Statins side effects are minimal, study argues
Analysis by NHS Choices.
“Cholesterol-lowering statins have almost no side effects,” The Guardian reports. A new UK study argues that the majority of reported side effects are actually due to the nocebo effect – symptoms that are “all in the mind”.
The researchers looked at the combined results of 29 studies and found there was no difference in the incidence of common side effects in the treated group compared to those in the placebo group. However, there was a slightly higher occurrence of diabetes.
Statins slightly reduced the risk of death from any cause, as well as the risk of heart attack and stroke in people with or without vascular disease.
However, the research did not include analysis for some reported side effects of statins, such as memory problems, blurred vision, ringing in the ears or skin problems.
The frequently reported side effect of muscle weakness was only considered if there was also a 10-fold rise in a muscle enzyme associated with muscle injury. Muscle aches, in particular, were no more common in the statin group than the placebo group.
This research has provided a novel approach to assessing the risks and benefits of using statins. Arguably, it provides the most comprehensive research yet on the number of people thought to have genuine side effects, and the risks and benefits of taking statins in both low- and high-risk groups for cardiovascular diseases such as heart attacks.
However, some headlines – such as “Statins are safe” – have overstated the case. There is no such thing as an entirely "safe" drug for everyone who takes it. If a drug doesn’t have side effects, it doesn’t work.
If you have any concerns about taking statins, you should discuss this with your GP or health advisor.
The nocebo effect
Most people have heard of the placebo effect – where people see an improvement in symptoms, despite having been given a dummy treatment; this is thought to be down to the power of the own mind.
Well, the nocebo effect is its evil twin. People can develop what they believe are side effects, even though they have been given a dummy treatment.
Ben Goldacre, one of the authors of the study in question, says that if you want to see the nocebo effect in action, when sitting on a sofa with friends suddenly ask: “does this things have fleas in it?”.
Where did the story come from?
The study was carried out by researchers from Imperial College London and the London School of Hygiene and Tropical Medicine. They say they did not receive any grants from any funding agency in the public, commercial or not-for-profit sectors. The authors are supported by the British Heart Foundation, the National Institute for Health Research and the Wellcome Trust.
The study was published in the peer-reviewed medical journal European Journal of Preventive Cardiology.
The media reported that this study shows that statins have no side effects in comparison to placebo.
This is misleading, as the research was aiming to ask a different question: “What proportion of symptomatic side effects in patients taking statins are genuinely caused by the drug?”
And the researchers were more cautious in their conclusion.
It has not comprehensively looked at all side effects, and it gives no indication of the severity or frequency of side effects experienced.
The media also did not report how small the benefits of statins were found to be in this study. This is an important consideration for people who want to make an informed choice when weighing up the risks and benefits of statin treatment.
What kind of research was this?
This was a meta-analysis of double-blind randomised controlled trials. This means the researchers added together and analysed the results of all studies that met their inclusion criteria. Double-blind randomised controlled trials are the gold standard for studies of whether a drug works or not, as they compare a drug directly with a placebo (dummy), and neither the participant nor the clinician knows which one they are taking. This removes any bias that could affect the results.
Studies of safety are often based on long-term observational studies, often without a placebo. The approach of reviewing randomised trials for safety data, as used by these researchers, would be particularly good at checking on differences between a drug and placebo.
What did the research involve?
The researchers found studies comparing statins to placebo and pooled the results to see if statins increase the risk of side effects, compared to rates in the placebo arm.
Two large databases were searched for relevant studies looking at statins being compared to placebo for cardiovascular disease prevention. Studies were excluded if they compared statins with standard therapy or no treatment. They also excluded studies that mainly included people on renal dialysis, those with organ transplants or if other non-statin medication was also started. This was because people in these categories did not represent the majority of people treated with statins.
They separately analysed studies of primary cardiovascular disease prevention (i.e. in people who had not had a heart attack or stroke) and secondary cardiovascular disease prevention (reducing the risk of a further heart attack or stroke in people who have already had one or the other).
