Patient and physician factors influence decision-making in hypercholesterolemia: a questionnaire-based survey

Abstract

Background: Goal attainment of guideline-recommended low-density lipoprotein cholesterol (LDL-C) is suboptimal. Little is known about how patient factors influence physicians' treatment decision-making in hypercholesterolemia. We examined physicians' treatment recommendations in high-risk patients whose LDL-C remained uncontrolled despite statin monotherapy.

Methods: Physicians completed a questionnaire prior to randomization into period I of a two-period randomized controlled trial evaluating LDL-C goal attainment in patients whose LDL-C remained ≥100 mg/dL after 5 weeks' treatment with atorvastatin 10 mg/day (NCT01154036). Physicians' treatment recommendations were surveyed for two hypothetical and one real scenario: (1) LDL-C presumed near goal (between 100-105 mg/dL), (2) LDL-C presumed far from goal (~120 mg/dL), and (3) observed baseline LDL-C of enrolled patients. Prognostic factors considered during decision-making were identified by regression analysis. Observed lipid outcomes at the end of period I (following 6 weeks' treatment with ezetimibe 10 mg plus atorvastatin 10 mg, atorvastatin 20 mg, or rosuvastatin 10 mg) were compared with estimated LDL-C outcomes for physicians' treatment recommendations after 6 weeks (based on individual patients' pre-randomization LDL-C and expected incremental change).

Results: Questionnaires were completed for 1,534 patients. No change in therapy, or double atorvastatin dose, were frequently recommended, even when LDL-C was far from goal (6.5% and 52.2% of patients, respectively). Double atorvastatin dose was commonly recommended in all scenarios (43-52% of patients). More intensive LDL-C-lowering regimens were recommended infrequently e.g. double atorvastatin dose and add ezetimibe only <12% in all scenarios. Overall, cardiovascular risk factors and desire to achieve a more aggressive LDL-C goal were prominent factors in decision-making for treatment. Comparison of observed and estimated LDL-C levels showed that physicians tended to overestimate the effectiveness of their recommendations.

Conclusions: This study provides insight into physicians' perspectives on clinical management of hypercholesterolemia and highlights a gap in knowledge translation from guidelines to clinical practice. The need for lower LDL-C and cardiovascular risk were key drivers in clinical decision-making, but physicians' treatment choices were more conservative than guideline recommendations, potentially resulting in poorer LDL-C reduction. When compared with actual outcomes, projected LDL-C control was better if physicians used more comprehensive strategies rather than simply doubling the statin dose.

Trial registration: Clinicaltrials.gov: NCT01154036.

Figures

Figure 1

Association of patient factors with physicians’ treatment recommendations relative to observed baseline LDL-C from RCT. Prognostic factors selected by forward stepwise regression model of physician treatment choice, relative to no change in therapy (n = 268), RR (95% CI). RR >1: prognostic factor more likely to be selected by the physician in their treatment choice compared to a choice of no change in therapy; RR

Figure 2

Association of patient factors with physicians’ treatment recommendations relative to LDL-C presumed near to goal (100–105 mg/dL). Prognostic factors selected by forward stepwise regression model of physician treatment choice, relative to no change in therapy (n = 648), RR (95% CI). RR >1: prognostic factor more likely to be selected by the physician in their treatment choice compared to a choice of no change in therapy; RR

Figure 3

Association of patient factors with physicians’ treatment recommendations relative to LDL-C presumed far from goal (~120 mg/dL). Prognostic factors selected by forward stepwise regression model of physician treatment choice, relative to no change in therapy (n = 100), RR (95% CI). RR >1: prognostic factor more likely to be selected by the physician in their treatment choice compared to a choice of no change in therapy; RR

Figure 4

LDL-C outcomes: estimated change from baseline by physician recommendation versus actual observed RCT LDL-C. (a) Percent change from baseline in LDL-C at Week 6 (b) Percent patients achieving LDL-C <100 mg/dL. Observed (RCT) outcomes at end of period I for randomized treatment. Estimated outcomes of physician-recommended treatments were based on expected reductions for treatment-naïve patients in product labels and literature. Estimated outcomes were calculated based on % incremental benefit expected if the recommended treatment were applied to the observed LDL-C value at the end of the run-in phase for each patient treated with atorvastatin 10 mg; individual estimates were averaged across all patients where a particular treatment was recommended. The estimated proportion of patients achieving a treatment goal (<100 or <70 mg/dL) was derived by applying each patient’s estimated LDL-C change associated with the recommended treatment. ATV, atorvastatin; EZE, ezetimibe; LDL-C, low-density lipoprotein cholesterol; RCT, randomized controlled trial; RSV, rosuvastatin.

Figure 5

Original primary study design. In the original RCT, LDL-C was determined at Week 5 (Period I) to determine eligibility for Period II of the RCT. At Week 6, patients whose LDL-C levels remained elevated (≥100 and ≤160 mg/dL) had their treatment changed to a more intensive regimen during Period II. Period II baseline LDL-C was the average of Week 5 and 6 data. Lipids were also assessed at Week 11 and 12. Final period II values were the average of Week 11 and 12 data. For this analysis, only period I data were used. For further details of the study design, see Bays et al. 2013 [23]. ATV, atorvastatin; EZE, ezetimibe; RSV, rosuvastatin.