FPIN Journal Club
RANDOMIZED CONTROLLED TRIAL
SPEAKER NOTES
Title: Ramipril for Claudication
Journal Club Author: Kate Rowland, MD – The University of Chicago
Journal Club Editor: Corey Lyon, DO – University of Colorado
PURL Citation: Not yet available
Original Article: Ahimastos AA, Walker PJ, Askew C et all. Effect of ramipril on walking times and
quality of life among patients with peripheral artery disease and intermittent claudication: a
randomized controlled trial. JAMA. 2013 Feb 6;309(5):453-60.
1. What question did the study attempt to answer?
Patients – people with peripheral arterial disease (PAD) with an ankle brachial index (ABI) <0.9
in at least one leg and claudication symptoms
Intervention – ramipril 10 mg daily
Comparison – placebo daily
Outcome – pain-free walking time (PFWT) and maximum walk time (MWT)
Did the study address an appropriate and clearly focused question
Yes
2. Determining Relevance:
a. Did the authors study a clinically meaningful
Yes
and/or a patient oriented outcome?
b. The patients covered by the review similar to your population
Yes
Other than none had undergone any revascularization procedures
3. Determining Validity:
Study design;
a. Was it a controlled trial?
b. Were patients randomly allocated to
comparison groups?
Yes
No
Yes
No
No
No
No
Unclear
c. Were groups similar at the start of a trial?
Yes
No
Unclear
d. Were patients and study personnel “blind” to treatment?
Yes
No
Unclear
e. Aside from allocated treatment, were groups treated equally?
Yes
No
Unclear
f. Were all patients who entered the trial properly accounted for at its conclusion
Yes
No
Unclear
4. What are the results?
a. What are the overall results of the study?
At the end of the study, the people who got the ramipril were able to walk 255 seconds
longer (maximum walk time, 95% CI 215-295, p<0.001) than those who got placebo. Their painfree walk time was 75 seconds longer than those who got placebo (95% CI 60-89s, p<0.001).
Patients were able to walk 255 seconds (about 4.25 minutes) longer with the ramipril. This does
not seem like a big difference, but it is about equivalent to their maximum walking time at the
beginning of the study (approximately 230 seconds), meaning that the people in the ramipril
group doubled their maximum walking time.
The median distance score improved by 13.8 (95% CI, 12.2 to 15.5), the speed score by 13.3
(95% CI, 11.9 to 15.2), and the stair climbing score by 25.2 (95% CI, 25.1 to 29.4). The physical
quality of life score improved b y 8.2 (95% CI, 3.6-11.4; p=.02) but ramipril was not associated
with change in the overall mental quality of life.
Dizziness was reported following initiation of treament in 5.6% of patients. Persisent cough was
noted by 6.6% of the patients. One patient reported chest pain and another had pronounced
ST-segment depression .
We think many patients would accept the addition of ramipril in exchange for doubling their
capacity to walk.
b. Are the results statistically significant?
c. Are the results clinically significant?
d. Were there other factors that might have
affected the outcome?
Yes
Yes
No
No
Yes
No
5. Applying the evidence:
a. If the findings are valid and relevant, will this change
your current practice?
Yes
No
b. Is the change in practice something that can be done in
a medical care setting of a family physician?
Yes
No
c. Can the results be implemented?
Yes
No
d. Are there any barrier to immediate implementation?
Yes
No
e. How was this study funded? It was funded by an Australian medical foundation.
Since the medication in question is generic and available for relatively cheap (quick internet
search shows 30 tabs for $34), the funding and the authors’ disclosures do not seem to play any
relevant conflict of interests.
6. Teaching Points
This article is an example of a well-done randomized controlled trial comparing a cheap,
available medication given for a common condition to improve an outcome that likely matters
to a patient. It also highlights the need for careful analysis of the types of outcomes studied.
When reading an article, you have to know whether the outcomes are ones that matter to your
patients.
We typically ask: are the outcomes patient-oriented or disease-oriented?
A disease-oriented outcome is one that measures only pathologic or physiologic markers. A
patient-oriented outcome is one that relates to patient care, patient experience, or patient
results. Examples of the differences between disease oriented and patient oriented outcomes
can be seen in the table below.
Disease oriented outcome
Blood pressure
Blood sugar
Newborn respiratory rate
LDL
HemoglobinA1c levels
Percentage of skin area
affected
Degrees of glenohumoral
separation seen on MRI
Patient oriented outcome
Strokes; disability from stroke
Diabetic nephropathy
NICU admissions
Cardiovascular mortality
Quality of life scale
Pain measured on a visual
analog scale
Clinical instability as
measured by re-dislocation
Patient-oriented outcomes are always preferable because disease-oriented outcomes can be
misleading. It is always tempting (and often reasonable) to assume that because the LDL goes
down, the rate of cardiovascular mortality will go down as well, but that’s not always the case.
Example: a study of the use of erythropoietin in patients on hemodialysis for end-stage kidney
disease (ESRD) found that patients whose anemia was corrected to a ‘normal’ level (mean
13.7mg/dl) actually had more adverse events such as stroke, CHF, and MI, than patients whose
anemia was corrected to a mean of 11.3 mg/dl. Quality of life indicators were similar in both
groups. The disease-oriented outcome is the hemoglobin level; it seemed reasonable that higher
would be better. However, when the patient-oriented outcomes (adverse events and quality of
life) were measured, the lower hemoglobin levels were found to be better.
Ref: Singh, Ajay K., Szczech, Lynda, Tang, Kezhen L., Barnhart, Huiman, Sapp, Shelly, Wolfson, Marsha,
Reddan, Donal, the CHOIR Investigators, Correction of Anemia with Epoetin Alfa in Chronic Kidney Disease N Engl J
Med 2006 355: 2085-2098
This study chose patient-oriented outcomes. In addition to studying ABIs or degree of blockage,
it studied walking times. It is just extra interesting that many of the disease-oriented outcomes
are equivalent, while the patient-oriented outcomes are markedly different.