I think all students who are preparing for USMLE step2 are still watching that edition of video.
On hakeem we made a discussion about aortic stenosis. and actually I relied on that information and asked about it, but I don’t know if it is still true or not especially that the treatment of choice in aortic stenosis is surgery.
My question on hakeem was about drugs that improve the murmur in aortic stenosis. I believe that diuretics can improve the murmur, but are they indicated in those patients? Do they delay the onset of symptoms?
SO, I have to assure that by searching the medical literature.
First of all, we usually write an appropriate PICO. and my PICO was:
P( problem, patient ): patients with aortic stenosis.
I( Intervention ): diuretics.
O( outcome ): delaying symptoms.
It is "therapy", so we have to search in Cochrane. The Cochrane library ,, advanced search ,, systematic reviews or DARE or RCTs.
I searched for: "aortic stenosis" AND "diuretics" AND "delaying symptoms". But didn’t get the search I’m looking for even when I typed just: “aortic stenosis” AND “diuretics”. I tried many strategies, but with no benefit. So the last choice was PubMed.
PubMed home ,, clinical queries. I didn’t find a result in systematic reviews, but found one in RCTs.
the MeSH also didn’t give me results.
The full text for the previous article wasn’t for free, so I applied to SAMS and they helped me with that.
SO, let’s appraise the article:
The four steps in critical appraisal for therapeutic article are: RVRA
1- R= relevance: to see if the article is relevant, we should read the title and the abstract:
The title is:
A randomized trial of the aldosterone-receptor antagonist eplerenone in asymptomatic moderate-severe aortic stenosis.
The abstract ,, the background:
The aim of the study is to determine whether the selective aldosterone-receptor antagonist eplerenone delays onset of left ventricular (LV) systolic dysfunction or reduces LV hypertrophy in asymptomatic patients with moderate to severe aortic stenosis. Effects of eplerenone on LV diastolic function and progression of valve stenosis were also evaluated.
From the title & the abstract --> the article is relevant.
2- V= validity: if the article is valid, it should start well, run well and finish well.
Start well: we should check the 3 Cs: control group, concealed randomization, comparability of groups.
- Control group:
Sixty-five asymptomatic patients with a peak aortic valve velocity N3.0 m/s and normal LV function were
randomized double blind to eplerenone, 100 mg daily (n = 33), or placebo (n = 32) for a median of 19 (interquartile range 15
to 25) months.
That’s mean there were treatment and control groups.
- Concealed randomization:
Concealment: they didn’t frankly mention if there was concealment or not. They just said:
Subjects were randomized by internet or telephone to the Green Lane Coordinating Center (Auckland, New Zealand).
randomization & double blinding:
After completing the baseline assessments, subjects were randomized doubleblind to eplerenone, 50 mg (1 tablet/d), or matched placebo provided by Pfizer (New York, NY).
- Comparability of groups: both treatment & control groups were similar at baseline assessment, the P value for age, sex, BMI, heart rate, medications .. etc, didn’t show statistically significant difference between treatment & control. You can check the schedule in page#4
--> the article started well.
Run well: we should check the 2nd 3 Cs: co-intervention, contamination, compliance.
Other medications were at the discretion of the patient's usual doctors.
Cardiac medication, hospital admissions, and possible adverse effects of medication were documented.
- Contamination: they didn’t mention anything about it –> there was no contamination.
- Compliance: not all patients were compliant. The figure 1 shows that 4 patients withdrew from treatment group, and 2 patients withdrew from control group. (one from each group because of non cardiac death).
--> the article maybe didn’t run well.
Finish well: we should check the 3rd 3 Cs: complete follow up, correct outcome measurement, credible analysis (ITT).
- Complete follow up: not all patients were able to be followed up (the withdrawers)
- Correct outcome measurement:
A clinical outcome committee reviewed all clinical data blind to treatment allocation and study investigations to decide whether symptomatic deterioration because of aortic stenosis had occurred.
- Credible analysis:
For subjects who withdrew from the study, a final assessment was performed, and all assessments before study withdrawal are included in the analysis.
--> the article finished well.
3- R= results: although they said:
Sensitivity analysis excluding and including influential patients did not change study results.
We have to assure that:
The study shows that there was no benefit from eplerenone --> best case scenario:
EER (Experimental Event Rate) = 13\33 = 39%
CER (Control Event Rate) = 12\32 = 37%
ARR (Absolute Risk Reduction) = 39 - 37 = +2
RR (Relative Risk) = 39\37 = 105%
RRR (Relative Risk Reduction) = 100 - 105 = -5%
So, the results were true, even in best case scenario --> there is no benefit from eplerenone in aortic stenosis.
- The study was too small to reliably evaluate effects of eplerenone on clinical outcomes.
- the study talked about aldosterone-receptor antagonist, not all diuretics
- any criticism is welcomed
finally, many thanks to research team