Methods
Patients in the Treating to New Targets (TNT), Incremental Decrease in Endpoints through Aggressive Lipid Lowering (IDEAL), and Stroke Prevention by Aggressive Reduction in Cholesterol Levels (SPARCL) trials (patient-level data) randomized to a statin arm (atorvastatin 80 mg/10 mg or simvastatin 20 mg) were chosen. Patients were divided into groups based on attained LDL-C levels (≤70 vs >70 mg/dL) and percent LDL-C reduction (≥50% vs <50%). Primary outcome was major cardiovascular event defined as death due to coronary heart disease, nonfatal myocardial infarction, resuscitated cardiac arrest, or stroke. Incremental prognostic value was assessed by using a forward conditional Cox proportional hazards model. Two models were tested: Model 1: Step 1 statin dose; Step 2 add attained LDL-C levels (continuous variable); Step 3 add percent LDL-C reduction (continuous variable). Model 2: Steps 2 and 3 were reversed.
Results
Among 13,937 patients included in this study, percent LDL-C reduction added incremental prognostic value over both statin dose and attained LDL-C levels (global chi-square increased from 3.64 to 26.1 to 47.5; P<.0001). However, attained LDL-C level did not provide incremental prognostic value over statin dose and percent LDL-C reduction (global chi-square increased from 3.64 to 47.5 to 47.5; P <.0001 and .94, respectively). Among patients with attained LDL-C ≤70 mg/dL, those with percent LDL-C reduction of <50% had a significantly higher risk of primary outcome (hazard ratio [HR], 1.51; 95% confidence interval [CI], 1.16-1.97;P = .002) and stroke (HR, 2.07; 95% CI, 1.46-2.93; P <.0001) and a numerically higher risk of death (HR, 1.37; 95% CI, 0.98-1.90; P = .06) when compared with the group with percent LDL-C reduction of ≥50%.
Conclusions
In patients with atherosclerotic cardiovascular disease, percent LDL-C reduction provides incremental prognostic value over statin dose and attained LDL-C levels. However, the attained LDL-C level does not provide additional prognostic value over statin dose and percent LDL-C reduction.
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-Sripal Bangalore, MD, MHA, Rana Fayyad, PhD, John J. Kastelein, MD, Rachel Laskey, PhD, Pierre Amarenco, MD, David A. DeMicco, PharmD, David D. Waters, MD
This article originally appeared in the April 2016 issue of The American Journal of Medicine.
