This article is intended for primary care clinicians, cardiologists, hepatologists, and other specialists caring for patients with abnormal liver test results in whom statins could be indicated.
The goal of this activity is to provide medical news to primary care clinicians and other healthcare professionals in order to enhance patient care.
Upon completion of this activity, participants will be able to:
As an organization accredited by the ACCME, Medscape, LLC requires everyone who is in a position to control the content of an education activity to disclose all relevant financial relationships with any commercial interest. The ACCME defines "relevant financial relationships" as financial relationships in any amount, occurring within the past 12 months, including financial relationships of a spouse or life partner, that could create a conflict of interest.
Medscape, LLC encourages Authors to identify investigational products or off-label uses of products regulated by the US Food and Drug Administration, at first mention and where appropriate in the content.
Medscape, LLC is accredited by the Accreditation Council for Continuing Medical Education (ACCME) to provide continuing medical education for physicians.
Medscape, LLC designates this educational activity for a maximum of 0.25 AMA PRA Category 1 Credit(s)™ . Physicians should only claim credit commensurate with the extent of their participation in the activity.
This activity, MedscapeCME Clinical Briefs has been reviewed and is acceptable for up to 300 Prescribed credits by the American Academy of Family Physicians. AAFP accreditation begins September 1, 2010. Term of approval is for 1 year from this date. Each issue is approved for .25 Prescribed credits. Credit may be claimed for 1 year from the date of this issue.
Note: Total credit is subject to change based on topic selection and article length.
Medscape, LLC staff have disclosed that they have no relevant financial relationships.
AAFP Accreditation Questions
Medscape, LLC is accredited as a provider of continuing nursing education by the American Nurses Credentialing Center's Commission on Accreditation.
Awarded 0.5 contact hour(s) of continuing nursing education for RNs and APNs; 0.5 contact hours are in the area of pharmacology.
Accreditation of this program does not imply endorsement by either Medscape, LLC or ANCC.
Medscape, LLC is accredited by the Accreditation Council for Pharmacy Education as a provider of continuing pharmacy education.
Medscape designates this continuing education activity for 0.25 contact hour(s) (0.025 CEUs) (Universal Activity Number 0461-0000-10-284-H04-P).
For questions regarding the content of this activity, contact the accredited provider for this CME/CE activity noted above. For technical assistance, contact [email protected]
There are no fees for participating in or receiving credit for this online educational activity. For information on applicability
and acceptance of continuing education credit for this activity, please consult your professional licensing board.
This activity is designed to be completed within the time designated on the title page; physicians should claim only those
credits that reflect the time actually spent in the activity. To successfully earn credit, participants must complete the
activity online during the valid credit period that is noted on the title page.
Follow these steps to earn CME/CE credit*:
You may now view or print the certificate from your CME/CE Tracker. You may print the certificate but you cannot alter it.
Credits will be tallied in your CME/CE Tracker and archived for 6 years; at any point within this time period you can print
out the tally as well as the certificates by accessing "Edit Your Profile" at the top of your Medscape homepage.
*The credit that you receive is based on your user profile.
CME/CE Released: 12/1/2010
Valid for credit through: 12/1/2011
processing....
December 1, 2010 — A post hoc analysis of the Greek Atorvastatin and Coronary Heart Disease Evaluation (GREACE) study suggests that physicians should not let mildly to moderately abnormal liver test results stop them from using a statin in patients with coronary heart disease [1]. Statin therapy is not only safe in these patients, report investigators, but it significantly reduces the risk of cardiovascular events and improves liver-function tests.
"The data in the last few years have shown that these patients with elevated liver-function tests are at a greater risk of vascular events, and we wanted to see if that were true," senior investigator Dr Dimitri Mikhailidis (University College London Medical School, UK) told heartwire . "Indeed, there was an increased risk among these patients, and we found that they also had a bigger benefit and that they improved their liver function with a statin. Also, we found the opposite in patients not treated with a statin, that their liver-function tests tended to become more abnormal over time, although this probably reflects them getting fatter over three years in the study."
In an editorial accompanying the study [2], Dr Ted Bader (University of Oklahoma Health Sciences Center, Oklahoma City) called the analysis "groundbreaking." He said it is unknown how many patients are denied statins because of preexisting changes in liver-function tests or how many have the lipid-lowering drugs stopped after elevations in liver-enzyme concentrations, but he suspects that 10% to 30% of patients who need statins might fall into this category.
"This large group represents a substantial source of cardiovascular disease, which is not being prevented," writes Bader. "Further harm ensues from the cost of monitoring with liver-function tests. One estimate conservatively placed the cost of monitoring statins with liver-function tests at US $10 billion per year."
