scholarly journals Aromatase Inhibitors and the Risk of Cardiovascular Outcomes in Women With Breast Cancer

Circulation ◽  
2020 ◽  
Vol 141 (7) ◽  
pp. 549-559 ◽  
Author(s):  
Farzin Khosrow-Khavar ◽  
Kristian B. Filion ◽  
Nathaniel Bouganim ◽  
Samy Suissa ◽  
Laurent Azoulay
Keyword(s):  
Breast Cancer ◽  
Myocardial Infarction ◽  
Heart Failure ◽  
Ischemic Stroke ◽  
Incidence Rate ◽  
Aromatase Inhibitors ◽  
Cardiovascular Mortality ◽  
Population Based ◽  
Increased Risk ◽  
Study Population

Background: The association between aromatase inhibitors and cardiovascular outcomes among women with breast cancer is controversial. Given the discrepant findings from randomized controlled trials and observational studies, additional studies are needed to address this safety concern. Methods: We conducted a population-based cohort study using the UK Clinical Practice Research Datalink linked to the Hospital Episode Statistics and Office for National Statistics databases. The study population consisted of women newly diagnosed with breast cancer initiating hormonal therapy with aromatase inhibitors or tamoxifen between April 1, 1998, and February 29, 2016. We usedCox proportional hazards models with inverse probability of treatment and censoring weighting to estimate hazard ratios (HRs) with 95% CIs comparing new users of aromatase inhibitors with new users of tamoxifen for each of the study outcomes (myocardial infarction, ischemic stroke, heart failure, and cardiovascular mortality). Results: The study population consisted of 23 525 patients newly diagnosed with breast cancer, of whom 17 922 initiated treatment with either an aromatase inhibitor or tamoxifen (8139 and 9783, respectively). The use of aromatase inhibitors was associated with a significantly increased risk of heart failure (incidence rate, 5.4 versus 1.8 per 1000 person-years; HR, 1.86 [95% CI, 1.14–3.03]) and cardiovascular mortality (incidence rate, 9.5 versus 4.7 per 1000 person-years; HR, 1.50 [95% CI, 1.11–2.04]) compared with the use of tamoxifen. Aromatase inhibitors were associated with elevated HRs, but with CIs including the null value, for myocardial infarction (incidence rate, 3.9 versus 1.8 per 1000 person-years; HR, 1.37 [95% CI, 0.88–2.13]) and ischemic stroke (incidence rate, 5.6 versus 3.2 per 1000 person-years; HR, 1.19 [95% CI, 0.82–1.72]). Conclusions: In this population-based study, aromatase inhibitors were associated with increased risks of heart failure and cardiovascular mortality compared with tamoxifen. There were also trends toward increased risks, although nonsignificant, of myocardial infarction and ischemic stroke. The increased risk of cardiovascular events associated with aromatase inhibitors should be balanced with their favorable clinical benefits compared with tamoxifen.

scholarly journals Cardiotoxicity of Use of Sequential Aromatase Inhibitors in Women With Breast Cancer

2020 ◽  
Vol 189 (10) ◽  
pp. 1086-1095 ◽  
Author(s):  
Farzin Khosrow-Khavar ◽  
Nathaniel Bouganim ◽  
Kristian B Filion ◽  
Samy Suissa ◽  
Laurent Azoulay
Keyword(s):  
Myocardial Infarction ◽  
Heart Failure ◽  
Ischemic Stroke ◽  
Confidence Intervals ◽  
Aromatase Inhibitors ◽  
Cardiovascular Mortality ◽  
Observational Studies ◽  
Cardiovascular Outcomes ◽  
Hazard Ratios ◽  
Increased Risk

