Results
From January 2009 through July 2014, 35,216 patients were initially screened. The majority of patients did not have a baseline LDL-C value and were excluded. A total of 1,183 patients with simvastatin 20 mg daily (BMI < 30 = 661; BMI ≥ 30 = 1,122) and 478 patients with simvastatin 40 mg daily (BMI < 30 = 259; BMI ≥ 30 = 219) met the inclusion criteria.
Baseline characteristics were similar between groups except for a slightly higher age in both groups without obesity (Table). Hepatic and renal serum markers indicated a baseline of adequate organ function for drug clearance for all groups. The mean baseline BMI of those without obesity was about 26 kg/m2, which is considered overweight. Baseline LDL-C values were clinically similar for those with and without obesity, though statistically different (145 mg/dL for the nonobese group and 141 mg/dL for the obese group, P < .05). The percent change in LDL-C was not statistically significant for those with and without obesity for simvastatin 20 mg daily (P = .293) or simvastatin 40 mg daily (P = .2773) (Figure). No correlation was found between the continuous percent change in LDL-C and continuous BMI for either simvastatin dosage (r2 = 0.0016 and 0.0028, respectively).
Discussion
In this retrospective chart review, it was determined that obesity did not affect the percent change in LDL-C from baseline with statin therapy. The HPS found similar results as a secondary endpoint, although that study was underpowered.10 In this study, all groups met power, and there was still no difference between those with and without obesity.
Nicholls and colleagues examined REVERSAL study data to determine whether BMI greater than the median BMI impacted inflammatory markers or lipid levels with atorvastatin 80 mg daily or pravastatin 40 mg daily. The REVERSAL study authors found no difference in percent change LDL-C between those above the median BMI compared with those below the median BMI for patients on pravastatin therapy. However, the authors did find a difference in percent change LDL-C with atorvastatin therapy.13 No difference in percent change LDL-C was present with simvastatin therapy in this study. As simvastatin is more lipophilic than is atorvastatin, lipophilicity remains an area for further study for statin therapy in patients with obesity.
The surrogate marker of percent change in LDL-C was used for the primary outcome in this study. The ACC/AHA 2013 guidelines and the National Lipid Association 2014 guidelines recommend an alternative goal of 30% to 50% change in LDL-C from baseline.14,15 Using this clinically relevant marker compensated for differences in baseline LDL-C and limited the effect of these differences on the primary outcome of this study.
Limitations
This study did not include patients who were underweight (BMI < 18 kg/m2), as these patients have previously demonstrated decreased outcomes with statin therapy.16 However, this limits these data to only those patients that have a BMI of at least 18 kg/m2. Limitations of this study also included the inability to consider adherence and lifestyle changes. These limitations were unavoidable due to the nature of a retrospective chart review.
Conclusion
The prevalence of obesity is increasing, and it is a disease that alters pharmacokinetics and lipid metabolism. Though this study did not find a difference between the LDL-C-lowering efficacy of simvastatin in those with and without obesity, continued study of the effect of obesity on the efficacy of medications is vital.
Acknowledgments
This material is the result of work supported with resources and the use of facilities at the James H. Qullen VAMC in Mountain Home, Tennessee.
