The effectiveness and relative effectiveness of intravenous inotropic drugs acting through the adrenergic pathway in patients with heart failure—a meta‐regression analysis

Abstract

Aims: To review systematically the use of intravenous (IV) inotropic agents acting through the adrenergic signalling pathway, compared with placebo or an active agent, in patients with heart failure. Methods: Studies investigating the use of intravenous inotropes in patients with heart failure published between 1966 and 2000 were identified using MEDLINE, the Cochrane register and Embase databases. Reference lists from relevant papers and reviews were hand searched for further papers. In total, 21 trials, that included 632 patients receiving IV inotropic drugs, placebo or non-treatment control, were identified. Drugs of the following classes were included, the b-agonists; dobutamine, high-dose ()2.5 mgykgymin) dopamine, dopexamine and the phosphodiesterase (PDE) inhibitors; amrinone, milrinone, enoximone and toborinone. Sixteen trials (474 patients) contributed data from acute invasive haemodynamic studies of symptomatically severe heart failure. Five trials (158 patients) were based on intermittent inotropic therapy in an outpatient context. Results: With few exceptions, trials of intravenous inotropic agents were small and often failed to report clinically important outcomes. Compared to placebo, intravenous inotropic agents acting through the adrenergic system tended to increase mortality (odds ratio 1.50 (95% CIs0.51 to 3.92) but this did not reach significance and insufficient data were available to determine whether symptoms improved. There appeared to be little difference in the effect of beta-agonists compared to PDE inhibitors on patient outcomes but this could be attributed to the paucity of data. Conclusions: Intravenous inotropic agents acting through the adrenergic pathway are often used in patients with worsening heart failure to achieve arbitrary haemodynamic targets. Our analyses show that there is very little evidence that such treatment improves symptoms or patient outcomes and may not be safe. This highlights the need for further well designed randomised clinical trials.

Advanced chronic heart failure: A position statement from the Study Group on Advanced Heart Failure of the Heart Failure Association of the European Society of Cardiology

“…Despite short-term haemodynamic improvement, these agents may have an adverse effect on mortality [56] and cause supraventricular and ventricular tachyarrhythmias [57]. Thus, they should be administered only when indicated (signs of peripheral hypoperfusion), at the lowest effective doses and for the shortest duration of time as possible [17].…”

I Diretriz Latino-Americana para avaliação e conduta na insuficiência cardíaca descompensada

“…Additionally, drugs that increase the levels of cAMP lead to a decreased sensitivity to calcium by means of phosphorylation of troponin-I. These actions can result in adverse clinical effects [62][63][64][65] .…”

Cardiorenal syndrome or renocardial syndrome:A review

“…Low-dose dopamine did not improve decongestion or increase renal function when added to diuretic therapy. The Outcomes of a Prospective Trial of Intravenous Milrinone for Exacerbations of Chronic Heart Failure (OPTIME) study tested and rejected the routine use of inotropes to permit more effective diuresis and treatment of patients with congestive heart failure [80]. In this study, the worst renal function, despite poorest outcome, did not show any benefit with milrinone.…”