aliskiren and Acute-Disease

A case of probable drug-induced liver injury (DILI) attributed to use of the antihypertensive agent aliskiren is reported.. A 61-year-old woman undergoing routine liver function monitoring in conjunction with long-term antiepileptic therapy was noted to have an asymptomatic acute hepatic cytolysis 1 month after the initiation of concomitant aliskiren therapy (150 mg/day). Liver enzyme testing showed dramatically elevated aspartate transaminase (AST) and alanine transaminase (ALT) concentrations, with substantial rises also noted in γ-glutamyltransferase (GGT) and alkaline phosphatase (ALP) levels. The calculated ALT:ALP value indicated hepatocellular injury. On discontinuation of aliskiren use, rapid biological improvement occurred, including normalization of serum AST and a sharp decline in serum ALT within one week and the return of GGT and ALP levels to baseline a few weeks later; the patient's AST and ALT concentrations remained normal during 18 months of subsequent monitoring. Using the algorithm of Naranjo et al. and a DILI-specific causality assessment instrument, it was determined that aliskiren use was the probable cause of the patient's liver injury. While this is believed to be the first report of aliskiren-associated DILI in the professional literature, a review of information from several European and North American pharmacovigilance databases (through October 2012) identified 117 reports of suspected aliskiren hepatotoxicity, including 6 reports of liver failure and 12 reports of deaths.. Asymptomatic acute hepatic cytolysis was observed in a 61-year-old woman approximately one month after initiation of aliskerin for treatment of hypertension. Improvement in AST and ALT concentrations was observed shortly after the drug was discontinued.

Topics: Acute Disease; Alanine Transaminase; Amides; Antihypertensive Agents; Aspartate Aminotransferases; Chemical and Drug Induced Liver Injury; Databases, Factual; Female; Fumarates; Humans; Liver Function Tests; Middle Aged; Pharmacovigilance

Unlike the prolonged benefit produced by the treatment of chronic heart failure, newer drugs tested for the treatment of acute heart failure in the last decade have failed to provide evidence of clinical benefit beyond some improvement in symptom relief. In particular, no drug has shown the ability to reduce the higher medium- and long-term risk of morbidity and mortality in these patients after an episode of decompensation. Current understanding of the pathophysiology of acute heart failure and its consequences has led to the hypothesis that, beyond symptom control, effective therapies for this syndrome should target not only the hemodynamic changes of the initial phase of the syndrome but should also "protect" the organism from the activation of neurohumoral and inflammatory pathways triggered by the decompensation episode, which persist in time and confer a risk of deleterious effects in several organs and tissues. Serelaxin, a new drug related to the peptidic endogenous hormones of the relaxin family, has recently been shown to provide multiple beneficial effects in terms of "organ protection" - not only in the cardiovascular and renal systems - from these acute heart failure-related deleterious changes. This drug has already been tested in acute heart failure patients with encouraging results in terms of medium-term clinical benefit, rendering serelaxin as a serious candidate for first-line, prognosis-modifying therapy in this syndrome.

Topics: Acute Disease; Amides; Benzazepines; Cardio-Renal Syndrome; Dobutamine; Fumarates; Heart Failure; Humans; Hydrazones; Inflammation; Kaplan-Meier Estimate; Multicenter Studies as Topic; Natriuretic Peptide, Brain; Prognosis; Pyridazines; Randomized Controlled Trials as Topic; Recombinant Proteins; Relaxin; Simendan; Therapies, Investigational; Tolvaptan

Topics: Acute Disease; Amides; Fumarates; Heart Failure; Hospitalization; Humans; Inpatients; Multicenter Studies as Topic; Randomized Controlled Trials as Topic; Treatment Outcome

This article provides information and a commentary on trials relevant to the pathophysiology, prevention and treatment of heart failure, presented at the European Society of Cardiology Congress 2007. Unpublished reports should be considered as preliminary data, as analyses may change in the final publication. In the 3CPO study, non-invasive ventilation produced a more rapid resolution of symptoms in patients hospitalised with acute cardiogenic pulmonary oedema; but had no effect on survival, compared to standard oxygen therapy. The ALOFT study showed that the selective oral renin inhibitor aliskiren reduces plasma BNP levels and is well tolerated in patients with heart failure receiving ACE inhibitors or ARBs, although the study was not powered to show clinical benefit. In the PROSPECT study, no echocardiographic measure of mechanical dyssynchrony was identified that was useful for identifying patients more or less likely to respond to CRT. Low dose atorvastatin reduced the incidence of sudden cardiac death in a small placebo controlled study of patients with advanced chronic heart failure.

Topics: Acute Disease; Amides; Atorvastatin; Cardiac Pacing, Artificial; Clinical Trials as Topic; Fumarates; Heart Failure; Heptanoic Acids; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Pulmonary Edema; Pyrroles; Renin; Respiration, Artificial