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

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.

Circulation ◽  
2020 ◽  
Vol 141 (7) ◽  
pp. 549-559 ◽  
Author(s):  
Farzin Khosrow-Khavar ◽  
Kristian B. Filion ◽  
Nathaniel Bouganim ◽  
Samy Suissa ◽  
Laurent Azoulay

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.


2019 ◽  
Vol 40 (Supplement_1) ◽  
Author(s):  
O L Rueda Ochoa ◽  
L R Bons ◽  
S Rohde ◽  
K E L Ghoud ◽  
R Budde ◽  
...  

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.


Biomolecules ◽  
2018 ◽  
Vol 8 (3) ◽  
pp. 60 ◽  
Author(s):  
Tanja Zeller ◽  
Christoph Waldeyer ◽  
Francisco Ojeda ◽  
Renate Schnabel ◽  
Sarina Schäfer ◽  
...  

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.


Author(s):  
Ahmad Hazem ◽  
Sunita Sharma ◽  
Amit Sharma ◽  
Cameron Leitch ◽  
Roopalakshmi Sharadanant ◽  
...  

Importance: Right bundle branch block (RBBB) is observed in approximately 5-14% of patients with heart failure (HF). Multiple observational studies have reported the association of RBBB with clinical outcomes in patients with HF. We performed a systematic review and meta-analysis to determine the prognostic significance of RBBB for patients with HF. Data Sources: We have systematically searched MEDLINE, EMBASE, Cochrane CENTRAL, Web of Science and Scopus through January 2014. Study Selection: Reviewers working independently and in duplicate screened all eligible abstracts that described all cause or cardiovascular mortality in patients with RBBB and HF. We excluded studies that reported unadjusted outcome, i.e.: unadjusted event rates. Knowledge synthesis: We pooled reported risk ratio and hazard ratio. Main Outcomes: All-cause mortality and cardiovascular mortality (death). Results: We found 12 relevant observational studies enrolling over 38,000 patients. Risk of bias was assessed using the Newcastle-Ottawa Scale. Included studies had at least a moderate quality. Seven of those evaluated prognosis of patients with RBBB and heart failure. After a mean follow up period of 2.5 years (range: 1-5 years), RBBB was associated with a statistically significant increased risk of all-cause mortality compared to patients with heart failure but no BBB, RR 1.27, 95% CI (1.08-1.50), Figure 1. The other 5 studies evaluated CHF patients receiving cardiac resynchronization therapy (CRT), comparing outcomes of patients with RBBB to those with LBBB. After a mean f/u period of 3 years, patients with RBBB were once again found to have an increased risk of all-cause mortality, RR 1.45, 95% CI 1.12-1.89. Conclusion and Relevance: RBBB in patients with HF is associated with higher all-cause mortality in comparison to patients without inter-ventricular conduction defects, as well as LBBB patients in patients undergoing CRT setting.


2021 ◽  
Vol 12 ◽  
Author(s):  
Lei Tian ◽  
Yuzi Cai ◽  
Huijuan Zheng ◽  
Sinan Ai ◽  
Mengqi Zhou ◽  
...  

Objective: We aimed to evaluate the efficacy of canagliflozin for the treatment of specific cardiovascular and renal outcomes in Type 2 diabetes mellitus (T2DM) patients by means of a systematic review and meta-analysis.Methods: We performed comprehensive searches of PubMed, the Cochrane Library, and Embase for randomized, placebo-controlled trials of the treatment of T2DM with canagliflozin that were published to 28 September 2020. The cardiovascular outcomes recorded were cardiovascular mortality, heart failure, myocardial infarction, and stroke. The renal composite outcomes recorded were end-stage renal disease (ESRD), renal death. The data for the principal cardiovascular outcomes, ESRD, and renal death were pooled and expressed as Hazard ratios (HRs) with 95% confidence intervals (CIs). Two reviewers independently selected the trials and extracted the data.Results: We identified a total of 1,741 publications, leaving 96 for their titles, abstracts and full-text review. Of these, 10 trials met the inclusion criteria and were finally included in our meta-analysis. The meta-analysis showed that canagliflozin significantly reduced the risk of heart failure in T2DM by 36% (HR 0.64, 95% CI 0.53 to 0.77, p = 0.000). The effects of canagliflozin on non-fatal myocardial infarction or non-fatal stroke (HR 0.84, 95% CI: 0.76 to 0.93, p = 0.001), cardiovascular mortality (HR 0.84, 95% CI 0.72 to 0.97, p = 0.021), and myocardial infarction (HR 0.84, 95% CI 0.70 to 1.00, p = 0.045) in patients with T2DM were relatively small, reducing the risks by 16%. In addition, canagliflozin reduced the risk of stroke in T2DM patients by 13% (HR 0.87, 95% CI 0.71 to 1.06, p = 0.166). Moreover, canagliflozin significantly reduced the risk of the composite renal event of ESRD or renal death by 36% (HR 0.64, 95% CI 0.54 to 0.75, p = 0.000).Conclusion: This meta-analysis suggests that canagliflozin protects against cardiovascular and renal outcomes in patients with T2DM.Systematic Review Registration: [https://www.crd.york.ac.uk/prospero], identifier [CRD42020210315]


