Review Article

Angiotensin Receptor Antagonists to Prevent Sudden Death in Heart Failure: Does the Dose Matter?

Table 1

Clinical studies assessing the impact of ARBs on SCD, RCA,or appropriate ICD intervention.

StudyAim of the study or primary endpointSCDMean daily dose of ARBResults

ELITE II [14] Losartan versus captopril to improve survival in patients with NYHA II–IV and FE ≤ 40%Secondary endpointLosartan 50 mg versus captopril 50 mg t.i.d.Losartan not superior for mortality
Higher incidence of SCD or RCA with losartan
HR 1.25
CI 95% (0.98–1.60) 

Val-HeFT [15]Valsartan for mortality and morbidity in NYHA II–IVValsartan 160 mg b.i.d. versus placeboTotal mortality similar in the two groups
RCA improved with valsartan
RR 1.02
CI 97.5% (0.88–1.18)
0.6% versus 1.0%

OPTIMAAL [16]Losartan versus captopril to decrease all-cause mortality after acute MISecondary endpointLosartan 50 mg versus captopril 50 mg t.i.d.Trend in favor of captopril (death from any cause)
Higher incidence of SCD or RCA with losartan
RR 1.13
CI 95% (0.99–1.28)

RR 1.19; CI 95% 0·98–1·43;

VALIANT [17]Valsartan versus captopril in patients with MI associated with HF and/or LVDValsartan 160 mg b.i.d. versus captopril 50 mg t.i.d. versus valsartan + captoprilValsartan noninferior to captopril for total mortalityHR 1.00
CI 97.5% (0.90–1.1)

CHARM post hoc analysis [22]Candesartan for cause-specific mortality in HF patientsCandesartan titrated to 32 mg versus placeboReduction of SCD with candesartanHR 0.85
CI 95% (0.73–0.99)

HEAAL [32]Losartan 50 mg versus 150 mg for death or admission for HFLosartan 50 mg versus losartan 150 mgReduction of death or admission for HF with 150 mg
No effects on mortality
HR 0.90, 95% CI
0.82–0.99;
HR 0.94, 95% CI 0.84–1.04;

COMPANION post-hoc analysis [26]Predictors of SCD or ICD intervention in patients receiving CRTUnknownBoth ACE-i and ARBs reduced the risk of appropriate shocksACE-i: HR 0.44
CI 95% (0.26–0.75)

ARBs: HR 0.53 CI 95% (0.28–0.996)
P 0.05

Obeyesekere et al. [27]Predictors of appropriate ICD interventions in a primary prevention populationUnknownAbsence of ACE-i/ARBs predicts appropriate ICD interventionOR 0.06
CI 95% (0.01–0.37)

Francia et al. [28]Predictors of appropriate ICD interventions in a primary prevention populationLosartan 50 mg (75% of patients)Low-dose ARBs associated with higher risk of ICD interventionHR 2.9
CI 95% (1.1–7)

ARBs: angiotensin receptor antagonists; SCD: sudden cardiac death; RCA: resuscitated cardiac arrest; CRT: cardiac resynchronization therapy.