Discontinuation of hormone replacement therapy after myocardial infarction and short term risk of adverse cardiovascular events: nationwide cohort study
Guidelines recommend discontinuation of hormone-replacement therapy (HRT) in women diagnosed with coronary artery disease. Discontinuation of HRT can be troublesome owing to the rebound of climacteric symptoms, as well as its theoretical favorable effects on endothelial function, inflammatory and haemostatic mechanisms.
Evidence regarding the risk-benefit of this strategy is lacking, especially in women after a myocardial infarction, a period which is a pathophysiologically vulnerable time, with endothelial dysfunction, elevated inflammatory markers, and high thrombogenecity.
Therefore a question has emerged whether the potential rebound effects of discontinuation of HRT on these mechanisms during this period may be more prone to cause adverse cardiovascular events.
Aim of the Study
The aim of this study was to assess whether women who discontinue HRT after myocardial infarction have a lower risk of re-infarction, cardiovascular death, or all cause death in the first year after myocardial infarction than do women who continue HRT.
The present study was a nationwide (Denmark) registry based cohort study that included all women (40 years of age or older) who had a myocardial infarction in the period 1997 to 2008 and were using HRT at the time of the incidence (n=3,322). Only women who were alie 30 days after discharge were included. HRT use was classified into four categories : oestrogen alone, combinations of oestrogen and progestogen, vaginal oestrogen alone, and “other HRT” and calculated exposure to and discontinuation for all prescriptions in the entire period from 1 January 1996 to 31 December 2008. Re-infarction, cardiovascular mortality, and all cause mortality 30 to 360 days after discharge were the outcome measures.
A total of 282 (8.5%) women experienced a re-infarction; 218 (6.6%) died of cardiovascular causes; and 357 (10.7%) died of any cause during follow-up.
Women who discontinued overall hormone replacement therapy in the first year after myocardial infarction did not have a significantly different risk of re-infarction (hazard ratio 0.90, 95% confidence interval 0.68 to 1.19), cardiovascular mortality (1.21, 0.90 to 1.62), or all cause mortality (1.22, 0.97 to 1.53) than women who continued use.
However, the discontinuation of vaginal oestrogen was associated with a lower risk of re-infarction (0.54, 0.34 to 0.86).
In a sub-group analysis, when analyzing the different durations of discontinuation, the authors found that discontinuation of overall HRT for 1-90 days was associated with an increased risk of cardiovascular mortality (1.90, 1.15 to 3.12) and all cause mortality (1.58, 1.04 to 2.39) for the periods of 30-90 days but no increased risk of re-infarction. Interestingly, for the same period (1-90 days) of discontinuation of vaginal oestrogen, we found a decreased risk of re-infarction during the first 30-90 days after discharge (0.36, 0.16 to 0.82).
The main finding was that women with myocardial infarction who followed treatment guidelines and discontinued HRT overall, were not characterized by a decreased or increased risk of re-infarction, cardiovascular mortality, or all cause mortality during the first year after the index myocardial infarction.
Discontinuation of vaginal oestrogen after myocardial infarction was associated with a decrease in risk of re-infarction. However, women in this sub-group had very different baseline characteristics and higher incidence rates compared with women in the other HRT categories, which is relevant when interpreting these results. Furthermore, discontinuation seems to have a greater effect in the first 30-90 days after myocardial infarction.
The main result of this study was that there was no certain increased or decreased risk of re-infarction or death with continuing HRT after a myocardial infarction.
The limitations of the study derive from the observational nature of the design concerning (mainly) unmeasured confounders. The authors have no information on clinical parameters such as obesity, smoking status, lipid levels and hypertension or diabetes mellitus control. Moreover, the HRT doses and treatment durations were calculated approximations.
Finally, clinical, functional and laboratory details (myocardial infarction location and size, diastolic or systolic dysfunction, concomitant mitral regurgitation) regarding coronary artery disease are not reported.
Nevertheless, these figures are valuable when a possible cardiovascular risk needs to be balanced with menopausal symptoms for the individual patient.
Corresponding author from original paper: D-M Bretler, Department of Cardiology, Copenhagen University Hospital Gentofte, Copenhagen, Denmark e-mail:firstname.lastname@example.org
Citation: BMJ 2012; 344:e1802