A randomized, comparative study evaluating the efficacy and tolerability of losartan-low dose chlorthalidone (6.25 mg) combination with losartan-hydrochlorothiazide (12.5 mg) combination in Indian patients with mild-to-moderate essential hypertension

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.

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“…The characteristics of studies used for the meta‐analysis were shown in Table . These studies were published from 1983 to 2016.…”

Section: Methodsmentioning

confidence: 99%

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

Liang

Cao

et al. 2017

J Cellular Molecular Medi

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“…Recently, in India, chlorthalidone is available for monotherapy as well as in various fixed dose combinations (with telmisartan, olmesartan, metoprolol XL and atenolol). Pareek et al, have reported the efficacy and safety of low dose chlorthalidone with losartan, metoprolol XL and atenolol [16][17][18]. However, there is no study which has evaluated the efficacy of the combination of chlorthalidone with telmisartan at present, though this combination is used frequently.…”

Section: Discussionmentioning

confidence: 99%

The Antihypertensive Efficacy of Chlorthalidone and Telmisartan in Indian Hypertensive Patients who were Uncontrolled with Hydrochlorothiazide and Telmisartan Combination-A Prospective and an Open Label Study

Sb²,

Kumar³

2013

JCDR

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Objective: The primary objective of this study was to evaluate the antihypertensive efficacy of the chlorthalidone and telmisartan combination in Indian hypertensive patients who remained uncontrolled after taking the hydrochlorothiazide and telmisartan combination. Methods:A total of 100 eligible patients were enrolled in this prospective, open label study. The patients were given telmisartan (40 mg) and chlorthalidone (12.5 mg), who had not achieved the target blood pressure (140/90 mmHg) despite taking the combination of telmisartan (40 mg) and hydrochlorothiazide (12.5 mg). The assessment was done at the end of 4 weeks and 8 weeks. Results:The mean SBP and DBP after taking telmisartan (40 mg) and hydrochlorothiazide (12.5 mg) were 154.88±9.57 (range 144 to 160) mmHg and 99.37±2.78 (range 92 to 106).At the end of 4 weeks of being on telmisartan (40 mg) and chlorthalidone (12.5 mg), the mean SBP and DBP were 145.56±5.12 (range 134 to 158) mmHg and 95.14±4.27 (range 84 to 100) mmHg. Significant falls in the SBP (5.32±2.64) and DBP (4.18±2.48) were noted at the end of the 4 week therapy. They were sustained at the end of 8 weeks also. The SBP target (<140 mmHg) was achieved in 24 % patients. The DBP target (<90 mmHg) was achieved in 19% patients. The combined SBP and DBP target (<140/90 mmHg) was achieved in 15% patients. No significant clinical adverse events were reported. Similar falls in the SBP and DBP were noted in the subgroups (smokers, females, diabetics, etc). Conclusions:The hypertensive patients who do not achieve the target blood pressures on telmisartan and hydrochlorothiazide can be switched on to the telmisartan and chlorthalidone combination. This combination is effective and well tolerated.

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“…These differences are not statistically significant. Indian studies done by Pareek et al 15,29,30 showed the following changes in blood glucose levels (Table 4). Thus, Indian studies have not shown cause for concern as regard to glucose levels for the duration of studies.…”

Section: Hyperglycemiamentioning

confidence: 92%

“…15 Chlorthalidone has a longer elimination of half-life, 45 to 60 hours, than HCTZ of 8 to 15 hours. The antihypertensive action of CTD may last for 48 to 72 hours.…”

Section: Comparison With Hctzmentioning

confidence: 98%

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Renaissance of Chlorthalidone

Pareek¹,

Abhyankar²,

Ghag³

2016

Hypertension Journal

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Hypertension is the major cardiovascular (CV) risk factor and remains inadequately treated in most populations. Thiazides have been the mainstay of hypertension treatment, either as monotherapy or in combination with other antihypertensives.The most overwhelming evidences of blood pressure (BP) reduction, CV risk reduction, stroke reduction and mortality reduction are demonstrated with chlorthalidone (CTD), established through many landmark studies including the latest SPRINT trial. Chlorthalidone has a longer elimination half life and is two-times more potent than hydrochlorothiazide (HCTZ). The 24 hours BP control, specially late-night to early-morning control is better with CTD compared to HCTZ.The American Diabetes Association recommends various drugs including a thiazide diuretic to achieve BP targets. Despite a less favorable metabolic profile, initial therapy with thiazide-like diuretics offers similar, and in some instances possibly superior CV outcomes in older hypertensive adults with metabolic syndrome, as compared to treatment with calcium channel blockers (CCB) and angiotensin converting enzyme inhibitor (ACE-I).Hypokalemia is the major concern associated with CTD use, probably because of use of high doses > 25 mg. Use of low-dose CTD, especially 6.25 mg, is not associated with any significant change in potassium and sodium levels. This further reduces the risk of new-onset diabetes. Published Indian evidence indicates that use of low-dose of CTD (6.25 mg) could reduce dose-related concerns about metabolic adverse effects.Thiazide-type diuretics offer added beneficial effects in terms of reduced risk of hip and pelvic fractures in elderly. ALLHAT and SHEP study have demonstrated that development of incident diabetes with CTD did not have significant associations with CV mortality rate or total mortality rate.In conclusion, the risk of diabetes associated with CTD should not discourage clinicians from using it long-term to reduce CV risks. CV risk reduction remains the ultimate goal of any antihypertensive therapy and the beneficial effects of CTD remain unsurpassed in this aspect.

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A randomized, comparative study evaluating the efficacy and tolerability of losartan-low dose chlorthalidone (6.25 mg) combination with losartan-hydrochlorothiazide (12.5 mg) combination in Indian patients with mild-to-moderate essential hypertension

Abstract: The losartan/low-dose chlorthalidone (6.25 mg) combination is as effective as the widely used losartan/hydrochlorothiazide combination in lowering BP and is well tolerated, thus providing a useful therapeutic option for treating mild-to-moderate hypertension.

Cited by 21 publications

References 11 publications

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

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

The Antihypertensive Efficacy of Chlorthalidone and Telmisartan in Indian Hypertensive Patients who were Uncontrolled with Hydrochlorothiazide and Telmisartan Combination-A Prospective and an Open Label Study

Renaissance of Chlorthalidone

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