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Study Critique:
Effect of Enalapril on Survival in Patients with Reduced Left Ventricular Ejection Fractions and
Congestive Heart Failure
Sonia Perdomo
Marisel Perigo
Maria Morejon
Alejandro Fabelo
Jose Chavez
Miami Regional University
MSN 5250

Introduction
The leading cause for hospitalization in those older than 65 years of age is heart failure, a
diagnosis that affects roughly 6 million Americans today (Beckerman, 2016). The condition
essentially means that the heart has a weak pumping power, typically the result of coronary heart
disease, heart attacks, cardiomyopathy, and other conditions that overwork the heart (Beckerman,
2016). With this in mind, it is important to note that patients with this diagnosis possess a high
mortality rate and prone to frequent hospitalizations (The SOLVD Investigators, 1991). A study
published in the New England Journal of Medicine was conducted to determine whether or not
the administration of a certain drug reduced the mortality rates and hospitalization frequencies
among patients with left ventricular ejection fractions and congestive heart failure. This study
critique will review the research study and give an insight on how relevant and applicable the
results are. In other words, it will serve as a systematic way of considering the truthfulness of
this piece of research (Vogel, 2014).
Abstract
The abstract of the paper provided a brief, but insightful, overview of the study that was
conducted. Essentially, the abstract provided a short background of the current facts about
congestive heart failure and the angiotensin-converting-enzyme inhibitor studied, enalapril.
Likewise, it gave a summary of the methods used in the study, the results obtained, and provided
a conclusion that was formed from the result. In sum, the effect of the drug enalapril on mortality
and hospitalization rates of patients with chronic heart failure and ejection fractions was studied
with a random placebo or enalapril assignment in double-blind trials. The results underwent
statistical analysis and revealed that there was a significant reduction in mortality and

hospitalizations of the patients when they were administered enalapril. Anyone that skims
through the abstract can have a general concept of the overall paper.
Method
Hypothesis/Aims/Objectives
A report released by the Veterans Administration Cooperative Vasodilator Heart Failure
Trial revealed that there was a lower mortality rate observed in patients with congestive heart
failure that were administered hydralazine and isosorbide dinitrate that in those on a placebo
(The SOLVD Investigators, 1991). The researchers noted that angiotensin-converting-enzyme
inhibitors seemed promising in improving hemodynamic indexes and a review of various shortterm trials suggested that these inhibitors reduced mortality. Furthermore, the paper discusses the
fact that previous patients that remained in New York Heart Association class IV did not receive
treatment with angiotensin-converting-enzyme inhibitors and no mortality data was available for
those with a milder type of the heart conditions. These observations resulted in the postulation
that a moderately effective angiotensin-converting-enzyme inhibitor could prevent thousands of
hospitalizations and premature deaths each year (The SOLVD Investigators, 1991). This
postulation was effective in presenting the way a reduction of 15 to 20 percent in the sample size
would be reflected in numbers in the general population suffering from the condition.
Furthermore, the postulation resulted in the designing of studies to determine whether or not an
angiotensin-converting-enzyme inhibitor, enalapril, would reduce mortality in these types of
patients. Ultimately, the study points that the main aim of the trials that were carried with 2569
enrolled patients was to study the effect of enalapril on mortality, with secondary aims that
included analyzing the effect of treatment on hospitalization for congestive heart failure.

Sample Size and Type

The sample size and type that was used by the investigators was clear. A total of 2569
patients with congestive heart failure and ejection fractions of 0.35 or less were enrolled for the
treatment trial. Of this total, 1284 were treated with placebo, while 1285 were treated with
enalapril. The patients in each group were chosen in such a fashion that the characteristics of the
two groups were similar. These characteristics included age, weight, ejection fraction, race, and
disease history, among many others. The screening process was crucial in order to be able to
carry out the study. The screening process of the patients was completed by utilizing
radionuclide techniques to measure ejection fraction, along with contrast angiography, and twodimensional echocardiography with Simpsons rule. Any patients over 80 or with certain
conditions could not participate. The sample size and type that was chosen by the investigators
were very adequate for the study at hand. The adequacy of the size and type of the sample
allowed the investigators to avoid inconsistencies that may result from the patients age, health
history, and medications similar to enalapril, to name a few.
Design of the Study/Study Level
The study was carried out by using randomized assignment and performing double-blind
trials. Once chosen for eligibility, patients were randomly assigned to treatment groups in 83
different hospitals that were linked to 23 centers in the United States, Canada, and Belgium. A
run-in period and stabilization phase was conducted first. During this stage, many patients were
excluded due to worsening congestive heart failure. Once the placebo run-in period was over, the
patients were categorized as either having overt congestive heart failure or as not having overt

