Aims: Diabetes mellitus is associated with worse outcomes and lower attainment of disease-modifying therapies in patients with heart failure with reduced ejection fraction (HFrEF). This post hoc analysis of TRANSITION compared the patterns of tolerability and uptitration of sacubitril/valsartan in patients with HFrEF stabilized after hospital admission due to acute decompensated HF depending on the presence or absence of diabetes as a co-morbidity.
Methods: TRANSITION, a randomized, open-label study compared sacubitril/valsartan initiation pre-discharge vs.
Curr Med Res Opin
December 2021
Objective: To assess the dose-response relationship for reduction in mean systolic blood pressure (MSBP) with valsartan solution, in young children with hypertension with or without chronic kidney disease (CKD).
Methods: In this multicenter, randomized, double-blind, double-dummy study, 127 young children aged 1-5 years with hypertension (MSBP ≥95th percentile) were randomized (1:1) to receive valsartan 0.25 or 4 mg/kg/day for 6 weeks, followed by a 20 week open-label phase, where patients received valsartan 1 mg/kg/day for 4 weeks, and then optionally titrated to 2 mg/kg/day or up to 4 mg/kg/day.
Background: Early treatment intensification leading to sustained good glycaemic control is essential to delay diabetic complications. Although initial combination therapy has been suggested to offer more opportunities than a traditional stepwise approach, its validity remains to be determined.
Methods: Vildagliptin Efficacy in combination with metfoRmIn For earlY treatment of type 2 diabetes (VERIFY) was a randomised, double-blind, parallel-group study of newly diagnosed patients with type 2 diabetes conducted in 254 centres across 34 countries.
Aims: To ensure the integrity of the planned analyses and maximize the clinical utility of the VERIFY study results by describing the detailed concepts behind its statistical analysis plan (SAP) before completion of data collection and study database lock. The SAP will be adhered to for the final primary data analysis of the VERIFY trial.
Materials And Methods: Vildagliptin efficacy in combination with metformin for early treatment of T2DM (VERIFY) is an ongoing, multicentre, randomized controlled trial aiming to demonstrate the clinical benefits of glycaemic durability and glucose control achieved with an early combination therapy in newly-diagnosed type 2 diabetes (T2DM) patients.
Eur J Heart Fail
January 2018
Aims: Because of concerns about the safety of aliskiren in patients with diabetes, study treatment was stopped prematurely in the Aliskiren Trial of Minimizing OutcomeS for Patients with HEart failuRE (ATMOSPHERE). We examined outcomes and treatment effect in these patients compared with those without diabetes.
Methods And Results: ATMOSPHERE included 7016 patients with heart failure and a reduced ejection fraction (HFrEF) randomly assigned to enalapril plus aliskiren, aliskiren alone, or enalapril.
Background: Among patients with chronic heart failure, angiotensin-converting-enzyme (ACE) inhibitors reduce mortality and hospitalization, but the role of a renin inhibitor in such patients is unknown. We compared the ACE inhibitor enalapril with the renin inhibitor aliskiren (to test superiority or at least noninferiority) and with the combination of the two treatments (to test superiority) in patients with heart failure and a reduced ejection fraction.
Methods: After a single-blind run-in period, we assigned patients, in a double-blind fashion, to one of three groups: 2336 patients were assigned to receive enalapril at a dose of 5 or 10 mg twice daily, 2340 to receive aliskiren at a dose of 300 mg once daily, and 2340 to receive both treatments (combination therapy).
Aims And Methods: To: (i) describe the baseline characteristics of patients in ATMOSPHERE and the changes in the planned analysis of ATMOSPHERE resulting from the mandated discontinuation of study treatment in patients with diabetes; (ii) compare the baseline characteristics of patients in ATMOSPHERE with those in the Prospective comparison of Angiotensin Receptor neprilysin inhibitors with Angiotensin converting enzyme inhibitors to Determine Impact on Global Mortality and morbidity in Heart Failure trial (PARADIGM-HF); and (iii) compare the characteristics of patients with and without diabetes at baseline in ATMOSPHERE.
Results: A total of 7063 patients were randomized into ATMOSPHERE April 2009-April 2014 at 755 sites in 43 countries. Their average age was 63 years and 78% were men.
