The Experts below are selected from a list of 84 Experts worldwide ranked by ideXlab platform
Salsbury Jackie - One of the best experts on this subject based on the ideXlab platform.
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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
Elsevier, 2016Co-Authors: Brown, Morris J., Williams Bryan, Morant Steve, Webb, David J., Caulfield, Mark J., Cruickshank J. Kennedy, Ford Ian, Mcinnes Gordon, Sever Peter, Salsbury JackieAbstract: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 diureti
Jackie Salsbury - One of the best experts on this subject based on the ideXlab platform.
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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
The Lancet Diabetes & Endocrinology, 2016Co-Authors: Morris J. Brown, Bryan Williams, Steve Morant, David J. Webb, Mark J. Caulfield, J. Kennedy Cruickshank, Ian Ford, Gordon T. Mcinnes, Peter S. Sever, Jackie SalsburyAbstract:Summary 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.
Ulf Landmesser - One of the best experts on this subject based on the ideXlab platform.
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The year in cardiology 2015: prevention
European Heart Journal, 2016Co-Authors: M. John Chapman, Stefan Blankenberg, Ulf LandmesserAbstract:Improved prevention of cardiovascular disease (CVD) is of critical importance, as coronary heart disease (CHD) still represents the most common cause of death worldwide, engendering inestimable socioeconomic cost. The year 2015 has witnessed dramatic progress in CVD prevention on several fronts. Notably, this includes (i) event reduction in high-risk patients in general practice following introduction of a comprehensive strategy to attenuate modifiable risk factors, including lifestyle and dietary habits; (ii) the study of hybrid imaging to detect subclinical atherosclerosis, with potential improvement in risk prediction/management; (iii) the clinical demonstration, that culprit plaque rupture was observed in only 50–77% of patients with acute coronary syndromes; (iv) the emergence of ‘omics’ technologies to identify new causal biofactors; (v) the validation in clinical trials of the efficacy of monoclonal antibodies targeted to proprotein convertase subtilisin/kexin type 9 (PCSK9) in markedly reducing levels of low-density lipoprotein cholesterol (LDL-C) across a spectrum of patients at high risk of premature CVD, with preliminary findings strongly suggestive of reduction in cardiovascular events; (vi) significant reduction of cardiovascular and all-cause mortality in diabetic patients in the EMPA-REG OUTCOME trial with the anti-hyperglycaemic agent, empagliflozin, a selective sodium-glucose co-transporter-2 (SGLAT-2) inhibitor; (vii) new pharmacotherapeutic strategies for superior control of hypertension emanating from the PATHWAY-2 and PATHWAY-3 clinical trials involving spironoloactone add-on therapy in resistant hypertension, and Amiloride Plus Hydrochlorothiazide in hypertensive patients requiring a diuretic, respectively; and finally (viii) a reduced mortality associated with a lower blood pressure target of 120 mmHg in patients at high cardiovascular risk in the SPRINT trial. Considered together, such progress augurs well for the future control of dyslipidaemia, hyperglycaemia, and hypertension, and with it, progressive reduction in atherosclerotic vascular disease and associated cardiovascular events in high-risk patients.
Brown, Morris J. - One of the best experts on this subject based on the ideXlab platform.
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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
Elsevier, 2016Co-Authors: Brown, Morris J., Williams Bryan, Morant Steve, Webb, David J., Caulfield, Mark J., Cruickshank J. Kennedy, Ford Ian, Mcinnes Gordon, Sever Peter, Salsbury JackieAbstract: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 diureti
Morris J. Brown - One of the best experts on this subject based on the ideXlab platform.
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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
The Lancet Diabetes & Endocrinology, 2016Co-Authors: Morris J. Brown, Bryan Williams, Steve Morant, David J. Webb, Mark J. Caulfield, J. Kennedy Cruickshank, Ian Ford, Gordon T. Mcinnes, Peter S. Sever, Jackie SalsburyAbstract:Summary 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.
