Comparison of thiazide‐like diuretics versus thiazide‐type diuretics: a meta‐analysis

Abstract

Thiazide diuretics are widely used for the management of hypertension. In recent years, it has been actively debated that there is interchangeability of thiazide‐type diuretics hydrochlorothiazide and thiazide‐like diuretics including indapamide and chlorthalidone for the treatment of hypertension. With the purpose of seeking out the best thiazide diuretic for clinicians, we summarized the existing evidence on the two types of drugs and conducted a meta‐analysis on their efficacy in lowering blood pressure and effects on blood electrolyte, glucose and total cholesterol. Twelve trials were identified: five based on the comparison of indapamide versus hydrochlorothiazide and seven based on the chlorthalidone versus hydrochlorothiazide. In the meta‐analysis of blood pressure reduction, thiazide‐like diuretics seemed to further reduce systolic BP ([95% CI]; −5.59 [−5.69, −5.49]; P < 0.001) and diastolic BP ([95% CI]; −1.98 [−3.29, −0.66]; P = 0.003). Meanwhile, in the analysis of side effects, the incidence of hypokalemia ([95% CI]; 1.58 [0.80, 3.12]; P = 0.19), hyponatremia ([95% CI]; −0.14 [−0.57, 0.30], P = 0.54), change of blood glucose ([95% CI];0.13 [−0.16, 0.41], P = 0.39) and total cholesterol ([95% CI]; 0.13 [−0.16, 0.41], P = 0.39) showed that there is no statistical significant differences between the two groups of drugs. In conclusion, using thiazide‐like diuretics is superior to thiazide‐type diuretics in reducing blood pressure without increasing the incidence of hypokalemia, hyponatraemia and any change of blood glucose and serum total cholesterol.

Combination Therapy Is Superior to Sequential Monotherapy for the Initial Treatment of Hypertension: A Double‐Blind Randomized Controlled Trial

“…It is likely that significant proportional reductions in cardiovascular events would accrue from treating all hypertensive patients with initial combination therapy. Some reviewers argued that more powerful ARBs have been identified since our study was initiated, citing a meta‐analysis of azilsartan, or that HCTZ 25 mg is a paltry and unacceptable diuretic because in combination with this same ARB, it reduced systolic BP by 5.6 mm Hg less than a combination with chlortalidone, weighting a meta‐analysis of thiazide‐like versus thiazide‐type diuretics . There is a paucity of outcome data for the latter at their widely used modern doses.…”

“…In a retrospective analysis of a nonrandomized, unmatched comparison of HCTZ and chlortalidone, the event rate was lower in patients receiving chlortalidone (>50 mg in 48%, specialist intervention in 84%) rather than HCTZ (>50 mg in 28%, specialist intervention in 45%) . Not all international guidelines have been convinced of the superiority of thiazide‐like over thiazide‐type diuretics, and these have been compared directly for >12 weeks in <100 patients …”

“…Some reviewers argued that more powerful ARBs have been identified since our study was initiated, citing a meta-analysis of azilsartan, 27 or that HCTZ 25 mg is a paltry and unacceptable diuretic because in combination with this same ARB, it reduced systolic BP by 5.6 mm Hg less than a combination with chlortalidone, weighting a meta-analysis of thiazide-like versus thiazide-type diuretics. 28,29 There is a paucity of outcome data for the latter at their widely used modern doses. These are potentiated by ARBs, with which they are frequently combined to block the compensatory effect of renin-angiotensin stimulation.…”

“…In the first phase, weeks 0-16, half of the participants started monotherapy with either losartan or HCTZ (hydrochlorothiazide), and half started a combination of losartan plus HCTZ. In the second phase (weeks [16][17][18][19][20][21][22][23][24][25][26][27][28][29][30][31][32], all participants received the same combination of losartan plus HCTZ. In the third phase, patients received additional openlabel medication with amlodipine and/or doxazosin, dependent on whether their BP was controlled and whether they tolerated the amlodipine.…”

The effect of indapamide vs. bendroflumethiazide for primary hypertension: a systematic review

“…The composition of the placebo was included in only one trial [29], whereas the other studies stated that placebo was essentially a ʻlook-alikeʼ version of the active treatment. Although there were studies of direct comparisons of hydrochlorothiazide vs. indapamide and hydrochlorothiazide vs. placebo [4,49], they were not included because these drugs are rarely used in the UK [48].…”