2020 ◽  
Vol 41 (Supplement_2) ◽  
Author(s):  
K Svendsen ◽  
H.W Krogh ◽  
J Igland ◽  
G.S Tell ◽  
L.J Mundal ◽  
...  

Abstract Background and aim We have previously reported that individuals with familial hypercholesterolemia (FH) have a two-fold increased risk of acute myocardial infarction (AMI) compared with the general population. The consequences of having an AMI on re-hospitalization and mortality are however less known. The aim of the present study was to compare the risk of re-hospitalization with AMI and CHD and risk of mortality after incident (first) AMI-hospitalization between persons with and without FH (controls). Methods The original study population comprised 5691 persons diagnosed with FH during 1992–2014 and 119511 age and sex matched controls randomly selected from the general Norwegian population. We identified 221 individuals with FH and 1947 controls with an incident AMI registered in the Norwegian Patient Registry (NPR) or the Cardiovascular Disease in Norway Project during 2001–2017. Persons with incident AMI were followed until December 31st 2017 for re-hospitalization with AMI or coronary heart disease (CHD) registered in the NPR, and for mortality through linkage to the Norwegian Cause of Death Registry. Risk of re-hospitalization was compared with sub-hazard ratios (SHR) from competing risk regression with death as competing event, and mortality was compared using hazard ratios (HR) from Cox regression. All models were adjusted for age. Results Risk of re-hospitalization was 2-fold increased both for AMI [SHR=2.53 (95% CI: 1.88–3.41)] and CHD [SHR=1.82 (95% CI: 1.44–2.28)]. However, persons with FH did not have increased 28-day mortality following an incident AMI (HR=1.05 (95% CI: 0.62–1.78), but the longer-term (>28 days) mortality after first AMI was increased in FH [HR=1.45 (95% CI: 1.07–1.95]. Conclusion This study yields the important finding that persons with FH have increased risk of re-hospitalization of both AMI and CHD after incident AMI. These findings call for more intensive follow-up of individuals with FH after an AMI. Funding Acknowledgement Type of funding source: Public Institution(s). Main funding source(s): University of Oslo and Oslo University Hospital


2020 ◽  
Vol 41 (Supplement_2) ◽  
Author(s):  
K.K.W Olesen ◽  
M Madsen ◽  
C Gyldenkerne ◽  
P.G Thrane ◽  
T Thim ◽  
...  

Abstract Background Patients with diabetes without obstructive coronary artery disease (CAD) by coronary angiography (CAG) have a risk of myocardial infarction (MI) similar to that of non-diabetes patients without CAD. Their cardiovascular risk compared to the general population is unknown. Purpose We examined the 10-year risks of myocardial infarction (MI), ischemic stroke, and death in diabetes patients without CAD after CAG compared to the general population. Methods We included all diabetes patients without obstructive CAD examined by CAG from 2003–2016 in Western Denmark and an age and sex matched comparison group, sampled from the general population in Western Denmark without previous history of coronary heart disease. Outcomes were MI, ischemic stroke, and death. The 10-year cumulative incidences were estimated. Adjusted hazard ratios (HRs) were estimated by stratified Cox regression using the general population as the reference group. Results We identified 5,760 diabetes patients without obstructive CAD and 29,139 individuals from the general population. Median follow-up was 7 years with 25% of participants followed for up to 10 years. Diabetes patients without obstructive CAD had an almost similar 10-year risk of MI (3.2% vs 2.9%, adjusted HR 0.91, 95% CI 0.70–1.17, Figure) compared to the general population cohort. Diabetes patients had an increased risk of ischemic stroke (5.2% vs 2.2%, adjusted HR 1.88, 95% CI 1.48–2.39), and death (29.7% vs 17.9%, adjusted HR 1.41, 95% CI 1.29–1.54). The duration of diabetes was associated with increased cardiovascular risk. Conclusions Absence of obstructive CAD by CAG in patients with diabetes ensures a low MI risk similar to the general population, but diabetes patients still have an increased risk of ischemic stroke and all-cause death despite absence of CAD. Figure 1 Funding Acknowledgement Type of funding source: Public hospital(s). Main funding source(s): Department of Cardiology, Aarhus University Hospital


