Valsartan reduces the incidence of atrial fibrillation in patients with heart failure: results from the Valsartan Heart Failure Trial (Val-HeFT).

Background Atrial fibrillation (AF) in heart failure (HF) is generally considered a negative prognostic factor. Recent studies indicate that the incidence of AF might be decreased by renin angiotensin aldosterone system inhibitors. The identification of a treatment to prevent its occurrence is likely to improve patients outcome. The aims of these subanalyses of Val-HeFT were to assess ( a ) the effects of valsartan in the prevention of AF, ( b ) the independent predictors of this event, and ( c ) the prognostic role of AF occurrence. Methods and Results The occurrence of AF was evaluated based on adverse event reports in the patients with HF enrolled in Val-HeFT. Patients were randomized to valsartan or placebo on top of their prescribed treatments for HF. During the mean 23 months of follow-up, AF was reported in 287/4395 patients (6.53%) in sinus rhythm at baseline, of whom 113/2205 (5.12%) were allocated to valsartan and 174/2190 (7.95%) to placebo ( P = .0002). Multivariable analysis showed that brain natriuretic peptide (BNP) levels at baseline above the median value (HR 2.28, 95% CI 1.75-2.98), age over 70 years (HR 1.51, 95% CI 1.17-1.95), male sex (HR 1.53, 95% CI 1.07-2.18), and the valsartan treatment (HR 0.63, 95% CI 0.49-0.81) were independently associated with AF occurrence. Cox multivariable regression analysis showed that occurrence of AF was independently associated with a worse prognosis, with the adjusted hazard risks for all-cause mortality and combined mortality/morbidity of 1.40 (95% CI 1.16-1.58) and 1.38 (95% CI 1.12-1.70), respectively. Conclusions The results of the present study demonstrate that ( a ) adding valsartan to prescribed therapy for HF significantly reduces the incidence of AF by 37%; ( b ) BNP level and advanced age were the strongest independent predictors for AF occurrence; and ( c ) AF occurrence further worsens the outcome in patients with HF.

[1]  P. Vardas,et al.  Low-dose amiodarone versus sotalol for suppression of recurrent symptomatic atrial fibrillation. , 1998, The American journal of cardiology.

[2]  P. Poole‐Wilson,et al.  Comparison of carvedilol and metoprolol on clinical outcomes in patients with chronic heart failure in the Carvedilol Or Metoprolol European Trial (COMET): randomised controlled trial , 2003, The Lancet.

[3]  Use of irbesartan to maintain sinus rhythm in patients with long-lasting persistent atrial fibrillation. A prospective and randomized study ☆ , 2002 .

[4]  S. Yusuf,et al.  Effects of candesartan in patients with chronic heart failure and reduced left-ventricular systolic function intolerant to angiotensin-converting enzyme inhibitors: the CHARM-alternative trial , 2004 .

[5]  A. Maggioni,et al.  Clinical correlates of elevated plasma natriuretic peptides and Big endothelin-1 in a population of ambulatory patients with heart failure. A substudy of the Italian Network on Congestive Heart Failure (IN-CHF) registry. IN-CHF Investigators. , 2000, Italian heart journal : official journal of the Italian Federation of Cardiology.

[6]  Nathan Mantel,et al.  Evaluation of Response-Time Data Involving Transient States: An Illustration Using Heart-Transplant Data , 1974 .

[7]  W. Kannel,et al.  Epidemiologic features of chronic atrial fibrillation: the Framingham study. , 1982, The New England journal of medicine.

[8]  M. Pfeffer,et al.  Effects of candesartan in patients with chronic heart failure and reduced left-ventricular systolic function intolerant to angiotensin-converting-enzyme inhibitors: the CHARM-Alternative trial , 2003, The Lancet.

[9]  D. Cox,et al.  Analysis of Survival Data. , 1985 .

[10]  S. Nattel,et al.  Effects of Angiotensin-Converting Enzyme Inhibition on the Development of the Atrial Fibrillation Substrate in Dogs With Ventricular Tachypacing–Induced Congestive Heart Failure , 2001, Circulation.

[11]  S. Yusuf,et al.  Incidence, predictive factors, and prognostic significance of supraventricular tachyarrhythmias in congestive heart failure. , 2000, Chest.

