Utilities and quality of life in cardiovascular disease : drivers, economic effects and clinical outcomes

Atrial fibrillation and chronic heart failure represent important contributors to cardiovascular disease burden, with high incidence, prevalence and mortality rates. The overall objective of this thesis is to enhance the knowledge on what drives preferences for different health st ates (utilities) in patients with atrial fibrillation and chronic heart failure, and how health-related quality of life and utilities in turn influence clinical and economic outcomes.

In Paper I, we used data from a European-wide observa tional study of patients with atrial fibrillation treated in cardiology clinics to estimate determinan ts of utility based on the EQ-5D. At baseline, increasing age, female gender, domestic status outside the own home, existing comorbidities, and symptoms of atrial fibrillation, chronic heart fail ure or angina were associated with reduced utility, while regular physical activity had a positive effect. At 1-year follow-up, significant determinants included atrial fibrillation symptoms and major adve rse events, including stroke, myocardial infarction and chronic heart failure.

In Paper II, we applied some of the results from Paper I in an economic evaluation of the anti- arrhythmic treatment dronedarone based on patient-level data from the ATHENA trial. The within- trial analysis indicated that dronedarone when used as in ATHENA is cost-effective within generally accepted thresholds (base case incremental cost-e ffectiveness ratio CAD$7560 per quality-adjusted life year), and that this also would hold in the light of subsequent label restrictions.

In Paper III, we used data from the Swedish nation al registry on chronic heart failure, which mainly covers hospitalised patients, to analyse drivers of utility based on the EQ-5D. Utility at baseline was negatively affected by female gender, increasing age, increasing New York Heart Association class, preserved left ventricular ejection fraction, lung disease, diabetes, and use of nitrates, antiplatelets or diuretics. Higher systolic blood pressure and haemoglobin levels and use of angiotensin converting enzyme inhibitors/angiotensin receptor blockers or beta-blockers were associated with increased utility. A significant interaction between age category and functional class indicated that patients in the youngest age group are more severely affected by worsening functional status than older patients. In our data set, the ordinary least squares model perf ormed slightly better than the two-part model on a population level and for capturing utility ranges.

In Paper IV, we investigated the role of health-related quality of life measured with a generic instrument on clinical outcomes in patients hospitalised with systolic heart failure as part of a randomised controlled study in Sweden. Physical m obility was a significant independent predictor for all-cause and cardiovascular rehospitalisation and mo rtality, with every 1% worsening resulting in a 1- 2% increase in the hazard ratio of being hospitalised or dying. Emotional reactions were an additional independent predictor for all-cause hospitalisatio ns, with a similar impact as physical mobility. Additional analyses suggest that the impact of heal th-related quality of life, specifically physical mobility, on cardiovascular mortality may be similar regardless of timing and setting of assessment.

In summary, the studies in this thesis support the us e of health-related quality of life and utilities as a value-added part of clinical and economic decision-making, due to their relationship with both clinical and economic outcomes.

List of scientific papers

I. Berg J, Lindgren P, Nieuwlaat R, Bouin O & Crijns H (2010). Factors determining utility measured with the EQ-5D in patients with atrial fibrillation. Qual Life Res ; 19: 381-390.
https://doi.org/10.1007/s11136-010-9591-y

II. Berg J, Sauriol L, Connolly S & Lindgren P (2013). Cost-effectiveness of dronedarone in patients with atrial fibrillation in the ATHENA trial. Can J Cardiol ; 29: 1249-1255.
https://doi.org/10.1016/j.cjca.2013.01.016

III. Berg J, Lindgren P, Mejhert M, Edner M, Dahlström U & Kahan T. Determinants of utility based on the EQ-5D in chronic heart failure patients and their change over time: results fr om the Swedish Heart Failure Registry. [Manuscript]

IV. Berg J, Lindgren P, Kahan T, Schill O, Persson H, Edner M & Mejhert M (2014). Health-related quality of life and long-term morbidity and mortality in p atients hospitalised with systolic heart failure. JRSM Cardiovasc Dis ; 3: 2048004014548735.
https://doi.org/10.1177/2048004014548735