Abstract The association between use of aromatase inhibitors (AIs) and cardiovascular outcomes is controversial. While some observational studies have assessed the cardiovascular safety of AIs as upfront treatments, their cardiotoxicity as sequential treatments with tamoxifen remains unknown. Thus, we conducted a population-based cohort study using data from the United Kingdom Clinical Practice Research Datalink linked to the Hospital Episode Statistics and Office for National Statistics databases. We employed a prevalent new-user design to propensity-score match, in a 1:2 ratio, patients switching from tamoxifen to AIs with patients continuing tamoxifen between 1998 and 2016. Cox proportional hazards models were used to estimate hazard ratios and 95% confidence intervals for the study outcomes (myocardial infarction, ischemic stroke, heart failure, and cardiovascular mortality). Overall, 1,962 patients switching to AIs were matched to 3,874 patients continuing tamoxifen. Compared with tamoxifen, AIs were associated with an increased risk of myocardial infarction (hazard ratio (HR) = 2.08, 95% confidence interval (CI): 1.02, 4.27). The hazard ratios were elevated for ischemic stroke (HR = 1.58, 95% CI: 0.85, 2.93) and heart failure (HR = 1.69, 95% CI: 0.79, 3.62) but not cardiovascular mortality (HR = 0.87, 95% CI: 0.49, 1.54), with confidence intervals including the null value. The elevated hazard ratios observed for the cardiovascular outcomes should be corroborated in future large observational studies.

scholarly journals Adjuvant Hormonotherapy and Cardiovascular Risk in Post-Menopausal Women with Breast Cancer: A Large Population-Based Cohort Study

Cancers ◽  
2021 ◽  
Vol 13 (9) ◽  
pp. 2254
Author(s):  
Matteo Franchi ◽  
Roberta Tritto ◽  
Luigi Tarantini ◽  
Alessandro Navazio ◽  
Giovanni Corrao
Keyword(s):  
Breast Cancer ◽  
Heart Failure ◽  
Adjuvant Therapy ◽  
Large Population ◽  
Positive Association ◽  
Population Based ◽  
Study Cohort ◽  
Increased Risk ◽  
Post Menopausal ◽  
New Diagnosis

Background: Whether aromatase inhibitors (AIs) increase the risk of cardiovascular (CV) events, compared to tamoxifen, in women with breast cancer is still debated. We evaluated the association between AI and CV outcomes in a large population-based cohort of breast cancer women. Methods: By using healthcare utilization databases of Lombardy (Italy), we identified women ≥50 years, with new diagnosis of breast cancer between 2009 and 2015, who started adjuvant therapy with either AI or tamoxifen. We estimated the association between exposure to AI and CV outcomes (including myocardial infarction, ischemic stroke, heart failure or any CV event) by a Cox proportional hazard model with inverse probability of treatment and censoring weighting. Results: The study cohort included 26,009 women starting treatment with AI and 7937 with tamoxifen. Over a median follow-up of 5.8 years, a positive association was found between AI and heart failure (Hazard Ratio = 1.20, 95% CI: 1.02 to 1.42) and any CV event (1.14, 1.00 to 1.29). The CV risk increased in women with previous CV risk factors, including hypertension, diabetes and dyslipidemia. Conclusions: Adjuvant therapy with AI in breast cancer women aged more than 50 years is associated with increased risk of heart failure and combined CV events.

P1818Descending aortic thoracic diameter: a risk marker for major adverse cardiovascular outcomes in women

2019 ◽  
Vol 40 (Supplement_1) ◽  
Author(s):  
O L Rueda Ochoa ◽  
L R Bons ◽  
S Rohde ◽  
K E L Ghoud ◽  
R Budde ◽  
...  
Keyword(s):  
Heart Failure ◽  
Cardiovascular Risk ◽  
Cardiovascular Mortality ◽  
Total Mortality ◽  
Population Based ◽  
Cardiovascular Outcomes ◽  
Increased Risk ◽  
Almost All