The results of the study and editorial are published online November 24, 2010 in the Lancet.
The GREACE Trial
To heartwire , Mikhailidis said that nonalcoholic fatty liver disease (NAFLD) is the most common cause of abnormal liver-function tests and that the severity of NAFLD increases in patients with higher body-mass index and triglyceride concentrations, as well as in patients with diabetes, hypertension, and insulin resistance. These patients also have a higher risk of all-cause mortality, mainly caused by an increased risk of cardiovascular events. Previously published data, however, as well as their own experience, suggested that statins were safe in patients with NAFLD.
Despite this, physicians can practice medicine defensively, said Mikhailidis, and might be reluctant to prescribe statins to patients with elevated liver enzymes at baseline. The purpose of the post hoc analysis was to assess the risk/benefit ratio in GREACE patients treated with a statin who had moderately abnormal liver tests, defined as serum alanine aminotransferase (ALT) or aspartate aminotransferase (AST) less than three times the upper limit of normal (<3x ULN).
In total, 227 patients were treated with statins, typically atorvastatin (Lipitor, Pfizer), over the three-year study. Statin therapy reduced baseline low-density lipoprotein cholesterol levels from 170 mg/dL to 95 mg/dL, as well as significantly reduced total cholesterol and triglyceride levels. Measures of liver function were also significantly improved, with ALT and AST concentrations reduced 35% and 47%, respectively. In a control cohort of 210 patients not treated with statins, lipid levels were unchanged, while liver-function tests showed increased ALT and AST concentrations.
In terms of cardiovascular morbidity, fewer patients with impaired liver-function tests treated with a statin had a cardiovascular event--nonfatal MI, revascularization, unstable angina, and congestive heart failure, as well as stroke and all-cause mortality--when compared with impaired liver-function-test patients who did not receive a statin. After three years, the event rate was 9.7%, or 3.2 events per 100-patient years, among the statin-treated patients, compared with 30.0%, or 10.0 cardiovascular events per 100-patient years, among those not treated with a statin.
Speaking with heartwire , Mikhailidis said the relative benefit among patients with mildly to moderately elevated liver-function tests was greater than that observed among patients with normal liver-function tests at baseline. For example, in those with normal ALT and AST concentrations at baseline, the relative reduction in cardiovascular events was 39%, compared with a 68% relative reduction in cardiovascular risk among those with mild to moderate elevations in liver enzymes.
Despite the results, Mikhailidis said there are important limitations to the study. "You have to remember, the numbers are small, with just 200 patients or so in each arm, and the duration is short, at three years," he said. "Most important of all, it's a post hoc analysis. You have to be very, very careful in post hoc analyses that you don't go about finding things and then proclaiming something huge. All of these factors are a considerable disadvantage, or weakness, in our conclusions."
Still, Mikhailidis told heartwire the data confirm the elevated risk of cardiovascular events among patients with NAFLD and hopes the work triggers similar post hoc analyses of the larger statin trials.
Statin-Induced Hepatotoxicity a Myth
In his editorial, Bader said that statin-induced liver toxicity is a myth, one that is fueled by the language in the package insert of the drugs. Large studies have shown no difference in the frequency or degree of ALT increases between treatment and placebo groups, and there are no reports of chronic carriers of drug-induced liver damage from statins.
Bader stressed that an elevation in ALT does not represent a disease state, yet many US physicians are reluctant to prescribe a statin to patients with ALT increases even 1.5x ULN. The finding of improved liver function among the statin-treated patients confirms studies performed in hepatitis-C patients treated with statins, another group in whom doctors are reluctant to prescribe the lipid-lowering drugs, writes Bader.
The authors report no conflicts of interest. Bader reports a patent application with the University of Oklahoma for the use of statins in patients with viral hepatitis. |
References
Additional Resource
The National Cholesterol Education Program provides ATP III Guidelines At-A-Glance Quick Desk Reference as a downloadable document.
By inhibiting hepatic production of cholesterol, statin treatment helps reduce the risk for cardiovascular events including myocardial infarction and stroke. Rarely, statin use may cause the adverse effect of increased levels of liver enzymes or serum transaminases such as ALT. Although statins have not been linked to liver injury, a survey showed that half of US academic physicians would be reluctant to give a statin to a patient with an ALT level of more than 1.5 times ULN and that 10% to 30% of patients who could benefit from statins would be denied this treatment.
NAFLD, which affects up to one third of adults in the United States, Europe, and Japan, is the most common cause of high ALT levels. The safety and efficacy of long-term statin treatment is unclear in patients with NAFLD, who often have high cholesterol levels and an increased risk for cardiovascular disease.