CLINICAL RESEARCH: TREATMENT OF HYPERLIPIDEMIA
Relative Efficacy of Atorvastatin 80 mg and Pravastatin 40 mg in Achieving the Dual Goals of Low-Density Lipoprotein Cholesterol <70 mg/dl and C-Reactive Protein <2 mg/l
An Analysis of the PROVE-IT TIMI-22 Trial
Paul M. Ridker, MD*, ,*,
David A. Morrow, MD, ,
Lynda M. Rose, MS*,,
Nader Rifai, PhD*,,
Christopher P. Cannon, MD and
Eugene Braunwald, MD
* Center for Cardiovascular Disease Prevention, Department of Medicine, Brigham and Women’s Hospital, Boston, Massachusetts
The Donald W. Reynolds Center for Cardiovascular Research, Department of Medicine, Brigham and Women’s Hospital, Boston, Massachusetts
The Thrombolysis In Myocardial Infarction (TIMI) Study Group, Department of Medicine, Brigham and Women’s Hospital, Boston, Massachusetts.
Manuscript received January 23, 2005;
revised manuscript received February 15, 2005,
accepted February 22, 2005.
* Reprint requests and correspondence: Dr. Paul M. Ridker, Center for Cardiovascular Disease Prevention, Brigham and Women’s Hospital, 900 Commonwealth Avenue East, Boston, Massachusetts 02215. (Email: pridker{at}partners.org).
OBJECTIVES: The aim of this research was to compare relative efficacy of different statin regimens in achieving the dual goals of low-density lipoprotein cholesterol (LDL-C) and C-reactive protein (CRP) reduction.
BACKGROUND: While secondary prevention guidelines for statin therapy suggest lowering LDL-C levels <70 mg/dl, we have recently shown that clinical outcomes are improved when CRP levels are also lowered <2 mg/l.
METHODS: We addressed the relative efficacy of pravastatin 40 mg and atorvastatin 80 mg daily to reduce LDL-C and CRP among 3,745 acute coronary syndrome patients.
RESULTS: A total of 1,018 participants (27.1%) achieved the dual goals of LDL-C <70 mg/dl and CRP <2 mg/l. After adjustment for age, gender, smoking, diabetes, hypertension, obesity, and HDL-C, these individuals had a 28% lower risk of recurrent myocardial infarction or vascular death (relative risk = 0.72; 95% confidence interval 0.52 to 0.99). Of those who achieved dual goals, 80.6% received atorvastatin 80 mg, while 19.4% received pravastatin 40 mg (p < 0.001). Only 11% allocated pravastatin and 44% allocated atorvastatin achieved the goals of LDL-C <70 mg/dl and CRP <2 mg/l, and only 5.8% allocated pravastatin 40 mg and 26.1% allocated atorvastatin 80 mg reached the even lower goals of LDL-C <70 mg/dl and CRP <1 mg/l. The correlation coefficient for CRP measured at 30 days and at end of study was 0.61 (p < 0.001), a value almost identical to that for LDL-C over the same follow-up period (r = 0.62, p < 0.001).
CONCLUSIONS: While atorvastatin 80 mg was superior to pravastatin 40 mg in terms of achieving the dual goals of aggressive LDL-C and CRP reduction, neither agent brought the majority of patients below thresholds needed to maximize patient benefit.
|
Abbreviations and Acronyms
| | CRP = C-reactive protein | | HDL-C = high-density lipoprotein cholesterol | | hsCRP = high-sensitivity C-reactive protein | | LDL-C = low-density lipoprotein cholesterol | | PROVE-IT = Pravastatin or Atorvastatin Evaluation and Infection trial | | TIMI = Thrombolysis In Myocardial Infarction |
|
This article has been cited by other articles:
|
|
|
|
 
P. M Ridker, E. Danielson, F. A.H. Fonseca, J. Genest, A. M. Gotto Jr., J. J.P. Kastelein, W. Koenig, P. Libby, A. J. Lorenzatti, J. G. MacFadyen, et al.
Rosuvastatin to Prevent Vascular Events in Men and Women with Elevated C-Reactive Protein
N. Engl. J. Med.,
November 20, 2008;
359(21):
2195 - 2207.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
W. E. Cayley
Monitoring Cholesterol Levels: Understanding Variance and Finding the Most Useful Data
Ann Intern Med,
September 16, 2008;
149(6):
436 - 437.
[Full Text]
[PDF]
|
|
|
|
|
|
|
H. Arima, M. Kubo, K. Yonemoto, Y. Doi, T. Ninomiya, Y. Tanizaki, J. Hata, K. Matsumura, M. Iida, and Y. Kiyohara
High-Sensitivity C-Reactive Protein and Coronary Heart Disease in a General Population of Japanese: The Hisayama Study
Arterioscler. Thromb. Vasc. Biol.,
July 1, 2008;
28(7):
1385 - 1391.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
M. Miller, C. P. Cannon, S. A. Murphy, J. Qin, K. K. Ray, E. Braunwald, and for the PROVE IT-TIMI 22 Investigators
Impact of Triglyceride Levels Beyond Low-Density Lipoprotein Cholesterol After Acute Coronary Syndrome in the PROVE IT-TIMI 22 Trial.
