Dataset Information

Blood pressure-lowering effects of nifedipine/candesartan combinations in high-risk individuals: subgroup analysis of the DISTINCT randomised trial.

ABSTRACT: The DISTINCT study (reDefining Intervention with Studies Testing Innovative Nifedipine GITS-Candesartan Therapy) investigated the efficacy and safety of nifedipine GITS/candesartan cilexetil combinations vs respective monotherapies and placebo in patients with hypertension. This descriptive sub-analysis examined blood pressure (BP)-lowering effects in high-risk participants, including those with renal impairment (estimated glomerular filtration rate<90?ml?min-1, n=422), type 2 diabetes mellitus (n=202), hypercholesterolaemia (n=206) and cardiovascular (CV) risk factors (n=971), as well as the impact of gender, age and body mass index (BMI). Participants with grade I/II hypertension were randomised to treatment with nifedipine GITS (N) 20, 30, 60?mg and/or candesartan cilexetil (C) 4, 8, 16, 32?mg or placebo for 8 weeks. Mean systolic BP and diastolic BP reductions after treatment in high-risk participants were greater, overall, with N/C combinations vs respective monotherapies or placebo, with indicators of a dose-response effect. Highest rates of BP control (ESH/ESC 2013 guideline criteria) were also achieved with highest doses of N/C combinations in each high-risk subgroup. The benefits of combination therapy vs monotherapy were additionally observed in patient subgroups categorised by gender, age or BMI. All high-risk participants reported fewer vasodilatory adverse events in the pooled N/C combination therapy than the N monotherapy group. In conclusion, consistent with the DISTINCT main study outcomes, high-risk participants showed greater reductions in BP and higher control rates with N/C combinations compared with respective monotherapies and lesser vasodilatory side-effects compared with N monotherapy.

SUBMITTER: Mancia G

PROVIDER: S-EPMC5301082 | biostudies-literature | 2017 Mar

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Blood pressure-lowering effects of nifedipine/candesartan combinations in high-risk individuals: subgroup analysis of the DISTINCT randomised trial.

Mancia G G Cha G G Gil-Extremera B B Harvey P P Lewin A J AJ Villa G G Kjeldsen S E SE

Journal of human hypertension 20160811 3

The DISTINCT study (reDefining Intervention with Studies Testing Innovative Nifedipine GITS-Candesartan Therapy) investigated the efficacy and safety of nifedipine GITS/candesartan cilexetil combinations vs respective monotherapies and placebo in patients with hypertension. This descriptive sub-analysis examined blood pressure (BP)-lowering effects in high-risk participants, including those with renal impairment (estimated glomerular filtration rate<90 ml min<sup>-1</sup>, n=422), type 2 diabete ...[more]

PMID: 27511476

Similar Datasets

Project description:BackgroundRandom assignment to the intensive systolic blood pressure (SBP) arm (<120mmHg) in the Systolic Blood Pressure Intervention Trial (SPRINT) resulted in more rapid declines in estimated glomerular filtration rates (eGFRs) than in the standard arm (SBP<140mmHg). Whether this change reflects hemodynamic effects or accelerated intrinsic kidney damage is unknown.Study designLongitudinal subgroup analysis of clinical trial participants.Settings & participantsRandom sample of SPRINT participants with prevalent chronic kidney disease (CKD) defined as eGFR<60mL/min/1.73m2 by the CKD-EPI (CKD Epidemiology Collaboration) creatinine-cystatin C equation at baseline.Outcomes & measurementsUrine biomarkers of tubule function (β2-microglobulin [B2M], α1-microglobulin [A1M]), and uromodulin), injury (interleukin 18, kidney injury molecule 1, and neutrophil gelatinase-associated lipocalin), inflammation (monocyte chemoattractant protein 1), and repair (human cartilage glycoprotein 40) at baseline, year 1, and year 4. Biomarkers were indexed to urine creatinine concentration and changes between arms were evaluated using mixed-effects linear models and an intention-to-treat approach.Results978 SPRINT participants (519 in the intensive and 459 in the standard arm) with prevalent CKD were included. Mean age was 72±9 years and eGFR was 46.1±9.4mL/min/1.73m2 at baseline. Clinical characteristics, eGFR, urinary albumin-creatinine ratio, and all 8 biomarker values were similar across arms at baseline. Compared to the standard arm, eGFR was lower by 2.9 and 3.3mL/min/1.73m2 in the intensive arm at year 1 and year 4. None of the 8 tubule marker levels was higher in the intensive arm compared to the standard arm at year 1 or year 4. Two tubule function markers (B2M and A1M) were 29% (95% CI, 10%-43%) and 24% (95% CI, 10%-36%) lower at year 1 in the intensive versus standard arm, respectively.LimitationsExclusion of persons with diabetes, and few participants had advanced CKD.ConclusionsAmong participants with CKD in SPRINT, random assignment to the intensive SBP arm did not increase any levels of 8 urine biomarkers of tubule cell damage despite loss of eGFR. These findings support the hypothesis that eGFR declines in the intensive arm of SPRINT predominantly reflect hemodynamic changes rather than intrinsic damage to kidney tubule cells.

