Should high-risk statin utilization rates be increased for complex AMI patients?

描述（由申请人提供）：填补心血管疾病（CVD）的证据空白已被医疗保健政策和研究机构（AHRQ）确定为优先事项，并且，正如AHRQ有效医疗保健计划的一份报告所强调的那样，关于大剂量他汀类药物在复杂患者亚群中二级预防CVD的有效性的重要问题仍然存在。随机对照试验表明，与中剂量他汀类药物相比，大剂量他汀类药物积极降低低密度脂蛋白胆固醇（LDL-C）可使CVD事件额外减少16%。试验数据的亚组分析也表明，大剂量他汀类药物对复杂心血管疾病患者的益处可能更大。目前的美国指南建议至少降低50%的LDL-C作为心血管预防的理想目标，对于非常高风险的患者应考虑更积极的LDL-C目标<70 mg/dl。尽管大多数患者需要大剂量他汀类药物来达到指南建议，但实际上只有<25%的高危患者接受了他汀类药物治疗。广泛的处方差异，由于成本考虑而使用效力较低的非专利他汀类药物，对安全性的担忧，以及“治疗风险悖论”的存在，即复杂患者不太可能得到治疗，表明提供者仍然不确定治疗对许多复杂心血管疾病患者的益处和危害。提供者可能认为，大剂量他汀类药物的益处和危害在患者中是不一样的，在实践中，他们根据这些信念对患者进行分类。提供者是否因为没有扩大复杂心血管疾病患者的高剂量他汀处方率而错过了获益的机会，或者目前的高剂量他汀处方率是否代表了提供者对患者的利弊的正确平衡？正如约翰·温伯格（John Wennberg）多年前所说，真正的问题是“哪种比率是正确的？”本提案是对RFA-HS- 10-009分析性流行病学研究部分的回应。在这项研究中，我们将进行一项回顾性队列研究，评估大剂量他汀类药物对急性心肌梗死（AMI）后复杂患者的相对有效性，因为AMI患者有明确的大剂量他汀类药物治疗适应症。我们将利用在医疗保险和医疗补助服务中心（CMS）慢性病数据仓库（CCW）中拥有医疗保险“D部分”处方药覆盖的大量患有AMI的医疗保险患者来分析大剂量他汀类药物在复杂AMI患者亚群中的有效性。复杂AMI患者将被定义为存在糖尿病、充血性心力衰竭（CHF）和慢性肾脏疾病（CKD），这些疾病使AMI患者具有非常高的心血管风险。3,39,40我们的分析框架包括使用风险调整（RA）估计器（包括倾向评分方法）和基于矩的工具变量（IV）估计器，并根据每个估计器产生的不同治疗效果概念解释它们的估计。由于高剂量他汀类药物的使用率似乎落后于指南建议，我们假设：(1)接受高剂量他汀类药物的患者无心血管事件生存期的增加足以证明副作用风险和医疗费用是合理的；(2)更高的高剂量他汀类药物治疗率将增加心血管无事件生存率，足以证明增加的副作用率和医疗费用是合理的。本研究的目的与AHRQ比较有效性组合的临床和方法学目标一致。我们的方法是创新的，因为我们将(1)根据对这些方法估计的正确解释，使用RA和IV方法评估高剂量他汀类药物的相对有效性；(2)利用CCW中大量的AMI医保患者来评估高剂量他汀类药物对AMI患者复杂亚群的相对有效性。研究团队拥有临床、方法学和实证专业知识的独特组合，这是开展拟议研究所必需的。

DESCRIPTION (provided by applicant): Filling the evidence gaps within cardiovascular disease (CVD) has been identified as a priority by the Agency for Healthcare Policy and Research (AHRQ), and, as emphasized by a report from the AHRQ Effective Healthcare Program, important questions remain regarding the effectiveness of high-dose statins for the secondary prevention of CVD in complex patient subgroups. Randomized controlled trials have shown that aggressively lowering low density lipoprotein cholesterol (LDL-C) with high-dose statins can result in an additional 16% reduction in CVD events compared to moderate-dose statins. Subgroup analyses of trial data also suggest that the benefits of high-dose statins may be even greater for complex CVD patients. Current US guidelines recommend at least a 50% reduction in LDL-C as desirable for cardiovascular prevention and that a more aggressive LDL-C goal <70 mg/dl be considered for very high risk patients. Although most patients require a high-dose statin to achieve guideline recommendations, only <25% of high risk patients in practice receive one. Wide prescribing variation, use of lower potency generic statins due to cost concerns, concerns about safety, and the existence of a "treatment risk paradox" in which complex patients are less likely treated, suggest that providers remain uncertain as to the benefits and harms of treatments for many complex CVD patients. Providers may believe that the benefits and harms of high-dose statins are heterogeneous across patients and in practice they are sorting patients based on these beliefs. Are providers missing benefit opportunities by not expanding high-dose statin prescribing rates among complex CVD patients or do current high-dose statin prescribing rates represent a correct balancing by providers of the benefits and harms across patients? As stated many years ago by John Wennberg, the real question is "Which rate is right?" This proposal is responding to the analytical epidemiological studies component of RFA-HS- 10-009. In this study we will conduct a retrospective cohort study assessing the comparative effectiveness of high-dose statins for complex patients post acute myocardial infarction (AMI) since those with AMI have a clear indication for high-dose statin therapy. We will take advantage of the large number of Medicare patients with AMI that have Medicare "Part D" prescription drug coverage in the Centers for Medicare & Medicaid Services (CMS) Chronic Condition Data Warehouse (CCW) to analyze the effectiveness of high-dose statins within subsets of complex AMI patients. Complex AMI patients will be defined by the presence of diabetes, congestive heart failure (CHF), and chronic kidney disease (CKD), conditions that place AMI patients at very high cardiovascular risk.3, 39, 40 Our analytical framework includes using both risk adjustment (RA) estimators (including propensity score methods) and moment-based instrumental variable (IV) estimators and interprets their estimates in terms of the distinct treatment effect concept produced by each estimator. Because it appears that high- dose statin utilization rates have lagged behind guideline recommendations, we hypothesize that (1) the patients that received high-dose statins had cardiovascular event-free survival gains sufficient to justify side-effect risks and healthcare costs; and (2) that higher high-dose statin treatment rates would increase cardiovascular event-free survival rates enough to justify increased side-effect rates and healthcare costs. The aims of this research are consistent with both the clinical and methodological goals of the AHRQ Comparative Effectiveness Portfolio. Our methodological approach is innovative because we will (1) assess the comparative effectiveness of high-dose statins using both RA and IV approaches in light of the correct interpretations of estimates from these methods; and (2) exploit the large number of AMI Medicare patients from the CCW to estimate the comparative effectiveness of high-dose statins complex subsets of AMI patients The research team has the unique combination of clinical, methodological, and empirical expertise that is necessary to perform the proposed research. PUBLIC HEALTH RELEVANCE: Current US guidelines suggest that high risk complex patients with CVD receive high-dose statins, yet providers are not prescribing high-dose statins to most complex elderly CVD patients. Because the benefits and harms of high-dose statins appear heterogeneous across patients, insufficient evidence exists to assess whether current high-dose statin treatment rates represent over- or under-utilization for complex CVD patients. The results of this study will help clinicians, guideline-makers, and policy-makers understand the benefits, risks, and costs associated with high-dose statin treatments for complex CVD patients.