Add-on effect of hydrochlorothiazide 12.5 mg in Japanese subjects with essential hypertension uncontrolled with losartan 50 mg and amlodipine 5 mg

Rakugi, Hiromi; Tsuchihashi, Takuya; Shimada, Kazuyuki; Numaguchi, Hirotaka; Nishida, Chisato; Yamaguchi, Hiroya; Shirakawa, Masayoshi; Azuma, Kyoichi; Fujita, Kenji

doi:10.1038/hr.2015.3

Cited by 11 publications

(10 citation statements)

References 17 publications

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“…The participants in their trial had a significantly reduced DBP and SBP compared with baseline levels after 30, 60 and 120 days of treatment. 13, 14 In addition, as a result of the add-on effect of hydrochlorothiazide in a short-term study, Rakugi et al 15 found that treatment with 50 mg losartan+12.5 mg hydrochlorothiazide+5 mg amlodipine for 8 weeks did not result in a significant difference in DBP reduction but did show a significant difference in SBP reduction compared with 50 mg losartan+5 mg amlodipine.…”

Section: Discussionmentioning

confidence: 99%

The efficacy and long-term safety of a triple combination of 80 mg telmisartan, 5 mg amlodipine and 12.5 mg hydrochlorothiazide in Japanese patients with essential hypertension: a randomized, double-blind study with open-label extension

et al. 2016

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The aim of this study was to compare 80 mg telmisartan/5 mg amlodipine/12.5 mg hydrochlorothiazide (T80/A5/H12.5) with 80 mg telmisartan/12.5 mg hydrochlorothiazide (T80/H12.5) to determine their relative blood pressure (BP) lowering effects in essential hypertensive patients with inadequate control and to evaluate the long-term safety of T80/A5/H12.5 in a 52-week extension period. Patients (n=132) were randomly assigned to receive double-blind treatment with T80/A5/H12.5 or T80/H12.5 for 8 weeks after a 6-week run-in-period of T80/H12.5. All 126 patients who completed the double-blind period entered the 52-week open-label extension and received T80/A5/H12.5. The adjusted mean changes from the reference baseline of the trough-seated systolic and diastolic BP (SBP/DBP) at week 8 were significantly larger in the T80/A5/H12.5 group (−10.6/−8.8 mm Hg) than in the T80/H12.5 group (−2.3/−1.3 mm Hg) (P<0.0001). The BP-lowering effect of T80/A5/H12.5 was maintained over the 52-week extension period. The adverse events (AEs) during both treatment periods were generally mild. Drug-related AEs were reported in one patient in each group in the double-blind period and in five patients exposed to T80/A5/H12.5 in the double-blind and/or open-label extension period. T80/A5/H12.5 therapy was clinically and statistically superior to T80/H12.5 therapy for the reduction of BP in patients with essential hypertension uncontrolled with T80/H12.5, and its BP-lowering effect was maintained in the long term. T80/A5/H12.5 was generally well-tolerated.

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Section: Discussionmentioning

confidence: 99%

The efficacy and long-term safety of a triple combination of 80 mg telmisartan, 5 mg amlodipine and 12.5 mg hydrochlorothiazide in Japanese patients with essential hypertension: a randomized, double-blind study with open-label extension

et al. 2016

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“…Post hoc sensitivity analyses using alternative methods for zero-cell correction and heterogeneity estimation were conducted according to previous recommendations. (32,(39)(40)(41)(42)(43) Publication bias was assessed by visual analysis of funnel plots and computation Ando (54) 2009 ONEAST (Japan) Genthon (56) 1994 (multinational) Giles (51,95) 1992 (USA) Kario (57,96) 2017 NOCTURNE (Japan) Kato (58) 2011 MOTHER (Japan) Lonn (61,97) 2016 Merck (74,98,99) 2010 Novartis (72,102,103) 2008 ACQUIRE (multinational) Perez-Castrillon (52) 2003 (Spain) Puttnam (11,26,109) 2017 ALLHAT (multinational) Rakugi (64,110) 2015 (Japan) Raveau-Landon (65) 1991 (France) Reid (47,111) 2000 (New Rodgers (66,112) 2011 (53,115,116) 1991 SHEP (multinational) Weidler (68) 1995 Yamada (70) 1989 (Japan) of Egger and Begg tests for outcomes with more than 10 studies. (44)(45)(46) Results…”

