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Abnormal Liver Enzymes No Reason to Avoid Statins
Abnormal Liver Enzymes No Reason to Avoid Statins
By Crystal Phend, Senior Staff Writer, MedPage Today
Published: November 23, 2010
Reviewed by Zalman S. Agus, MD; Emeritus Professor
University of Pennsylvania School of Medicine.
Statins are not only safe and effective for patients with liver enzyme abnormalities but also appear to improve their liver function, researchers found.
Liver test results in patients with moderately abnormal liver tests at baseline -- possibly associated with non-alcoholic fatty liver disease -- improved with statin treatment but continued to worsen on usual care without statin treatment (P<0.0001), Dimitri P. Mikhailidis, MD, of University College London, and colleagues reported online in The Lancet.
Their retrospective analysis of the Greek Atorvastatin and Coronary Heart Disease Evaluation (GREACE) trial showed a greater statin effect on cardiovascular risk reduction in these high-risk patients than in those with normal liver tests (P=0.0074).
The findings add to evidence that should render liver tests irrelevant when prescribing statins, Ted Bader, MD, of the University of Oklahoma Health Sciences Center in Oklahoma City, argued in an accompanying commentary.
"Statin-induced hepatotoxicity is a myth," he wrote in Lancet.
About 10% of patients see liver enzymes rise after starting a statin, which can exceed the threshold of three times the upper limit of normal for 1%, but these eventually return to normal even when continuing the same statin, Bader noted.
His group reported a small pilot study in 2007 that actually suggested a liver function boost on statin treatment for patients with chronic hepatitis C infection.
Yet reluctance to start statins in patients with out-of-range alanine aminotransferase (ALT) levels, and discontinuation of statins for ALT increases, might keep statins from 10% to 30% of those who need them, he estimated.
The language of package inserts is likely to blame for the misperception that statins cause liver disease, according to Bader. He encouraged drug companies to request label modification for all the statins.
"Although most patients [in the trial] took atorvastatin, there is no reason to believe that other statins would behave differently," Bader wrote in the commentary.
The single-center, prospective GREACE trial originally compared statin treatment with usual care (which could include a statin) with regard to survival effects in 1,600 patients with coronary artery disease. Study participants were under age 75, had serum concentrations of LDL cholesterol over 2.6 mmol/L, and had triglycerides under 4.5 mmol/L.
The post-hoc analysis included the 437 patients in the study with moderately abnormal ALT, asparte aminotransferase (AST), and gamma-glutamyl transpeptidase (GGT) concentrations at baseline, all believed to be due to fatty liver or non-alcoholic steatohepatitis (NASH) since alcohol misuse and other liver diseases were excluded.
Of these participants, 227 received a statin, predominantly 24 mg daily of atorvastatin (Lipitor), in the trial.
The main analysis showed that statin treatment reduced the risk of first occurrence of any cardiovascular event -- defined as death from any cause or from coronary heart disease as well as nonfatal myocardial infarction, revascularization, unstable angina, congestive heart failure, and stroke.
Overall in the trial, statins were associated with a lower cardiovascular event rate (13% or 4.2 per 100 patient-years versus 25% or 8.3 per 100 patient-years) for a 49% relative risk reduction compared with the usual care group (P<0.0001).
The post-hoc analysis showed that the patients with abnormal liver tests gained proportionately more from statin treatment.
Among participants with abnormal liver tests, statins reduced the risk of a first cardiovascular event by a relative 68% compared with usual care (10% or 3.2 per 100 patient-years versus 30% or 10.0 per 100 patient-years, P<0.0001).
By comparison, statins produced a 39% relative risk reduction among patients with normal liver tests (14% or 4.6 per 100 patient-years versus 23% or 7.6 per 100 patient-years, P<0.0001).
The reason for the greater benefit might be the elevated cardiovascular risk of patients with nonalcoholic fatty liver disease, the researchers speculated.
In the overall study, liver enzyme concentration increases on statins led to dose reductions in three of 880 patients. Less than 1% (seven of 880) withdrew from the study because of liver-related adverse effects attributed to statin treatment.
No patients required liver biopsy because of elevated liver enzymes or developed an increase in bilirubin to more than 34.2 μmol/L or alkaline phosphatase concentrations to more than twice the upper limit of normal.
Estimated glomerular filtration rates (eGFRs) actually rose by the end of the study in statin-treated patients compared with the others (P<0.0001).
The researchers cautioned that their study was faced by the same limitations characteristic of post-hoc analyses generally, and the small number of patients with liver test abnormalities in the study.
Whether the results generalize to patients with more than moderately elevated liver test results still needs to be established, they added.
By Crystal Phend, Senior Staff Writer, MedPage Today
Published: November 23, 2010
Reviewed by Zalman S. Agus, MD; Emeritus Professor
University of Pennsylvania School of Medicine.
