Validation study definition of validation study by. A direction of change in ntprobnp values over time closely reflected changes in prognosis. Patient information for cuenca 80mg filmcoated tablets including dosage instructions and possible side effects. Heart failure with improved ejection fraction aha journals. Isosorbide dinitratehydralazine combination therapy in african. The value study also showed that the treatment with valsartan significantly inhibited the new. Angiotensin ii contributes to cardiac remodeling that leads to decreased left ventricular function and progressive heart failure. In the valsartan heart failure trial valheft study, 14 a fourmonth logtransformed continuous ntprobnp value added incremental prognostic value to a baseline measurement in a multivariable model to predict mortality hr 1. Angiotensin receptor blockers for chronic heart failure and. Study design and patient selection valheft was a randomized, placebocontrolled, doubleblind trial that enrolled 5010 patients with new york heart association functional class ii to iv hf and an ef of val heft, journal of cardiac failure on deepdyve, the largest online rental service for scholarly research with thousands of academic publications available at your fingertips. In total, 300 sites from 16 countries participated in the valheft trial.
Study design and patient selection val heft was a randomized, placebocontrolled, doubleblind trial that enrolled 5010 patients with new york heart association functional class ii to iv hf and an ef of val heft end points5. According to the american college of cardiologyamerican heart association practice guidelines, echocardiography is the single most useful test in the evaluation of patients with heart failure hf. Additional trials established this was a class effect for aceinhibitors. A total of 5,010 patients with stable, symptomatic hf who were on prescribed hf therapy and had left ventricular ejection fraction lvef 40% and left ventricular diameter in diastole. Combination of isosorbide dinitrate and hydralazine in. Valheft was a randomized, doubleblind parallelarm study in which hf patients new york heart association class iiiv received either valsartan n 2511, forcetitrated to 160 mg twice daily or placebo n 2499 in addition to prescribed hf.
Mean doses of acei at randomisation, during and at the conclusion of the study are listed in table 2. In hf patients not receiving aceis, valsartan reduced allcause mortality by 33 % and composite mortality and morbidity risk by 44 % compared with placebo in the val heft trial. Among other things, it offers the ability to assess chamber size, shape, and function, filling pressures, pulmonary artery pressure, valvular disease, congenital abnormalities, and. Valheft was a randomized, doubleblind parallelarm study in which hf patients new york heart association class iiiv received either valsartan n 2511, forcetitrated to 160 mg twice daily. In the original valheft study, a total of 5,010 symptomatic hf patients were enrolled, 3,374 67% of whom were on digoxin at baseline. In summary, this trial demonstrated that treating patients with congestive heart failure with.
The val heft study was a randomized, placebocontrolled, doubleblind, parallelarm multicenter trial. An echocardiographic substudy of valheft reported a modest reversal of lv remodeling in patients treated with valsartan, with an average reduction in the enddiastolic diameter of 0. A second large trial, val heft, was presented at the scientific sessions of the american heart association in 2000. Serge masson, roberto latini, inder s anand, tarcisio vago, laura angelici, simona barlera, emil d missov, aldo clerico, gianni tognoni, jay n cohn, direct comparison of btype natriuretic peptide bnp and aminoterminal probnp in a large population of patients with chronic and symptomatic heart failure. To compare the efficacy of the ace inhibitor enalapril with that of hydralazine plus isosorbide dinitrate in patients with chronic. Effect of carvedilol on outcome after myocardial infarction.
A total of 5,010 patients with stable, symptomatic hf who were on prescribed hf therapy and had left ventricular ejection fraction lvef ii. Similarly, in the valheft study, change in st2 values over time was significantly and independently associated with mortality. Specifically, the v heft ii trial demonstrated that enalapril was superior to isdnhydralazine in patients with mildtomoderate heart failure. The valheft study was a randomized, placebocontrolled, doubleblind, parallelarm multicenter trial. Val heft enrolled 5010 patients, mainly new york heart association nyha functional class ii and iii with low ejection fraction and evidence of left ventricular dilatation. Natera announced results of a prospective validation study published in the journal of clinical medicine demonstrating 100% accuracy of its panorama noninvasive prenatal test in determining zygosity, fetal sex, and chromosomal abnormalities in twins as early as 9 weeks of gestation. In summary, the valheft trial demonstrated an important role for arbs in the management of heart failure. Simultaneously published, the v heft ii and solvd trials were landmark studies that were the first to demonstrate mortality benefit with ace inhibition in patients with mildtomoderate heart failure. The role of angiotensin receptor blockers in reducing the. Finally, valsartan was associated with only a moderate increase in ejection fraction when compared with other prior trials involving ace inhibitors and betablockers. The africanamerican heart failure trial aheft was a randomized, placebocontrolled, doubleblind trial with patients recruited at 161 centers in the united states.
