Article

Safety and efficacy of long-term statin treatment for cardiovascular events in patients with coronary heart disease and abnormal liver tests in the Greek Atorvastatin and Coronary Heart Disease Evaluation (GREACE) Study: A post-hoc analysis

Second Propedeutic Department of Internal Medicine, Medical School, Aristotle University of Thessaloniki, Hippokration Hospital, Thessaloniki, Greece.
The Lancet (Impact Factor: 45.22). 12/2010; 376(9756):1916-22. DOI: 10.1016/S0140-6736(10)61272-X
Source: PubMed

ABSTRACT Long-term statin treatment reduces the frequency of cardiovascular events, but safety and efficacy in patients with abnormal liver tests is unclear. We assessed whether statin therapy is safe and effective for these patients through post-hoc analysis of the Greek Atorvastatin and Coronary Heart Disease Evaluation (GREACE) study population.
GREACE was a prospective, intention-to-treat study that randomly assigned by a computer-generated randomisation list 1600 patients with coronary heart disease (aged <75 years, with serum concentrations of LDL cholesterol >2·6 mmol/L and triglycerides <4·5 mmol/L) at the Hippokration University Hospital, Thessaloniki, Greece to receive statin or usual care, which could include statins. The primary outcome of our post-hoc analysis was risk reduction for first recurrent cardiovascular event in patients treated with a statin who had moderately abnormal liver tests (defined as serum alanine aminotransferase or aspartate aminotransferase concentrations of less than three times the upper limit of normal) compared with patients with abnormal liver tests who did not receive a statin. This risk reduction was compared with that for patients treated (or not) with statin and normal liver tests.
Of 437 patients with moderately abnormal liver tests at baseline, which were possibly associated with non-alcoholic fatty liver disease, 227 who were treated with a statin (mainly atorvastatin 24 mg per day) had substantial improvement in liver tests (p<0·0001) whereas 210 not treated with a statin had further increases of liver enzyme concentrations. Cardiovascular events occurred in 22 (10%) of 227 patients with abnormal liver tests who received statin (3·2 events per 100 patient-years) and 63 (30%) of 210 patients with abnormal liver tests who did not receive statin (10·0 events per 100 patient-years; 68% relative risk reduction, p<0·0001). This cardiovascular disease benefit was greater (p=0·0074) than it was in patients with normal liver tests (90 [14%] events in 653 patients receiving a statin [4·6 per 100 patient-years] vs 117 [23%] in 510 patients not receiving a statin [7·6 per 100 patient-years]; 39% relative risk reduction, p<0·0001). Seven (<1%) of 880 participants who received a statin discontinued statin treatment because of liver-related adverse effects (transaminase concentrations more than three-times the upper limit of normal).
Statin treatment is safe and can improve liver tests and reduce cardiovascular morbidity in patients with mild-to-moderately abnormal liver tests that are potentially attributable to non-alcoholic fatty liver disease.
None.