Statins are not only safe and effective for patients with liver enzyme abnormalities but also appear to improve their liver function, researchers found.
Liver test results in patients with moderately abnormal liver tests at baseline -- possibly associated with non-alcoholic fatty liver disease -- improved with statin treatment but continued to worsen on usual care without statin treatment (P<0.0001), Dimitri P. Mikhailidis, MD, of University College London, and colleagues reported online in The Lancet.
Their retrospective analysis of the Greek Atorvastatin and Coronary Heart Disease Evaluation (GREACE) trial showed a greater statin effect on cardiovascular risk reduction in these high-risk patients than in those with normal liver tests (P=0.0074).
The findings add to evidence that should render liver tests irrelevant when prescribing statins, Ted Bader, MD, of the University of Oklahoma Health Sciences Center in Oklahoma City, argued in an accompanying commentary.
"Statin-induced hepatotoxicity is a myth," he wrote in Lancet.
About 10% of patients see liver enzymes rise after starting a statin, which can exceed the threshold of three times the upper limit of normal for 1%, but these eventually return to normal even when continuing the same statin, Bader noted.
His group reported a small pilot study in 2007 that actually suggested a liver function boost on statin treatment for patients with chronic hepatitis C infection.
Yet reluctance to start statins in patients with out-of-range alanine aminotransferase (ALT) levels, and discontinuation of statins for ALT increases, might keep statins from 10% to 30% of those who need them, he estimated.
The language of package inserts is likely to blame for the misperception that statins cause liver disease, according to Bader. He encouraged drug companies to request label modification for all the statins.
"Although most patients [in the trial] took atorvastatin, there is no reason to believe that other statins would behave differently," Bader wrote in the commentary.
The single-center, prospective GREACE trial originally compared statin treatment with usual care (which could include a statin) with regard to survival effects in 1,600 patients with coronary artery disease. Study participants were under age 75, had serum concentrations of LDL cholesterol over 2.6 mmol/L, and had triglycerides under 4.5 mmol/L.
The post-hoc analysis included the 437 patients in the study with moderately abnormal ALT, asparte aminotransferase (AST), and gamma-glutamyl transpeptidase (GGT) concentrations at baseline, all believed to be due to fatty liver or non-alcoholic steatohepatitis (NASH) since alcohol misuse and other liver diseases were excluded.
Of these participants, 227 received a statin, predominantly 24 mg daily of atorvastatin (Lipitor), in the trial.
The main analysis showed that statin treatment reduced the risk of first occurrence of any cardiovascular event -- defined as death from any cause or from coronary heart disease as well as nonfatal myocardial infarction, revascularization, unstable angina, congestive heart failure, and stroke.
Overall in the trial, statins were associated with a lower cardiovascular event rate (13% or 4.2 per 100 patient-years versus 25% or 8.3 per 100 patient-years) for a 49% relative risk reduction compared with the usual care group (P<0.0001).
The post-hoc analysis showed that the patients with abnormal liver tests gained proportionately more from statin treatment.
Among participants with abnormal liver tests, statins reduced the risk of a first cardiovascular event by a relative 68% compared with usual care (10% or 3.2 per 100 patient-years versus 30% or 10.0 per 100 patient-years, P<0.0001).
By comparison, statins produced a 39% relative risk reduction among patients with normal liver tests (14% or 4.6 per 100 patient-years versus 23% or 7.6 per 100 patient-years, P<0.0001).
The reason for the greater benefit might be the elevated cardiovascular risk of patients with nonalcoholic fatty liver disease, the researchers speculated.
In the overall study, liver enzyme concentration increases on statins led to dose reductions in three of 880 patients. Less than 1% (seven of 880) withdrew from the study because of liver-related adverse effects attributed to statin treatment.
No patients required liver biopsy because of elevated liver enzymes or developed an increase in bilirubin to more than 34.2 μmol/L or alkaline phosphatase concentrations to more than twice the upper limit of normal.
Estimated glomerular filtration rates (eGFRs) actually rose by the end of the study in statin-treated patients compared with the others (P<0.0001).
The researchers cautioned that their study was faced by the same limitations characteristic of post-hoc analyses generally, and the small number of patients with liver test abnormalities in the study.
Whether the results generalize to patients with more than moderately elevated liver test results still needs to be established, they added.
I wondered - to be quite candid with you.
I saw a recent article which stated that the claims of cancer benefits and non-cardiac benefits are not substantiated. I should point out, however, that it was a British article. Again, tongue in cheek.
Mike
I saw a recent article which stated that the claims of cancer benefits and non-cardiac benefits are not substantiated. I should point out, however, that it was a British article. Again, tongue in cheek.