Background: The Avoiding Cardiovascular Events through Combination Therapy in Patients Living with Systolic Hypertension (ACCOMPLISH) trial showed that initial antihypertensive therapy with benazepril plus amlodipine was superior to benazepril plus hydrochlorothiazide in reducing cardiovascular morbidity and mortality. We assessed the effects of these drug combinations on progression of chronic kidney disease.
Methods: ACCOMPLISH was a double-blind, randomised trial undertaken in five countries (USA, Sweden, Norway, Denmark, and Finland).
Background: By blocking the renin-angiotensin-aldosterone system (RAAS) at its rate-limiting step, renin inhibition may provide improved RAAS suppression. We investigated the blood pressure (BP)-lowering effects of the oral direct renin inhibitor aliskiren, alone or in combination with the angiotensin receptor blocker valsartan.
Methods: In this multicenter, randomized, placebo-controlled, 8-week trial, 1123 patients with mild-to-moderate hypertension underwent a 3 to 4 week single-blind placebo run-in and were then randomized in a modified factorial study design to receive once-daily, double-blind oral treatment with placebo, aliskiren monotherapy (75, 150, or 300 mg), valsartan monotherapy (80, 160, or 320 mg), aliskiren and valsartan in combination, or valsartan/hydrochlorothiazide (160/12.
Background: Clinical trials emphasize mortality and morbidity endpoints.
Aims: To bring relevance of trial results to point of care by examining the prognostic and therapeutic value of individual signs and symptoms (S&S).
Methods: We analysed data from 5010 patients with stable chronic heart failure and left ventricular dysfunction who were participants in the Val-HeFT study.
Background: Stopping the detrimental effects of the renin-angiotensin system at the most upstream point of the cascade offers theoretical advantages for cardiovascular protection. This study compares the antihypertensive efficacy and safety of the novel oral renin inhibitor aliskiren with placebo and an active comparator.
Methods And Results: The study was a randomized, multicenter, double-blind, placebo-controlled, active-comparator 8-week trial in patients with mild-to-moderate hypertension (mean sitting diastolic blood pressure [DBP] > or =95 and <110 mm Hg).
Aims: To investigate the effect of valsartan in the Valsartan-Heart Failure Trial (Val-HeFT) when added to angiotensin-converting enzyme inhibitor (ACEi) alone in patients with heart failure (HF).
Methods: Subjects in Val-HeFT receiving ACEi but not beta-blocker at baseline were analysed; 1532 were assigned to valsartan and 1502 assigned to placebo. Primary outcome events (all-cause mortality, hospitalisation for adjudicated heart failure, sudden death with resuscitation and need for >4 h of parenteral therapy for worsening heart failure) were monitored.
Background: Aldosterone has been implicated in the progression of heart failure. The Valsartan Heart Failure Trial (Val-HeFT) provided the first opportunity to examine the long-term effects of an angiotensin receptor blocker on plasma aldosterone levels in patients with NYHA class II through IV heart failure.
Methods And Results: Plasma aldosterone was measured by radioimmunoassay in core laboratories at baseline and during follow-up in patients assigned to valsartan at a target dose of 160 mg twice daily or placebo.
Background: Neurohormones are considered markers of heart failure progression. We examined whether changes in brain natriuretic peptide (BNP) and norepinephrine (NE) over time are associated with corresponding changes in mortality and morbidity in the Valsartan Heart Failure Trial.
Methods And Results: Plasma BNP and NE were measured before randomization and during follow-up in approximately 4300 patients in the Valsartan Heart Failure Trial.
Background: Brain natriuretic peptide (BNP) and norepinephrine (NE) are strongly related to severity of and are independent predictors of outcome in heart failure. The long-term effects of angiotensin receptor blockers on BNP and NE in heart failure patients are not known.
Methods And Results: Both BNP and NE were measured in 4284 patients randomized to valsartan or placebo in the Valsartan Heart Failure Trial (Val-HeFT) at baseline and 4, 12, and 24 months after randomization.
Objectives: The objective of the study was to evaluate the effect of an angiotensin receptor blocker on left ventricular (LV) structure and function when added to prescribed heart failure therapy.
Background: The clinical benefit derived from heart failure therapy is attributed to the regression of LV remodeling.
Methods: At 302 multinational sites, 5,010 patients in New York Heart Association (NYHA) classification II to IV heart failure taking angiotensin-converting enzyme inhibitor (ACEI) and/or beta-blocker (BB) were randomized into valsartan and placebo groups and followed for a mean of 22.