Molecular and clinical investigations in patients with low-renin hypertension

Mackenzie, Isla S.

doi:10.1007/s10157-008-0071-4

Cited by 14 publications

(9 citation statements)

References 26 publications

(27 reference statements)

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“…But potassium-sparing diuretics target a common site of sodium retention in hypertension, and might be essential in the prevention of compensatory responses to the more proximally acting thiazide and loop diuretics. 9 Thus, the hypothesis arose for the present study that an adequate dose of potassium-sparing diuretic would have opposite effects on potassium and glucose to those of a thiazide diuretic, but would have similar or additional effects on blood pressure when the two were compared or combined.…”

Section: Introductionmentioning

confidence: 94%

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

Williams

Morant

et al. 2016

The Lancet Diabetes & Endocrinology

108

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SummaryBackgroundPotassium 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.MethodsWe 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.FindingsBetween 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 occ...

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Section: Introductionmentioning

confidence: 94%

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

Williams

Morant

et al. 2016

The Lancet Diabetes & Endocrinology

108

View full text Add to dashboard Cite

show abstract

“…Published data on the epidemiology of PRA are limited, but it is generally accepted that PRA declines with advancing age in hypertensive individuals and that older hypertensive subjects tend to have low PRA [21][22][23]. However, more recent and larger studies suggest that a substantial proportion of the elderly hypertensive population does not have low renin.…”

Section: Discussionmentioning

confidence: 92%

Antihypertensive Response to Thiazide Diuretic or Angiotensin Receptor Blocker in Elderly Hypertensives Is Not Influenced by Pretreatment Plasma Renin Activity

Weintraub

Duprez

Cushman

et al. 2012

Cardiovasc Drugs Ther

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“…The answer is almost certainly "No". In at least 3 series of hypertensive patients given spironolactione, the blood pressure response was not correlated with ARR or plasma aldosterone levels [30][31][32].…”

Section: Response To Mineralocorticoid Receptor Antagonistsmentioning

confidence: 92%

Primary aldosteronism: A contrarian view

Kaplan

2011

Rev Endocr Metab Disord

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This paper provides evidence that primary aldosteronism is likely much less common than is believed by the other authors of this collection. The basis for this contrarian view is simple: there is no way to know the true prevalence of PA because of the uncertain validity of all of the diagnostic procedures used to find and characterize this disease. Moreover, even if these uncertainties are overcome, the eventual treatment of most who have PA can be provided without the need for extensive testing and expensive treatment.

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Molecular and clinical investigations in patients with low-renin hypertension

Cited by 14 publications

References 26 publications

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

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

Antihypertensive Response to Thiazide Diuretic or Angiotensin Receptor Blocker in Elderly Hypertensives Is Not Influenced by Pretreatment Plasma Renin Activity

Primary aldosteronism: A contrarian view

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