Mike
"There can be some risk." I hope everyone realizes that I meant that tongue in cheek. 2 people out of a million is about as low a risk as you can get.
There can be some risk.
http://www.medicinenet.com/drug_induced_liver_disease/page8.htm
Here's an excerpt:
Nevertheless, idiosyncratic liver toxicity capable of causing severe liver damage (including liver failure leading to liver transplantation) has been reported with statins. The frequency of severe liver disease caused by satins is likely in the range of 1-2 per million users. As a precaution, the FDA labeling information advises that liver enzyme blood tests should be performed before and 12 weeks following the initiation of statin treatment or increase in dose, and periodically thereafter (for example, every six months).
http://www.medicinenet.com/drug_induced_liver_disease/page8.htm
Here's an excerpt:
Nevertheless, idiosyncratic liver toxicity capable of causing severe liver damage (including liver failure leading to liver transplantation) has been reported with statins. The frequency of severe liver disease caused by satins is likely in the range of 1-2 per million users. As a precaution, the FDA labeling information advises that liver enzyme blood tests should be performed before and 12 weeks following the initiation of statin treatment or increase in dose, and periodically thereafter (for example, every six months).
I'm very happy to hear that. I sometimes think statins are magic pills. I am definitely going to look into them further despite having very normal range lipid profile.
Mike
Mike
"Statins are not only safe and effective for patients with liver enzyme abnormalities but also appear to improve their liver function."
Definitely quite a step away from previous cautions about statins and preexisting liver disease, and reinforces my family's experience. My husband was prescribed statins almost 4 years ago despite Stage 4 disease and high liver enzymes, but it has not appeared to have caused him any ill effects. He actually reduced his statin dosage to 1/2 dose about a year ago, not because of elevated liver enzymes, but because his total cholesterol went down to 75 (during treatment).
nygirl: More to rationalize that extra piece of cake and a cigarette! ;)
Definitely quite a step away from previous cautions about statins and preexisting liver disease, and reinforces my family's experience. My husband was prescribed statins almost 4 years ago despite Stage 4 disease and high liver enzymes, but it has not appeared to have caused him any ill effects. He actually reduced his statin dosage to 1/2 dose about a year ago, not because of elevated liver enzymes, but because his total cholesterol went down to 75 (during treatment).
nygirl: More to rationalize that extra piece of cake and a cigarette! ;)
I recently had a doctor tell me I needed to be on a statin. I emailed Dr D and asked him if it's ok. He said I could only take them if I was frequently monitored. I decided not to take them.
"My enzymes are fine but my liver is not so I guess I still can't take them?"
I wonder about that because everything I have read regarding statin side effects and warnings refers only to liver enzymes.
I have read so many good things about statins that I've considered taking them but I refrained from pursuing it because of what I'd read about enzyme elevation. I'm reconsidering looking into this further.
How about this:
Statins Slow Lung Function Decline in Smokers
"October 24, 2006 (Salt Lake City) — Lung function decline in smokers taking statins for hypercholesterolemia experience a slower decline in lung function than ex-smokers who have no signs of lung disease, investigators reported here Monday at CHEST 2006, the 72nd annual meeting of the American College of Chest Physicians.
A study of smokers and former smokers conducted at the University of Oklahoma Medical Center in Oklahoma City, shows that statins retard lung function decline to rates that are slower than for the average person, according to Walid G. Younis, MD, from the university's Section for Pulmonary and Critical Care Medicine, who presented the study findings.......'
http://www.medscape.com/viewarticle/546528?sssdmh=dm1.221018&src=nldne
I've got a bunch of articles about the benefits of statins. This one just stuck out because it seems so unlikely.
Mike
I wonder about that because everything I have read regarding statin side effects and warnings refers only to liver enzymes.
I have read so many good things about statins that I've considered taking them but I refrained from pursuing it because of what I'd read about enzyme elevation. I'm reconsidering looking into this further.
How about this:
Statins Slow Lung Function Decline in Smokers
"October 24, 2006 (Salt Lake City) — Lung function decline in smokers taking statins for hypercholesterolemia experience a slower decline in lung function than ex-smokers who have no signs of lung disease, investigators reported here Monday at CHEST 2006, the 72nd annual meeting of the American College of Chest Physicians.
A study of smokers and former smokers conducted at the University of Oklahoma Medical Center in Oklahoma City, shows that statins retard lung function decline to rates that are slower than for the average person, according to Walid G. Younis, MD, from the university's Section for Pulmonary and Critical Care Medicine, who presented the study findings.......'
http://www.medscape.com/viewarticle/546528?sssdmh=dm1.221018&src=nldne
I've got a bunch of articles about the benefits of statins. This one just stuck out because it seems so unlikely.
Mike
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