Re: Effect of hormone replacement therapy on cardiovascular events in recently postmenopausal women: randomised trial
Schierbeck and colleagues fail to address whether their primary composite outcome was defined in the original protocol. In other words is their analysis exploratory or confirmatory? The main question is whether the results should lead to changes in clinical practice. Schierbeck has advocated for the safety of HRT (1), whereas we believe that the study results should be interpreted with caution and put in the context of previous findings.
In their response Schierbeck and colleagues state that “the outcomes in the present study were secondary outcome measures in the original protocol” and “The primary end-point of the present study was defined in the protocol as safety measures for cardiovascular events.”
A previous publication of the design of the DOPS study comments on coronary heart disease (defined as angina and myocardial infarction), but nothing is mentioned about the composite outcome (2). In the published trial of fracture outcomes the term “cardiovascular incidents” is used, but it is not described what this means (3). Nothing is stated on clinicaltrials.gov about cardiovascular outcomes. In the protocol, we received from Schierbeck (the version is from 1995, though the study enrolled patients from 1990-1993), it is stated that myocardial infarction would be assessed as a side-effect, but not specified as either a primary or secondary outcome in the data analysis section. In the statistical analysis section it is stated that “incidence of ischemic heart disease” will be evaluated, but not described what this means.
We cannot find information about neither the outcome, admission to hospital for heart failure, nor the chosen composite outcome in previous publications or the provided protocol. Would Schierbeck and colleagues please clarify whether the composite outcome of death, admission to hospital for heart failure, and myocardial infarction was defined before the trial started enrolling patients in 1990 or whether it was defined after, as this is still not clear to us.
1. [Hormones halve risk of cardiovascular disease among women in menopause]. Dagens Medicin; 19th of October 2012.
2. Mosekilde L, Hermann AP, Beck-Nielsen H, Charles P, Nielsen SP, Sorensen OH. The Danish Osteoporosis Prevention Study (DOPS): project design and inclusion of 2000 normal perimenopausal women. Maturitas 1999;31:207-19.
3. Mosekilde L, Beck-Nielsen H, Sorensen OH, Nielsen SP, Charles P, Vestergaard P, et al. Hormonal replacement therapy reduces forearm fracture incidence in recent postmenopausal women—results of the Danish Osteoporosis Prevention Study. Maturitas 2000;36:181-93.
Competing interests: No competing interests