Early pharmacological treatment of acute heart failure syndromes: A systematic review of clinical trials

Context: Acute Heart Failure Syndromes (AHFS) is a common admission diagnosis associated with high mortality and hospital readmissions. Given the mixed results of recent clinical trials, the early management of AHFS remains controversial. Objective: To review the recent evidence regarding current and investigational therapies for the early management of AHFS. Data Sources: A systematic search of peer‐reviewed publications was performed on MEDLINE and EMBASE from January 1990 to August 2006. The results of unpublished or ongoing trials were obtained from presentations at national and international meetings and pharmaceutical industry releases. Bibliographies from these references were also reviewed, as were additional articles identified by content experts. Study Selection and Data Extraction: Criteria used for study selection were controlled study design, relevance to clinicians and validity based on venue of publication and power analysis. Data Synthesis: Although all current intravenous therapies for the early management of AHFS appear to improve hemodynamics, this may not always translate into short‐term clinical benefit. Conclusion: The results of the trials conducted to date in AHFS have generally been disappointing. There is, therefore, an unmet need for new therapeutic approaches for the early management of AHFS that may improve the short‐term and long‐term outcomes.

[1]  S. Silvers,et al.  Clinical policy: Critical issues in the evaluation and management of adult patients presenting to the emergency department with acute heart failure syndromes. , 2007, Annals of emergency medicine.

[2]  David D. Shin,et al.  Review of current and investigational pharmacologic agents for acute heart failure syndromes. , 2007, The American journal of cardiology.

[3]  E. Vanoli,et al.  Istaroxime: a new luso-inotropic agent for heart failure. , 2007, The American journal of cardiology.

[4]  David D. Shin,et al.  Improvement in hyponatremia during hospitalization for worsening heart failure is associated with improved outcomes: insights from the Acute and Chronic Therapeutic Impact of a Vasopressin Antagonist in Chronic Heart Failure (ACTIV in CHF) trial , 2007, Acute cardiac care.

[5]  P. Seferovic,et al.  Haemodynamic and clinical effects of ularitide in decompensated heart failure. , 2006, European heart journal.

[6]  Nancy M Albert,et al.  Systolic blood pressure at admission, clinical characteristics, and outcomes in patients hospitalized with acute heart failure. , 2006, JAMA.

[7]  M. Nieminen,et al.  Evidence-based use of levosimendan in different clinical settings. , 2006, European heart journal.

[8]  A. Boyle,et al.  Large volume ultrafiltration for acute decompensated heart failure using standard peripheral intravenous catheters. , 2006, Journal of cardiac failure.

[9]  M. Gheorghiade,et al.  Contemporary Use of Digoxin in the Management of Cardiovascular Disorders , 2006, Circulation.

[10]  J. Moran,et al.  Effect of non-invasive positive pressure ventilation (NIPPV) on mortality in patients with acute cardiogenic pulmonary oedema: a meta-analysis , 2006, The Lancet.

[11]  M. Mehra Optimizing outcomes in the patient with acute decompensated heart failure. , 2006, American heart journal.

[12]  R. Fernandez,et al.  Noninvasive ventilation in acute cardiogenic pulmonary edema: systematic review and meta-analysis. , 2005, JAMA.

[13]  Luigi Tavazzi,et al.  Acute Heart Failure Syndromes: Current State and Framework for Future Research , 2005, Circulation.

[14]  R. Bonow,et al.  Neurohormonal inhibition in heart failure: insights from recent clinical trials. , 2005, The American journal of cardiology.

[15]  F. Fedele,et al.  Overview of vasopressin receptor antagonists in heart failure resulting in hospitalization. , 2005, The American journal of cardiology.

[16]  P. Sobotka,et al.  Early ultrafiltration in patients with decompensated heart failure and diuretic resistance. , 2005, Journal of the American College of Cardiology.

[17]  R. Bourge,et al.  Ultrafiltration: a new approach toward mechanical diuresis in heart failure. , 2005, Journal of the American College of Cardiology.

[18]  V. Mitrović,et al.  Effects of the renal natriuretic peptide urodilatin (ularitide) in patients with decompensated chronic heart failure: a double-blind, placebo-controlled, ascending-dose trial. , 2005, American heart journal.

[19]  M. Gheorghiade,et al.  Vasopressin antagonism in heart failure. , 2005, Journal of the American College of Cardiology.

[20]  L. Tavazzi,et al.  Nationwide survey on acute heart failure in cardiology ward services in Italy. , 2005, European heart journal.

[21]  Gerasimos Filippatos,et al.  Pathophysiologic targets in the early phase of acute heart failure syndromes. , 2005, The American journal of cardiology.

