Treatment with pravastatin and fenofibrate improves atherogenic lipid profiles but not inflammatory markers in ACTG 5087

doi:10.1016/j.jacl.2010.04.003

Journal of Clinical Lipidology

Volume 4, Issue 4, July–August 2010, Pages 279-287

https://doi.org/10.1016/j.jacl.2010.04.003 Get rights and content

Objectives

Statins and fibrates alter lipids, apolipoproteins, and inflammatory markers in persons without HIV. The objective of this study was to evaluate changes in lipoproteins, apolipoproteins, and other markers of inflammation with the use of pravastatin and fenofibrate.

Design

Evaluation of participants in ACTG A5087, a randomized trial of pravastatin 40 mg/day or fenofibrate 200 mg/day for the treatment of dyslipidemia. Participants that failed single-agent therapy at week 12 were given the combination.

Methods

Participants with available specimens were tested for apolipoproteins A1 and B, adiponectin, plasminogen-activator inhibitor type 1 (PAI-1), P-selectin, and high-sensitivity C-reactive protein (hs-CRP).

Results

A total of 74 participants (37 per randomized arm) received either pravastatin or fenofibrate for 12 weeks with 60 receiving combination treatment from weeks 12 to 48. There were no significant changes in hs-CRP, PAI-1, and P-selectin. From baseline to week 12, the median Apo B levels (−8 mg/dL, P = .01 for fenofibrate and −27 mg/dL, P < .01 for pravastatin) and ApoB/A1 ratios (−0.16, P < .01 for both arms) significantly decreased. From baseline to week 48, median adiponectin (−1 ng/dL, P < .01), Apo B (−22 mg/dL, P < .01) and Apo B/A1 ratios (−0.2, P < .01) all decreased in those who went on combination therapy, whereas Apo A1 (9.5 mg/dL, P = .01) levels increased.

Conclusion

Treatment with pravastatin or fenofibrate improves the atherogenic lipid profile within the first 12 weeks and is sustained through 48 weeks with combination therapy. Adiponectin levels decrease with lipid-lowering therapy. However, markers of inflammation and platelet activation were not appreciably changed suggesting that the biologic properties of these agents differ in persons with HIV infection.

Section snippets

Methods

ACTG A5087 was a randomized, multicenter, 48-week open-label noninferiority study of two lipid-lowering agents in HIV-infected persons with combined hyperlipidemia.¹⁸ All participants were on stable antiretroviral therapy before enrollment. Participants were randomized to micronized fenofibrate 200 mg or pravastatin 40 mg daily for 12 weeks followed by dual-agent therapy for 36 weeks for persons that did not meet National Cholesterol Education Project goals for LDL-C or study-defined desirable

Results

Seventy-four participants were included in this analysis. The baseline characteristics are shown in Table 1. There were five participants in the fenofibrate arm and nine participants in the pravastatin arm that continued on monotherapy for the entire 48 weeks. There were no significant differences in baseline study characteristics, median CD4 counts, or percentage of participants with an undetectable HIV viral load. Baseline glucose levels were similar in the pravastatin and fenofibrate groups

Discussion

The main finding in this study is that the use of pravastatin, fenofibrate, or the combination was generally associated with favorable changes in atherogenic lipoproteins and apolipoproteins. Pravastatin and fenofibrate were both associated with significant decreases in Apo B and the Apo B/A1 ratio after 12 weeks. Fenofibrate was also associated with increases in Apo A1 at week 12. As expected, fenofibrate use was associated with LDL-C particle generation at week 12, but there were differences

Financial disclosures

This multicenter trial was conducted by the AIDS Clinical Trials Group (ACTG), funded by the National Institute of Allergy and Infectious Diseases (AI38558 and AI068636) and the National Institutes of Health. Support for the assays were provided by Abbott Laboratories and Bristol-Myers Squibb Company. Neither pharmaceutical company was involved in the design, conduct or analysis of data from this study, or in the writing of this paper.

Grant support was provided, in part, to Dr. Fichtenbaum from

Acknowledgments

The authors would like to thank the patient volunteers and participating sites in the ACTG for donating and collecting samples and data to make this study possible. Other members of the ACTG 5087 team were B. L. Alston, MD (National Institute of Allergy and Infectious Diseases), medical officer; W. K. Henry, MD (University of Minnesota), investigator; M. J. Glesby, MD, PhD (Weill Medical College of Cornell University), investigator; F. J. Torriani, MD (University of California, San Diego),

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Original ArticleTreatment with pravastatin and fenofibrate improves atherogenic lipid profiles but not inflammatory markers in ACTG 5087

Objectives

Design

Methods

Results

Conclusion

Section snippets

Methods

Results

Discussion

Financial disclosures

Acknowledgments

J Am Coll Cardiol

Int J Cardiol

J Am Coll Cardiol

Atherosclerosis

Atherosclerosis

Inflammation, atherosclerosis and coronary artery disease

N Engl J Med

Combination antiretroviral therapy and the risk of myocardial infarction

N Engl J Med

Increased risk of myocardial infarction with duration of protease inhibitor therapy in HIV-infected men

AIDS

Quantifying effect of statins on low density lipoprotein cholesterol, ischaemic heart disease and stroke: systematic review and meta-analysis

BMJ

Gemfibrozil for the secondary prevention of coronary heart disease in men with low levels of high-density lipoprotein cholesterol

N Engl J Med

High-dose statins in acute coronary syndromes. Not just lipid levels

JAMA

Statin therapy, LDL cholesterol, C-reactive protein, and coronary artery disease

N Engl J Med

Relationship between lipid levels and clinical outcomes in the long-term intervention with pravastatin in ischemic disease (LIPID) trial

Circulation

Effects of HMG-CoA Reductase Inhibitors on Endothelial Function: Role of Microdomains and Oxidative Stress

Circulation

The effect of pravastatin on coronary events after myocardial infarction in patients with average cholesterol levels

N Engl J Med

Gemfibrozil for the secondary prevention of coronary heart disease in men with low levels of high-density lipoprotein cholesterol

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Original Article
Treatment with pravastatin and fenofibrate improves atherogenic lipid profiles but not inflammatory markers in ACTG 5087