Thiazide and thiazide-like diuretics are widely used in the management of hypertension, but recently the equivalence of hydrochlorothiazide and chlorthalidone for blood pressure (BP) lowering and prevention of cardiovascular disease has been questioned. We performed a meta-analysis to characterize the dose-response relationships for 3 commonly prescribed thiazide diuretics, hydrochlorothiazide, chlorthalidone, and bendroflumethiazide, on BP, serum potassium, and urate. Randomized, double-blind, parallel placebo-controlled trials meeting the following criteria, ≥2 different monotherapy dose arms, follow-up duration ≥4 weeks, and baseline washout of medication ≥2 weeks, were identified using Embase (1980–2010 week 50), Medline (1950–2010 November week 3), metaRegister of Controlled Trials, and Cochrane Central. A total of 26 trials examined hydrochlorothiazide, 3 examined chlorthalidone, and 1 examined bendroflumethiazide. Studies included a total of 4683 subjects in >53 comparison arms. Meta-regression of the effect of thiazides on systolic BP showed a log-linear relationship with a potency series: bendroflumethiazide>chlorthalidone>hydrochlorothiazide. The estimated dose of each drug predicted to reduce systolic BP by 10 mm Hg was 1.4, 8.6, and 26.4 mg, respectively, and there was no evidence of a difference in maximum reduction of systolic BP by high doses of different thiazides. Potency series for diastolic BP, serum potassium, and urate were similar to those seen for systolic BP. Hydrochlorothiazide, chlorthalidone, and bendroflumethiazide have markedly different potency. This may account for differences in the antihypertensive effect between hydrochlorothiazide and chlorthalidone using standard dose ranges.

Meta-Analysis of Dose-Response Relationships for Hydrochlorothiazide, Chlorthalidone, and Bendroflumethiazide on Blood Pressure, Serum Potassium, and Urate

The central nervous system has a key role in regulating the circulatory system by modulating the sympathetic and parasympathetic nervous systems, pituitary hormone release, and the baroreceptor reflex. Digoxin- and ouabain-like immunoreactive materials were found >20 years ago in the hypothalamic nuclei. These factors appeared to localize to the paraventricular and supraoptic nuclei and the nerve fibers at the circumventricular organs and supposed to affect electrolyte balance and blood pressure. The turnover rate of these materials increases with increasing sodium intake. As intracerebroventricular injection of ouabain increases blood pressure via sympathetic activation, an endogenous digitalis-like factor (EDLF) was thought to regulate cardiovascular system-related functions in the brain, particularly after sodium loading. Experiments conducted mainly in rats revealed that the mechanism of action of ouabain in the brain involves sodium ions, epithelial sodium channels (ENaCs) and the renin–angiotensin–aldosterone system (RAAS), all of which are affected by sodium loading. Rats fed a high-sodium diet develop elevated sodium levels in their cerebrospinal fluid, which activates ENaCs. Activated ENaCs and/or increased intracellular sodium in neurons activate the RAAS; this releases EDLF in the brain, activating the sympathetic nervous system. The RAAS promotes oxidative stress in the brain, further activating the RAAS and augmenting sympathetic outflow. Angiotensin II and aldosterone of peripheral origin act in the brain to activate this cascade, increasing sympathetic outflow and leading to hypertension. Thus, the brain Na+–ENaC–RAAS–EDLF axis activates sympathetic outflow and has a crucial role in essential and secondary hypertension. This report provides an overview of the central mechanism underlying hypertension and discusses the use of antihypertensive agents.

/pdf/the-central-mechanism-underlying-hypertension-a-review-of-56isaolh5a.pdf

The central mechanism underlying hypertension: a review of the roles of sodium ions, epithelial sodium channels, the renin-angiotensin-aldosterone system, oxidative stress and endogenous digitalis in the brain.