Section: Heterogeneity and Publication Biasmentioning

confidence: 99%

Thiazide Diuretics and Fracture Risk: A Systematic Review and Meta‐Analysis of Randomized Clinical Trials

et al. 2022

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Thiazide diuretics are commonly used antihypertensive agents. Until today, whether their use reduces fracture risk remains unclear. Our objective was to conduct a systematic review of thiazide diuretics' effects on fractures and bone mineral density (BMD) in randomized clinical trials (RCT) of adults. MEDLINE, EMBASE, CENTRAL, and the WHO's ICTRP registry were searched from inception to July 31, 2019. Two reviewers assessed studies for eligibility criteria: (i) RCTs; (ii) including adults; (iii) comparing thiazides, alone or in combination; (iv) to placebo or another medication; and (v) reporting fractures or BMD. Conference abstracts and studies comparing thiazides to antiresorptive or anabolic bone therapy were excluded. Bias was assessed using Cochrane Collaboration's Risk of Bias Tool-2. The primary outcome was fracture at any anatomical site. Secondary outcomes were osteoporotic fractures, hip fractures, and BMD at femoral neck, lumbar spine, and/or total hip. Fractures were pooled as risk ratios (RRs) using random-effect models. Prespecified subgroup analyses and post hoc sensitivity analyses were conducted. From 15,712 unique records screened, 32 trials (68,273 patients) met eligibility criteria. Thiazides were associated with decreased fractures at any site (RR = 0.87, 95% confidence interval [CI] 0.77-0.98; I 2 = 0%) and osteoporotic fractures (RR = 0.80; 95% CI 0.69-0.94; I 2 = 0%). Results were consistent in most subgroups and sensitivity analyses. Few studies reported hip fractures, and no association was found between thiazides and this outcome (RR = 0.84; 95% CI 0.67-1.04; I 2 = 0%). Only four studies reported BMD; a meta-analysis was not conducted because BMD reporting was inconsistent. Trials were deemed at low (3 studies, weight = 3%), some concerns (16 studies; 71%), or high (11 studies; 26%) risk of bias for the primary outcome. In conclusion, thiazide diuretics decreases the risk of fractures at any and at osteoporotic sites in a meta-analysis of RCTs. Additional studies are warranted in patients with high fracture risk.

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“…The other nine trials [20][21][22][23][24][25][26][27][28] including a total of 3307 participants, had a variable 4 to 8 weeks pre-randomisation run-in on sub-maximal dual therapy, in all but one trial [20], before randomisation to either triple therapy (with the addition of an extra drug) or continued dual therapy.…”

Section: Characteristics Of Included Trialsmentioning

confidence: 99%

“…Goal BP levels to define BP control were similar across trials: <140 & <90 in seven trials [16][17][18][21][22][23][24], <140 & <90 or (<130 & <80 in those with diabetes and/or kidney disease) in five trials [15,19,20,27,28], DBP <90 or ≥10 mmHg reduction in DBP from baseline in two trials [25,26].…”

Section: Characteristics Of Included Trialsmentioning

confidence: 99%

Efficacy and safety of triple versus dual combination blood pressure-lowering drug therapy

Salam

Atkins

Hsu

et al. 2019

Journal of Hypertension

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Background and objectives: Most patients with hypertension need ≥2 drugs to achieve goal blood pressure. This systematic review assessed efficacy and safety of triple vs. dual combination therapy for the management of hypertension. Methods: Publication databases, clinical trials registries and regulatory agency websites were searched until April 2018 for double-blind randomised controlled trials (RCTs) comparing triple with dual therapy of BP lowering drugs, for ≥3 weeks, among patients with hypertension. Meta-analyses for efficacy and safety outcomes were performed using random-effects model. Regimen efficacy was predicted using the Therapeutic Intensity Score (TIS) and the Law et al. method (which predict dose doubling increases efficacy by 100% and around 20%, respectively), and compared with observed efficacy. Results: Fourteen RCTs (11,457 participants) were included. Overall, triple compared to dual therapy reduced BP by 5.4/3.2 mmHg (P<0.001), and improved BP control by 58% vs. 45%, (relative risk (RR) 1.33 [95% CI 1.25-1.41]), while incidence of withdrawals due to adverse events (AEs) were 3.3% vs. 3.4% (RR 1.24 [95% CI 1.00-1.54], p=0.05). Law et al. method was superior to TIS in predicting differences in efficacy between triple and dual therapies. For patients uncontrolled on sub-maximal dose dual therapy, adding a third drug achieved on average approximately four times more BP reduction than doubling the dose of dual therapy component drugs (6.0/3.7 vs. 1.5/0.8 mmHg, respectively). Conclusion: Addition of a third drug is likely to be more efficacious without increasing AEs, compared to increasing dose of existing dual therapy. Early use of triple therapy can significantly improve hypertension control.

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Add-on effect of hydrochlorothiazide 12.5 mg in Japanese subjects with essential hypertension uncontrolled with losartan 50 mg and amlodipine 5 mg

Cited by 11 publications

References 17 publications

The efficacy and long-term safety of a triple combination of 80 mg telmisartan, 5 mg amlodipine and 12.5 mg hydrochlorothiazide in Japanese patients with essential hypertension: a randomized, double-blind study with open-label extension

The efficacy and long-term safety of a triple combination of 80 mg telmisartan, 5 mg amlodipine and 12.5 mg hydrochlorothiazide in Japanese patients with essential hypertension: a randomized, double-blind study with open-label extension

Thiazide Diuretics and Fracture Risk: A Systematic Review and Meta‐Analysis of Randomized Clinical Trials

Efficacy and safety of triple versus dual combination blood pressure-lowering drug therapy

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