Antihypertensive effect of Hydrochlorthiazide

A meta-analysis of use of hydrochlorthiazide (HCTZ) in management of hypertension has been published in the January issue of J Am Coll Cardiol (1) .

The trials with the following criteria were included in the meta-analysis: 1) randomized trials involving patients with hypertension that assessed the antihypertensive efficacy by 24-h Ambulatory Blood Pressure (ABP) monitoring comparing HCTZ with other antihypertensive drug classes; 2) use of HCTZ as a monotherapy in the trial; and 3) trial duration of at least 4 weeks.

The main outcome of the present analysis was BP (systolic/diastolic) reduction from baseline to follow-up.

Results: The antihypertensive efficacy of HCTZ in the dose of 12.5 to 25 mg was assessed from 14 randomized controlled trials.

·       The mean baseline BP in these studies was 148 ± 7.5/92 ± 5.6 mm Hg.

·       After treatment with HCTZ for a mean duration of 17 weeks, systolic ABP decreased by 6.5 mm Hg  and diastolic ABP by 4.5 mm Hg.

·       Other antihypertensive agents such as ACE inhibitors, ARBs, beta-blockers, and calcium antagonists were significantly more efficacious than HCTZ in the dose of 12.5 to 25 mg.

·       In head-to-head comparisons with other antihypertensive drug classes, HCTZ in the usual dose of 12.5 to 25 mg lowered systolic ABP less well than ACE inhibitors by 4.5 mm Hg (p = 0.001), ARBs by 5.1 mm Hg, beta-blockers by 6.2 mm Hg (p < 0.00001), and calcium antagonists by 4.5 mm Hg (p = 0.02).

·        HCTZ lowered diastolic ABP less well than ACE inhibitors by 4.0 mm Hg (p < 0.0001), ARBs by 2.9 mm Hg (p = 0.002), beta-blockers by 6.7 mm Hg (p < 0.00001), and calcium antagonists by 4.2 mm Hg (p = 0.0001)

·   The antihypertensive effect of HCTZ was similar to other antihypertensives in controlling the office BP, whereas it was inferior to other antihypertensives in controlling ABP.

·    The authors have mentioned that assessing the antihypertensive efficacy of HCTZ by office BP measurements only is deceptive and is prone to provide to physicians and patients a false sense of security.

·       At a daily dose of 50 mg and above, HCTZ's antihypertensive efficacy seems to be similar to most other drug classes. However, all biochemical adverse effects such as hypokalemia, hyponatremia, hyperuricemia, insulin resistance, and visceral fat accumulation are dose dependent and become clinically more significant with daily doses exceeding 25 mg (2).  

·       In its commonly used dose of 12.5 to 25 mg once a day, there has been no evidence that HCTZ reduces myocardial infarction, stroke, or death.

·       Numerous, mostly factorial design studies have shown that when combined with these drug classes, HCTZ, even at low doses, elicits a distinct incremental fall in BP. That indicates that HCTZ is more useful as an "enhancer" or "sensitizer" for the antihypertensive effect of renin-angiotensin system blockers than as a monotherapeutic agent. The ACCOMLISH trial shows HCTZ to be inferior to amlodipine.(3)

·       The authors concluded that HCTZ in its commonly used dose of 12.5 to 25 mg daily lowers BP significantly less well than do all other drug classes as measured in head-to-head studies by ABP monitoring.

The meta-analysis has also been discussed on: http://www.theheart.org/article/1176571.do#bib_2

References:

1.     http://content.onlinejacc.org/cgi/content/long/57/5/590

2.     Messerli FH, Bangalore S, Julius S. Risk/benefit assessment of beta-blockers and diuretics precludes their use for first-line therapy in hypertension Circulation 2008;117:2706-2715discussion 2715

3.     Jamerson K, Weber MA, Bakris GL, et al. Benazepril plus amlodipine or hydrochlorothiazide for hypertension in high-risk patients N Engl J Med 2008;359:2417-2428.

Budesonide for eosinophilic esophagitis

Results of a  randomized, double-blind, placebo-controlled trial to evaluate the effect of oral budesonide (1 mg twice daily for 15 days) in adolescent and adult patients with active EoE. Eosinophilic esophagitis has been published in November 2010 issue of Gastroenterology journal.(1)

 (EoE) is a chronic inflammatory disease of the esophagus characterized by dense tissue eosinophilia; it is refractory to proton pump inhibitor therapy.

EoE affects all age groups but most frequently individuals between 20 and 50 years of age. Topical corticosteroids are effective in pediatric patients with EoE, but no controlled studies of corticosteroids have been reported in adult patients.

METHODS: A pretreatment and post-treatment disease activity was assessed clinically, endoscopically, and histologically.

 The primary end point was reduced mean numbers of eosinophils in the esophageal epithelium (number per high-power field [hpf] = esophageal eosinophil load). Esophageal biopsy and blood samples were analyzed using immunofluorescence and immunoassays, respectively, for biomarkers of inflammation and treatment response.

