Abstract
Background
In the Studies of Left Ventricular Dysfunction (SOLVD) treatment trial, similar clinical
benefits were observed between starting doses of enalapril and the target dose achieved
by postrandomization up-titration. In our current analysis, protecting the randomization,
we examined the early effects of starting doses of enalapril.
Methods
There were 2569 patients with mild-to-moderate chronic heart failure with reduced
ejection fraction (ejection fraction ≤35%) randomized to receive starting doses (5-10 mg/day) of placebo (n = 1284) or enalapril
(n = 1285). At day 14, both study drugs were blindly up-titrated to the target dose
(20 mg/day). Overall, 96% (2458/2569) of the patients returned for dose up-titration,
which was achieved in 59% (1444/2458), 48% (696/1444) of whom were in the enalapril
group. Hazard ratios (HRs) and 95% confidence intervals (CIs) for outcomes in the
enalapril group were estimated.
Results
HRs (95% CIs) for all-cause mortality, heart failure hospitalization, and the combined
endpoint of heart failure hospitalization or all-cause mortality at 14 days after
randomization were 0.80 (0.32-2.03), 0.63 (0.35-1.12), and 0.65 (0.39-1.06), respectively.
Corresponding HRs (95% CIs) at 30 days were 0.82 (0.41-1.67), 0.43 (0.27-0.68), and
0.43 (0.27-0.68), respectively. The magnitude of these early effects of starting doses
of enalapril is similar to its previously reported long-term effects at the target
dose.
Conclusion
These data suggest that in stable ambulatory patients with heart failure with reduced
ejection fraction, the magnitude of the early effect of starting doses of enalapril
is similar to that observed during longer-term therapy with the target doses of the
drug.
Keywords
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Article info
Publication history
Published online: August 08, 2019
Footnotes
Funding: AA was in part supported by the National Institutes of Health through grants (R01-HL085561, R01-HL085561-S and R01-HL097047) from the National Heart, Lung, and Blood Institute.
Conflict of Interest: GCF reports consulting with Abbott, Amgen, Bayer, Janssen, Novartis, and Medtronic. He serves as an Associate Editor of JAMA Cardiology. None of the other authors report any conflicts of interest related to this manuscript.
Authorship: All authors verify that they had access to the data outputs and contributed to writing the manuscript.
Identification
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Published by Elsevier Inc.
