rate (HR 1.043) or total mortality rate (HR 1.151). Diuretic treatment in subjects who had diabetes was strongly associated with lower long-term CV mortality rate (HR 0.688) and total mortality rate (HR 0.805). Long-term effect of diuretic-based therapy on fatal outcomes in subjects with isolated systolic hypertension with and without diabetes. Kostis JB, et al. UMDNJ-Robert Wood Johnson Medical School. kostis@umdnj.edu <kostis@umdnj.edu. Am J Cardiol 2005 Jan 1;95(1):29-35. Ed: 3% of participants saved from death after 14 years seems small to me.

Syst-Eur Study Found Treating Systolic Hypertension Over 160 Helpful: The 2.0 year 4,695 patient (systolic 160-219) DB PC Systolic Hypertension in Europe (Syst-Eur) trial was followed by an open-label study lasting 4 years. They received open-label treatment consisting of nitrendipine (10-40 mg daily) with the possible addition of enalapril (5-20 mg daily), hydrochlorothiazide (12.5-25 mg daily), or both add-on drugs. Systolic pressure decreased to below 150 mmHg (target level) in 75.0%. During the 4-year open-label follow-up, stroke and cardiovascular complications occurred at similar frequencies in patients formerly randomized to placebo and those continuing active treatment. Immediate compared with delayed antihypertensive treatment reduced the occurrence of stroke and cardiovascular complications by 28% (P = 0.01) and 15% (P = 0.03), respectively, with a similar tendency for total mortality (13%, P = 0.09). In 492 diabetic patients, the corresponding estimates of long-term benefit (P < 0.02) were 60, 51 and 38%, respectively. Immediate compared with delayed treatment prevented 17 strokes or 25 major cardiovascular events per 1000 patients followed up for 6 years. These findings underscore the necessity of early treatment of isolated systolic hypertension. Effects of immediate versus delayed antihypertensive therapy on outcome in the Systolic Hypertension in Europe Trial. Staessen JA, et al. J Hypertension 2004 Apr;22(4):847-57.

Diuretic in ALLHAT Only Slightly Better Than Alpha-Blocker: In the DB Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial (ALLHAT), doxazosin, an alpha-blocker, had the same mortality rate as chlorthalidone, a diuretic (RR 1.03). Patients were over 54 with hypertension and at least 1 other CHD risk factor. The primary outcome measure was the combined occurrence of fatal CHD or nonfatal myocardial infarction (MI), analyzed by intent to treat, as also the same (RR 1.02). The doxazosin arm compared with the chlorthalidone arm had a higher risk of stroke (RR, 1.26) and combined CVD (RR 1.20). Diuretic versus alpha-blocker as first-step antihypertensive therapy: final results from the Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial (ALLHAT). Hypertension 2003 Sep;42(3):239-46.

Indapamide SR Did Best: In a metanalysis of 72 studies of hypertensive medications since 1973 comparing hydrochlorothiazide, indapamide sustained release (SR), furosemide and spironolactone for diuretics; amlodipine and lercanidipine for calcium channel antagonists; atenolol for beta-adrenoceptor antagonists (beta-blockers); enalapril and ramipril for ACE inhibitors; and candesartan cilexetil, irbesartan, losartan, and valsartan for angiotensin II receptor antagonists, indapamide was most successful at reducing systolic hypertension: 22 mmHg in the first 2-3 months. Baguet JP, Robitail S, et al. Grenoble University. Am J Cardiovasc Drugs. 2005;5(2):131-40