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确定有可能发展癌症治疗的癌症患者的特征- 与心脏毒性相关，并在优化癌症预后的同时缓解心血管功能障碍。预付款 在癌症的早期发现和治疗方面提高了5年存活率。然而，多模式癌症 治疗往往会导致心脏毒性。治疗期间的心血管疾病(CVD)事件可能会干扰 从而导致癌症预后不佳，并增加了下游发病率、成本和 死亡率。美国心脏协会(2019年)指南建议使用抗病毒药物进行一级预防 基于动脉粥样硬化的高危人群中的高脂血症和降压药物 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 心血管疾病的长期结局。美国临床肿瘤学会(ASCO)(2017)指南已将 大剂量的蒽环类药物，靶向治疗，以及这些药物的某些组合，作为心脏毒性疗法。这个 这种心脏毒性疗法对患者的一级预防的影响尚不清楚。对这些进行评估 问题，我们将通过合并Kaiser Permanente(KP)的S电子病历来创建一个独特的数据集 与KP的SEER癌症登记、KP的医疗经济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17,000多例乳腺癌队列中 4例纵向随访5年以上。我们将根据ASCVD风险对乳腺癌患者进行风险分层 用探索治疗效果的高级因果推理模型评价一级预防效果 政策和决策角度的异质性。研究目标1：比较有效性 一级预防药物治疗：1)化疗期间癌症和心血管疾病的结果；2) 成年乳腺癌患者化疗后的癌症和心血管疾病预后。目标2：评估以下项目的影响 初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：评估初级预防的增量医疗费用和成本效益 使用净收益回归框架对成年乳腺癌患者进行药物治疗。完成 这项建议将回答改善患者预后的关键问题(1)初级预防是否可以预防 未来的心血管事件，改善/优化癌症治疗和结果，降低财务毒性、残疾和 费用？(2)有多少患者需要接受治疗才能避免一个不良的心血管或癌症后果？(2) 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或应该 社会将其资源投向别处？

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?