1.
Effect of amiloride, or amiloride plus hydrochlorothiazide, versus hydrochlorothiazide on glucose tolerance and blood pressure (PATHWAY-3): a parallel-group, double-blind randomised phase 4 trial.
Brown, MJ, Williams, B, Morant, SV, Webb, DJ, Caulfield, MJ, Cruickshank, JK, Ford, I, McInnes, G, Sever, P, Salsbury, J, et al
The lancet. Diabetes & endocrinology. 2016;(2):136-47
Abstract
BACKGROUND Potassium depletion by thiazide diuretics is associated with a rise in blood glucose. We assessed whether addition or substitution of a potassium-sparing diuretic, amiloride, to treatment with a thiazide can prevent glucose intolerance and improve blood pressure control. METHODS We did a parallel-group, randomised, double-blind trial in 11 secondary and two primary care sites in the UK. Eligible patients were aged 18-80 years; had clinic systolic blood pressure of 140 mm Hg or higher and home systolic blood pressure of 130 mmHg or higher on permitted background drugs of angiotensin-converting enzyme inhibitors, angiotensin-receptor blockers, β blockers, calcium-channel blockers, or direct renin inhibitors (previously untreated patients were also eligible in specific circumstances); and had at least one component of the metabolic syndrome in addition to hypertension. Patients with known diabetes were excluded. Patients were randomly assigned (1:1:1) to 24 weeks of daily oral treatment with starting doses of 10 mg amiloride, 25 mg hydrochlorothiazide, or 5 mg amiloride plus 12·5 mg hydrochlorothiazide; all doses were doubled after 12 weeks. Random assignment was done via a central computer system. Both participants and investigators were masked to assignment. Our hierarchical primary endpoints, assessed on a modified intention-to-treat basis at 12 and 24 weeks, were the differences from baseline in blood glucose measured 2 h after a 75 g oral glucose tolerance test (OGTT), compared first between the hydrochlorothiazide and amiloride groups, and then between the hydrochlorothiazide and combination groups. A key secondary endpoint was change in home systolic blood pressure at 12 and 24 weeks. This trial is registered with ClinicalTrials.gov, number NCT00797862, and the MHRA, Eudract number 2009-010068-41, and is now complete. FINDINGS Between Nov 18, 2009, and Dec 15, 2014, 145 patients were randomly assigned to amiloride, 146 to hydrochlorothiazide, and 150 to the combination group. 132 participants in the amiloride group, 134 in the hydrochlorothiazide group, and 133 in the combination group were included in the modified intention-to-treat analysis. 2 h glucose concentrations after OGTT, averaged at 12 and 24 weeks, were significantly lower in the amiloride group than in the hydrochlorothiazide group (mean difference -0·55 mmol/L [95% CI -0·96 to -0·14]; p=0·0093) and in the combination group than in the hydrochlorothiazide group (-0·42 mmol/L [-0·84 to -0·004]; p=0·048). The mean reduction in home systolic blood pressure during 24 weeks did not differ significantly between the amiloride and hydrochlorothiazide groups, but the fall in blood pressure in the combination group was significantly greater than that in the hydrochlorothiazide group (p=0·0068). Hyperkalaemia was reported in seven (4·8%) patients in the amiloride group and three (2·3%) patients in the combination group; the highest recorded potassium concentration was 5·8 mmol/L in a patient in the amiloride group. 13 serious adverse events occurred but the frequency did not differ significantly between groups. INTERPRETATION The combination of amiloride with hydrochlorothiazide, at doses equipotent on blood pressure, prevents glucose intolerance and improves control of blood pressure compared with montherapy with either drug. These findings, together with previous data about morbidity and mortality for the combination, support first-line use of amiloride plus hydrochlorothiazide in hypertensive patients who need treatment with a diuretic. FUNDING British Heart Foundation and National Institute for Health Research.
2.
Effects of recommendations to follow the Dietary Approaches to Stop Hypertension (DASH) diet v. usual dietary advice on childhood metabolic syndrome: a randomised cross-over clinical trial.
Saneei, P, Hashemipour, M, Kelishadi, R, Rajaei, S, Esmaillzadeh, A
The British journal of nutrition. 2013;(12):2250-9
Abstract
The effects of the Dietary Approaches to Stop Hypertension (DASH) eating plan on childhood metabolic syndrome (MetS) and insulin resistance remain to be determined. The present study aimed to assess the effects of recommendations to follow the DASH diet v. usual dietary advice (UDA) on the MetS and its features in adolescents. In this randomised cross-over clinical trial, sixty post-pubescent adolescent girls with the MetS were randomly assigned to receive either the recommendations to follow the DASH diet or UDA for 6 weeks. After a 4-week washout period, the participants were crossed over to the alternate arm. The DASH group was recommended to consume a diet rich in fruits, vegetables and low-fat dairy products and low in saturated fats, total fats and cholesterol. UDA consisted of general oral advice and written information about healthy food choices based on healthy MyPlate. Compliance was assessed through the quantification of plasma vitamin C levels. In both the groups, fasting venous blood samples were obtained at baseline and at the end of each phase of the intervention. The mean age and weight of the participants were 14.2 (SD 1.7) years and 69 (SD 14.5) kg, respectively. Their mean BMI and waist circumference were 27.3 kg/m2 and 85.6 cm, respectively. Serum vitamin C levels tended to be higher in the DASH phase than in the UDA phase (860 (SE 104) v. 663 (SE 76) ng/l, respectively, P= 0.06). Changes in weight, waist circumference and BMI were not significantly different between the two intervention phases. Although changes in systolic blood pressure were not statistically significant between the two groups (P= 0.13), recommendations to follow the DASH diet prevented the increase in diastolic blood pressure compared with UDA (P= 0.01). We found a significant within-group decrease in serum insulin levels (101.4 (SE 6.2) v. 90.0 (SE 5.5) pmol/l, respectively, P= 0.04) and a non-significant reduction in the homeostasis model assessment for insulin resistance score (P= 0.12) in the DASH group. Compared with the UDA group, the DASH group experienced a significant reduction in the prevalence of the MetS and high blood pressure. Recommendations to follow the DASH eating pattern for 6 weeks among adolescent girls with the MetS led to reduced prevalence of high blood pressure and the MetS and improved diet quality compared with UDA. This type of healthy diet can be considered as a treatment modality for the MetS and its components in children.