Candesartan in heart failure

Figures & data

Table 1 Summary of clinical trials evaluating candesartan in heart failure

Trial	N	EF	Design	Intervention/evaluation	Primary endpoints	Statistical result
RESOLVD	768	<40%	PR, MC, R, DB, PC	Cand 4 mg, 8 mg, or 16 mg QD alone vs Cand 4 mg or 8 mg QD + Enal 10 mg bid vs Enal 10 mg bid alone	Change in 6MWD; EF; Ventricular volumes; Neurohormone levels; QOL; NYHA-FC	NS NS p<0.05, 0.01^a p<0.05, 0.01b NS NS
SPICE	270	<35%	PR, R, DB, PC, pilot	Cand 4 mg QD (start) up to 16 mg QD (goal) vs placebo in patients intolerant of ACE-I	Discontinuation rates	NS
CHARM-Added	2548	<40%	PR, R, DB, PC, P	Cand 4 mg QD (start) up to 16 mg QD (goal) vs placebo in addition to established ACE-I therapy	CV death or unplanned heart failure hospital admission	HR 0.85, 0.75–0.96, p=0.011
CHARM-Alternative	2028	<40%	PR, R, DB, PC, P	Cand 4 mg QD (start) up to 16 mg QD (goal) vs placebo as alternative to ACE-I therapy	CV death or unplanned heart failure hospital admission	HR 0.77, 0.67–0.89, p=0.0004
CHARM-Preserved	3023	>40%	PR, R, DB, PC, P	Cand 4 mg QD (start) up to 16 mg QD (goal) vs placebo +/− ACE-I therapyc	CV death or unplanned heart failure hospital admission	HR 0.89, 0.77–1.03, p=0.118
CHARM-Overall	7599	——	PR, R, DB, PC, P	Intervention per individual CHARM protocol	All-cause death	HR 0.91, 0.83–1.00, p=0.055; Adjusted HR 0.90 (0.82–0.99), p=0.032
Cause-specific	1831	——	Post-hoc CHARM	Compare cause of mortality	Sudden death	HR 0.85, 0.73–0.99,
mortality – CHARM	deaths to evaluate		data	between candesartan and placebo	Death from progressive HF	p=0.036 HR 0.78, 0.65–0.94, p=0.008
NYHA-FC – CHARM	7587	——	Post-hoc CHARM data	Compare % improved and % deteriorated between candesartan and placebo	Last visit carried forwardd Worst rank carried forwardd	p=0.003e p=0.003e
Adherence – CHARM	7412f	——	Post-hoc CHARM data	Compare outcomes in patients with good adherence (defined as adherent 80% of the time)	Rate of adherence	89% good adherence; 11% poor adherence
					Mortality overall (good vs poor adherence)	HR 0.66, 0.58–0.76, p<0.0001
					Candesartan	HR 0.70, 0.57–0.86, p<0.0001
					Placebo	HR 0.62, 0.51–0.76, p<0.001

Notes: ^aLevel of significance depends of parameter measured and intervention compared (refer to full text for detail);

^bRefer to full text for detail; variations in which neurohormones reached significance exists;

^cACE-I were allowed after results of Heart Outcomes Prevention Evaluation were presented;

^dTwo methods were used to assess change in NYHA-FC (refer to full text for description);

^eIn favor of candesartan;

^f187 patients were excluded because of missing data; rates of missing data similar between treatment groups.

Abbreviations: ACE-I, Angiotensin-converting enzyme inhibitor; bid, twice daily; Cand, candesartan; CHARM, Candesartan in Heart Failure Assessment of Reduction in Mortality and morbidity; DB, double-blind; EF, ejection fraction; Enal, enalapril; HR, Hazard Ratio; MC, multi-centered; NS, not significant; NYHA-FC, New York Heart Association Functional Class; P, parallel; PC, placebo-controlled; PR, prospective; QD, once daily; QOL, quality of life; R, randomized; RESOLVD, Randomized Evaluation of Strategies for Left Ventricular Dysfunction; SPICE, Study of Patients Intolerant of Converting Enzyme Inhibitors; 6MWD, 6 minute walk distance.

Figure 1 CHARM protocol and outcomes.