The potential benefit of statin prescription based on prediction of treatment responsiveness in older individuals: an application to the PROSPER randomized controlled trial

AIMS: Clinical guidelines often recommend treating individuals based on their cardiovascular risk. We revisit this paradigm and quantify the efficacy of three treatment strategies: (i) overall prescription, i.e. treatment to all individuals sharing the eligibility criteria of a trial; (ii) risk-stratified prescription, i.e. treatment only to those at an elevated outcome risk; and (iii) prescription based on predicted treatment responsiveness.

METHODS AND RESULTS: We reanalysed the PROSPER randomized controlled trial, which included individuals aged 70-82 years with a history of, or risk factors for, vascular diseases. We conducted the derivation and internal-external validation of a model predicting treatment responsiveness. We compared with placebo (n = 2913): (i) pravastatin (n = 2891); (ii) pravastatin in the presence of previous vascular diseases and placebo in the absence thereof (n = 2925); and (iii) pravastatin in the presence of a favourable prediction of treatment response and placebo in the absence thereof (n = 2890). We found an absolute difference in primary outcome events composed of coronary death, non-fatal myocardial infarction, and fatal or non-fatal stroke, per 10 000 person-years equal to: -78 events (95% CI, -144 to -12) when prescribing pravastatin to all participants; -66 events (95% CI, -114 to -18) when treating only individuals with an elevated vascular risk; and -103 events (95% CI, -162 to -44) when restricting pravastatin to individuals with a favourable prediction of treatment response.

CONCLUSION: Pravastatin prescription based on predicted responsiveness may have an encouraging potential for cardiovascular prevention. Further external validation of our results and clinical experiments are needed.

TRIAL REGISTRATION: ISRCTN40976937.