Heart failure clinical evidence

Elkayam U, Bitar F. Effects of nitrates and hydralazine in heart failure clinical evidence before the African American heart failure trial. AmJ Cardiol. 2005 96 37i-43i. 

Despite the advances in pharmacological therapy, cardiovascular surgery and cardiology, more than half of the patients with clinically evident heart failure die within 5 years of the initial diagnosis. The myocardial injury is usually irreversible because healing pathways are only expressed for a short time (Penn et al., 2004). 

On the other hand, clinical evidence suggests that p-blockers produce favorable effects in certain forms of congestive heart failure (idiopathic dilated cardiomyopathy). 

Heart failure Some ACEIs are effective in the management of CHF, usually as adjunctive therapy and in patients who demonstrate clinical signs of CHF or have evidence of left ventricular systolic dysfunction within the first few days after an acute myocardial infarction (Ml). 

Congestive heart failure (CHF) post-myocardial infarction (Ml) To improve survival of stable patients with left ventricular systolic dysfunction (ejection fraction 40% or less) and clinical evidence of CHF after an acute Ml. 

Fluid status - Prior to administration, assess the patient s volume (fluid) status carefully. It is imperative, especially prior to the first few doses, that there be no clinical evidence of volume overload or uncompensated heart failure, including a clear chest X-ray and weight restriction of less than or equal to 3% above the patient s minimum weight during the week prior to injection. 

The effects of CRT in mild heart failure have not been established. There have been two large-scale trials that included patients with NYHA functional class II heart failure—the CONTAK CD trial and the MIRACLE ICD trial [115, 116]. Although there was no consistent clinical benefit seen in either trial, both studies revealed evidence of reverse... 

Outside the AMI setting, stem cells have been used to treat patients with ischemic heart disease with or without systolic functional compromise and patients unsuitable for myocardial revascularization (Tables 7.3 and 7.4). Autologous bone marrow stem cells have been used to treat patients with chronic myocardial ischemia, including ischemic heart failure with or without systolic functional compromise, and patients ineligible for myocardial revascularization (Table 7.4). The preliminary clinical evidence supports the efficacy of this new therapy and, at this point, all the evidence appears to substantiate its safety. 

Most clinical trials have been carried out in patients with systolic dysfunction, so the evidence regarding the superiority or inferiority of drugs in heart failure with preserved ejection fraction is meager. Most authorities support the use of the drug groups described above. Control of hypertension is particularly important, and revascularization should be considered if coronary artery disease is present. Tachycardia limits filling time therefore bradycardic drugs may be particularly useful, at least in theory. 

AIRE (87) Acute MI within 3-10 days Clinical evidence of HF 2006 Ramipril, 5-mg twice a day vs. placebo 27% Reduction of overall mortality significant reduction of severe heart failure, myocardial infarction, and stroke... 

The-Acute-Infarction-Rami pri I-Efficacy-(AIRE)-Study-Investigators. Effect of ramipril on mortality and morbidity of survivors of acute myocardial infarction with clinical evidence of heart failure. The Acute Infarction Ramipril Efficacy (AIRE) Study Investigators, Lancet 1993 342 821-828. 

The phase I clinical testing of enalapril began in 1980 in a study in which its efficacy to inhibit intravenously administered angiotensin I was determined. Oral doses as low as 2.5 mg produced a substantial decrease in ACE, activity and lowering was evident even 21-24 hours after the drug was given (129). Phase II and phase III trials began in 1981, and the first approval to use enalapril in hypertension came in 1984 and in heart failure in 1986. 

Patients with advanced heart failure have increased levels of circulating TNFa. The biological effects of TNFa may explain several clinical features of heart failure, such as ventricular dysfunction and pulmonary edema (61, 62). These data are also supported by experimental evidence (63, 64). Thus, the efficacy of TNFa blockade is currendy under investigation in cardiomyopathy and congestive heart failure, and in vitro studies support the concept (65). 

What is the role of beta-blockers in heart failure Summarise the clinical trial evidence to date. 

Clinical evidence of valve disease or heart failure, or impaired LV function on echocardiography ... 

On the other hand, convincing clinical evidence demonstrates that, under appropriate conditions (prior testing of tolerability, low dosage), p-blockers are able to improve prognosis in congestive heart failure. Protection against heart rate increases and arrhythmias may be important underlying factors. 

Biochemical evidence and transfection studies suggest that a and p isoforms can assemble in different combinations and potentially form functional pumps. The sodium pump is specifically inhibited by a series of naturally occurring steroids, such as ouabain (Hansen 1984). Based on their clinical use, these substances are also referred to as cardiac glycosides or cardioactive steroids. Cardiac glycoside sensitivity is conferred by the a subunit of the Na-K-ATPase, and this class of drags is used to treat congestive heart failure (Scheiner-Bobis and Schneider 1997). 

Further support for using blood pressure as a surrogate endpoint is provided by the concordance of evidence from a number of clinical trials in which blood pressure lowering with low-dose diuretics and P-blockers was shown to reduce the incidence of stroke/ coronary artery disease/ and congestive heart failure in hypertensive patients (19). Of particular interest is a meta-analysis that was conducted to compare the extent of blood pressure reduction achieved in different clinical trials with the maximum benefit that was anticipated on epidemiolgic grounds (Table 17.3) (20). The decrease in stroke incidence anticipated for a 5- to 6-mm Hg average reduction in diastolic blood pressure was fully realized with only 2 to 3 years of antihypertensive therapy. 

SAVE = Survival and Ventricular Enlargement Trial AIRE = Acute Infarction Ramipril Efficacy study CONSENSUS = Cooperative New Scandinavian Enalapril Survival Study. References Rutherford J D et al 1994 Effects of captopril on ischemic events after myocardial infarction. Results of the Survival and Ventricular Enlargement trial. SAVE Investigators. Circulation 90 1731-1738. AIRE Study Investigators 1993 Effect of ramipril on mortality and morbidity of survivors of acute myocardial infarction with clinical evidence of heart failure. Lancet 342 821-828. Swedberg K P et al 1992 Effects of the early administration of enalapril on mortality in patients with acute myocardial infarction. New England Journal of Medicine 327 678-684. 

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