Determining the cost-effectiveness of preventing cardiovascular disease: are estimates calculated over the duration of a clinical trial adequate?

Background: Economic analyses of randomized clinical trials often focus only on the results that are observed during the study. However, for many preventive interventions, associated costs and benefits will accrue over a patient's remaining lifetime. To determine the importance of the chosen time horizon, the cost-effectiveness (C/E) of ramipril therapy was calculated and compared in the Heart Outcomes Prevention Evaluation (HOPE), the Microalbuminuria, Cardiovascular, and Renal Outcomes in HOPE (MICRO-HOPE) and the Acute Infarction Ramipril Efficacy (AIRE) study versus the entire life expectancy (L/E) of potential patients.

Methods: The Cardiovascular Disease Life Expectancy model, a validated Markov model, was calibrated to accurately forecast the results of each trial. These results were then extrapolated over the remaining L/E of hypothetical patients 55 to 75 years of age. The predicted change in L/E and associated direct health care costs for Canadians were calculated and discounted 3% annually.

Results: In HOPE, the forecasted increased L/E averaged 0.06 years during the five-year study versus 1.3 years over the remaining years of L/E. The associated C/E of ramipril was $15,000 per year of life saved (YOLS) over the study duration and $8,500/YOLS over the remaining lifetime. For hypothetical patients, the C/E of ramipril over 4.5 years ranged from $6,700/YOLS to more than $58,300/YOLS and was lowest among elderly men. When the remaining L/E was considered, the C/E of ramipril was similar for men and women of all ages, ranging from $8,100/YOLS to $10,200/YOLS. The analyses of MICRO-HOPE and AIRE provided similar results.

Conclusion: The estimated efficacy and associated C/E of ramipril in HOPE, MICRO-HOPE and the AIRE study is extremely sensitive to the selected time horizon. Economic analyses beyond the duration of randomized clinical trials are required to fully evaluate the potential costs and benefits of long-term preventive therapies.