They recorded any serious events for each trial and pooled the results, including:
mortality of any cause
fatal heart attack
non-fatal heart attack
any life-threatening condition
They also recorded other side effects, but only if they were reported in at least two trials and the sample size was at least 500 people:
increased liver enzymes
newly diagnosed diabetes mellitus
myopathy symptoms (muscular weakness)
increased creatine kinase (a muscle enzyme that raises during muscle injury) more than 10 times the upper limit of normal
newly diagnosed cancer
gastrointestinal disturbance, nausea
dyspepsia (indigestion), diarrhoea or constipation
They performed internationally recognised statistical analysis to pool the results together. They then calculated the increased risk of experiencing each side effect for participants taking the statins and for participants taking placebo. They subtracted the placebo risk from the statin risk to find the absolute increase in risk for being on statins. By doing this, they worked out the proportion of symptoms that would not have been attributable to taking medication.
The researchers reported risks as “absolute risks” and calculated the reduction in risk by subtracting the risk in one arm from that in the other. This makes a direct comparison of the possible risks and benefits.
What were the basic results?
They found 14 randomised controlled trials, which included 46,262 people without previous heart disease or stroke (primary prevention). They also found 15 randomised controlled trials, including 37,618 people who already had heart disease or stroke (secondary prevention). On average, the trials lasted between 6 months and 5.4 years, and those included were mostly men.
In the studies, on people who had not already suffered from a heart attack or stroke, the rate of new-onset diabetes for people on statins was 2.7% and on placebo was 2.2%.
The difference between rates on treatment and on placebo is 0.5% (95% confidence interval [CI] 0.1 to 1%), meaning there was a small, statistically significant increase in the rate of developing diabetes with a statin.
This means that in 100 people taking statins, 20 cases of newly diagnosed diabetes mellitus could be due to taking this medicine. In people who had already suffered from a heart attack or stroke, there was only one study that reported new onset diabetes, and no significant effect was seen.
In the studies on people who had not already suffered from a heart attack or stroke, the risk of death from any cause on statins was 0.5% (CI -0.9 to -0.2%) less than the risk on placebo. The risk of a heart attack was 1% (CI -1.4 to -0.7%) less and the risk of stroke 0.3% (CI -0.5 to -0.1%) less.
In the studies on people who had already suffered from a heart attack or stroke, the reduction in absolute risk of death from any cause was even more: 1.4% (CI -2.1 to -0.7%) less compared to placebo. Statins also significantly reduced the risk of a heart attack by 2.3% (CI -2.8 to -1.7%) and the risk of stroke was 0.7% (-1.2 to -0.3%) less.
The proportion of people developing symptoms or other blood test abnormalities was as follows:
In both study groups, liver enzymes rose in 0.4% of people on statins. No symptoms were reported, and it is unclear if this was harmful.
There was no significant difference between
taking statins or placebo for any of the other adverse events or side effects listed above.
With regards to muscle weakness, this was only recorded if the muscle enzyme (creatinine kinase) level was greater than 10 times the upper limit of normal, so was found in just 16/19,286 people on statins and 10/17,888 on placebo in the primary prevention group. A separate category for muscle aches were experienced in 1744/22,058 (7.9%) in people on statins and 1646/21,624 (7.6%) on placebo.
How did the researchers interpret the results?
At the doses tested in these 83,880 patients, only a small minority of symptoms reported on statins are genuinely due to the statins; almost all reported symptoms occurred just as frequently when patients were administered placebo. New-onset diabetes mellitus was the only potentially or actually symptomatic side effect whose rate was significantly higher on statins than placebo; nevertheless, only one in five of these new cases were actually caused by statins.
This meta-analysis pooled results from 29 studies and has shown a very small increased risk of newly diagnosed diabetes mellitus. This is the same as the decreased risk of any cause of death in people taking statins, compared to placebo, to prevent a heart attack or stroke.
The researchers point out some limitations to the meta-analysis:
Each study did not report on all of the side effects, meaning that for each category of side effect, the number of participants differed. The side effect categories were only included if at least 500 people had reported suffering from it. This means there may be numerous other side effects that were not covered by this research.