RESULTS:

·       A 15-day course of therapy significantly decreased the number of eosinophils in the esophageal epithelium in patients given budesonide (from 68.2 to 5.5 eosinophils/hpf; P < .0001) but not in the placebo group (from 62.3 to 56.5 eosinophils/hpf; P = .48).

·       Dysphagia scores significantly improved among patients given budesonide compared with those given placebo (5.61 vs 2.22; P < .0001).

·       White exudates and red furrows were reversed in patients given budesonide, based on endoscopy examination. Budesonide, but not placebo, also reduced apoptosis of epithelial cells and molecular remodeling events in the esophagus; no serious adverse events were observed.

The authors concluded that a 15-day course of treatment with budesonide is well tolerated and highly effective in inducing a histologic and clinical remission in adolescent and adult patients with active EoE.

(1) http://www.ncbi.nlm.nih.gov/pubmed/20682320?dopt=Abstract

Consumption of Added Sugars and Risk of cardiovascular diseases

In the January issue of Circulation, a cross-sectional study ‘Consumption of Added Sugars and Indicators of Cardiovascular Disease Risk among US Adolescents’ has been published.(1)

Methods: In a cross-sectional study of 2157 US adolescents in the National Health and Nutrition Examination Survey (NHANES) 1999 to 2004, dietary data from one 24-hour recall were merged with added sugar content data from the US Department of Agriculture MyPyramid Equivalents databases.

Measures of cardiovascular disease risk were estimated by added sugar consumption level (<10%, 10 to <15%, 15 to <20%, 20 to <25%, 25 to <30%, and 30% of total energy).

Multivariable means were weighted to be representative of US adolescents and variances adjusted for the complex sampling methods.

Results:

·       Daily consumption of added sugars averaged 21.4% of total energy.

·       Added sugars intake was inversely correlated with mean high-density lipoprotein cholesterol levels (mmol/L) which were 1.40 (95% confidence interval [CI] 1.36 to 1.44) among the lowest consumers and 1.28 (95% CI 1.23 to 1.33) among the highest (P trend =0.001).

·       Added sugars were positively correlated with low-density lipoproteins (P trend =0.01) and geometric mean triglycerides (P trend =0.05).

·       Among the lowest and highest consumers, respectively, low-density lipoproteins (mmol/L) were 2.24 (95% CI 2.12 to 2.37) and 2.44 (95% CI 2.34 to 2.53), and triglycerides (mmol/L) were 0.81 (95% CI 0.74, 0.88) and 0.89 (95% CI 0.83 to 0.96).

·       Among those overweight/obese ( 85th percentile body-mass-index), added sugars were positively correlated with the homeostasis model assessment (P linear trend =0.004).

The authors concluded that the consumption of added sugars among US adolescents is positively associated with multiple measures known to increase cardiovascular disease risk.



(1) http://circ.ahajournals.org/cgi/content/abstract/123/3/249?etoc

ACCELERATE results

The results of a randomized, parallel group trial comparing Aliskiren and the calcium channel blocker amlodipine combination as an initial treatment strategy for hypertension control (ACCELERATE) have been published in the recent issue of Lancet.(1)

The researchers tested whether a combination of aliskiren and amlodipine is superior to each monotherapy in early control of blood pressure without excess of adverse events, and if initial control by monotherapy impairs subsequent control by combination therapy.

Methods:

·       It was a double-blind, randomised, parallel-group, superiority trial at 146 primary and secondary care sites in ten countries, with enrolment from Nov 28, 2008, to July 15, 2009.

·       Eligible patients were suffering from essential hypertension, aged 18 years or older, and had systolic blood pressure between 150 and 180 mm Hg.

·       Patients were randomly assigned (1:1:2) to treatment with

o   150 mg aliskiren plus placebo,

o   5 mg amlodipine plus placebo,

o   or 150 mg aliskiren plus 5 mg amlodipine.

·       From 16-32 weeks, all patients received combination therapy with 300 mg aliskiren plus 10 mg amlodipine.

·       The primary endpoints, assessed on an intention-to-treat basis (ie, in patients who received the allocated treatment), were the adjusted mean reduction in systolic blood pressure from baseline over 8 to 24 weeks, and then the final reduction at 24 weeks.

Results:

·       318 patients were randomly assigned to aliskiren, 316 to amlodipine, and 620 to aliskiren plus amlodipine.

·       Patients given initial combination therapy had a 6·5 mm Hg (95% CI 5·3 to 7·7) greater reduction in mean systolic blood pressure than the monotherapy groups (p<0·0001).

·        At 24 weeks, when all patients were on combination treatment, the difference was 1·4 mm Hg (95% CI -0·05 to 2·9; p=0·059).

·       Adverse events caused withdrawal of 85 patients (14%) from the initial aliskiren plus amlodipine group, 45 (14%) from the aliskiren group, and 58 (18%) from the amlodipine group. Adverse events were peripheral oedema, hypotension, or orthostatic hypotension.

The authors have concluded that routine initial reduction in blood pressure (>150 mm Hg) with a combination such as aliskiren plus amlodipine can be recommended.

(1) http://www.ncbi.nlm.nih.gov/pubmed/21236483?dopt=Abstract