Abstract Background Thoracic aortic diameters have been associated with cardiovascular risk factors and atherosclerosis. However, limited evidence regarding the role of thoracic aortic diameters as risk markers for major cardiovascular outcomes among women and men exist. Purpose To evaluate the independent associations between crude and indexed ascending and descending aortic (AA and DA) diameters with major cardiovascular outcomes among women and men and to provide optimal cutoff values associated with increased cardiovascular risk. Methods and results 2178 women and men ≥55 years from the prospective population-based Rotterdam Study underwent multi-detector CT scan of thorax. Crude diameters of the AA and DA were measured and indexed by height, weight, body surface area (BSA) and body mass index (BMI). Incidence of stroke, coronary heart disease (CHD), heart failure (HF), cardiovascular and all-cause mortality were evaluated during 13 years of follow-up. Weight-, BSA-, or BMI-indexed AA diameters showed significant associations with total or cardiovascular mortality in both sexes and height-indexed values showed association with HF in women. Crude AA diameters were associated with stroke in men and HF in women. For DA, crude and almost all indexed diameters showed significant associations with either stroke, HF, cardiovascular or total mortality in women. Only weight-, BSA- and BMI-indexed values were associated with total mortality in men. For crude DA diameter, the risk for stroke increased significantly at the 75th percentile among men while the risks for HF and cardiovascular mortality increased at the 75th and 85th percentiles respectively in women. Conclusions Our study suggests a role for descending thoracic aortic diameter as a marker for increased cardiovascular risk, in particular for stroke, heart failure and cardiovascular mortality among women. The cut points for increased risk for several of cardiovascular outcomes were below the 95th percentile of the distribution of aortic diameters.

scholarly journals Adverse Outcome Prediction of Iron Deficiency in Patients with Acute Coronary Syndrome

Biomolecules ◽  
2018 ◽  
Vol 8 (3) ◽  
pp. 60 ◽  
Author(s):  
Tanja Zeller ◽  
Christoph Waldeyer ◽  
Francisco Ojeda ◽  
Renate Schnabel ◽  
Sarina Schäfer ◽  
...  
Keyword(s):  
Myocardial Infarction ◽  
Heart Failure ◽  
Acute Coronary Syndrome ◽  
Iron Deficiency ◽  
Cardiovascular Mortality ◽  
Adverse Outcome ◽  
Smoking Status ◽  
Coronary Syndrome ◽  
Iron Deficient ◽  
Increased Risk

Acute myocardial infarction remains a leading cause of morbidity and mortality. While iron deficient heart failure patients are at increased risk of future cardiovascular events and see improvement with intravenous supplementation, the clinical relevance of iron deficiency in acute coronary syndrome remains unclear. We aimed to evaluate the prognostic value of iron deficiency in the acute coronary syndrome (ACS). Levels of ferritin, iron, and transferrin were measured at baseline in 836 patients with ACS. A total of 29.1% was categorized as iron deficient. The prevalence of iron deficiency was clearly higher in women (42.8%), and in patients with anemia (42.5%). During a median follow-up of 4.0 years, 111 subjects (13.3%) experienced non-fatal myocardial infarction (MI) and cardiovascular mortality as combined endpoint. Iron deficiency strongly predicted non-fatal MI and cardiovascular mortality with a hazard ratio (HR) of 1.52 (95% confidence interval (CI) 1.03-2.26; p = 0.037) adjusted for age, sex, hypertension, smoking status, diabetes, hyperlipidemia, body-mass-index (BMI) This association remained significant (HR 1.73 (95% CI 1.07–2.81; p = 0.026)) after an additional adjustment for surrogates of cardiac function and heart failure severity (N-terminal pro B-type natriuretic peptide, NT-proBNP), for the size of myocardial necrosis (troponin), and for anemia (hemoglobin). Survival analyses for cardiovascular mortality and MI provided further evidence for the prognostic relevance of iron deficiency (HR 1.50 (95% CI 1.02–2.20)). Our data showed that iron deficiency is strongly associated with adverse outcome in acute coronary syndrome.

scholarly journals Endocrine therapy use and the risk of cardiovascular disease in postmenopausal breast cancer survivors: two cohort studies in the UK and US