Sep 19, 2001 although the study populations were similar in most respects, differences were noted with regard to the number of patients treated with an ace inhibitor elite ii 23% prior to randomisation, valheft 92% and with a betablocker elite ii 22%, valheft 33%. Data from patients with hfref val heft valsartan heart failure trial and hfpef ipreserve irbesartan in heart failure with preserved ejection fraction study trials show that despite significantly higher baseline levels of np in hfref, the hazard for mortality associated with 1 log unit increase in nterminal probtype natriuretic. A comparison of the prognostic value of bnp versus nt. Oct 25, 2018 similarly, in the valheft study, change in st2 values over time was significantly and independently associated with mortality. A subgroup analysis of the valsartan heart failure trial val heft was performed to evaluate the effects of the angiotensin ii receptor blocker, valsartan, in the patients with chronic heart. Cardiac biomarkers and heart failure american college of. The trial randomized 5,010 with lvef 90% of the patients were on aceinhibitors but only 25% were on metoprolol or carvedilol. Effect of valsartan added to background ace inhibitor therapy. Effect of valsartan on hospitalization in valheft request pdf. Gdf15 increases during tissue injury and inflammatory states and is associated with cardiometabolic risk. Arbs or angiontension ii receptor blockers, were evaluated as substitutes for acei in the 2001 valsartan heart failure trial or valheft. The explanation for these discrepancies is not clear.
The key features of the design of valheft trial are shown in tables 1 and 2. Angiotensin receptor blockers for chronic heart failure. Over 10 million scientific documents at your fingertips. The valsartan heart failure trial valheft was a randomized, placebocontrolled, doubleblind, parallelgroup trial. A randomized trial of the angiotensinreceptor blocker. Sudden cardiac death in heart failure trial scdheft. Additional studies are needed, however, to fully define the role of angiotensin ii receptor antagonists in the management of this very. The demographic and baseline characteristics of this subgroup were similar to the overall val. A total of 5,010 patients with stable, symptomatic hf who were on prescribed hf therapy and had left ventricular ejection fraction lvef study. Publications home of jama and the specialty journals of the. Dec 14, 2004 the demographic and baseline characteristics of this subgroup were similar to the overall val. Effects of valsartan on circulating brain natriuretic.
Pdf previous trials metoprolol crxl randomised intervention trial in. The study was designed with two primary end points. A preliminary report also revealed that changes in ef over time were associated with corresponding changes in mortality and morbidity risks. In this study of stable outpatients with systolic hf, good adherence to the home exercise training intervention over a median of 30 months occurred in only. Design valheft was an international, randomized, multicenter, doubleblind trial that compared valsartan and placebo added to prescribed treatment in. Patients with stable, symptomatic hf n5010 who were on prescribed hf therapy and had lv ejection fraction 2. Valheft, which included serial echocardiograms in all patients randomized, confirmed the relationship between attenuation or reversal of remodeling and clinical benefit. In the valheft study the prognostic values of bnp and ntprobnp were compared in patients with stable chronic hf and in that study ntprobnp was better in terms of predicting outcome. Severity of left ventricular remodeling defines outcomes and. The valheft study supports the use of valsartan in patients with chronic hf who are intolerant to ace inhibitors. Pdf the carvedilol prospective randomized cumulative survival.
A posthoc subgroup analysis found increased mortality in individuals on valsartan, ace inhibitor therapy, and beta blockers. In a post hoc analysis of the combined end point and mortality in subgroups defined according to baseline treatment with. In patients treated longterm after an acute myocardial infarction complicated by leftventricular systolic dysfunction, carvedilol reduced the frequency of allcause and cardiovascular mortality, and recurrent, nonfatal myocardial infarctions. Growth differentiation factor15 gdf15 is a stress responsive cytokine. Although the study populations were similar in most respects, differences were noted with regard to the number of patients treated with an ace inhibitor elite ii 23% prior to randomisation, val heft 92% and with a betablocker elite ii 22%, val heft 33%. Thus, the results of the charmalternative study, along with subgroup analysis in the valheft trial of 7% of patients who were not on ace inhibitors, have shown that arbs specifically candesartan and valsartan confer significant benefit on mortality and morbidity in patients with hf who are intolerant of ace inhibitors and therefore. However, predicting outcome after hospital discharge for worsening hf may be more difficult, but is clinically relevant. The vasodilatorheart failure trial i vheft i sought to explore the effects of using a combination of hydralazine and isosorbide dinitrate in managing heart failure.
The aim of this study was to determine echocardiographic predictors of outcome in patients with advanced heart failure hf due to severe left ventricular lv systolic dysfunction in the betablocker evaluation of survival trial best. The current study assesses the ability of nterminal probtype natriuretic peptide ntprobnp and highsensitivity cardiac troponin t hsctnt to improve the prediction of cardiovascular events and death in patients with type 2 diabetes. Severity of left ventricular remodeling defines outcomes. These beneficial effects are additional to those of evidencebased treatments for acute myocardial infarction including ace inhibitors. Vasodilatorheart failure trial 1 vheft ii vasodilatorheart failure trial. Smith r, fletcher r, for the vheft va cooperative studies.
