ClassificationEF (%)Description HF with reduced EF (HFrEF) ≤40 “systolic HF”; RCTs have mainly enrolled these HF patients; only in these pts have efficacious therapies been demonstrated HF with preserved EF (HFpEF) ≥50 “diastolic HF”; dx is challenging due to excluding other noncardiac causes of symptoms suggestive of HF; efficacious therapies have not been identified HFpEF, borderline41-49Characteristics, treatment patterns, and outcomes appear similar to those of pts with HFpEF HFpEF, improved>40Subset of pts who previously had HFrEF
Randomized, double-blind trial, N=3,445 Mean duration: 3.3 years Sponsor: NHLBI Treatment Spironolactone ▪ 15mg QD; increased to max of 45mg/day by month 4 Placebo Outcome Primary: death from CV causes, aborted cardiac arrest, or hospitalization for HF Endpoints adjudicated N Engl J Med 2014;370:1383-92.
Inclusion criteria ≥ 50 years of age At least one sign of HF (at screening) ▪ PND, orthopnea, or dyspnea with exertion At least one symptom of HF (w/i 1 year) ▪ Rales, ↑ JVD, edema, or + CXR (effusions, cardiomegaly) LVEF ≥45% BP: SBP <140 or SBP <160 (if on ≥3 BP meds) K+ < 5.0 HF hospitalization within previous 12 months (non- adjudicated) OR BNP >100 or NT-proBNP >360
Exclusion criteria GFR <30 ml/min Scr ≥2.5 mg/dL COPD requiring steroids, home oxygen, or hospitalized exacerbation within 1 yr Stats Intention-to-treat Power: 80% to detect 20% relative reduction Assumption: 17.4% outcome rate at 3 yrs ▪ Target enrollment is 3,515
Spironolactone did not reduce primary outcome in HFpEF Adequately powered for primary outcome Spironolactone associated with 36% RRR in HF hospitalizations among BNP enrolled stratum Were patients enrolled in Russia/Georgia (i.e. more likely to be in prior HF hospitalization stratum) less likely to have actual heart failure? If HFpEF and elevated BNP, spironolactone worth consideration