[22]  M. Gheorghiade,et al.  Reassessment of dobutamine, dopamine, and milrinone in the management of acute heart failure syndromes. , 2005, The American journal of cardiology.

[23]  K. Adams,et al.  In-hospital mortality in patients with acute decompensated heart failure requiring intravenous vasoactive medications: an analysis from the Acute Decompensated Heart Failure National Registry (ADHERE). , 2005, Journal of the American College of Cardiology.

[24]  A. Hoes,et al.  Guidelines for the diagnosis and treatment of chronic heart failure: executive summary (update 2005): The Task Force for the Diagnosis and Treatment of Chronic Heart Failure of the European Society of Cardiology. , 2005, European heart journal.

[25]  R. Califf,et al.  Lower Serum Sodium Is Associated With Increased Short-Term Mortality in Hospitalized Patients With Worsening Heart Failure: Results From the Outcomes of a Prospective Trial of Intravenous Milrinone for Exacerbations of Chronic Heart Failure (OPTIME-CHF) Study , 2005, Circulation.

[26]  W. Peacock Morphine for Acute Decompensated Heart Failure: Valuable Adjunct or a Historical Remnant? , 2005 .

[27]  D. DeMets,et al.  Rationale and design of the multicenter, randomized, double-blind, placebo-controlled study to evaluate the Efficacy of Vasopressin antagonism in Heart Failure: Outcome Study with Tolvaptan (EVEREST). , 2005, Journal of cardiac failure.

[28]  K. Aaronson,et al.  Short-term risk of death after treatment with nesiritide for decompensated heart failure: a pooled analysis of randomized controlled trials. , 2005, JAMA.

[29]  V. Hasselblad,et al.  Demographics, clinical characteristics, and outcomes of patients hospitalized for decompensated heart failure: observations from the IMPACT-HF registry. , 2005, Journal of cardiac failure.

[30]  I. Jóna,et al.  Modulation of Sarcoplasmic Reticulum Function by Na+/K+ Pump Inhibitors with Different Toxicity: Digoxin and PST2744 [(E,Z)-3-((2-Aminoethoxy)imino)androstane-6,17-dione Hydrochloride] , 2005, Journal of Pharmacology and Experimental Therapeutics.

[31]  K. Aaronson,et al.  Risk of Worsening Renal Function With Nesiritide in Patients With Acutely Decompensated Heart Failure , 2005, Circulation.

[32]  Eduardo R Perna,et al.  Minor myocardial damage detected by troponin T is a powerful predictor of long-term prognosis in patients with acute decompensated heart failure. , 2005, International journal of cardiology.

[33]  Y. Seino,et al.  Multicenter prospective investigation on efficacy and safety of carperitide for acute heart failure in the 'real world' of therapy. , 2005, Circulation journal : official journal of the Japanese Circulation Society.

[34]  W John Boscardin,et al.  Risk stratification for in-hospital mortality in acutely decompensated heart failure: classification and regression tree analysis. , 2005, JAMA.

[35]  K. Adams,et al.  Characteristics and outcomes of patients hospitalized for heart failure in the United States: rationale, design, and preliminary observations from the first 100,000 cases in the Acute Decompensated Heart Failure National Registry (ADHERE). , 2005, American heart journal.

[36]  K. Dickstein,et al.  [Executive summary of the guidelines on the diagnosis and treatment of acute heart failure]. , 2005, Italian heart journal. Supplement : official journal of the Italian Federation of Cardiology.

[37]  Christopher M O'Connor,et al.  Risk stratification after hospitalization for decompensated heart failure. , 2004, Journal of cardiac failure.

[38]  A. Ferreira,et al.  N-Terminal–Pro-Brain Natriuretic Peptide Predicts Outcome After Hospital Discharge in Heart Failure Patients , 2004, Circulation.

[39]  J. Hollander,et al.  Primary results of the Rapid Emergency Department Heart Failure Outpatient Trial (REDHOT). A multicenter study of B-type natriuretic peptide levels, emergency department decision making, and outcomes in patients presenting with shortness of breath. , 2004, Journal of the American College of Cardiology.

[40]  J. Verbalis,et al.  Novel Vasopressin V1A and V2 Antagonist (Conivaptan) Increases Serum Sodium Concentration and Effective Water Clearance in Patients with Hyponatremia , 2004 .

[41]  W. Peacock,et al.  368 Impact of intravenous diuretics on the outcomes of patients hospitalized with acute decompensated heart failure: insights from the ADHERE® Registry , 2004 .

[42]  C. O'connor,et al.  Effects of Tolvaptan, a Vasopressin Antagonist, in Patients Hospitalized with Worsening Heart Failure: A Randomized Controlled Trial , 2004 .

