Manon Slob

Individualized cardiovascular disease prevention in clinical practice. Estimation of treatment benefit and cost

Samenvatting

For treatment decisions in clinical practice, group-level treatment effects need to be translated into benefit for an individual patient. In both the primary and secondary cardiovascular prevention setting (Chapter 2), patients differ widely in the risk for cardiovascular events, and the benefit they receive from preventive strategies. Individualized cardiovascular disease prevention in daily practice focuses on optimization of therapy for individual patients. With prediction models consisting of readily available patient characteristics, those who benefit (most) from strategies for prevention of cardiovascular disease can be identified. In this thesis we translate group level evidence on cardiovascular preventive strategies into benefit for the individual patient in clinical practice. The benefits of treatment are weighed against potential harms on an individual patient level. Furthermore, the cost-effectiveness of individualized cardiovascular medicine is assessed. Part I: From cardiovascular risk to individual treatment benefit Individualized cardiovascular medicine is based on the results from randomized controlled trials, the ‘golden standard’ for assessment of treatment effects. In Chapter 3, we assessed the applicability of major lipid-lowering trial results to contemporary patients with coronary artery disease. The eligibility of these patients for trial participation ranged from 29%-71%. Patients who fulfilled the eligibility criteria differed only little from ineligible patients in cardiovascular risk factors and risk of major cardiovascular events. The next step in the process of individualized cardiovascular disease prevention, is to assess whether patient characteristics modify the relative treatment effect of an intervention strategy. If there is no underlying biologic mechanism for a single variable treatment interaction, relative treatment effect heterogeneity is preferably assessed with a multivariable risk score (Chapter 4). When relative treatment effect heterogeneity has been assessed, individual absolute benefit from preventive treatment can be estimated. In Chapter 5, we estimated the 5- and 10-year absolute treatment benefit of a statin for secondary and primary prevention of MACE in individual elderly patients (aged ≥70 years). Ninety-eight percent of patients with vascular disease had a 5-year absolute risk reduction ≥2.0%, compared to 31% of patients without vascular disease. In Chapter 6, we estimated the absolute benefit (stroke risk reduction) and harm (increase in bleeding risk) from dabigatran treatment, a direct oral anticoagulant, in 2 doses for individual patients with atrial fibrillation. Part II Cost-effectiveness of benefit-based treatment decisions Finally, the monetary cost of treatment should be weighed against expected treatment benefit and harm before implementing individualized treatment strategies in clinical practice. In Chapter 7, the cost of intensive lipid-lowering therapy (LLT) for all patients with coronary artery disease was reasonable (€17,223 per quality-adjusted life year [QALY] gained). Yet, selective benefit-based treatment increased the QALY gain per intensively treated patient. In Chapter 8, we assessed the cost-effectiveness of proprotein convertase subtilisin-kexin type 9 (PCSK9) inhibitors in addition to standard lipid-lowering treatment in patients at high risk for MACE. PCSK9 inhibition could be cost-effective in patients with Familial Hypercholesterolemia, but is unlikely to reach an acceptable cost-effectiveness ratio for patients with vascular disease. This model may aid treatment and reimbursement decisions regarding PCSK9 inhibitors.