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Comparative Study
. 2012 Mar 27:344:e1802.
doi: 10.1136/bmj.e1802.

Discontinuation of hormone replacement therapy after myocardial infarction and short term risk of adverse cardiovascular events: nationwide cohort study

Ditte-Marie Bretler  1 , Peter Riis Hansen, Rikke Sørensen, Jesper Lindhardsen, Ole Ahlehoff, Charlotte Andersson, Steen Zabell Abildstrøm, Christian Torp-Pedersen, Gunnar Hilmar Gislason
Affiliations
Comparative Study

Discontinuation of hormone replacement therapy after myocardial infarction and short term risk of adverse cardiovascular events: nationwide cohort study

Ditte-Marie Bretler et al. BMJ. .

Abstract

Objective: To assess the risk of adverse cardiovascular events in women who discontinue hormone replacement therapy after myocardial infarction compared with those who continue.

Design: Nationwide register based cohort study.

Setting: All hospitals in Denmark.

Population: All 3322 women aged 40 years or over who survived 30 days after a myocardial infarction and were prescribed hormone replacement therapy at the time of myocardial infarction in the period 1997 to 2008.

Main outcome measures: Reinfarction, cardiovascular mortality, and all cause mortality 30 to 360 days after discharge.:

Results: A total of 282 (8.5%) women had a reinfarction, 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 reinfarction (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, discontinuation of vaginal oestrogen was associated with a lower risk of reinfarction (hazard ratio 0.54, 0.34 to 0.86).

Conclusion: No certain conclusions can be drawn regarding increased or decreased risk of adverse cardiovascular events with continuing hormone replacement therapy after myocardial infarction. The results rule out neither a modest benefit nor a worrisome increase in risk. These figures may be valuable when a possible cardiovascular risk of hormone replacement therapy needs to be balanced with menopausal symptoms for the individual patient.

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Conflict of interest statement

Competing interests: All authors have completed the ICMJE uniform disclosure form at www.icmje.org/coi_disclosure.pdf (available on request from the corresponding author) and declare: CT-P has received consultant fees from Sanofi, Neurosearch, Cardiome, and Merck. All other authors declare no support from any organisations for the submitted work; no financial relationships with any organisations that might have an interest in the submitted work in the previous three years; no other relationships or activities that could appear to have influenced the submitted work.

Figures

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Fig 1 Study population
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Fig 2 Hazard ratios (95% CI) for reinfarction, cardiovascular mortality, and all cause mortality for discontinuation of hormone replacement therapy (HRT) overall and HRT categories. Hazard ratios are for discontinuation with continued use as reference. Multivariable Cox proportional hazards analysis was adjusted for age group, year of myocardial infarction (MI), comorbidity (previous MI, revascularisation within 30 days of MI, cerebrovascular disease, congestive heart failure, malignancy, cardiac dysrhythmias, chronic renal failure, acute renal failure, diabetes with complications, pulmonary oedema, shock), concomitant drug use (β blockers, angiotensin converting enzyme inhibitors, statins, loop diuretics, clopidogrel, glucose lowering drugs), and income. No interactions were found or included in model
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Fig 3 Required size of unmeasured confounder to fully explain decrease in risk from 1.00 to 0.54 (solid blue line) and to render results statistically insignificant (dashed red line), assuming prevalence of confounder of 20% in population and prevalence of discontinuation of 20%
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Fig 4 Required size of unmeasured confounder to fully explain decrease in risk from 1.00 to 0.41 (solid blue line) and to render results statistically insignificant (dashed red line), assuming prevalence of confounder of 20% in population and prevalence of discontinuation of 20%
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