New onset diabetes was only documented in 3 of the 29 trials, though the numbers were still reasonably large.
Many trials do not state clearly how and how often adverse events were assessed. This is particularly important, as it is not clear from this type of analysis how often the side effects were experienced or the severity.
Side effects not covered by this review include memory problems, blurred vision, ringing in the ears and skin problems.
Anecdotally, muscle aches or weakness is one of the main reasons people stop taking statins. In this review, the category for muscle weakness was only looked at if the person also had a 10-fold increase in creatinine kinase level (indicating muscle damage). Muscle aches were separately recorded, as this is more common and not always experienced alongside muscle weakness. No firm conclusions can therefore be drawn from this meta-analysis regarding whether statins have an effect on the risk of muscle weakness, if there was less than a 10-fold increase in creatinine levels.
This research was limited to studying the side effects reported in the included studies. Although it was not a comprehensive study of all side effects, it has provided a novel approach to assessing the balance of risks and benefits.
It provides extremely useful data on the proportion of people expected to have genuine side effects and the balance of risks and benefits when taking statins in both low- and high-risk groups.
There are other ways you can lower your cholesterol levels, such as eating a healthy diet low in saturated fat and taking regular exercise.
Read more about preventing high cholesterol.
Analysis by NHS Choices.
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Links to the headlines
Statin side-effects minimal, study finds.
The Guardian, March 13 2014
Statins do NOT have major side effects, claims study: Research finds users less likely to suffer maladies than control group.
Mail Online, March 13 2014
Statins found to have 'almost no side effects'.
ITV News, March 13 2014
Statin heart pills are safe, according to experts.
Daily Express, March 13 2014
Links to the science
Finegold JA, Manisty CH, Goldacre B, et al. What proportion of symptomatic side effects in patients taking statins are genuinely caused by the drug? Systematic review of randomized placebo-controlled trials to aid individual patient choice.
European Journal of Preventive Cardiology. Published online March 12 2014
Statins side effects are minimal, study argues
Statins may protect cirrhotic patients from infection
August 2, 2013
Veterans with cirrhosis who used statins were at reduced risk for developing severe infection compared with nonusers, according to recent results.
Rifaximin improved outcomes of lactulose therapy for hepatic encephalopathy
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Yaron Rotman, MD, MSc, discusses the results of his study of 60 treatment-naive patients.
Statins tied to lowered liver cancer risk with hepatitis C
By Genevra Pittman
NEW YORK (Reuters Health) - People infected with chronic hepatitis C are less likely to develop liver cancer if they are taking cholesterol-lowering drugs, new research from Taiwan suggests.
The report doesn't prove statins ward off cancer, and one researcher not involved in the study says it's not reason enough to recommend using the popular medications solely for liver cancer prevention.
Previous studies have come to ambiguous and conflicting conclusions on the question of statins' cancer-preventing abilities, researchers noted.
"Observational studies do suggest a significant, modest reduction in the risk of (liver cancer) among patients with chronic liver disease who take statins," said Dr. Hashem El-Serag, a liver disease researcher from the Baylor College of Medicine and Michael E. DeBakey VA Medical Center in Houston.
Those trials, which follow different groups of patients to see who develops cancer over time, can't prove cause-and-effect.
"The downside to the observational studies, including this study, is because they are non-randomized, the decision to give statins to a patient with hepatitis C may or not may depend on factors that have a lot to do with severity of liver disease," El-Serag told Reuters Health.
For their study, Dr. Pau-Chung Chen from the National Taiwan University College of Public Health in Taipei and his colleagues used nationwide data to track about 261,000 people with hepatitis C from 1999 through 2010.
During that span, about 13 percent of them filled a prescription for statins.
A total of 28,000 people were diagnosed with liver cancer by 2011 - or about one percent of those with hepatitis C each year. After the researchers accounted for patients' age, gender and other diseases, they found those who took statins were about half as likely to get cancer as non-statin users.
Higher doses of statins, as well as longer-term use, were linked to a further drop in cancer risk, according to the findings published this week in the Journal of Clinical Oncology.