[43]  E. Adamopoulou,et al.  835-6 The effect of a calcium sensitizer or an inotrope or none in chronic low output decompensated heart failure: Results from the calcium sensitizer or inotrope or none in low output heart failure study (CASINO) , 2004 .

[44]  C. O'connor,et al.  Relationship between heart failure treatment and development of worsening renal function among hospitalized patients. , 2004, American heart journal.

[45]  Peter C Austin,et al.  Predicting mortality among patients hospitalized for heart failure: derivation and validation of a clinical model. , 2003, JAMA.

[46]  K. Adams,et al.  Risk stratification for in-hospital mortality in heart failure using classification and regression tree (CART) methodology: analysis of 33,046 patients in the ADHERE registry , 2003 .

[47]  C. O'connor,et al.  Results of a twelve week double-blind, placebo-controlled, multicenter study of oral conivaptan to assess functional capacity in patients with class III chronic heart failure , 2003 .

[48]  C. O'connor,et al.  Usefulness of anemia as a predictor of death and rehospitalization in patients with decompensated heart failure. , 2003, The American journal of cardiology.

[49]  G. Fonarow,et al.  Cardiac Troponin I Is Associated With Impaired Hemodynamics, Progressive Left Ventricular Dysfunction, and Increased Mortality Rates in Advanced Heart Failure , 2003, Circulation.

[50]  P. Schwartz,et al.  Hemodynamic Effects of a New Inotropic Compound, PST-2744, in Dogs With Chronic Ischemic Heart Failure , 2003, Journal of cardiovascular pharmacology.

[51]  B. Lewis,et al.  Hemodynamic and clinical effects of tezosentan, an intravenous dual endothelin receptor antagonist, in patients hospitalized for acute decompensated heart failure. , 2003, Journal of the American College of Cardiology.

[52]  N. Freemantle,et al.  The EuroHeart Failure Survey programme--a survey on the quality of care among patients with heart failure in Europe. Part 2: treatment. , 2003, European heart journal.

[53]  W. Abraham,et al.  Peripherally inserted veno-venous ultrafiltration for rapid treatment of volume overloaded patients. , 2003, Journal of cardiac failure.

[54]  V. Hasselblad,et al.  Tezosentan in patients with acute heart failure and acute coronary syndromes: results of the Randomized Intravenous TeZosentan Study (RITZ-4). , 2003, Journal of the American College of Cardiology.

[55]  H. Krumholz,et al.  Outcomes in heart failure patients with preserved ejection fraction: mortality, readmission, and functional decline. , 2003, Journal of the American College of Cardiology.

[56]  Christopher M O'Connor,et al.  Heart failure etiology and response to milrinone in decompensated heart failure: results from the OPTIME-CHF study. , 2003, Journal of the American College of Cardiology.

[57]  M. Packer,et al.  Development of a comprehensive new endpoint for the evaluation of new treatments for acute decompensated heart failure: results with levosimendan in the REVIVE 1 study , 2003 .

[58]  N. Freemantle,et al.  The EuroHeart Failure Survey programme - a survey on the quality of care among patients with heart failure in Europe. Part 2: treatment , 2003 .

[59]  N Freemantle,et al.  The EuroHeart Failure survey programme-- a survey on the quality of care among patients with heart failure in Europe. Part 1: patient characteristics and diagnosis. , 2003, European heart journal.

[60]  R. Zimlichman,,et al.  RITZ-5: randomized intravenous TeZosentan (an endothelin-A/B antagonist) for the treatment of pulmonary edema: a prospective, multicenter, double-blind, placebo-controlled study. , 2003, Journal of the American College of Cardiology.

[61]  G. Fonarow Pharmacologic therapies for acutely decompensated heart failure. , 2002, Reviews in cardiovascular medicine.

[62]  J. Cleland,et al.  Efficacy and safety of intravenous levosimendan compared with dobutamine in severe low-output heart failure (the LIDO study): a randomised double-blind trial , 2002, The Lancet.

[63]  Alan S Maisel,et al.  Rapid measurement of B-type natriuretic peptide in the emergency diagnosis of heart failure. , 2002, The New England journal of medicine.

[64]  C. O'connor,et al.  Diuretic resistance predicts mortality in patients with advanced heart failure. , 2002, American heart journal.

[65]  James B. Young Intravenous nesiritide vs nitroglycerin for treatment of decompensated congestive heart failure: A randomized controlled trial , 2002 .

[66]  S. Gottlieb,et al.  BG9719 (CVT-124), an A1 Adenosine Receptor Antagonist, Protects Against the Decline in Renal Function Observed With Diuretic Therapy , 2002, Circulation.