congestive heart failure. Those that did were enrolled in the treatment trial while the others were
enrolled in the prevention trial. The patients were then subject to dose titration.
The follow up measures included obtaining a record of the patients clinical and
functional status. The patients would undergo follow ups and chart reviews by physicians that
were blinded to the treatment assignments. This eliminated any diagnostic bias, and make certain
that the diagnosis was the same. Finally, a statistical analysis was performed to determine the
effects of enalapril on mortality and hospitalization.
Instruments
There were several instruments that were utilized by the investigators to collect data.
These included those used in the screening process like the radionuclide techniques and contrast
angiography. During the screening process, logs were carefully maintained to collect and retain
data. Charts and logs were also utilized during run-in and stabilization periods, as well as patient
follow-ups. All deaths that occurred during the period of the study were recorded and collected in
order to perform the statistical analysis. The instruments used were critical and definitely served
well in this particular scenario. Their reliability and effectiveness in carrying data were clear.
Procedure
The procedure was described in the Design of the Study section of this critique. To
briefly summarize, patients were screened for eligibility using several methods. Then, the
remaining patients underwent a run-in and stabilization stage. Next, the patients went through
double-blinded trials with titrated doses of placebo and enalapril. Finally, follow-ups were
performed by physicians that were blinded to the treatment the patients received. Deaths and

hospitalization incidents were carefully recorded in order to use for the statistical analysis. The
careful design and delivery of the procedure resulted in a successful determination of whether or
not enalapril reduced mortality and hospitalization rates.
Statistical Analysis
The investigators provided with a thorough statistical analysis of the data that was
collected throughout the study. A one-sided test with a significance level of 0.025 was used in all
analyses in order to show if enalapril reduced mortality or not. Life-table survival curves for all
patients were compared by using a stratified log-rank statistic. The deaths data recorded was used
and a Lan-DeMes boundary was utilized for formal guidelines during the interim analyses and
the Z value for 0.025 that was used was 2.11. Furthermore, life-table plots were constructed by
using the Kaplan-Meier method and the percentage reduction in mortality reported as (1- RR) x
100, where RR is the estimated relative risk of an event in the enalapril group as compared with
the placebo group estimated from the life tables (The SOLVD Investigators, 1991).
The results were reported in tables and graphs, with the ultimate focus in the risk
reduction percentage as calculated from the log-rank test, with a 95 percent confidence interval.
In the placebo group, 510 patients died while 452 died in the enalapril group. The risk reduction
here was 16 percent with a 95 percent confidence interval, 5 to 26 percent and a P being valued
at 0.0036.
One thing to note is that the investigators were not clear as to why 2.11 was used instead
of the usual value of 1.96 for the Z value in the analysis. Additionally, although the study carried
out the traditional approach perhaps future analyses could apply other sequential designs during

the interim analysis in order to cease recruitment to the study as soon as there is sufficient
evidence to reach a firm conclusion (Todd, 2001).
Conclusion
The hypothesis of the study was that angiotensin-converting-enzyme inhibitors such as
enalapril would induce a reduction in mortality rates in patients with congestive heart failure and
ejection fractions less than 0.35. The results of the study agree with the original hypothesis. The
enalapril group demonstrated a significant reduction of 16 percent in the mortality rate of the
patients with the condition. In addition, reductions of mortality and hospitalization rates were
prevalent as soon as randomization took place. The conclusion of the study is adequately brought
about in accordance to the results obtained from the study.

References
Beckerman, James, MD. "Congestive Heart Failure Symptoms, Causes, and Treatment."
WebMD. WebMD, 05 Sept. 2016. Web. 11 Oct. 2016. <http://www.webmd.com/heartdisease/guide-heart-failure#1>.
The SOLVD Investigators. "Effect of Enalapril on Survival in Patients with Reduced Left
Ventricular Ejection Fractions and Congestive Heart Failure." New England Journal of
Medicine 325.5 (1991): 293-302. Web.
Todd, S., Whitehead, A., Stallard, N., & Whitehead, J. (2001). Interim analyses and sequential
designs in phase III studies. British Journal of Clinical Pharmacology, 51(5), 394399.
http://doi.org/10.1046/j.1365-2125.2001.01382.x
"Vasotec (Enalapril)." RxList. N.p., 24 Sept. 2012. Web. 11 Oct. 2016.
<http://www.rxlist.com/vasotec-drug/clinical-pharmacology.htm>.
Vogel, Sarah. "How to Critique a Research Article." Ausmed Education. Ausmed Education, 16
Apr. 2014. Web. 11 Oct. 2016. <http://www.ausmed.com.au/blog/entry/how-to-critique-aresearch-article>.