Similar clinical benefits from below‐target and target dose enalapril in patients with heart failure in the SOLVD Treatment trial

Lam, Phillip H.; Dooley, Daniel J.; Fonarow, Gregg C.; Butler, Javed; Bhatt, Deepak L.; Filippatos, Gerasimos; Deedwania, Prakash; Forman, Daniel E.; White, Michel; Fletcher, Ross D.; Arundel, Cherinne; Blackman, Marc R.; Adamopoulos, Chris; Kanonidis, Ioannis; Aban, Inmaculada; Patel, Kanan; Aronow, Wilbert S.; Allman, Richard M.; Anker, Stefan D.; Pitt, Bertram; Ahmed, Ali

doi:10.1002/ejhf.937

Cited by 20 publications

(13 citation statements)

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“…It should also be highlighted that other subgroups such as men/women, diabetes/no-diabetes, ACEi/ARB . Differently from ACEi/ARBs and -blockers in which randomized trials compared different doses of these drugs, [21][22][23][24][25][26] no trials have compared different MRA doses. So far, the best available evidence comes from the EMPHASIS-HF trial, where patients were stratified to different eplerenone or placebo doses according to renal function.…”

Section: Discussionmentioning

confidence: 99%

Spironolactone dose in heart failure with preserved ejection fraction: findings from TOPCAT

Ferreira

Rosselló

Pocock

et al. 2020

European J of Heart Fail

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Spironolactone up-titration may be limited by side effects that could be minimized at lower than target doses, but whether lower than target doses remain efficacious is unknown. In TOPCAT, spironolactone (or placebo) were started at 15 mg/day, and increased up to a maximum of 45 mg/day. The prognostic implications related to spironolactone dose are yet to be reported. We aimed to assess the average spironolactone/placebo doses provided during the trial, overall and within high-risk subgroups (e.g. elderly, renal dysfunction, high potassium); discontinuation rates; and the efficacy of lower than target doses in heart failure with preserved ejection fraction.

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Section: Discussionmentioning

confidence: 99%

Spironolactone dose in heart failure with preserved ejection fraction: findings from TOPCAT

Ferreira

Rosselló

Pocock

et al. 2020

European J of Heart Fail

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“…It was confirmed in the CONSENSUS study already that in the period examined the administration of enalapril in the case of 253 patients suffering from NYHA IV heart failure reduced the development of SCD by 27% (CONSENSUS Trial Study Group, 1987). In the SOLVD study examining 2569 patients Lam et al found that the administration of 20 mg enalapril per day reduced overall mortality by 12% and cardiovascular mortality by 4% in the case of heart failure patients (Lam et al, 2018). In the SAVE trial on 2,231 patients the administration of 3x25 mg captopril daily reduced overall cardiovascular mortality by a few percent compared to the placebo group but it did not meaningfully affect the risk of sudden cardiac death (Pfeffer et al, 1992).…”

Section: Long-term Treatment After Aborted Cardiac Deathmentioning

confidence: 99%

Handling of Ventricular Fibrillation in the Emergency Setting

et al. 2020

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Ventricular fibrillation (VF) and sudden cardiac death (SCD) are predominantly caused by channelopathies and cardiomyopathies in youngsters and coronary heart disease in the elderly. Temporary factors, e.g., electrolyte imbalance, drug interactions, and substance abuses may play an additive role in arrhythmogenesis. Ectopic automaticity, triggered activity, and reentry mechanisms are known as important electrophysiological substrates for VF determining the antiarrhythmic therapies at the same time. Emergency need for electrical cardioversion is supported by the fact that every minute without defibrillation decreases survival rates by approximately 7%-10%. Thus, early defibrillation is an essential part of antiarrhythmic emergency management. Drug therapy has its relevance rather in the prevention of sudden cardiac death, where early recognition and treatment of the underlying disease has significant importance. Cardioprotective and antiarrhythmic effects of beta blockers in patients predisposed to sudden cardiac death were highlighted in numerous studies, hence nowadays these drugs are considered to be the cornerstones of the prevention and treatment of life-threatening ventricular arrhythmias. Nevertheless, other medical therapies have not been proven to be useful in the prevention of VF. Although amiodarone has shown positive results occasionally, this was not demonstrated to be consistent. Furthermore, the potential proarrhythmic effects of drugs may also limit their applicability. Based on these unfavorable observations we highlight the importance of arrhythmia prevention, where echocardiography, electrocardiography and laboratory testing play a significant role even in the emergency setting. In the following we provide a summary on the latest developments on cardiopulmonary resuscitation, and the evaluation and preventive treatment possibilities of patients with increased susceptibility to VF and SCD.

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Section: High Vs Low Enalapril Doses In the Solvd Trialmentioning

confidence: 99%

“…The SOLVD trial was designed to achieve and test enalapril (20 mg daily) vs. placebo, but at the end of the study the mean enalapril dose was only 11 mg daily and more than half of the patients enrolled failed to reach the target dose of the study drug. Thus, in this issue of the Journal, Lam et al 13 hypothesize that the beneficial effects of enalapril in the SOLVD trial may not depend on the dose achieved, and report a post-hoc analysis of this trial assessing the associations between below-target (5-10 mg daily) vs. target dose (20 mg daily) enalapril and outcomes in patients with HFrEF. In particular, they show that both target dose enalapril vs. target dose placebo and below-target enalapril vs. below-target placebo achieved a reduction in the risk of all-cause mortality by 10% (absolute risk reduction of 5%), and of HF hospitalization (by 30% and 21%, respectively), leading to a reduction in the risk of the composite of mortality and HF hospitalization (by 30% and 22%, respectively).…”

Section: High Vs Low Enalapril Doses In the Solvd Trialmentioning

confidence: 99%

Up‐titrating angiotensin‐converting enzyme inhibitors in heart failure: evidence and challenges

Savarese

Lund

2017

European J of Heart Fail

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Similar clinical benefits from below‐target and target dose enalapril in patients with heart failure in the SOLVD Treatment trial

Abstract: In patients with HFrEF, the clinical benefits of ACE inhibitors appear to be similar at both below-target and target doses.

Cited by 20 publications

References 20 publications

Spironolactone dose in heart failure with preserved ejection fraction: findings from TOPCAT

Spironolactone dose in heart failure with preserved ejection fraction: findings from TOPCAT

Handling of Ventricular Fibrillation in the Emergency Setting

Up‐titrating angiotensin‐converting enzyme inhibitors in heart failure: evidence and challenges

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