Soluble Guanylate Cyclase Inhibitors for HFpEF: Another Disappointment

The drug class does not improve physical limitation or exercise tolerance in the common syndrome of heart failure with preserved ejection fraction.

Unlike the panoply of agents that improve outcomes for heart failure with reduced ejection fraction (HFrEF), therapies for HF with preserved ejection fraction (HFpEF) have been elusive despite numerous clinical trials. Mechanistic studies implicate deficient cyclic guanosine monophosphate (cGMP) signaling in the pathophysiology of HFpEF. Soluble guanylate cyclase stimulators — not yet approved by the FDA — enhance cGMP production and sensitivity to endogenous nitrates, which in theory would be beneficial in HFpEF. Two manufacturer-sponsored, phase II studies examined this issue.

Armstrong and colleagues randomized 789 individuals with chronic HF and New York Heart Association II or III symptoms (mean age, 73; 49% women) to one of two target …

Reviewing Author

Frederick A. Masoudi, MD, MSPH, FACC, FAHA

Disclosures

Consultant/Advisory BoardBristol Myers Squibb; CPC Clinical Research

Grant/Research SupportNational Heart, Lung, and Blood Institute

Editorial BoardsUpToDate; American College of Cardiology Self-Assessment Program (SAP)

Leadership Positions in Professional SocietiesAmerican College of Cardiology (Chair, Innovations Committee)