The challenges associated with current clinical trials for diastolic heart failure

Diastolic heart failure (DHF) is the culmination of various cardiovascular insults, producing a proportionally greater alteration of diastolic performance, subtle reductions of systolic function and the clinical syndrome of heart failure. Over half of heart failure patients aged 65 years or older have DHF, which carries similar morbidity and mortality to systolic heart failure (SHF). The aging population and increased prevalence of hypertension, diabetes mellitus and obesity will result in disproportionately higher incidence of DHF.

To date, seven large placebo-controlled trials have been conducted in DHF and none have convincingly demonstrated substantial morbidity or mortality reductions. This review will highlight DHF clinical trial efforts and provide explanations for the discordance between clinical trial patients and clinical practice patients.

Greater parity between clinical trial and clinical practice can be achieved by selecting DHF patients in the context of a few general principles: trials should enroll patients on the basis of the diagnostic criteria set forth by the European Study Group on Diastolic Heart Failure. A history of (<6 months) or current hospitalization for heart failure along with prespecified higher grades of diastolic dysfunction insures that a sufficiently at-risk population is studied. Patients with DHF are older, with multiple noncardiovascular comorbidities, and longer trial duration (>3 years) may be plagued with competing risks.