How delayed treatment benefits and harms would impact the optimal timing of statin initiation for cardiovascular primary prevention

Abstract

AbstractBackgroundGenetic studies suggest that the relative risk reduction (RRR) of statins may increase over time, potentially resulting in much greater long-term benefit if statins are started before cardiovascular (CV) risk is high.MethodsWe used a nationally representative sample of American adults to estimate effects of initiating a statin when 10-year CV risk reaches 5%, 10% or 15%. We examined scenarios in which a statin’s initial RRR (30%) gradually doubles over 10 to 30 years of treatment.ResultsInitiating a statin when 10-year CV risk is 5% resulted in a mean of 20.1 years on a statin before age 75 (8 years more than starting when CV risk reaches 10%). If a statin’s RRR doubles over 20 years, starting when CV risk is 5% would save about 5.1 to 6.1 additional QALYs per 1000 additional treatment years than starting when CV risk is 10%. Most of this additional benefit was accrued by those who reach a 5% risk at a younger age. Due to the prolonged treatment period, however, early treatment could also result in net harm if the treatment slowly increased a major complication of aging, such as muscular or neurological aging.ConclusionsIn a thought experiment exploring the impact of delayed effects, we found that if the relative effectiveness of statin therapy gradually doubles over a 10 to 30 year period, starting a statin when 10-year CV risk is 5% could have much more long-term benefit than starting a statin when CV risk is 10%. Most of the additional benefit occurred in those at elevated age-adjusted CV risk. Unfortunately, given the long duration of treatment, substantial delayed statin harms, if present, could outweigh these potential benefits and result in substantial net harm.