SUMMARY Objective: To compare the efficacy of valsartan in systolic (SBP) and diastolic blood pressure (DBP) reduction with other angiotensin II receptor blockers (ARBs) in essential hypertension. Methods: Systematic literature search of databases between October 1997 and May 2008. Meta-analysis of short-term, double-blind, parallel group, randomised controlled trials (RCTs) for treatment of adult hypertension (DBP: 90–115 mmHg). Random-effects meta-regression adjusting for baseline blood pressure (BP) was used to analyse the data. Mean change in SBP and DBP was estimated for each individual drug and dose combination. Results: In all, 31 RCTs (n = 13,110 patients) were included in the analysis. Six studies include trial arms with candesartan, six irbesartan, 13 losartan, two olmesartan, five telmisartan and 12 valsartan. The weighted average reduction in mean SBP and DBP for valsartan 160 mg was )15.32 mmHg (95% CI: )17.09, )13.63) and )11.3 mmHg (95% CI: )12.15, )10.52) and for 320 mg was )15.85 mmHg (95% CI: )17.60, )14.12) and )11.97 mmHg (95% CI: )12.81, )11.16); these are statistically significantly greater reductions compared with losartan 100 mg, which was )12.01 mmHg (95% CI: )13.78, )10.25) and )9.37 mmHg (95% CI: )10.18, )8.54) for SBP and DBP respectively. There is evidence that valsartan 160 mg reduces SBP and DBP more than irbesartan 150 mg and reduced DBP more than candesartan 16 mg. No other statistically significant difference in efficacy is demonstrated. Conclusion: Valsartan administered at 160 or 320 mg is more effective at lowering BP than losartan 100 mg and shows comparable efficacy to other ARBs in patients with essential hypertension. Review Criteria Data was gathered from prospective double-blind randomised controlled trials, with at least one ARBs monotherapy arm with no or forced titration. Studies had to report change in office systolic or diastolic blood pressure from baseline to follow-up six to 12 weeks later. A random-effect metaregression model was used to estimate the overall mean change in blood pressure from baseline to follow-up.

https://onlinelibrary.wiley.com/doi/pdf/10.1111/j.1742-1241.2009.02028.x

Valsartan vs. other angiotensin II receptor blockers in the treatment of hypertension: a meta-analytical approach

http://diposit.ub.edu/dspace/bitstream/2445/113843/1/665391.pdf

Treatment efficacy of anti-hypertensive drugs in monotherapy or combination: ATOM systematic review and meta-analysis of randomized clinical trials according to PRISMA statement.

Background and objective:
Despite advances in the treatment of hypertension, control rates continue to be suboptimal in both Europe and the US. Strategies that improve hypertension control are therefore urgently needed. This study aimed to assess the relative efficacies of various antihypertensive drugs commonly used in France in reducing systolic and diastolic blood pressure (SBP and DBP) by using a meta-analytical approach. This update of a previously published meta-analytical approach extends the number of drugs evaluated from 13 to 19.

Updated Meta-Analytical Approach to the Efficacy of Antihypertensive Drugs in Reducing Blood Pressure

Introduction: Hypertension constitutes a veritable public health issue. Several classes of drugs are available for the treatment of hypertension. The objective of this meta-analytical approach was to assess the efficacy of antihypertensive drugs most commonly used in France in reducing clinical SBP and DBP. Methods: The antihypertensive drugs selected were hydrochlorothiazide, indapamide sustained release (SR), furosemide and spironolactone for diuretics; amlodipine and lercanidipine for calcium channel antagonists; atenolol for β-adrenoceptor antagonists (β-blockers); enalapril and ramipril for ACE inhibitors; and candesartan cilexetil, irbesartan, losartan, and valsartan for angiotensin II receptor antagonists. The trials selected were published between 1973 and 2004, evaluated monotherapy with trial drugs as fixed-dosage or with dosage increase, and assessed blood pressure reduction between 2 and 3 months. The analysis method used was based on the calculation of the sum weighted for the trial size. Results: A total of 72 trials (comprising 9094 patients) were selected and analyzed. No trial evaluating furosemide or spironolactone satisfied the inclusion criteria for this analysis. For SBP, the reduction was more marked with diuretics, calcium channel antagonists, and ACE inhibitors. Of all the drugs studied, indapamide SR gave the greatest SBP reduction (−22.2mm Hg). Evaluated therapeutic classes had a similar magnitude of effect on DBP, i. e. reduction between −11.4mm Hg with β-adrenoceptor antagonists and −10.3mm Hg with angiotensin II type 1 receptor antagonists. Conclusion: Indapamide SR 1.5mg appeared to be the most effective drug for a significant reduction in SBP within 2–3 months, which is an essential element in optimizing cardiovascular prevention among hypertensive patients. The clinical application of these results should take into consideration all the limitations discussed in this analysis.

A meta-analytical approach to the efficacy of antihypertensive drugs in reducing blood pressure.

Évaluation de la satisfaction des patients : quels enjeux ?

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A meta-analytical approach to the efficacy of antihypertensive drugs in reducing blood pressure.

Évaluation de la satisfaction des patients : quels enjeux ?