The sudden cardiac death in heart failure trial scd heft was designed to evaluate the hypothesis that amiodarone or a conservatively programmed shockonly, singlelead implantable cardioverter defibrillator icd would decrease the risk of death from any cause in a broad population of patients with mildtomoderate heart failure. Design val heft was an international, randomized, multicenter, doubleblind trial that compared valsartan and placebo added to prescribed treatment in 5010 patients with chronic heart. Aims of the present study were 1 to confirm the prognostic role of anemia in patients with heart failure hf and 2 to analyze this aspect in relatively unselected patients with hf monitored prospectively in a community setting inchf, and in patients selected for enrolment into the valsartan heart failure trial valheft. In this viewpoint, milton packer and colleagues argue that reliance on a threshold of lvef. Diabetes and heart failure the two diseases entities are highly coprevalent diabetes contributes to disease progression in hf and is associated with substantially worse prognosis, even when. However, among those patients who received ace inhibitors and. Angiotensin receptor blockers the cardiology advisor.
Valheft was a randomized, placebocontrolled, doubleblind, parallelarm multicenter trial. The 2001 valsartan heart failure trial val heft provided an interesting window to the role of arb therapy in hfref. Study design the valsartan heart failure trial valheft was a randomized, placebocontrolled, doubleblind, parallelgroup trial. While the valheft study found that combination therapy was beneficial, 16 the astronaut 17 and atmosphere 26 studies did not. Preventing readmission after hospitalization for acute. The vasodilatorheart failure trial i v heft i sought to explore the effects of using a combination of hydralazine and isosorbide dinitrate in managing heart failure. Objective current methods of risk stratification in patients with type 2 diabetes are suboptimal. The valsartan heart failure trial valheft was a randomized, place.
Valsartan treatment lowered plasma crp concentrations in the valsartan heart failure trial valheft. Although the study populations were similar in most respects, differences were noted with regard to the number of patients treated with an ace inhibitor elite ii 23% prior to randomisation, valheft 92% and with a betablocker elite ii 22%, valheft 33%. In a dosedependent fashion, hyd suppressed the production of the free radicals. As the studies of vasodilator therapies in heart failure developed, there. There was little change in mean dose of acei over the duration of the val. In hf patients not receiving aceis, valsartan reduced allcause mortality by 33 % and composite mortality and morbidity risk by 44 % compared with placebo in the valheft trial. The relative and combined ability of highsensitivity. Valsartan benefits left ventricular structure and function in heart failure. The vheft i study enrolled 642 men, of which 180 or 28% were african american.
Direct comparison of btype natriuretic peptide bnp and aminoterminal probnp in a large population of patients with chronic and symptomatic heart failure. The key features of the design of val heft trial are shown in tables 1 and 2. Metaanalyses of mortality and morbidity effects of. The 1992 solvd treatment study established enalapril as first line therapy in preventing hf progression. Our metaanalysis provides some insights into the controversy surrounding the effect of dual ras blockade in the treatment of patients with hf. Combination of isosorbide dinitrate and hydralazine in blacks. Direct comparison of btype natriuretic peptide bnp and. Lead investigator of the trial, dr salim yusuf mcmaster university, hamilton, on, commented. Patients at 302 centers in 16 countries gave written informed. The valsartan heart failure trial valheft was a randomized. In the overall study population, valsartan caused significant improvements in new york heart association nyha class, ejection fraction, and hf signs and symptoms and. Effects of valsartan on circulating brain natriuretic peptide. Effects of dual blockade in heart failure and renal.
A randomized trial of the angiotensinreceptor blocker valsartan. The valsartan heart failure valheft data, clinical chemistry, volume 52, issue 8, 1. Future studies of betablockade may focus on these patients or patients. Objectives the guideit guiding evidence based therapy using biomarker intensified treatment in heart failure study is designed to determine the safety, efficacy, and costeffectiveness of a strategy of adjusting therapy with the goal of achieving and maintaining a target nterminal probtype natriuretic peptide ntprobnp level of study of stable outpatients with systolic hf, good adherence to the home exercise training intervention over a median of 30 months occurred in only. In summary, the val heft trial demonstrated an important role for arbs in the management of heart failure. It is highly expressed in cardiomyocytes, adipocytes, macrophages, endothelial cells, and vascular smooth muscle cells in normal and pathological condition. In the resolvd and valheft studies, not all patients were treated with an acei, and only the subgroups that were are included in this metaanalysis. The 2001 valsartan heart failure trial valheft provided an interesting window to the role of arb therapy in hfref. Effects of valsartan on morbidity and mortality in. Baseline demographics of the valsartan heart failure trial cohn. Val heft was a randomized, placebocontrolled, doubleblind, parallelarm multicenter trial. Publications home of jama and the specialty journals of. In both elite ii and valheft, patients were stratified according to background beta. Valheft was a randomized, doubleblind parallelarm study in which hf patients new york heart association class iiiv received either valsartan n 2511, forcetitrated to 160 mg twice daily or placebo n 2499 in addition to prescribed hf therapy.