[12]  K. Arakawa,et al.  Angiotensin II antagonist prevents electrical remodeling in atrial fibrillation. , 2000, Circulation.

[13]  Amiodarone to Prevent Recurrence of Atrial Fibrillation , 2000 .

[14]  S. Nattel.  New ideas about atrial fibrillation 50 years on , 2002, Nature.

[15]  S. Nattel,et al.  Ionic Remodeling in the Heart: Pathophysiological Significance and New Therapeutic Opportunities for Atrial Fibrillation , 2000, Circulation research.

[16]  Fach,et al.  Effect of metoprolol CR/XL in chronic heart failure: Metoprolol CR/XL Randomised Intervention Trial in-Congestive Heart Failure (MERIT-HF) , 1999, The Lancet.

[17]  K. Arakawa,et al.  Effects of angiotensin II type 1 receptor antagonist on electrical and structural remodeling in atrial fibrillation. , 2003, Journal of the American College of Cardiology.

[18]  S. Connolly,et al.  Antiarrhythmic effects of azimilide in atrial fibrillation: efficacy and dose-response. Azimilide Supraventricular Arrhythmia Program 3 (SVA-3) Investigators. , 2000, Journal of the American College of Cardiology.

[19]  K. Stangl,et al.  Use of metoprolol CR/XL to maintain sinus rhythm after conversion from persistent atrial fibrillation: a randomized, double-blind, placebo-controlled study. , 2000, Journal of the American College of Cardiology.

[20]  M. Pfeffer,et al.  Effects of candesartan on mortality and morbidity in patients with chronic heart failure: the CHARM-Overall programme , 2003, The Lancet.

[21]  M. Nieminen,et al.  For Personal Use. Only Reproduce with Permission from the Lancet Publishing Group , 2022 .

[22]  J. Bauman,et al.  Comparison of sotalol versus quinidine for maintenance of normal sinus rhythm in patients with chronic atrial fibrillation. , 1999, The American journal of cardiology.

[23]  A. Goette,et al.  Blockade of atrial angiotensin II type 1 receptors: a novel antiarrhythmic strategy to prevent atrial fibrillation? , 2003, Journal of the American College of Cardiology.

[24]  L. Køber,et al.  Trandolapril reduces the incidence of atrial fibrillation after acute myocardial infarction in patients with left ventricular dysfunction. , 1999, Circulation.

[25]  M. Allessie,et al.  Atrial fibrillation begets atrial fibrillation. A study in awake chronically instrumented goats. , 1995, Circulation.

[26]  H. Crijns,et al.  Comparison of plasma neurohormones in congestive heart failure patients with atrial fibrillation versus patients with sinus rhythm. , 1998, The American journal of cardiology.

[27]  M A Waclawiw,et al.  Atrial fibrillation is associated with an increased risk for mortality and heart failure progression in patients with asymptomatic and symptomatic left ventricular systolic dysfunction: a retrospective analysis of the SOLVD trials. Studies of Left Ventricular Dysfunction. , 1998, Journal of the American College of Cardiology.

[28]  J. Cohn,et al.  A randomized trial of the angiotensin-receptor blocker valsartan in chronic heart failure. , 2001, The New England journal of medicine.

[29]  A. Ducharme,et al.  Enalapril Decreases the Incidence of Atrial Fibrillation in Patients With Left Ventricular Dysfunction Insight From the Studies Of Left Ventricular Dysfunction (SOLVD) Trials , 2003, Circulation.

[30]  J. Cohn,et al.  Rationale and design of the Valsartan Heart Failure Trial: a large multinational trial to assess the effects of valsartan, an angiotensin-receptor blocker, on morbidity and mortality in chronic congestive heart failure. , 1999, Journal of cardiac failure.

[31]  Karl Swedberg,et al.  Effects of candesartan in patients with chronic heart failure and reduced left-ventricular systolic function taking angiotensin-converting-enzyme inhibitors: the CHARM-Added trial , 2003, The Lancet.

[32]  F. Morady,et al.  Short-term effect of atrial fibrillation on atrial contractile function in humans. , 1999, Circulation.

[33]  L. Tavazzi,et al.  Predictors of primary atrial fibrillation and concomitant clinical and hemodynamic changes in patients with chronic heart failure: a prospective study in 344 patients with baseline sinus rhythm. , 1998, Journal of the American College of Cardiology.