[67]  M. Gheorghiade,et al.  Vasopressin receptor blockade with tolvaptan in chronic heart failure: differential effects in normonatremic and hyponatremic patients , 2002 .

[68]  J. Cleland,et al.  Clinical trials update: highlights of the scientific sessions of the XXIII Congress of the European Society of Cardiology — WARIS II, ESCAMI, PAFAC, RITZ‐1 and TIME , 2001, European journal of heart failure.

[69]  J. Ghali,et al.  Acute Hemodynamic Effects of Conivaptan, a Dual V1A and V2 Vasopressin Receptor Antagonist, in Patients With Advanced Heart Failure , 2001 .

[70]  J. Feinglass,et al.  Systolic function, readmission rates, and survival among consecutively hospitalized patients with congestive heart failure. , 1997, American heart journal.

[71]  E. Philbin,et al.  Association between diuretic use, clinical response, and death in acute heart failure. , 1997, The American journal of cardiology.

[72]  E. J. Brown,et al.  The effect of digoxin on mortality and morbidity in patients with heart failure. , 1997, The New England journal of medicine.

[73]  D. Annane,et al.  Placebo-controlled, randomized, double-blind study of intravenous enalaprilat efficacy and safety in acute cardiogenic pulmonary edema. , 1996, Circulation.

[74]  F. Russel,et al.  Diuretic efficacy of high dose furosemide in severe heart failure: bolus injection versus continuous infusion. , 1996, Journal of the American College of Cardiology.

[75]  K. Swedberg,et al.  Effects of the early administration of enalapril on mortality in patients with acute myocardial infarction. Results of the Cooperative New Scandinavian Enalapril Survival Study II (CONSENSUS II) , 1992, The New England journal of medicine.

[76]  J. McMurray,et al.  Plasma Endothelin in Chronic Heart Failure , 1992, Circulation.

[77]  J. Rouleau,et al.  Elevated Endothelin‐1 in Heart Failure and Loss of Normal Response to Postural Change , 1992, Circulation.

[78]  M. Gheorghiade,et al.  Hemodynamic effects of intravenous digoxin in patients with severe heart failure initially treated with diuretics and vasodilators. , 1987, Journal of the American College of Cardiology.

[79]  J. Cohn,et al.  Acute vasoconstrictor response to intravenous furosemide in patients with chronic congestive heart failure. Activation of the neurohumoral axis. , 1985, Annals of internal medicine.

[80]  F. Tristani,et al.  Effect of short-term infusion of sodium nitroprusside on mortality rate in acute myocardial infarction complicated by left ventricular failure: results of a Veterans Administration cooperative study. , 1982, The New England journal of medicine.

[81]  D. Tepper,et al.  Characterization and Prognostic Value of Persistent Hyponatremia in Patients With Severe Heart Failure in the ESCAPE Trial , 2008 .

[82]  Prakash Deedwania,et al.  HFSA 2006 comprehensive heart failure practice guideline , 2006 .

[83]  C. Lindsell,et al.  Prevalence of negative chest radiography results in the emergency department patient with decompensated heart failure. , 2006, Annals of emergency medicine.

[84]  M. Gheorghiade,et al.  ACUTE AND CHRONIC THERAPEUTIC IMPACT OF A VASOPRESSIN ANTAGONIST IN CONGESTIVE HEART FAILURE (ACTIV IN CHF) INVESTIGATORS. EFFECTS OF TOLVAPTAN, A VASOPRESSIN ANTAGONIST, IN PATIENTS HOSPITALIZED WITH WORSENING HEART FAILURE: A RANDOMIZED CONTROLLED TRIAL , 2004 .

[85]  S. Russell,et al.  Rationale for use of an exercise end point and design for the ADVANCE (A Dose evaluation of a Vasopressin ANtagonist in CHF patients undergoing Exercise) trial. , 2003, American heart journal.

[86]  V. Hasselblad,et al.  RANDOMIZED INTRAVENOUS TEZOSENTAN STUDY-4 INVESTIGATORS TEZOSENTAN IN PATIENTS WITH ACUTE HEART FAILURE AND ACUTE CORONARY SYNDROMES , 2003 .

[87]  J. Ghali,et al.  Acute hemodynamic effects of conivaptan, a dual V(1A) and V(2) vasopressin receptor antagonist, in patients with advanced heart failure. , 2001, Circulation.

[88]  M. Gheorghiade,et al.  Comparative hemodynamic and neurohormonal effects of intravenous captopril and digoxin and their combinations in patients with severe heart failure. , 1989, Journal of the American College of Cardiology.

[89]  G. L. Neifeld Acute vasoconstrictor response to intravenous furosemide in patients with chronic congestive heart failure , 1985 .