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Reply to Dr. Dujovne’s editorial
READERS’ COMMENTS Reply to Dr. Dujovne’s Editorial
Dr. Dujovne (in this issue, page 1411) has carefully addressed the issue of “transaminitis” and given us some practical suggestions. The problem, of course, is separating out the commonly seen mild elevations of alanine aminotransferase (ALT) that reverse with continuing statin therapy from those that signal underlying liver disease or hepatotoxicity. Fortunately, the liver is a resilient organ that adapts and heals itself with remarkable consistency. Thus, is seems appropriate, when less than threefold elevations of ALT occur, to keep that patient on medication with frequent monitoring (perhaps monthly). If the patient’s ALT continues to rise or the patient develops symptoms, medication should be withdrawn and an alternative treatment considered. If ALT remains elevated in the same general range, a workup for underlying liver disease is appropriate, because it is now known that isolated minor elevations of ALT mean underlying liver disease ⬎90% of the time. The most likely underlying condition in this group of patients is nonalcoholic fatty liver disease. This is usually a benign condition, but some of these patients (perhaps 10% to 20%) will progress to cirrhosis. This often can be predicted by a baseline liver biopsy showing a necroinflammatory or fibrotic response. The etiology can then be Letters (from the United States) concerning a particular article in The American Journal of Cardiology姞 must be received within 2 months of the article’s publication, and should be limited (with rare exceptions) to 2 doublespaced typewritten pages. Two copies must be submitted.
1452
determined (usually insulin resistance, dyslipidemia, or obesity) and treatment either directed to the underlying condition or nonspecifically with bile acid therapy if no underlying etiology is found. If the ALT returns to normal, it is almost certainly safe to rechallenge the patient with either the same or a different statin. It is not known if monitoring this situation is helpful, but it seems unlikely given that the patient’s initial response to medication was benign and that acute liver failure is so rare with statins. Dr. Dujovne alludes to the fact that monitoring ALT and discontinuing medication may place patients with severe dyslipidemia at risk for increased morbidity and mortality. I agree with this important point. An analysis of the costbenefit ratio of monitoring is needed. Keith G. Tolman, MD Salt Lake City, Utah 14 February 2002 PII S0002-9149(02)02371-8
Correction
In the January 1, 2002, issue of the AJC, there is an error in the last sentence of the article, “Incidence of New Coronary Events in Older Persons With Prior Myocardial Infarction and Serum Low-Density Lipoprotein Cholesterol ⱖ125 mg/dl Treated With Statins Versus No Lipid-Lowering Drug,” by Drs. Aronow and Ahn. On page 69, the correct sentence should read: “Persons treated with statins who had the last serum LDL cholesterol level ⬍100 mg/dl, and especially ⬍90 mg/dl, had the lowest inci-
©2002 by Excerpta Medica, Inc. All rights reserved. The American Journal of Cardiology Vol. 89 June 15, 2002
dence of new coronary events (p ⬍0.001).” PII S0002-9149(02)02222-1
Correction
In the article, “Dose Response, Safety, and Efficacy of an Extended-Release Formulation of Lovastatin in Adults With Hypercholesterolemia,” by John Robert Crouse III et al, which appears in the January 15, 2002 issue of the AJC, one of the author’s names was inadvertently left out of the article. His name is Lawrence Friedhoff, MD, PhD. He is affiliated with Aura Laboratories, Inc., Division of Andrx Corporation, Fort Lauderdale, Florida. PII S0002-9149(02)02374-3
Correction
In the article, “Suboptimal Early Inhibition of Platelets by Treatment With Tirofiban and Implications for Coronary Interventions,” by Samer S. Kabbani et al, which appears in the March 1, 2002 issue of the AJC, there is an error that appears on page 649, the right-hand column, last paragraph, fourth line from the last line. The sentence, “However, the greater inhibitory effects seen immediately after a bolus of tirofiban (after 5 to 10 minutes) by Neumann and colleagues17 is not maintained during the remainder of the first hour,” should read: “However, the greater inhibitory effects seen immediately after a bolus of tirofiban (after 5 to 10 minutes) by Kereiakes and colleagues6 are not maintained during the remainder of the first hour.” PII S0002-9149(02)02373-1
