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The Other Side of the Bezafibrate Infarction Prevention Trial Data—Reply

The Other Side of the Bezafibrate Infarction Prevention Trial Data—Reply In reply We thank McCormack and Loewen for their interest and the opportunity to further discuss and clarify our results. They are concerned about a possible “increase in mortality,” particularly from cardiovascular causes, in patients without MS treated with bezafibrate on the basis of their cross-referencing subset analysis of our report1 and the originally published BIP study data.2 However, McCormack and Loewen had overlooked our statement in the “Methods” section that in our report “[t]he follow-up period for mortality registration lasted until March 2000 (mean ± SD, 8.1 ± 0.8 years; range, 4.9-9.7 years).”1(p1155) In contrast, in the originally published BIP study data, the follow-up period lasted until May 1998 (mean ± SD follow-up, 6.2 ± 0.8 years). This point was also clarified in the abstract and emphasized additionally in Figure 2B and its legend. We believe that McCormack and Loewen's erroneous “cross-referencing” comparison of the mortality data from the 2 different reports with the different follow-up periods has lead to a gross miscalculation and consequently to a proposed concluding statement that has no scientific validity. We present the actual mortality data for patients without MS in the Table. Table. View LargeDownload Deaths in Patients With Less Than 3 Risk Factors for Metabolic Syndrome* Based on McCormack and Loewen's proposal and on the actual mortality data, we would like to state the following: “In patients with MS, bezafibrate treatment was associated with reduced risk of myocardial infarction and cardiac mortality. In patients without MS this favorable effect was not presented: there was no significant difference in the cardiovascular end points between bezafibrate and placebo groups.” Regarding the financial disclosure, as was stated in the originally published BIP study article,2 the BIP study was supported by a grant from Boehringer-Mannheim GmbH (Mannheim, Germany)—now part of F. Hoffmann-La Roche, Ltd (Basel, Switzerland). The current post hoc analysis1 was conducted independently of the original or any other sponsor. Therefore, we have no conflict of interests to disclose. Finally, as McCormack and Loewen commented, given the limitations of a post hoc analysis, caution should be used in interpreting our finding. However, similar to the data of our analysis, in the 2 large independent trials (Helsinki Heart Study and the Veterans Affairs high-density lipoprotein intervention trial), the reduction of cardiovascular events with gemfibrozil was more pronounced in patients displaying features of MS.3,4 Fibrates are the pharmacological ligands for peroxisome proliferator-activated receptors alpha, which controls primarily the expression of genes involved in lipid metabolism and also plays a role in the development of insulin resistance—a cornerstone of MS.5 Therefore, our data are in line with other fibrate’s independent studies and have reasonable biological basis that support the validity of the results. Correspondence: Dr Tenenbaum, Cardiac Rehabilitation Institute, Chaim Sheba Medical Center, Tel-Hashomer, 52621 Israel (altenen@post.tau.ac.il or altenen@yahoo.com). Author Contributions: Dr Tenenbaum had full access to all the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis. References 1. Tenenbaum AMotro MFisman EZTanne DBoyko VBehar S Bezafibrate for the secondary prevention of myocardial infarction in patients with metabolic syndrome. Arch Intern Med 2005;1651154- 1160PubMedGoogle ScholarCrossref 2. Secondary prevention by raising HDL cholesterol and reducing triglycerides in patients with coronary artery disease: the Bezafibrate Infarction Prevention (BIP) study. Circulation 2000;10221- 27PubMedGoogle ScholarCrossref 3. Manninen VTenkanen LKoskinen P et al. Joint effects of serum triglyceride and LDL cholesterol and HDL cholesterol concentrations on coronary heart disease risk in the Helsinki Heart Study: implications for treatment. Circulation 1992;8537- 45PubMedGoogle ScholarCrossref 4. Rubins HBRobins SJCollins D et al. Diabetes, plasma insulin, and cardiovascular disease: subgroup analysis from the Department of Veterans Affairs high-density lipoprotein intervention trial (VA-HIT). Arch Intern Med 2002;1622597- 2604PubMedGoogle ScholarCrossref 5. Despres JPLemieux IRobins SJ Role of fibric acid derivatives in the management of risk factors for coronary heart disease. Drugs 2004;642177- 2198PubMedGoogle ScholarCrossref http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png Archives of Internal Medicine American Medical Association