Download full-text

Full-text

Available from: Vasilios Gabriel Athyros, Mar 29, 2014
3 Followers
 · 
293 Views
  • Source
    • "We may never know how many more recommendations are known by guideline signatories to be harmful since public revelations like this [3] [4] are the exception and not the rule when incorrect reports enter the literature. [10] [11] [12] [13] [14] [15]. When the guideline maintenance system produced a scientifically incorrect [6] response to realisation that recommendations appear to be "
    [Show abstract] [Hide abstract]
    ABSTRACT: Background Cardiologists frequently advise on perioperative care for non-cardiac surgery, and require guidance based on randomised controlled trials that are not discredited by misconduct or misreporting. Regional political bodies currently do not provide this. We therefore examined the credible randomised controlled trial (RCT) evidence on key cardiac perioperative questions which currently have 14 recommendations. Methods Three aspects of perioperative measures were considered: perioperative statins, preoperative stress-testing and perioperative beta-blockade. One author searched Pubmed for RCTs considering these topics. All authors independently assessed the RCTs and then collaboratively composed guidelines. Results Perioperative statin therapy has been examined by three RCTs, DECREASE III and IV which are discredited and a third containing serious inconsistencies undermining its validity. Preoperative stress testing has been examined by two RCTs: one discredited trial, DECREASE II, and a second which found no benefit. Perioperative beta blockade has been examined by eleven RCTs, two of which are discredited. The nine remaining trials together suggest that perioperative beta-blockade increases mortality. Conclusions When the non-credible RCTs are omitted, the evidence base on these three subjects is much smaller than previously believed: 14 recommendations can be replaced by 3. Current guideline arrangements collectively paralyse the numerous signatories from making urgent amendments after initial publication, even when important new information comes to light. Clinicians simply have to wait for the routine five-year expiry. We present in the accompanying document a concise scientifically-based guideline and commit to updating it responsibly.
    International journal of cardiology 03/2014; 172(1). DOI:10.1016/j.ijcard.2013.12.309 · 6.18 Impact Factor
  • Source
    • "Although statins are commonly associated with liver damage, the evidence supporting causality is not clear (Mills et al., 2010; National Cholesterol Education Program, 2002). Statin therapy is usually safe in patients with mild to moderately elevated transaminase levels and can reduce morbidity from cardiovascular events when elevated liver enzymes are because of NAFLD (Athyros et al., 2010). Patients with elevated ALT and AST should have seriologic testing for Hepatitis B and C. Millions of Americans have undiagnosed Hepatitis B and C. Testing for anti-HBc, HBsAg, and anti-HCV can identify individuals who would benefit by therapeutic interventions. "
    [Show abstract] [Hide abstract]
    ABSTRACT: This article reviews autoimmune hepatitis (AIH) to promote early recognition, diagnosis, and referral for nurse practitioners (NPs) encountering this rare condition. Selected research and clinical articles from Medline, PubMed, and CINAHL. AIH is a rare condition of unknown etiology affecting women 3.6 times more than men and may result in liver failure, subsequent liver transplantation, and death. Untreated AH is associated with up to 80% mortality. Collaboration and referral to gastroenterologists, hepatologists, and other specialists are needed to improve outcomes for this potentially devastating disease. Corticosteroid treatment has long been the mainstay of treatment of AIH, although newer therapies are promising. NPs can dramatically improve outcomes by early recognition, diagnosis, referral, and monitoring for common side effects of treatment working collaboratively with specialists.
    01/2014; 26(1). DOI:10.1002/2327-6924.12055
  • Source
    • "In the GREACE study (comparing atorvastatin to usual care in patients with CAD and hyperlipidemia), among 437 patients with baseline ALT or AST elevations up to 3Â ULN, those receiving a statin experienced a 68% relative risk reduction in cardiovascular events as compared to those not receiving a statin. Patients on statins also experienced a significant reduction in transaminases [13]. A meta-analysis of large randomized, placebo controlled trials of statins at low to moderate dose for primary or secondary prevention of cardiovascular disease found that statin therapy was not associated with a significant increase in the odds of having liver function test (LFT) abnormalities, except in the case of fluvastatin [14]. "
    [Show abstract] [Hide abstract]
    ABSTRACT: Lipid lowering, particularly with HMG CoA reductase inhibitors (“statins”), reduces the risk of cardiovascular disease. Patients with chronic liver and kidney disease present challenges to the use of lipid medications. In the case of most liver disorders, the concern has been one of safety. There is evidence that most lipid-lowering medications can be used safely in many situations, although large outcomes trials are not available. In contrast, in chronic kidney disease, dosing of lipid medications may require substantial modification depending on creatinine clearance. There are significant alterations in lipid metabolism in chronic kidney disease with concomitant increases in cardiovascular risk. Some data are available on cardiovascular outcomes with dyslipidemia treatment in renal patients. This review will examine lipid physiology and cardiovascular risk in specific liver and kidney diseases and review the evidence for lipid lowering and the use of statin and non-statin therapies in chronic liver and kidney disease.
    Best Practice & Research: Clinical Endocrinology & Metabolism 01/2013; 28(3). DOI:10.1016/j.beem.2013.11.006 · 4.91 Impact Factor
Show more