PII S0002-9149(02)02371-8
Dr. Dujovne (in this issue, page 1411) has carefully addressed the issue of “transaminitis” and given us some practical suggestions. The problem, of course, is separating out the commonly seen mild elevations of alanine aminotransferase (ALT) that reverse with continuing statin therapy from those that signal underlying liver disease or hepatotoxicity. Fortunately, the liver is a resilient organ that adapts and heals itself with remarkable consistency. Thus, is seems appropriate, when less than threefold elevations of ALT occur, to keep that patient on medication with frequent monitoring (perhaps monthly). If the patient’s ALT continues to rise or the patient develops symptoms, medication should be withdrawn and an alternative treatment considered. If ALT remains elevated in the same general range, a workup for underlying liver disease is appropriate, because it is now known that isolated minor elevations of ALT mean underlying liver disease ⬎90% of the time. The most likely underlying condition in this group of patients is nonalcoholic fatty liver disease. This is usually a benign condition, but some of these patients (perhaps 10% to 20%) will progress to cirrhosis. This often can be predicted by a baseline liver biopsy showing a necroinflammatory or fibrotic response. The etiology can then be Letters (from the United States) concerning a particular article in The American Journal of Cardiology姞 must be received within 2 months of the article’s publication, and should be limited (with rare exceptions) to 2 doublespaced typewritten pages. Two copies must be submitted.
1452
determined (usually insulin resistance, dyslipidemia, or obesity) and treatment either directed to the underlying condition or nonspecifically with bile acid therapy if no underlying etiology is found. If the ALT returns to normal, it is almost certainly safe to rechallenge the patient with either the same or a different statin. It is not known if monitoring this situation is helpful, but it seems unlikely given that the patient’s initial response to medication was benign and that acute liver failure is so rare with statins. Dr. Dujovne alludes to the fact that monitoring ALT and discontinuing medication may place patients with severe dyslipidemia at risk for increased morbidity and mortality. I agree with this important point. An analysis of the costbenefit ratio of monitoring is needed. Keith G. Tolman, MD Salt Lake City, Utah 14 February 2002 PII S0002-9149(02)02371-8
Correction
In the January 1, 2002, issue of the AJC, there is an error in the last sentence of the article, “Incidence of New Coronary Events in Older Persons With Prior Myocardial Infarction and Serum Low-Density Lipoprotein Cholesterol ⱖ125 mg/dl Treated With Statins Versus No Lipid-Lowering Drug,” by Drs. Aronow and Ahn. On page 69, the correct sentence should read: “Persons treated with statins who had the last serum LDL cholesterol level ⬍100 mg/dl, and especially ⬍90 mg/dl, had the lowest inci-
©2002 by Excerpta Medica, Inc. All rights reserved. The American Journal of Cardiology Vol. 89 June 15, 2002
dence of new coronary events (p ⬍0.001).” PII S0002-9149(02)02222-1
Correction
In the article, “Dose Response, Safety, and Efficacy of an Extended-Release Formulation of Lovastatin in Adults With Hypercholesterolemia,” by John Robert Crouse III et al, which appears in the January 15, 2002 issue of the AJC, one of the author’s names was inadvertently left out of the article. His name is Lawrence Friedhoff, MD, PhD. He is affiliated with Aura Laboratories, Inc., Division of Andrx Corporation, Fort Lauderdale, Florida. PII S0002-9149(02)02374-3
Correction
In the article, “Suboptimal Early Inhibition of Platelets by Treatment With Tirofiban and Implications for Coronary Interventions,” by Samer S. Kabbani et al, which appears in the March 1, 2002 issue of the AJC, there is an error that appears on page 649, the right-hand column, last paragraph, fourth line from the last line. The sentence, “However, the greater inhibitory effects seen immediately after a bolus of tirofiban (after 5 to 10 minutes) by Neumann and colleagues17 is not maintained during the remainder of the first hour,” should read: “However, the greater inhibitory effects seen immediately after a bolus of tirofiban (after 5 to 10 minutes) by Kereiakes and colleagues6 are not maintained during the remainder of the first hour.” PII S0002-9149(02)02373-1
PII S0002-9149(02)02371-8