2019 ◽  
Author(s):  
Anthony Matthews ◽  
Sharon Peacock Hinton ◽  
Susannah Stanway ◽  
Alexander R Lyon ◽  
Liam Smeeth ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Venous Thromboembolism ◽  
Aromatase Inhibitor ◽  
Incidence Rate ◽  
Aromatase Inhibitors ◽  
Cardiovascular Outcomes ◽  
Increased Risk ◽  
The Us ◽  
Venous Thromboembolic ◽  
The Uk

ABSTRACTObjectiveExamine the effect of tamoxifen and aromatase inhibitors on 12 clinically relevant individual cardiovascular outcomes in postmenopausal female breast cancer survivors using large-scale datasets from the UK and US.DesignTwo prospective cohort studiesSettingPopulation-based using data from the UK Clinical Practice Datalink linked with Hospital Episode Statistics (2002-2016), and the US Surveillance, Epidemiology and End Results-Medicare database (2008-2013).Participants10005 and 22027 postmenopausal women with breast cancer in the UK and US respectively.ExposuresAromatase inhibitor compared with tamoxifen use; the US cohort additionally included a comparison with an “unexposed” group of women with oestrogen or progesterone receptor positive breast cancer but no endocrine therapy use.Outcomes12 clinically relevant individual cardiovascular outcomes (and two composite coronary and venous thromboembolic outcomes)ResultsIn both the UK and the US, there was evidence of an increased risk of coronary artery disease in aromatase inhibitor compared with tamoxifen users (UK incidence rate: 10.18 vs 6.87 per 1000 person-years, HR: 1.29, 0.94-1.76; US incidence rate: 35.26 vs 26.95 per 1000 person-years, HR: 1.29, 1.06-1.55), but the US data showed no increase in risk compared with the unexposed group (incidence rate for tamoxifen vs unexposed: 26.95 vs 38.70 per 1000 person-years, HR: 0.74, 0.60-0.92; incidence rate for aromatase inhibitors vs unexposed: 35.26 vs 28.70, HR: 0.96, 0.83-1.10). Similar patterns were seen for other cardiovascular outcomes such as arrhythmia, heart failure, and valvular heart disease. As expected, there were more venous thromboembolic events in tamoxifen users compared with both aromatase inhibitor users and those unexposed. There was a high degree of consistency between results in the two countries.ConclusionsIncreased risks of several cardiovascular diseases among aromatase inhibitor compared with tamoxifen users appeared to be driven by protective effects of tamoxifen, rather than toxic effects of aromatase inhibitors. We also confirmed the known increased risk of venous thromboembolic events in tamoxifen users.WHAT THIS PAPER ADDSWhat is already known on this topicIt is known that tamoxifen use increases venous thromboembolism risk, but evidence for other cardiovascular outcomes is less clear.Patterns of results are suggestive of a lower risk of coronary heart disease outcomes with tamoxifen compared to both aromatase inhibitor use and no tamoxifen or placebo, but cardiovascular events are often a secondary consideration and inconsistently reported in trials, and most observational studies use composite cardiovascular definitions, ignoring potentially differential effects on specific cardiovascular outcomes.What this study addsAmong postmenopausal women with breast cancer, we found an increased risk of several cardiovascular diseases in aromatase inhibitor compared with tamoxifen users across two countries, which appeared to be driven by protective effects of tamoxifen, rather than toxic effects of aromatase inhibitors. We also found the known increased venous thromboembolism risk in tamoxifen users.There was no evidence that aromatase inhibitors or tamoxifen increases cardiovascular disease risk, other than the known increased venous thromboembolism risk with tamoxifen use. However, there was an apparent protective effect of tamoxifen on other cardiovascular outcomes.

scholarly journals Association of Insomnia, Depressive Disorders, and Mood Disorders as Risk Factors With Breast Cancer: A Nationwide Population-Based Cohort Study of 232,108 Women in Taiwan

