Last week, the 9th of October, the BMJ published research on the ‘Effect of hormone replacement therapy on cardiovascular events in recently postmenopausal women: randomised trial’
The paper created furious debate on the Evidence-Based Healthcare mailing list, with over thirty posts.The conclusion of this paper was the following: ‘After 10 years of randomised treatment, women receiving hormone replacement therapy early after menopause had a significantly reduced risk of mortality, heart failure, or myocardial infarction, without any apparent increase in risk of cancer, venous thromboembolism, or stroke.
‘The following is my posting based on some simple biases, that you should look for in any paper, which seriously undermine the conclusions of this paper.
I agree with your methodological concerns:
‘Between 1990 and 1993, 2016 women were enrolled in a prospectively followed cohort. Of these, 1006 were randomly allocated (open label) to receive hormone replacement therapy (n=502) or no treatment (n=504);
The open label issue is of major concern, given what we now know about blinding (which at the time of the start of the trial may not have been so obvious)
The planned duration of the study was 20 years. However, as data published from other trials at the time of the 10 year visit indicated that use of hormone replacement therapy might result in more harm than benefit in postmenopausal women we advised our study participants to stop treatment.11 After their 10 year visit we followed the participants in national registers, which provide data on all hospital contacts or deaths.’
So why didn’t they publish the results then at ten years which would be 2002, 2003? If the trial was stopped in 2008 why did it take 4 years to publish? So, why publish now?
The primary endpoint for this study was a composite of death, admission to hospital for myocardial infarction, or heart failure.
Woudn’t you be more interested in an objective diagnosis of myocardial infarction or heart failure? Particularly given over the time course of this trial, the definitions have changed so much. AMI was diagnosed with CK at the beginning of the trial, and is now a diagnosis using troponin, and is a spectrum from unstable angina to STEMI.
In addition, wouldn’t someone with a diagnosis of heart failure generally proceed this with a diagnosis of AMI. I therefore suspect objective outcomes provide a different answer.
I too found the following statement hard to understand
‘This study was funded by the University of Aarhus, Karen Elise Jensen’s Foundation, Novo Nordic, Novartis, and LEO Pharma. None of the funders had any influence on the study design, interpretation of data, or the decision to publish the results.’
Given the authors relationship