Project description:BackgroundMorning hypertension is a risk factor for cardiovascular and cerebrovascular events, and consequently diagnosis and control of morning hypertension are considered very important. We previously reported the results of the Azelnidipine Treatment for Hypertension Open-label Monitoring in the Early morning (At-HOME) Study, which indicated that azelnidipine effectively controlled morning hypertension.ObjectivesThe objective of this At-HOME subgroup analysis was to evaluate the sustained blood pressure (BP)-lowering effect of azelnidipine, using mean morning and evening systolic BP [ME average] and morning systolic BP minus evening systolic BP (ME difference).MethodsWe analyzed the self-measured home BP data (measured in the morning and at bedtime) from this 16-week prospective observational study to clarify the effect of morning dosing of azelnidipine (mean [± standard deviation] maximum dose 14.3 ± 3.6 mg/day). A subgroup of patients from the At-HOME Study who had an evening home BP measurement within 28 days prior to the baseline date were used for efficacy analysis (n = 2,546; mean age, 65.1 years; female, 53.6 %).ResultsHome systolic BP/diastolic BP levels in the morning and evening were significantly lowered (p < 0.0001) by -19.4 ± 17.1/-10.3 ± 10.6 and -16.9 ± 17.0/-9.4 ± 10.6 mmHg, respectively. Home pulse rates in the morning and evening were also significantly lowered (p < 0.0001) by -3.5 ± 7.8 and -3.5 ± 7.3 beats/min, respectively. At baseline, patients whose ME average was ≥135 mmHg and whose ME difference was ≥15 mmHg (defined as morning-predominant hypertension) accounted for 20.4 % of the study population. However, at the end of the study, the number of such patients was significantly reduced to 7.9 % (p < 0.0001). Patients whose ME average was ≥135 mmHg and whose ME difference was <15 mmHg (defined as sustained hypertension) accounted for 71.1 % of the study population at baseline. This was reduced significantly to 42.8 % at the end of the study (p < 0.0001). ME average decreased significantly from 153.8 ± 15.5 mmHg to 135.6 ± 11.9 mmHg, and ME difference also decreased significantly from 6.7 ± 13.1 mmHg to 4.7 ± 10.8 mmHg (both p < 0.0001).ConclusionThese results suggest that azelnidipine improved morning hypertension with its sustained BP-lowering effect.