The Other Side of the Bezafibrate Infarction Prevention Trial Data—Reply

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Publisher
American Medical Association
Copyright
Copyright © 2005 American Medical Association. All Rights Reserved.
ISSN
0003-9926
eISSN
1538-3679
DOI
10.1001/archinte.165.20.2432-a
Publisher site
See Article on Publisher Site

Abstract

In reply We thank McCormack and Loewen for their interest and the opportunity to further discuss and clarify our results. They are concerned about a possible “increase in mortality,” particularly from cardiovascular causes, in patients without MS treated with bezafibrate on the basis of their cross-referencing subset analysis of our report1 and the originally published BIP study data.2 However, McCormack and Loewen had overlooked our statement in the “Methods” section that in our report “[t]he follow-up period for mortality registration lasted until March 2000 (mean ± SD, 8.1 ± 0.8 years; range, 4.9-9.7 years).”1(p1155) In contrast, in the originally published BIP study data, the follow-up period lasted until May 1998 (mean ± SD follow-up, 6.2 ± 0.8 years). This point was also clarified in the abstract and emphasized additionally in Figure 2B and its legend. We believe that McCormack and Loewen's erroneous “cross-referencing” comparison of the mortality data from the 2 different reports with the different follow-up periods has lead to a gross miscalculation and consequently to a proposed concluding statement that has no scientific validity. We present the actual mortality data for patients without MS in the Table. Table. View LargeDownload Deaths in Patients With Less Than 3 Risk Factors for Metabolic Syndrome* Based on McCormack and Loewen's proposal and on the actual mortality data, we would like to state the following: “In patients with MS, bezafibrate treatment was associated with reduced risk of myocardial infarction and cardiac mortality. In patients without MS this favorable effect was not presented: there was no significant difference in the cardiovascular end points between bezafibrate and placebo groups.” Regarding the financial disclosure, as was stated in the originally published BIP study article,2 the BIP study was supported by a grant from Boehringer-Mannheim GmbH (Mannheim, Germany)—now part of F. Hoffmann-La Roche, Ltd (Basel, Switzerland). The current post hoc analysis1 was conducted independently of the original or any other sponsor. Therefore, we have no conflict of interests to disclose. Finally, as McCormack and Loewen commented, given the limitations of a post hoc analysis, caution should be used in interpreting our finding. However, similar to the data of our analysis, in the 2 large independent trials (Helsinki Heart Study and the Veterans Affairs high-density lipoprotein intervention trial), the reduction of cardiovascular events with gemfibrozil was more pronounced in patients displaying features of MS.3,4 Fibrates are the pharmacological ligands for peroxisome proliferator-activated receptors alpha, which controls primarily the expression of genes involved in lipid metabolism and also plays a role in the development of insulin resistance—a cornerstone of MS.5 Therefore, our data are in line with other fibrate’s independent studies and have reasonable biological basis that support the validity of the results. Correspondence: Dr Tenenbaum, Cardiac Rehabilitation Institute, Chaim Sheba Medical Center, Tel-Hashomer, 52621 Israel (altenen@post.tau.ac.il or altenen@yahoo.com). Author Contributions: Dr Tenenbaum had full access to all the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis. References 1. Tenenbaum AMotro MFisman EZTanne DBoyko VBehar S Bezafibrate for the secondary prevention of myocardial infarction in patients with metabolic syndrome. Arch Intern Med 2005;1651154- 1160PubMedGoogle ScholarCrossref 2. Secondary prevention by raising HDL cholesterol and reducing triglycerides in patients with coronary artery disease: the Bezafibrate Infarction Prevention (BIP) study. Circulation 2000;10221- 27PubMedGoogle ScholarCrossref 3. Manninen VTenkanen LKoskinen P et al. Joint effects of serum triglyceride and LDL cholesterol and HDL cholesterol concentrations on coronary heart disease risk in the Helsinki Heart Study: implications for treatment. Circulation 1992;8537- 45PubMedGoogle ScholarCrossref 4. Rubins HBRobins SJCollins D et al. Diabetes, plasma insulin, and cardiovascular disease: subgroup analysis from the Department of Veterans Affairs high-density lipoprotein intervention trial (VA-HIT). Arch Intern Med 2002;1622597- 2604PubMedGoogle ScholarCrossref 5. Despres JPLemieux IRobins SJ Role of fibric acid derivatives in the management of risk factors for coronary heart disease. Drugs 2004;642177- 2198PubMedGoogle ScholarCrossref

Journal

Archives of Internal MedicineAmerican Medical Association

Published: Nov 14, 2005

Keywords: bezafibrate,infarction

References