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      Aromatase inhibitors use and risk for cardiovascular disease in breast cancer patients: A population-based cohort study

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          Abstract

          Background

          Prior studies regarding use of Aromatase inhibitors (AIs) and risk for cardiovascular disease (CVD) have shown conflicting results. This retrospective cohort study aimed to investigate whether AIs use affects risk for CVD events in postmenopausal breast cancer survivors.

          Methods

          Using a retrospective cohort study design, four CVD outcomes; heart failure or cardiomyopathy, arrhythmia, acute ischemic heart disease and ischemic stroke or Transient Ischemic Attack were compared with uni- and multivariate Cox regression analyses according to exposure to endocrine therapy (use of AI, tamoxifen or AI/tamoxifen sequentially) or no endocrine therapy.

          Results

          In total 15815 postmenopausal women, surgically treated to early breast cancer during 2006–2012, were included. No significantly increased risk for CVD events was observed in patients with AI use in the whole cohort. However, two subgroup analyses showed increased risk for CVD events in the AI/tamoxifen sequential group; heart failure in patients older than 75 years (Hazard Ratio (HR) 2.44; 95% Confidence Interval (CI): 1.32–4.54) and arrhythmia in patients without prior CVD (HR 1.45; 95% CI: 1.01–2.10). An increased risk for arrhythmia and acute ischemic heart disease in patients with at least four years of AI treatment compared with no or short-time exposure was observed (HR 2.12; 95% CI: 1.40–3.25 for arrhythmia; HR 2.03; 95% CI: 1.15–3.58 for ischemic heart disease).

          Conclusion

          Our results indicate an increased risk for ischemic heart disease and arrhythmia in patients treated for more than four years with AIs. This should be considered in the risk-benefit assessment concerning endocrine therapy.

          Highlights

          • A potential negative impact of aromatase inhibitors as adjuvant treatment on risk for cardiovascular events has been proposed.

          • We investigated the risk for cardiovascular events in breast cancer patients treated with aromatase inhibitors in a retrospective cohort study.

          • Use of aromatase inhibitors for four years or more was associated with increased risk for ischemic heart disease and arrhythmia.

          • Our findings support the need to include this information to the risk-benefit assessment concerning endocrine therapy.

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          Most cited references37

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          External review and validation of the Swedish national inpatient register

          Background The Swedish National Inpatient Register (IPR), also called the Hospital Discharge Register, is a principal source of data for numerous research projects. The IPR is part of the National Patient Register. The Swedish IPR was launched in 1964 (psychiatric diagnoses from 1973) but complete coverage did not begin until 1987. Currently, more than 99% of all somatic (including surgery) and psychiatric hospital discharges are registered in the IPR. A previous validation of the IPR by the National Board of Health and Welfare showed that 85-95% of all diagnoses in the IPR are valid. The current paper describes the history, structure, coverage and quality of the Swedish IPR. Methods and results In January 2010, we searched the medical databases, Medline and HighWire, using the search algorithm "validat* (inpatient or hospital discharge) Sweden". We also contacted 218 members of the Swedish Society of Epidemiology and an additional 201 medical researchers to identify papers that had validated the IPR. In total, 132 papers were reviewed. The positive predictive value (PPV) was found to differ between diagnoses in the IPR, but is generally 85-95%. Conclusions In conclusion, the validity of the Swedish IPR is high for many but not all diagnoses. The long follow-up makes the register particularly suitable for large-scale population-based research, but for certain research areas the use of other health registers, such as the Swedish Cancer Register, may be more suitable.
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            A new method of classifying prognostic comorbidity in longitudinal studies: development and validation.

            The objective of this study was to develop a prospectively applicable method for classifying comorbid conditions which might alter the risk of mortality for use in longitudinal studies. A weighted index that takes into account the number and the seriousness of comorbid disease was developed in a cohort of 559 medical patients. The 1-yr mortality rates for the different scores were: "0", 12% (181); "1-2", 26% (225); "3-4", 52% (71); and "greater than or equal to 5", 85% (82). The index was tested for its ability to predict risk of death from comorbid disease in the second cohort of 685 patients during a 10-yr follow-up. The percent of patients who died of comorbid disease for the different scores were: "0", 8% (588); "1", 25% (54); "2", 48% (25); "greater than or equal to 3", 59% (18). With each increased level of the comorbidity index, there were stepwise increases in the cumulative mortality attributable to comorbid disease (log rank chi 2 = 165; p less than 0.0001). In this longer follow-up, age was also a predictor of mortality (p less than 0.001). The new index performed similarly to a previous system devised by Kaplan and Feinstein. The method of classifying comorbidity provides a simple, readily applicable and valid method of estimating risk of death from comorbid disease for use in longitudinal studies. Further work in larger populations is still required to refine the approach because the number of patients with any given condition in this study was relatively small.
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              The Swedish cause of death register

              Sweden has a long tradition of recording cause of death data. The Swedish cause of death register is a high quality virtually complete register of all deaths in Sweden since 1952. Although originally created for official statistics, it is a highly important data source for medical research since it can be linked to many other national registers, which contain data on social and health factors in the Swedish population. For the appropriate use of this register, it is fundamental to understand its origins and composition. In this paper we describe the origins and composition of the Swedish cause of death register, set out the key strengths and weaknesses of the register, and present the main causes of death across age groups and over time in Sweden. This paper provides a guide and reference to individuals and organisations interested in data from the Swedish cause of death register. Electronic supplementary material The online version of this article (doi:10.1007/s10654-017-0316-1) contains supplementary material, which is available to authorized users.
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                Author and article information

                Contributors
                Journal
                Breast
                Breast
                The Breast : Official Journal of the European Society of Mastology
                Elsevier
                0960-9776
                1532-3080
                07 July 2021
                October 2021
                07 July 2021
                : 59
                : 157-164
                Affiliations
                [a ]Department of Oncology, Faculty of Medicine and Health, Örebro University, SE 70182, Örebro, Sweden
                [b ]Clinical Epidemiology and Biostatistics, Örebro University, School of Medical Sciences, Örebro, Sweden
                [c ]Regional Cancer Center Mellansverige, Uppsala, Sweden
                [d ]Translational Oncology & Urology Research (TOUR), School of Cancer and Pharmaceutical Sciences, King's College London, London, UK
                [e ]Department of Oncology, Sundsvall Hospital, 85186, Sundsvall, Sweden
                [f ]Department of Breast, Endocrine Tumors and Sarcoma, Karolinska University Hospital, Stockholm, Sweden
                [g ]Department of Molecular Medicine and Surgery, Karolinska Institutet, Stockholm, Sweden
                [h ]Department of Oncology, Uppsala University Hospital, Uppsala, Sweden
                Author notes
                []Corresponding author. Antonios.valachis@ 123456oru.se
                Article
                S0960-9776(21)00412-4
                10.1016/j.breast.2021.07.004
                8281646
                34265496
                461c6a56-0c34-4bea-b59a-21da67274e97
                © 2021 Published by Elsevier Ltd.

                This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).

                History
                : 28 May 2021
                : 4 July 2021
                : 6 July 2021
                Categories
                Original Article

                Obstetrics & Gynecology
                breast cancer,aromatase inhibitors,cardiovascular disease,survivorship
                Obstetrics & Gynecology
                breast cancer, aromatase inhibitors, cardiovascular disease, survivorship

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