Baseline Low-Density Lipoprotein Cholesterol Is an Important Predictor of the Benefit of Intensive Lipid-Lowering TherapyA PROVE IT–TIMI 22 (Pravastatin or Atorvastatin Evaluation and Infection Therapy–Thrombolysis In Myocardial Infarction 22) Analysis
Roberto R. Giraldez, MD,
Robert P. Giugliano, MD, SM, FACC*,
Satishkumar Mohanavelu, MS,
Sabina A. Murphy, MPH,
Carolyn H. McCabe, BS,
Christopher P. Cannon, MD, FACC and
Eugene Braunwald, MD, MACC
TIMI Study Group, Cardiovascular Division, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts
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Figure 1 LDL-C at Baseline and After 4 Months of Therapy Stratified by Quartiles of Baseline LDL-C
In the statin-naïve patients enrolled in the PROVE IT–TIMI 22 trial, baseline LDL-C ranged from a median 81 mg/dl in the lowest quartile to 148 mg/dl in the highest quartile. Lipid-lowering therapy decreased LDL-C in all quartiles except for patients in the lowest quartile treated with pravastatin 40 mg. A lower LDL-C level at 4 months was achieved with atorvastatin 80 mg compared with pravastatin 40 mg in each quartile regardless of baseline values. A stepwise increase in LDL-C achieved at 4 months was observed from the lowest to the highest quartile of baseline LDL-C in patients randomized to both pravastatin 40 mg and atorvastatin 80 mg (ptrend < 0.001 for both). LDL-C = low-density lipoprotein cholesterol; Q = quartile.
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Figure 2 Median Absolute Difference in LDL-C From Baseline to 4 Months Stratified by Quartiles of Baseline LDL-C
A progressive increase in the difference from baseline to 4-month LDL-C values was seen across quartiles of baseline LDL-C (ptrend < 0.001 for both treatments). The absolute median difference in LDL-C between patients randomized to pravastatin 40 mg and atorvastatin 80 mg also increased as quartiles of baseline LDL-C increased (ptrend < 0.001). Abbreviations as in Figure 1.
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Figure 3 HR for the Primary End Point at 2 Years Stratified by Quartiles of Baseline LDL-C
A decrease in the benefit of atorvastatin 80 mg over pravastatin 40 mg was seen from the highest to the lowest quartiles of baseline LDL-C. Treatment with atorvastatin 80 mg reduced the primary end point compared with pravastatin 40 mg in patients in the highest baseline LDL-C quartile, whereas similar outcomes were observed in the lowest quartile of baseline LDL-C. An adjusted interaction term between treatment assigned and quartile 1 versus 4 was significant (p = 0.03) for the primary end point. A = atorvastatin; HR = hazard ratio; P = pravastatin; other abbreviations as in Figure 1.
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Figure 4 Logit of the Primary End Point Stratified by Continuous Baseline LDL-C
When LDL-C was treated as a continuous variable, the benefit of atorvastatin 80 mg over pravastatin 40 mg for the prevention of the primary end point was not present at baseline levels of LDL-C <66 mg/dl. A significant multivariate-adjusted interaction between treatment and baseline LDL-C was observed (adjusted interaction p = 0.02). Abbreviations as in Figure 1.
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Figure 5 HR for the Secondary End Point at 2 Years in Quartiles of Baseline LDL-C
A progressive decrease in the benefit of atorvastatin 80 mg over pravastatin 40 mg with respect to the secondary end point was seen from the highest to the lowest baseline LDL-C quartile. Significant adjusted interactions for the outcome were seen between therapy and quartiles 1 and 4 (p = 0.007), 2 and 4 (p = 0.02), and 3 and 4 (p = 0.05). Abbreviations as in Figures 1 and 3.
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