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Ambulatory Blood Pressure Reduction With SGLT-2 Inhibitors: Dose-Response Meta-analysis and Comparative Evaluation With Low-Dose Hydrochlorothiazide.
Georgianos, PI, Agarwal, R
Diabetes care. 2019;(4):693-700
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Abstract
OBJECTIVE Sodium-glucose cotransporter (SGLT)-2 inhibitors lower clinic and ambulatory blood pressure (BP), possibly through their natriuretic action. However, it remains unclear whether this BP-lowering effect is dose dependent and different from that of low-dose hydrochlorothiazide. The purpose of this meta-analysis was to quantify the association of the dose with response of ambulatory BP to SGLT-2 inhibition and to provide comparative evaluation with low-dose hydrochlorothiazide. RESEARCH DESIGN AND METHODS PubMed/MEDLINE, Embase, and Cochrane database of clinical trials from inception of each database through 22 August 2018. Randomized controlled trials (RCTs) reporting treatment effects of SGLT-2 inhibitors on ambulatory BP. We extracted data on the mean difference between the active treatment and placebo groups in change from baseline (CFB) of ambulatory systolic and diastolic BP. RESULTS We identified seven RCTs (involving 2,381 participants) comparing SGLT-2 inhibitors with placebo. Of these, two RCTs included low-dose hydrochlorothiazide as active comparator. CFB in 24-h systolic BP between SGLT-2 inhibitor and placebo groups was -3.62 mmHg (95% CI -4.29, -2.94) and in diastolic BP was -1.70 mmHg (95% CI -2.13, -1.26). BP lowering with SGLT-2 inhibition was more potent during daytime than during nighttime. The CFB in ambulatory BP was comparable between low-dose and high-dose subgroups and was similar to that for low-dose hydrochlorothiazide. Eligible RCTs did not evaluate cardiovascular outcomes/mortality. CONCLUSIONS This meta-analysis shows that SGLT-2 inhibitors provoke an average reduction of systolic/diastolic BP 3.62/1.70 mmHg in 24-h ambulatory BP. This BP-lowering effect remains unmodified regardless of the dose of SGLT-2 inhibitor and is comparable with BP-lowering efficacy of low-dose hydrochlorothiazide.
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Hydrochlorothiazide is not the most useful nor versatile thiazide diuretic.
Vongpatanasin, W
Current opinion in cardiology. 2015;(4):361-5
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Abstract
PURPOSE OF REVIEW To determine usefulness and versatility of hydrochlorothiazide (HCTZ) relative to other thiazide diuretics in the treatment of hypertension. RECENT FINDINGS HCTZ was found to be less potent in lowering blood pressure (BP) than other thiazide diuretics, including chlorthalidone (CTD) and bendroflumethiazide. A recent meta-analysis also suggested HCTZ (12.5-25 mg daily) to be less potent than antihypertensive agents from several other classes, including angiotensin-converting enzyme inhibitors, angiotensin-receptor blockers, and calcium antagonists. The risk of hyponatremia, hypokalemia, and hyperuricemia associated with HCTZ was lower than with CTD, while the risk of gouty arthritis was similar. Despite lower risks of metabolic side-effects, meta-analysis of clinical trials showed that, for any given difference in achieved clinic SBP, HCTZ therapy was associated with 18% higher adverse cardiovascular events when compared with CTD. SUMMARY Increasing evidence suggests inferiority of HCTZ in lowering BP and cardiovascular outcomes in hypertensive patients when compared with other drugs in the same class, particularly CTD and indapamide. Thus, HCTZ is neither more useful nor more versatile than other thiazide diuretics. CTD and indapamide should be preferred over HCTZ in most hypertensive patients when diuretics are required for treatment of hypertension.
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[Kinzalkomb, a fixed telmisartan-hydrochlorothiazide combination for the treatment of hypertension].
Kulbertus, H
Revue medicale de Liege. 2003;(9):580-4
Abstract
Kinzalkomb marketed in Belgium by Bayer is a fixed combination of telmisartan 80 mg and hydrochlorothiazide 125 mg for the treatment of hypertension. New guidelines for the treatment of hypertension were recently released both in Europe and the United States (see article by J.M. Krzesinski in this issue). They offer the choice of using a fixed biotherapy even as first line treatment. Hydrochlorothiazide at low dose is a frequent component of such biotherapies: it is efficacious and secure. Telmisartan is a highly selective blocker of angiotensin II AT1 receptors ("sartans"); it is at least as effective as the classical antihypertensive agents; thanks to its half-life, the longest of all sartans', it provides adequate antihypertensive coverage throughout the whole 24-hour postdose interval and particularly over the last 6 hours of the dosage interval. Its tolerability profile is equivalent to placebo. The combination telmisartan-hydrochlorothiazide is more effective than each agent alone at lowering blood pressure; furthermore telmisartan possesses a potassium-sparing effect that when the two drugs are coadministered attenuates the kaliuretic effect of hydrochlorothiazide. Various large trials are currently under way (ONTARGET, TRANSCEND, PROFESS, PROTECTION, DETAIL). These studies which together involve some 50,000 patients will hopefully help to further specify the role of telmisartan in condition which require an intervention on the renin-angiotensin system.