RESUMEN
AIMS: To investigate ethnic disparities in the treatment and incidence of cardiotoxicity for patients prescribed clozapine in New Zealand. METHODS: A post hoc analysis was undertaken using data from four studies investigating clozapine cardiotoxicities in New Zealand: two population studies (one prospective, one retrospective) conducted in the Auckland District Health Board (2011-2017), and two studies of coronial autopsy records (2001-2016). The relationship between ethnicity and cases (N=26) of myocarditis and/or cardiomyopathy was examined in comparison to non-cases in the rest of the study population (N=161). Patient demographics, comorbidities, and risk factors were investigated for any associations with ethnicity, where data was available. RESULTS: Maori and Pacific patients were over-represented in the population studies. Moreover, across the cohorts investigated 46% of myocarditis and cardiomyopathy cases were Maori. In contrast, only one case (4%) of cardiomyopathy was identified in a patient of Pacific descent. Where clozapine titration data was available, the rate of dose escalation was higher in Maori and Pacific peoples, as was the cumulative dose received before the first case of cardiotoxicity (day 13 of dose titration). Maori patients were more likely to be co-medicated with sodium valproate than others during clozapine titration, and sodium valproate was also significantly associated with myocarditis in these patients. CONCLUSIONS: The factors underpinning the more rapid titration of Maori and Pacific patients onto clozapine and the increased use of concomitant sodium valproate in Maori are unclear. While the latter may explain the heightened risk of clozapine-induced myocarditis in Maori, further work is required to mitigate the effects of this inequity on the safe use of clozapine in New Zealand.
Asunto(s)
Cardiotoxicidad , Clozapina , Etnicidad , Disparidades en el Estado de Salud , Cardiotoxicidad/etnología , Clozapina/efectos adversos , Humanos , Nueva Zelanda/epidemiología , Estudios Prospectivos , Estudios RetrospectivosRESUMEN
Minority and underresourced communities experience disproportionately high rates of fatal cancer and cardiovascular disease. The intersection of these disparities within the multidisciplinary field of cardio-oncology is in critical need of examination, given the risk of perpetuating health inequities in the growing vulnerable population of patients with cancer and cardiovascular disease. This review identifies 13 cohort studies and 2 meta-analyses investigating disparate outcomes in treatment-associated cardiotoxicity and situates these data within the context of oncologic disparities, preexisting cardiovascular disparities, and potential system-level inequities. Black survivors of breast cancer have elevated risks of cardiotoxicity morbidity and mortality compared with White counterparts. Adolescent and young adult survivors of cancer with lower socioeconomic status experience worsened cardiovascular outcomes compared with those of higher socioeconomic status. Female patients treated with anthracyclines or radiation have higher risks of cardiotoxicity compared with male patients. Given the paucity of data, our understanding of these racial and ethnic, socioeconomic, and sex and gender disparities remains limited and large-scale studies are needed for elucidation. Prioritizing this research while addressing clinical trial inclusion and access to specialist care is paramount to reducing health inequity.
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Cardiotoxicidad , Inequidades en Salud , Cardiotoxicidad/etnología , Enfermedades Cardiovasculares/etnología , Enfermedades Cardiovasculares/terapia , Humanos , Neoplasias/etnología , Neoplasias/terapia , Resultado del TratamientoRESUMEN
Breast cancer and cardiovascular-specific mortality are higher among blacks compared with whites, but disparities in cancer therapy-related adverse cardiovascular outcomes have not been well studied. We assessed for the contribution of race and socioeconomic status on cardiotoxicity among women with HER2-positive breast cancer. This retrospective cohort analysis studied women diagnosed with stage I-III HER2-positive breast cancer from 2004-2013. All underwent left ventricular ejection fraction assessment at baseline and at least one follow-up after beginning trastuzumab. Multivariable logistic regression was used to assess the association between race and socioeconomic status (SES) on cardiotoxicity, defined by clinical heart failure (New York Heart Association class III or IV) or asymptomatic left ventricular ejection fraction decline (absolute decrease ≥ 10% to < 53%, or ≥ 16%). Blacks had the highest prevalence of hypertension, diabetes, and increased BMI. Neighborhood-level SES measures including household income and educational attainment were lower for blacks compared with whites and others. The unadjusted cardiotoxicity risk was significantly higher in black compared with white women (OR, 2.10; 95% CI, 1.42 to 3.10). In a multivariable analysis, this disparity persisted after controlling for relevant cardiovascular risk factors (adjusted OR, 1.88; 95% CI, 1.25 to 2.84). Additional models adjusting for SES factors of income, educational attainment, and insurance status did not significantly alter the association between race and cardiotoxicity. In conclusion, black women are at increased risk of cardiotoxicity during HER2-targeted breast cancer therapy. Future etiologic analyses, particularly studies exploring biologic or genetic mechanisms, are needed to further elucidate and reduce racial disparities in cardiotoxicity.
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Negro o Afroamericano/estadística & datos numéricos , Neoplasias de la Mama/etnología , Cardiotoxicidad/etnología , Disparidades en el Estado de Salud , Población Blanca/estadística & datos numéricos , Adulto , Antineoplásicos Inmunológicos/efectos adversos , Neoplasias de la Mama/tratamiento farmacológico , Neoplasias de la Mama/patología , Femenino , Humanos , Persona de Mediana Edad , Estadificación de Neoplasias , Receptor ErbB-2 , Estudios Retrospectivos , Factores Socioeconómicos , Volumen Sistólico , Trastuzumab/efectos adversosRESUMEN
BACKGROUND: Human epidermal growth factor receptor 2 (HER2)-targeted therapies are highly effective at preventing breast cancer recurrence but are associated with cardiotoxicity in some patients, and minimal data are available regarding racial disparities in the incidence of this toxicity. The authors conducted a retrospective study to analyze the association of black or white race with treatment-induced cardiotoxicity and incomplete therapy among patients with HER2-positive early breast cancer. METHODS: Women with HER2-positive, stage I through III breast cancer who initiated (neo)adjuvant HER2-targeted therapy (trastuzumab with or without pertuzumab) from January 2005 to March 2015 at the authors' institution were eligible. We analyzed differences in the incidence of cardiotoxicity (a decline in the left ventricular ejection fraction to <50% AND an absolute drop in the left ventricular ejection fraction of ≥10% from baseline) and incomplete therapy (<52 weeks of HER2-targeted therapy) between black and white women in univariate and multivariable analyses. RESULTS: The authors identified 59 black patients and 157 white patients who had a median follow-up 5.2 years. The median patient age was 53 years and was similar for black and white patients. The 1-year cardiotoxicity incidence was 12% overall (95% confidence interval [CI], 7%-16%), 24% in black women (95% CI, 12%-34%), and 7% in white women (95% CI, 3%-11%). Black patients had a significantly greater probability of incomplete therapy compared with white patients (odds ratio, 4.61; 95% CI, 1.70-13.07; P = .002). High correlation was observed between a cardiotoxicity event and incomplete therapy (96% concordance). CONCLUSIONS: Black patients have a higher rate of cardiotoxicity and resultant incomplete adjuvant HER2-targeted therapy than white patients. This patient population may benefit from enhanced cardiac surveillance, cardioprotective strategies, and early referral to cardiology when appropriate. Cancer 2018;124:1904-11. © 2018 American Cancer Society.
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Antineoplásicos Inmunológicos/efectos adversos , Neoplasias de la Mama/terapia , Cardiotoxicidad/etnología , Disparidades en el Estado de Salud , Receptor ErbB-2/antagonistas & inhibidores , Adulto , Anciano , Anciano de 80 o más Años , Anticuerpos Monoclonales Humanizados/administración & dosificación , Anticuerpos Monoclonales Humanizados/efectos adversos , Antineoplásicos Inmunológicos/administración & dosificación , Población Negra/estadística & datos numéricos , Neoplasias de la Mama/inmunología , Neoplasias de la Mama/patología , Cardiotoxicidad/etiología , Cardiotoxicidad/prevención & control , Quimioterapia Adyuvante/efectos adversos , Quimioterapia Adyuvante/métodos , Femenino , Estudios de Seguimiento , Humanos , Mastectomía , Persona de Mediana Edad , Terapia Neoadyuvante/efectos adversos , Terapia Neoadyuvante/métodos , Recurrencia Local de Neoplasia/prevención & control , Estadificación de Neoplasias , Receptor ErbB-2/inmunología , Receptor ErbB-2/metabolismo , Estudios Retrospectivos , Trastuzumab/administración & dosificación , Trastuzumab/efectos adversos , Población Blanca/estadística & datos numéricosRESUMEN
INTRODUCTION: Domperidone is a dopamine receptor antagonist with peripheral prokinetic and central antiemetic properties. Prolongation of the QTc interval with chronic use of oral domperidone in standard doses has been reported in the literature. Our goal was to investigate cardiac toxicity in patients receiving 2-fold greater doses than in previous reports. METHODS: A retrospective chart review was conducted of patients with nausea (N) and vomiting (V) receiving domperidone from 2009 to 2013 under an Investigational New Drug (IND) protocol. Patient demographics, indications for therapy, clinical outcomes, cardiac symptoms and electrocardiogram tracings were reviewed. Prolonged QTc was verified if >470 milliseconds in females (F) and >450 milliseconds in males (M). RESULTS: A total of 64 patients, 44 female (37% Hispanic, 60% white, 3% African American), were taking domperidone for diabetic gastroparesis 45%; idiopathic gastroparesis 36%; chronic N&V 8%; dumping syndrome 5%; cyclic vomiting 5% and conditioned vomiting 1%. Mean duration of therapy was 8 months (range, 3 months to 4 years). Doses ranged from 40 to 120 mg/d with 90% receiving 80 to 120 mg compared with the standard dose of 40 mg. Of note, 73% of subjects benefited from treatment with reduced nausea and vomiting. Thirty-seven patients had follow-up electrocardiograms available, and they showed that the mean QTc at baseline was 424 milliseconds ± 28.4 (SD) compared with 435 milliseconds ± 27.2 (SD) at follow-up (not significant). Ten of these patients had prolonged QTc at F/U ranging from 453 to 509 milliseconds, without any cardiovascular complaints. There was no relationship between prolonged QTc and daily dose of domperidone, body mass index or age. CONCLUSIONS: Our data indicate that at very high dosing, the prokinetic/antiemetic agent domperidone has a low risk of adverse cardiovascular events while exhibiting good clinical efficacy.