Contemporary menopausal hormone therapy and risk of cardiovascular disease: Swedish nationwide register based emulated target trial.

Autor:	Johansson T; Department of Immunology, Genetics and Pathology, SciLifeLab, Uppsala University, Uppsala, Sweden therjoha@kth.se.; Centre for Women's Mental Health during the Reproductive Lifespan - Womher, Uppsala University, Uppsala, Sweden.; Garvan Institute of Medical Research, Sydney, NSW, Australia., Karlsson T; Department of Immunology, Genetics and Pathology, SciLifeLab, Uppsala University, Uppsala, Sweden., Bliuc D; Garvan Institute of Medical Research, Sydney, NSW, Australia.; Clinical School, St Vincent's Hospital, Faculty of Medicine and Health, University of New South Wales Sydney, Sydney, NSW, Australia., Schmitz D; Department of Immunology, Genetics and Pathology, SciLifeLab, Uppsala University, Uppsala, Sweden., Ek WE; Department of Immunology, Genetics and Pathology, SciLifeLab, Uppsala University, Uppsala, Sweden., Skalkidou A; Department of Women's and Children's Health, Uppsala University, Uppsala, Sweden., Center JR; Garvan Institute of Medical Research, Sydney, NSW, Australia.; Clinical School, St Vincent's Hospital, Faculty of Medicine and Health, University of New South Wales Sydney, Sydney, NSW, Australia., Johansson Å; Department of Immunology, Genetics and Pathology, SciLifeLab, Uppsala University, Uppsala, Sweden therjoha@kth.se.
Jazyk:	angličtina
Zdroj:	BMJ (Clinical research ed.) [BMJ] 2024 Nov 27; Vol. 387, pp. e078784. Date of Electronic Publication: 2024 Nov 27.
DOI:	10.1136/bmj-2023-078784
Abstrakt:	Objective: To assess the effect of contemporary menopausal hormone therapy on the risk of cardiovascular disease according to the route of administration and combination of hormones. Design: Nationwide register based emulated target trial. Setting: Swedish national registries. Participants: 919 614 women aged 50-58 between 2007 and 2020 without hormone therapy use in the previous two years, identified from the Swedish population. Interventions: 138 nested trials were designed, starting each month from July 2007 until December 2018. Using the prescription registry data for that specific month, women who had not used hormone therapy in the previous two years were assigned to one of eight treatment groups: oral combined continuous, oral combined sequential, oral unopposed oestrogen, oral oestrogen with local progestin, tibolone, transdermal combined, transdermal unopposed oestrogen, or non-initiators of menopausal hormone therapy. Main Outcome Measures: Hazard ratios with 95% confidence intervals were estimated for venous thromboembolism, as well as for ischaemic heart disease, cerebral infarction, and myocardial infarction separately and as a composite cardiovascular disease outcome. Treatment effects were estimated by contrasting initiators and non-initiators in observational analogues to "intention-to-treat" analyses and continuous users versus never users in "per protocol" analyses. Results: A total of 77 512 women were initiators of any menopausal hormone therapy and 842 102 women were non-initiators. 24 089 women had an event recorded during the follow-up: 10 360 (43.0%) had an ischaemic heart disease event, 4098 (17.0%) had a cerebral infarction event, 4312 (17.9%) had a myocardial infarction event, and 9196 (38.2%) had a venous thromboembolic event. In intention-to-treat analyses, tibolone was associated with an increased risk of cardiovascular disease (hazard ratio 1.52, 95% confidence interval 1.11 to 2.08) compared with non-initiators. Initiators of tibolone or oral oestrogen-progestin therapy had a higher risk of ischaemic heart disease (1.46 (1.00 to 2.14) and 1.21 (1.00 to 1.46), respectively). A higher risk of venous thromboembolism was observed for oral continuous oestrogen-progestin therapy (1.61, 1.35 to 1.92), sequential therapy (2.00, 1.61 to 2.49), and oestrogen-only therapy (1.57, 1.02 to 2.44). Additional results in per protocol analyses showed that use of tibolone was associated with a higher risk of cerebral infarction (1.97, 1.02 to 3.78) and myocardial infarction (1.94, 1.01 to 3.73). Conclusions: Use of oral oestrogen-progestin therapy was associated with an increased risk of heart disease and venous thromboembolism, whereas the use of tibolone was associated with an increased risk of ischaemic heart disease, cerebral infarction, and myocardial infarction but not venous thromboembolism. These findings highlight the diverse effects of different hormone combinations and administration methods on the risk of cardiovascular disease. Competing Interests: Competing interests: All authors have completed the ICMJE uniform disclosure form at www.icmje.org/disclosure-of-interest/ and declare: funding for the study as detailed above; 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 have influenced the submitted work. (© Author(s) (or their employer(s)) 2019. Re-use permitted under CC BY. No commercial re-use. See rights and permissions. Published by BMJ.)
Databáze:	MEDLINE
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