Challenging aspects of treatment strategies in heart failure with preserved ejection fraction: “Why did recent clinical trials fail?”

Table 1 Clinical trials in heart failure with preserved ejection fraction

Acronym (yr)	Drug	Number of patients	Age (mean)	Percentage female(mean, %)	LVEF(mean, %)	Primary outcome	Follow upperiod
Swedish heart failure registry[17]	Beta-Blocker	8244	78	45	40-49; > 50	ACM, HFH	24 mo
TOPCAT[33]	Aldactone	3445	68.6	52	60.1	CVD-HFH: NS	27 mo
PARAMOUNT[51]	LCZ696	292	70.6	56	57.7	Reductions in NT-proBNP levels	36 wk
RELAX[43]	Sildenafil	216	69	48	60	EC-CS: NS	24 wk
ALDO-DHF[27]	Spironolactone	422	67	52	67	Reduced E/É	12 mo
I-Preserve[24]	Irbesartan	4128	72	60	59.5	D-CVH: NS	49.5 mo
PEP-CHF[22]	Perindopril	850	75	55.5	65	D-HFH: NS	26.2 mo
DIG[26]	Digoxin	6800	63.8	22.7	28.6	ACM: NS; improvements in DFWHF, HFWHF	37 mo
SENIORS[14]	Nebivolol	2128	76.1	38.4	36	Improvements CVD, HFH	21 mo
CHARM-Preserved[23]	Candesartan	3023	67.1	40	54	CVD-HFH: NS	36.6 mo

ALDO-DHF: Aldosterone Receptor Blockade in Diastolic Heart failure; CHARM-Preserved: Effects of candesartan in patients with chronic HF and preserved left-ventricular ejection fraction trial; DIG: The Effect of Digoxin on Mortality and Morbidity in Patients with HF trial; I-Preserve: The irbesartan in HF with preserved systolic function trial; PARADIGM: Angiotensin–Neprilysin Inhibition vs Enalapril in HF trial; PARAMOUNT: The angiotensin receptor neprilysin inhibitor LCZ696 in HF with preserved ejection fraction: a phase 2 double-blind randomised controlled trial; PEP-CHF: The perindopril in elderly people with chronic HF trial; RELAX: Phosphodiesterase-5 Inhibition in Diastolic HF: The RELAX Trial Rationale and Design; SENIORS: Randomized trial to determine the effect of nebivolol on mortality and cardiovascular hospital admission in elderly patients with HF trial; TOPCAT: Spironolactone for HF with Preserved Ejection Fraction trial; ACM: All-cause mortality; CS: Clinical status; CVA: Cardiovascular admission; CVD: Cardiovascular death; CVH: Cardiovascular hospilization; DFWHF: Death from worsening HF; EC: Exercise capacity; FHCVE: First hospitalization for a cardiovascular event; HF: Heart failure; HFAR: Hospitalization for any reason; HFH: Heart failure hospitalization; HFWHF: Hospitalization for worsening HF; NS: Not significant.