J. Am. Coll. Cardiol.,
February 19, 2008;
51(7):
724 - 730.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
T. T. Issac, H. Dokainish, and N. M. Lakkis
Role of Inflammation in Initiation and Perpetuation of Atrial Fibrillation: A Systematic Review of the Published Data
J. Am. Coll. Cardiol.,
November 20, 2007;
50(21):
2021 - 2028.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
J. Afilalo, A. A Majdan, and M. J Eisenberg
Intensive statin therapy in acute coronary syndromes and stable coronary heart disease: a comparative meta-analysis of randomised controlled trials
Heart,
August 1, 2007;
93(8):
914 - 921.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
A. A. Alsheikh-Ali, P. V. Maddukuri, H. Han, and R. H. Karas
Effect of the Magnitude of Lipid Lowering on Risk of Elevated Liver Enzymes, Rhabdomyolysis, and Cancer: Insights From Large Randomized Statin Trials
J. Am. Coll. Cardiol.,
July 31, 2007;
50(5):
409 - 418.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
E. Rohde, C. Bartmann, K. Schallmoser, A. Reinisch, G. Lanzer, W. Linkesch, C. Guelly, and D. Strunk
Immune Cells Mimic the Morphology of Endothelial Progenitor Colonies In Vitro
Stem Cells,
July 1, 2007;
25(7):
1746 - 1752.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
K. K. Ray, D. A. Morrow, M. S. Sabatine, A. Shui, N. Rifai, C. P. Cannon, and E. Braunwald
Long-Term Prognostic Value of Neopterin: A Novel Marker of Monocyte Activation in Patients With Acute Coronary Syndrome
Circulation,
June 19, 2007;
115(24):
3071 - 3078.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
O. Ben-Yehuda
High-Sensitivity C-Reactive Protein in Every Chart?: The Use of Biomarkers in Individual Patients
J. Am. Coll. Cardiol.,
May 29, 2007;
49(21):
2139 - 2141.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
P. M. Ridker
C-Reactive Protein and the Prediction of Cardiovascular Events Among Those at Intermediate Risk: Moving an Inflammatory Hypothesis Toward Consensus
J. Am. Coll. Cardiol.,
May 29, 2007;
49(21):
2129 - 2138.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
A. I. Kakafika, D. P. Mikhailidis, A. Karagiannis, and V. G. Athyros
The Role of Endocannabinoid System Blockade in the Treatment of the Metabolic Syndrome
J. Clin. Pharmacol.,
May 1, 2007;
47(5):
642 - 652.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
M. S. Sabatine, D. A. Morrow, K. A. Jablonski, M. M. Rice, J. W. Warnica, M. J. Domanski, J. Hsia, B. J. Gersh, N. Rifai, P. M Ridker, et al.
Prognostic Significance of the Centers for Disease Control/American Heart Association High-Sensitivity C-Reactive Protein Cut Points for Cardiovascular and Other Outcomes in Patients With Stable Coronary Artery Disease
Circulation,
March 27, 2007;
115(12):
1528 - 1536.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
T. N. Patel, M. H. Shishehbor, and D. L. Bhatt
A review of high-dose statin therapy: targeting cholesterol and inflammation in atherosclerosis
Eur. Heart J.,
March 2, 2007;
28(6):
664 - 672.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
D. A. Morrow, J. A. de Lemos, M. S. Sabatine, S. D. Wiviott, M. A. Blazing, A. Shui, N. Rifai, R. M. Califf, and E. Braunwald
Clinical Relevance of C-Reactive Protein During Follow-Up of Patients With Acute Coronary Syndromes in the Aggrastat-to-Zocor Trial
Circulation,
July 25, 2006;
114(4):
281 - 288.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
R. P. Giugliano and E. Braunwald
The Year in Non-ST-Segment Elevation Acute Coronary Syndromes
J. Am. Coll. Cardiol.,
July 18, 2006;
48(2):
386 - 395.
[Full Text]
[PDF]
|
|
|
|
|
|
|
A. R. Lucas, R. Korol, and C. J. Pepine
Inflammation in Atherosclerosis: Some Thoughts About Acute Coronary Syndromes
Circulation,
May 2, 2006;
113(17):
e728 - e732.
[Full Text]
[PDF]
|
|
|
|
|
|
|
K. K. Ray, C. P. Cannon, R. Cairns, D. A. Morrow, N. Rifai, A. J. Kirtane, C. H. McCabe, A. M. Skene, C. M. Gibson, P. M. Ridker, et al.
Relationship Between Uncontrolled Risk Factors and C-Reactive Protein Levels in Patients Receiving Standard or Intensive Statin Therapy for Acute Coronary Syndromes in the PROVE IT-TIMI 22 Trial
J. Am. Coll. Cardiol.,
October 18, 2005;
46(8):
1417 - 1424.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
A. M. Gotto Jr
Evolving Concepts of Dyslipidemia, Atherosclerosis, and Cardiovascular Disease: The Louis F. Bishop Lecture
J. Am. Coll. Cardiol.,
October 4, 2005;
46(7):
1219 - 1224.
[Full Text]
[PDF]
|
|
|
|
|
|
|
R. P. Giugliano and E. Braunwald
The Year in Non--ST-Segment Elevation Acute Coronary Syndromes
J. Am. Coll. Cardiol.,
September 6, 2005;
46(5):
906 - 919.
[Full Text]
[PDF]
|
|
|
|
|
|
|
P. M Ridker, N. Rifai, N. R. Cook, G. Bradwin, and J. E. Buring
Non-HDL Cholesterol, Apolipoproteins A-I and B100, Standard Lipid Measures, Lipid Ratios, and CRP as Risk Factors for Cardiovascular Disease in Women
JAMA,
July 20, 2005;
294(3):
326 - 333.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