2021 ◽  
Vol 11 ◽  
Author(s):  
Hui-Pu Liu ◽  
James Cheng-Chung Wei ◽  
Hei-Tung Yip ◽  
Ming-Hsin Yeh
Keyword(s):  
Breast Cancer ◽  
Cohort Study ◽  
Incidence Rate ◽  
Mood Disorders ◽  
Depressive Disorders ◽  
Population Based ◽  
General View ◽  
Research Database ◽  
Sleep Medication ◽  
Increased Risk

BackgroundInsomnia, depressive disorders, and to a more general view, mood disorders are raising people’s concerns and causing disability of life. Herein, we try to seek the association of such illnesses with subsequent breast cancer.MethodsThis population-based, retrospective cohort study used data from the Taiwan National Health Insurance Research Database. This study included 232,108 women diagnosed with insomnia, depressive disorders, and mood disorders from January 1, 2000 to December 31, 2013. Physician diagnosed insomnia, depressive disorders, or mood disorders using outpatient and inpatient records before diagnosis of breast cancer. Cox proportional hazards regression analysis is adjusted for women with insomnia, depressive disorders, mood disorders, and other factors like insured amount, urbanization, and comorbidities such as having subsequent breast cancer.ResultsSleep medication was associated with a significantly increased incidence rate of breast cancer (aHR = 1.23 (95% CI = 1.13, 1.35), p < 0.001). Insomnia was associated with significant increased hazard of breast cancer (aHR = 1.16 (95% CI = 1.07, 1.27), p < 0.001). Annual insured amount >20,000 (TWD), high urbanization area, and hyperlipidemia were associated with increased hazard of breast cancer (aHR = 1.13 (95% CI = 1.01, 1.27), p = 0.04; aHR = 1.41 (95% CI = 1.17, 1.71), p < 0.001; aHR = 1.14 995% CI = 1.02, 1.29), p = 0.02, respectively). There was a positive correlation between depressive disorders and increased incidence rate of breast cancer but not statistically significant (aHR = 1.11 (95% CI = 0.99, 1.25), p = 0.08). Mood disorders were not associated with increased hazard (aHR = 1.11 (95% CI = 0.91, 1.34), p = 0.31).ConclusionIn this study, women with insomnia had increased risk of breast cancer, particularly those in high urbanization or with high insured amounts. Sleep medication (benzodiazepine (BZD) or non-BZD) and hyperlipidemia were independently associated with a higher hazard ratio of breast cancer. Insomnia along with sleep medication did not yield more hazards than each alone. Mood disorders appeared to be not associated with subsequent breast cancer. However, depressive disorders, the subgroups of mood disorders, could possibly increase the incidence rate of breast cancer though not statistically significant.

scholarly journals Are aromatase inhibitors associated with higher myocardial infarction risk in breast cancer patients? A Medicare population‐based study

2018 ◽  
Vol 42 (1) ◽  
pp. 93-100 ◽  
Author(s):  
Sailaja Kamaraju ◽  
Yushu Shi ◽  
Elizabeth Smith ◽  
Ann B. Nattinger ◽  
Purushottam Laud ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Myocardial Infarction ◽  
Cancer Patients ◽  
Aromatase Inhibitors ◽  
Population Based ◽  
Breast Cancer Patients ◽  
Population Based Study ◽  
Medicare Population

scholarly journals Association between Atrial Fibrillation, Myocardial Infarction, Heart Failure and Mortality in Patients with Nontuberculous Mycobacterial Infection: a nationwide population-based study

2019 ◽  
Vol 9 (1) ◽  
Author(s):  
Chan Soon Park ◽  
Eue-Keun Choi ◽  
Bongseong Kim ◽  
Kyung-Do Han ◽  
So-Ryoung Lee ◽  
...  
Keyword(s):  
Myocardial Infarction ◽  
Heart Failure ◽  
Atrial Fibrillation ◽  
Mycobacterial Infection ◽  
Population Based ◽  
Newly Diagnosed ◽  
Increased Risk ◽  
Significant Difference ◽  
Risk Patients ◽  
The Impact

