We examined the influence of phosphodiesterase inhibitors (PDIs) on mortality in patients with overt chronic heart failure. A total of 13 randomised, placebocontrolled trials of PDIs involving 2808 patients were selected.

Meta-analysis, using data for all patients, showed that there was a non-significant (P=0.16) increase of about 17% in the mortality rate of patients receiving a PDI [odds ratio (OR) 1.17, 95% confidence interval (CI) 0.94–1.46]. However, the observed treatment effects were found to be heterogeneous due to the results from the trials on vesnarinone. The heterogeneity became non-significant (P=0.77) when these trials were removed, and a significant increase in the mortality rate was observed under treatment with the other PDIs (OR 1.41, 95% CI 1.11–1.79). In the subgroups of patients with or without additional vasodilator (VD) treatment, similar results were observed (PDI with VD: OR 1.3, 95% CI 1.03–1.7; PDI without VD: OR 2.04, 95% CI 1.1–3.8).

These results indicate that PDIs (with the exception of vesnarinone) should not be prescribed for long-term use in patients with overt chronic heart failure. Additional vasodilator treatment in patients receiving PDIs for chronic heart failure does not explain the increased mortality seen with PDIs. This toxicity must, therefore, arise by other mechanisms. Further experimental and clinical evaluation is needed to confirm the beneficial influence of vesnarinone on survival in chronic heart failure patients and to identify the mechanism(s) differentiating this agent's therapeutic effect from that of other PDIs.