Hemodynamics as surrogate end points for survival in advanced heart failure: An analysis from FIRST

Background Hemodynamics often are used as surrogate end points in phase II trials of acute heart failure (HF). We reviewed the Flolan International Ra ndomized Survival Trial (FIRST) database to identify the hemodynamic variab les that best predict survival in patients with advanced HF receiving epopr ostenol therapy and to determine whether hemodynamics could predict the ove rall effect of a drug. Methods The trial enrolled 471 patients with class IIIb/IV HF and election fraction less than or equal to 25% for greater than or equal to3 months, al l of whom underwent screening pulmonary artery catheter insertion. Patients were randomly assigned to receive either epoprostenol (n = 201) or placebo (n = 235); epoprostenol therapy was guided by pulmonary artery catheter me asures, and standard treatment was guided by clinical findings. Multivariab le modeling was used to identify and quantify the demographic, clinical, an d hemodynamic variables most associated with 1-year survival. Results In multivariable modeling, HF class, decreased pulmonary capillary wedge pressure (PCWP), and age best predicted 1 year survival. After adjust ment For age and HF class, decreased PCWP still significantly predicted sur vival (hazard ratio, 0.96 for every 1-mm Hg decrease; 95% confidence interv al, 0.94 to 0.99; P = .003). Survival was significantly higher with decreas es in PCWP greater than or equal to9 versus <9 mm Hg, even after adjustment for age and HF class. Survival of patients in the PWP <greater than or equ al to>9 group was comparable with, and that of the PCWP <9 group was signif icantly higher than, survival of patients in the control group (hazard rati o, 1.44; 95% confidence interval, 1.05 to 1.99; P = .024). Conclusions The reduction in PCWP was the hemodynamic measure most predicti ve of survival in patients with advanced HF. However, patients with a <grea ter than or equal to>9-mm Hg decrease had no better survival than patients in the control group, who had limited changes in hemodynamics. Thus, improv ement in hemodynamics may not predict the overall effect of a drug.