Sufficiency of Low Density Lipoprotein as Surrogate Endpoint for Cardiovascular Outcomes in Hypercholesterolemia Therapeutic Adoption

Low density lipoprotein (LDL) lowering therapies have been attributed to decreased rates of cardiovascular deaths, yet only 30% of patients achieve optimal LDL levels. While novel LDL lowering therapies are being developed, it will take years after LDL surrogate data is available to determine if reductions in LDL will lead to improved cardiovascular outcomes. The problem explored was that novel hypercholesterolemia therapies might attain regulatory clearance for treatment of cardiovascular disease predicated on surrogate endpoints, without a robust theory of how physician prescriptive behavior is differentially impacted by surrogate data and cardiovascular risk stratification.;The purpose of this quantitative nonexperimental study was to determine physician proclivity to prescribe novel hypercholesterolemia agents predicated on the LDL surrogate endpoint as a proxy for cardiovascular outcomes. The population being studied was physicians who treat hypercholesterolemia, targeted through a survey of 140 physicians. The key criterion variable was the sufficiency of LDL cholesterol as a surrogate endpoint in the prescription of novel hypercholesterolemia patients, stratified by the predictor variable of patient risk type. The survey indicated that 81% of responding physicians would prescribe novel therapy prior to outcomes data, chi2(1, N=140) = 55.31, p<.0001. Surveyed physicians would prescribe therapy to 26.8% of patients at high risk prior to outcomes data, relative to 9.1% of patients who are not at high risk, which is significant, t(139) = 6.83, p<.0001. Upon availability of outcomes data, the percentage of physicians that would prescribe novel hypercholesterolemia therapy increased 19% for high risk patients versus 176% for patients not at high risk, chi2(1, N=140) = 135.52, p<.0001. This study reinforces the theoretical construct that physicians will prescribe novel therapy prior to outcomes data, and that propensity and frequency of surrogate prescription is related to the risk profile of the patient. Larger hypercholesterolemia studies including subgroup analysis and studies evaluating the impact of outcomes data and risk for other diseases could enhance theories of the utility of surrogate endpoints.