Loop diuretics : translating pharmacokinetic properties into improved clinical outcomes

Furosemide and torasemide have the same mechanism of action. However, they differ substantially in their pharmacokinetic properties. Furosemide is incompletely absorbed with substantial inter- and intra-individual variability. This contrasts with the complete and predictable absorption of torasemide. Theoretically, incomplete absorption could result in sodium accumulation that over time would cause cardiac decompensation in patients with congestive heart failure (CHF), Several studies have addressed this issue: two retrospective analyses, one pre/post-comparison and one randomized clinical trial consistently showed that heart failure patients treated with torasemide had fewer hospital admissions due to worsening heart failure or due to all cardiovascular causes. Moreover, functional state improved in comparison with furosemide in equipotent doses. In the two prospective trials there was also a decrease in cardiovascular and/or total mortality in comparison with furosemide, although this was not significant; the studies were not powered to show this. Most recently, a prospective cohort study that followed 2303 patients randomized in a 1:1 ratio to either torasemide or furosemide treatment for 1 year showed significantly fewer symptoms in the torasemide group and a significant decrease in cardiac as well as total mortality. Overall these data indicate that the complete and predictable absorption of torasemide extrapolates to improved clinical outcome in patients with CHF.