New pharmacologic therapies in heart failure: Immunotherapy, endothelin-1 antagonists, brain natriuretic peptides, and neurohormonal interventions

Approaches under clinical investigation to modify systemic mediators of heart failure progression include specific and broad-spectrum immunotherapies, agents targeting the activity of endothelin-1, the use of synthetic homologues of human B-type natriuretic peptide, vasopeptidase inhibitors, and vasopressin antagonists for both chronic and acute heart failure. Although experimental observations from the laboratory follow a logical process for development into clinical practice, it has become clear that the clinical utility of individual therapies requires meticulous clinical research that frequently encounters failure. Active clinical studies utilizing broad-spectrum antiinflammatory therapies, including immunomodulatory strategies, may provide the next generation of therapy in chronic heart failure. With regards to acute heart failure, we have seen clear documentation of hemodynamic benefits with the therapeutic use of recombinant type-B natriuretic peptide, and further investigation is ongoing with the nonspecific endothelin-1 antagonist tezosentan. Most importantly, the latest generation of clinical trials for heart failure has shown us that further development in this area will require the demonstration not only of hemodynamic, serologic, and symptomatic improvement, but also of disease-modifying effects on morbidity and mortality.