Q: What are the new treatment options in acute decompensated heart failure?
A: The new treatment options are the two recently introduced drugs, the calcium sensitiser, levosimendan which has been introduced in many European countries, and a B-type natriuretic peptide (BNP) Analogon nesiritide, utilised primarily in the US. This BNP causes basal dilation and improves diuresis.
Q: How do these differ from the more established treatments?
A: In acute heart failure, there are three types of established treatments. Firstly, high-ceiling diuretics, the most utilised of these is furosemide. It is usually the first choice for physicians to reduce fluid overload. Then, the nitrates, long standing standard agents that produce a basal dilation. Their intravenous forms are utilised to reduce the filling pressures of basal dilation. Both treatments are part of the first line drug treatments in most intensive care units in patients. The second group of agents, are the inotropic agents, increase cardiac output, blood pressure and improve cardiac contractility. The most frequently prescribed of these are debutamine and dopamine. There are also phosphodiesterase inhibitors, such as milrinone or enoximone. These drugs also improve cardiac contractility; they also produce some basal dilation.
Q: What are the benefits of these treatments?
A: With nesiritide, the physician will unload the failing heart by basal dilation and reduce the filling pressures in the lung and veins and that reduces the left ventricular filling pressure, and some of the blood pressure, so cardiac function is improved. The effects are like those of nitroglycerin, but nitrates have the disadvantage that with continuous use over 24-48 hours, there is a loss of efficacy due to the tachyphylaxis, so their action is reduced with continuous infusion. This drug nesiritide has no such disadvantage, so there is a continuous effect and no tachyphylaxis. The initial data in the US has been encouraging, however recently there has been a debate about whether there is a real benefit for example, the renal function doesn't improve, and doubts about the efficacy reducing mortality. In my opinion, this is probably due to the wrong dosage schedules being used, so the whole question is being restudied.
The benefits of levosimendan is well documented and has been studied in several large-scale trials. In addition to basal dilation, the drug also increases contractility, so it is an inidilator. Clinical experience and reports from intensive care physicians and cardiologists who use the drug are very positive. It rapidly reduces symptoms, improves cardiac function and the overall experience has been positive. However, two recent studies have been a bit disappointing. The Randomized Multicenter Evaluation of Intravenous Levosimendan Efficacy (REVIVE) trial showed that there was a more rapid improvement of symptoms than the standard therapy, but there were some adverse observations regarding the occurrence of cardiac arrhythmias. The second comparative trial, Survival Of Patients With Acute Heart Failure In Need Of Intravenous Inotropic Support (SURVIVE) trial could not confirm the more beneficial effect of levosimendan found in the Levosimendan Infusion versus Dobutamine (LIDO) study. This was probably due to a different patient selection, surveillance and dosage.
Q: What are the limitations?
A: The main problem is the proper selection of patients and the dosage. It is likely that in recent trials, many of the patients have been given a high dose of diuretics and had been receiving basal dilators. When levosimendan was given in the standard, uniform high dose it produced additional basal dilation and a relatively high incidence of low blood pressure and hypotension, which can explain the disappointing results. The main issue is that if you have experience with a drug then utilisation is much better.
Q: What are the goals of treatment when prescribing levosimendan to an acute heart failure patient?
A: Acute heart failure is, by definition, an acute worsening of a pre-existing heart failure or the first manifestation of a previously unknown heart disease. Patients are very distressed, usually they have a very marked shortness of breath, poor peripheral and organ perfusion. With this new treatment, a physician is able to rapidly improve the hemodynamic state, and patients feel better. Also, this drug has long acting metabolites that is; if you administer a 24-hour infusion there is a persisting effect for a several days, so the benefits can be maintained.