Abstract NTM infection demonstrates an increasing incidence and prevalence. We studied the impact of NTM in cardiovascular events. Using the Korean nationwide database, we included newly diagnosed 1,730 NTM patients between 2005 and 2008 and followed up for new-onset atrial fibrillation (AF), myocardial infarction (MI), heart failure (HF), ischemic stroke (IS), and death. Covariates-matched non-NTM subjects (1:5, n = 8,650) were selected and analyzed. Also, NTM infection was classified into indolent or progressive NTM for risk stratification. During 4.16 ± 1.15 years of the follow-up period, AF, MI, HF, IS, and death were newly diagnosed in 87, 125, 121, 162, and 468 patients. In multivariate analysis, NTM group showed an increased risk of AF (hazard ratio [HR] 2.307, 95% confidence interval [CI] 1.560–3.412) and all-cause death (HR 1.751, 95% CI 1.412–2.172) compared to non-NTM subjects, whereas no significant difference in MI (HR 0.868, 95% CI 0.461–1.634), HF (HR 1.259, 95% CI 0.896–2.016), and IS (HR 1.429, 95% CI 0.981–2.080). After stratification, 1,730 NTM patients were stratified into 1,375 (79.5%) indolent NTM group and 355 (20.5%) progressive NTM group. Progressive NTM showed an increased risk of AF and mortality than indolent NTM group. Screening for AF and IS prevention would be appropriate in these high-risk patients.

scholarly journals Outcome and presentation of heart failure in breast cancer patients: findings from a Swedish register-based study

2019 ◽  
Vol 6 (2) ◽  
pp. 147-155
Author(s):  
Elham Hedayati ◽  
Antroula Papakonstantinou ◽  
Sofie A M Gernaat ◽  
Renske Altena ◽  
Judit S Brand ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Myocardial Infarction ◽  
Heart Failure ◽  
Cardiovascular Mortality ◽  
Coronary Revascularization ◽  
Breast Cancer Patients ◽  
Risk Of Death ◽  
Cox Proportional Hazard ◽  
National Patient ◽  
Cox Proportional Hazard Models

Abstract Aims Heart failure (HF) patients diagnosed with breast cancer (BC) may have a higher risk of death, and different HF presentation and treatment than patients without BC. Methods and results A total of 14 998 women with incident HF (iHF) or prevalent HF (pHF) enrolled in the Swedish HF Registry within and after 1 month since HF diagnosis, respectively, between 2008 and 2013. Patients were linked with the National Patient-, Cancer-, and Cause-of-Death Registry. Two hundred and ninety-four iHF and 338 pHF patients with BC were age-matched to 1470 iHF and 1690 pHF patients without BC. Comorbidity and treatment characteristics were compared using the χ2 tests for categories. Cox proportional hazard models assessed the hazard ratio (HR) and 95% confidence intervals (95% CIs) of all-cause and cardiovascular mortality among HF patients with and without BC. In the pHF group, BC patients had less often myocardial infarction (21.6% vs. 28.6%, P < 0.01) and received less often aspirin (47.6% vs. 55.1%, P = 0.01), coronary revascularization (11.8% vs. 16.2%, P < 0.01), or device therapy (0.9% vs. 3.0%, P = 0.03). After median follow-up of 2 years, risk of all-cause mortality (iHF: HR = 1.04, 95% CI = 0.83–1.29 and pHF: HR = 0.94, 95% CI = 0.79–1.12), cardiovascular mortality (iHF: HR = 0.94, 95% CI = 0.71–1.24 and pHF: HR = 0.89, 95% CI = 0.71–1.10), and HF mortality (iHF: HR = 0.80, 95% CI = 0.34–1.90 and pHF: HR = 0.75, 95% CI = 0.43–1.29) were similar for patients with and without BC in the iHF and pHF groups. Conclusion Risk of all-cause and cardiovascular mortality in HF patients did not differ by BC status. Differences in pre-existing myocardial infarction and HF treatment among pHF patients with and without BC may suggest differences in pathogenesis of HF.

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