2021 ◽  
Vol 26 (1) ◽  
pp. 4200
Author(s):  
I. V. Zhirov ◽  
N. V. Safronova ◽  
Yu. F. Osmolovskaya ◽  
S. N. Тereschenko

Heart failure (HF) and atrial fibrillation (AF) are the most common cardiovascular conditions in clinical practice and frequently coexist. The number of patients with HF and AF is increasing every year.Aim. To analyze the effect of clinical course and management of HF and AF on the outcomes.Material and methods. The data of 1,003 patients from the first Russian register of patients with HF and AF (RIF-CHF) were analyzed. The endpoints included hospitalization due to decompensated HF, cardiovascular mortality, thromboembolic events, and major bleeding. Predictors of unfavorable outcomes were analyzed separately for patients with HF with preserved ejection fraction (AF+HFpEF), mid-range ejection fraction (AF+HFmrEF), and reduced ejection fraction (AF+HFrEF).Results. Among all patients with HF, 39% had HFpEF, 15% — HFmrEF, and 46% — HFrEF. A total of 57,2% of patients were rehospitalized due to decompensated HF within one year. Hospitalization risk was the highest for HFmrEF patients (66%, p=0,017). Reduced ejection fraction was associated with the increased risk of cardiovascular mortality (15,5% vs 5,4% in other groups, p<0,001) but not ischemic stroke (2,4% vs 3%, p=0,776). Patients with HFpEF had lower risk to achieve the composite endpoint (stroke+MI+cardiovascular death) as compared to patients with HFmrEF and HFrEF (12,7% vs 22% and 25,5%, p<0,001). Regression logistic analysis revealed that factors such as demographic characteristics, disease severity, and selected therapy had different effects on the risk of unfavorable outcomes depending on ejection fraction group.Conclusion. Each group of patients with different ejection fractions is characterized by its own pattern of factors associated with unfavorable outcomes. The demographic and clinical characteristics of patients with mid-range ejection fraction demonstrate that these patients need to be studied as a separate cohort.


2021 ◽  
Vol 8 ◽  
Author(s):  
Zhuo-Ming Huang ◽  
Wen-Rong Chen ◽  
Qi-Wen Su ◽  
Zhuo-Wen Huang

Background: The metabolic syndrome (MS) is significantly associated with the risk of incident heart failure (HF). However, there are still great controversies about the impact of MS on the prognosis in patients with established HF. This meta-analysis aimed to ascertain the effect of MS on the prognosis in patients with HF.Methods: We searched multiple electronic databases, including PubMed, Opengrey, EMBASE, and Cochran Library, for potential studies up to February 15, 2021. Observational studies that reported the impact of MS on the prognosis in patients with established HF were included for meta-analysis.Results: Ten studies comprising 18,590 patients with HF were included for meta-analysis. The median follow-up duration of the included studies was 2.4 years. Compared with HF patients without MS, the risk of all-cause mortality and cardiovascular mortality was not increased in HF with MS (HR = 1.04, 95% CI = 0.88–1.23 for all-cause mortality; HR = 1.66, 95% CI = 0.56–4.88 for cardiovascular mortality, respectively). However, there was a significant increase in composited cardiovascular events in the HF patients with MS compared with those without MS (HR = 1.73, 95% CI = 1.23–2.45).Conclusions: In patients with established HF, the presence of MS did not show an association on the risk of all-cause mortality or cardiovascular mortality, while it may increase the risk of composite cardiovascular events.


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