Project description:ObjectiveTo determine the average reduction in blood pressure, prevalence of adverse effects, and reduction in risk of stroke and ischaemic heart disease events produced by the five main categories of blood pressure lowering drugs according to dose, singly and in combination.DesignMeta-analysis of 354 randomised double blind placebo controlled trials of thiazides, beta blockers, angiotensin converting enzyme (ACE) inhibitors, angiotensin II receptor antagonists, and calcium channel blockers in fixed dose.Subjects40,000 treated patients and 16,000 patients given placebo.Main outcome measuresPlacebo adjusted reductions in systolic and diastolic blood pressure and prevalence of adverse effects, according to dose expressed as a multiple of the standard (recommended) doses of the drugs.ResultsAll five categories of drug produced similar reductions in blood pressure. The average reduction was 9.1 mm Hg systolic and 5.5 mm Hg diastolic at standard dose and 7.1 mm Hg systolic and 4.4 mm Hg diastolic (20% lower) at half standard dose. The drugs reduced blood pressure from all pretreatment levels, more so from higher levels; for a 10 mm Hg higher blood pressure the reduction was 1.0 mm Hg systolic and 1.1 mm Hg diastolic greater. The blood pressure lowering effects of different categories of drugs were additive. Symptoms attributable to thiazides, beta blockers, and calcium channel blockers were strongly dose related; symptoms caused by ACE inhibitors (mainly cough) were not dose related. Angiotensin II receptor antagonists caused no excess of symptoms. The prevalence of symptoms with two drugs in combination was less than additive. Adverse metabolic effects (such as changes in cholesterol or potassium) were negligible at half standard dose.ConclusionsCombination low dose drug treatment increases efficacy and reduces adverse effects. From the average blood pressure in people who have strokes (150/90 mm Hg) three drugs at half standard dose are estimated to lower blood pressure by 20 mm Hg systolic and 11 mm Hg diastolic and thereby reduce the risk of stroke by 63% and ischaemic heart disease events by 46% at age 60-69.

Project description:BackgroundThe landmark Antihypertensive and Lipid-Lowering treatment to prevent Heart Attack Trial (ALLHAT) placed a new spotlight on thiazide diuretics as the first-line therapy for hypertension. This is concerning as thiazide-diuretics may contribute to comorbidities associated with the current epidemic of obesity. Previous randomized clinical trials have linked thiazide diuretic treatment to insulin resistance, metabolic syndrome, and increased incidence of type 2 diabetes.MethodsThis proof of concept, longitudinal, randomized, double-blind study evaluated the effects of the angiotensin II receptor blocker Valsartan and the specific thiazide diuretic Hydrochlorothiazide (HCTZ) on hepatic triglyceride level (primary outcome), as well as triglyceride levels within other organs including the heart, skeletal muscle, and pancreas. Additionally, we evaluated whether myocardial function, insulin sensitivity, and insulin secretion were affected by these treatments.ResultsHepatic TG levels increased by 57% post HCTZ treatment: ∆hTG HCTZ = 4.12% and remained unchanged post Valsartan treatment: ∆hTG V = 0.06%. The elevation of hepatic TG levels after HCTZ treatment was additionally accompanied by a reduction in insulin sensitivity: ∆SI HCTZ = -1.14. Treatment with Valsartan resulted in improved insulin sensitivity: ∆SI V = 1.24. Treatment-induced changes in hepatic TG levels and insulin sensitivity were statistically significant between groups (phTG = 0.0098 and pSI = 0.0345 respectively). Disposition index, DI, remained unchanged after HCTZ treatment: ∆DI HCTZ = -141 but it was increased by a factor of 2 after treatment with Valsartan: ∆DI V =1018). However, the change between groups was not statistically significant. Both therapies did not modify abdominal visceral and subcutaneous fat mass as well as myocardial structure and function. Additionally, myocardial, pancreatic, and skeletal muscle triglyceride deposits remained unchanged in both therapeutic arms.ConclusionsOur findings are two-fold and relate to hepatic steatosis and insulin sensitivity. HCTZ treatment worsened hepatic steatosis measured as hepatic triglyceride content and reduced insulin sensitivity. Valsartan treatment did not affect hepatic triglyceride levels and improved insulin sensitivity. The results of this study reinforce the message that in patients at risk for type 2 diabetes it is particularly important to choose an antihypertensive regimen that lowers blood pressure without exacerbating patient's metabolic profile.

Dataset Information

Blood pressure-lowering effects of nifedipine/candesartan combinations in high-risk individuals: subgroup analysis of the DISTINCT randomised trial.

Publications

Blood pressure-lowering effects of nifedipine/candesartan combinations in high-risk individuals: subgroup analysis of the DISTINCT randomised trial.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets