Primary Prevention to Reduce Cardiovascular Morbidity and Optimize Cancer Outcomes

项目摘要 我们的首要目标是识别和描述有癌症治疗风险的癌症患者- 相关的心脏毒性和减轻心血管功能障碍，同时优化癌症的结果。进展 早期发现和治疗癌症提高了5年生存率。然而，多模式癌症 治疗常常导致心脏毒性。治疗期间的心血管疾病（CVD）事件可能会干扰 并因此导致次优的癌症结果和增加的下游发病率、成本， mortality.美国心脏协会（2019）指南建议使用抗- 高血压和抗高血压药物在高危人群中，基于动脉粥样硬化 心血管疾病（ASCVD）风险。然而，癌症患者的一级预防是否有所改善还不确定 长期CVD结果。美国临床肿瘤学会（ASCO）（2017）指南已将 高剂量蒽环类药物、靶向治疗以及这些药物的某些组合，作为心脏毒性方案。的 一级预防对此类心脏毒性方案患者的影响尚不清楚。评估这些 问题，我们将通过合并Kaiser Permanente（KP）的电子医疗记录来创建一个独特的数据集 与KP的SEER癌症登记处，KP的医疗财政援助计划，和社会保障 政府的补充收入，残疾和死亡率数据，在一个队列的17，000+乳腺癌 患者纵向随访5年以上。我们将根据ASCVD风险对乳腺癌患者进行风险分层， 使用探索治疗效果的高级因果推理模型评估一级预防的效果 从政策和决策的角度来看。研究目标1：比较有效性 一级预防药物治疗对1）化疗期间的癌症和CVD结局和2） 成人乳腺癌化疗后的癌症和心血管疾病结果。目标2：评估 一级预防药物治疗对成年乳腺癌患者经济毒性和残疾的影响。 目标3：评估一级预防的增量医疗费用和成本效益 使用净效益回归框架对成年乳腺癌患者进行药物治疗。完成 这一建议将回答改善患者预后的关键问题：（1）一级预防是否能预防 未来的CVD事件，改善/优化癌症治疗和结果，减少经济毒性，残疾， 成本？(2)有多少患者需要接受治疗以避免一种不良心血管或癌症结局？（二） 初级预防的长期效果是什么？(3)初级预防是否具有成本效益， 社会将资源投资到其他地方？

Project Summary Our overarching goal is to identify and characterize cancer patients at risk of developing cancer treatment- related cardiotoxicity and to mitigate cardiovascular dysfunction while optimizing cancer outcomes. Advances in early detection and treatment of cancer has improved 5-year survival. However, multi-modal cancer treatment often leads to cardiotoxicity. Cardiovascular disease (CVD) events during treatment can interfere with its delivery and thus lead to sub-optimal cancer outcomes and increased downstream morbidity, cost, and mortality. American Heart Association (2019) guidelines recommend primary prevention with anti- hyperlipidemic and anti-hypertensive medication in high-risk individuals, based on atherosclerotic cardiovascular disease (ASCVD) risk. However, it’s uncertain if primary prevention in cancer patients improves long-term CVD outcomes. American Society of Clinical Oncology (ASCO) (2017) guidelines has categorized high-dose anthracyclines, targeted therapy, and certain combinations of these, as cardiotoxic regimens. The impact of primary prevention in patients on such cardiotoxic regimens is unknown. To evaluate these questions, we will create a unique dataset by merging Kaiser Permanente (KP)’s electronic medical records with KP’s SEER cancer registry, KP’s medical financial assistance program, and Social Security Administration’s supplemental income, disability, and mortality data, in a cohort of 17,000+ breast cancer patients followed longitudinally for 5+years. We will risk stratify breast cancer patients on ASCVD risk and evaluate the effect of primary prevention using advanced causal inference models exploring treatment effect heterogeneity from policy and decision-making perspectives. The study aims are Aim 1: Compare effectiveness of primary prevention pharmacological therapy on 1) cancer and CVD outcomes during chemotherapy and 2) cancer and CVD outcomes post- chemotherapy in adults with breast cancer. Aim 2: Evaluate the impact of primary prevention pharmacological therapy on financial toxicity and disability in adults with breast cancer. Aim 3: Evaluate the incremental medical expenditure and cost-effectiveness of primary prevention pharmacological therapy in adults with breast cancer using a net-benefit regression framework. Completion of this proposal will answer crucial questions to improve patient outcomes (1) Does primary prevention prevent future CVD events, improve/optimize cancer treatment and outcomes, reduce financial toxicity, disability, and cost? (2) How many patients need to be treated to avoid one adverse cardiovascular or cancer outcome? (2) What are the long-term effects of primary prevention? (3) Is primary prevention cost-effective or should society invest its resources elsewhere?