The researchers said statins may prevent the hepatitis C virus from replicating or slow the growth of malignant cells. But they can't prove the drugs stopped people from getting cancer.
One limitation, they noted, is that they weren't able to measure other health and lifestyle factors that influence people's risk of liver cancer, including their weight and whether they smoked or drank heavily.
Chen said a large study in which people with hepatitis C are assigned to take statins or not, known as a randomized clinical trial, is needed to clarify the drugs' effects in those patients.
In the United States, about 3.2 million people are chronically infected with hepatitis C, which is spread through blood. Having hepatitis C increases a person's chance of liver cancer up to 20-fold, Chen's team wrote.
The National Cancer Institute estimates 30,640 Americans will be diagnosed with liver cancer in 2013 and 21,670 will die of the disease.
The researchers did not find a link between statins and any serious complications.
"We feel more confident that statins do not cause harm in patients with liver disease," Chen told Reuters Health in an email.
Until recently, El-Serag said, many doctors feared prescribing statins to people with liver disease, believing they might cause liver-related complications. He agreed that the new study should allay those concerns.
"Do not avoid statins because of underlying liver disease, because you may help the statin-related indication, such as cholesterol and heart disease, but you may still get additional benefit for reducing the risk of liver cancer," he advised.
Still, El-Serag said, "I would stop shy of recommending it just to (prevent) liver cancer."
SOURCE: http://bit.ly/Ze6jf8 Journal of Clinical Oncology, online March 18, 2013.
GI & HEPATOLOGY NEWS July 2012 Issue
Statins Safe in Cirrhosis and May Even Have Benefit
BY DIANA MAHONEY
Elsevier Global Medical News
Statin therapy is not only safe for patients with cirrhosis, it may slow the progression of their liver disease to hepatic decompensation and help them live longer, a retrospective study has shown.
The findings, reported at the annual Digestive Disease Week, should help allay fears that decreased hepatic clearance of statins could lead to complications in patients with advanced liver disease, as was previously hypothesized, said lead investigator Dr. Sonal Kumar.
“In fact, it seems the opposite may be true,” said Dr. Kumar of Brigham and Women’s Hospital, Boston, referring to the results of her study in which statin therapy in cirrhosis patients was associated with a decreased risk of hepatic decompensation, a delay in the time to decompensation, and reduced all-cause mortality, compared with cirrhosis patients not taking statins.
The investigators were aware that some clinicians either do not initiate statin therapy or discontinue statins in patients with advanced liver disease because of perceived safety concerns. Dr. Kumar and her colleagues sought to determine the actual effect of statin therapy on the risk of hepatic decomposition in cirrhosis.
They identified all patients with biopsy-proven cirrhosis who had taken statins for at least 3 months for dyslipidemia. Cirrhosis patients not on statins were matched 2:1 for age, gender, and Child-Pugh class. The patients had been treated at Massachusetts General Hospital and Brigham and Women’s Hospital. The primary outcomes of the study were hepatic decompensation, defined as the development of ascites, jaundice, hepatic encephalopathy, or variceal hemorrhage, and time to decompensation. Mortality was a secondary outcome.
The investigators created a Cox proportional hazards model for decompensation to control for age, Child-Pugh class, diabetes, coronary artery disease, and hepatocellular carcinoma, and used conditional logistic regression to assess mortality, she said.
Of the 243 cirrhosis patients, 81 were statin users and 162 were matched controls. “In each group, approximately 70% of patients were Child-Pugh A and 30% were Child-Pugh B/C. The MELD [Model for End- Stage Liver Disease] score, albumin, presence of varices, and beta-blocker use were similar between groups,” Dr. Kumar noted. In the statin group, which was followed for a mean of 1,756 days, decompensation was reported in 31 patients (38.2%), compared with 80 patients (50.6%) in the control group.
The control patients were followed for a mean of 1,503 days, and on Cox analysis, “statin therapy was the only factor significantly associated with lower decompensation risk, with a hazard ratio of 0.46.” Additionally, Kaplan-Meier curves showed a significantly longer time to decompensation in patients receiving statin therapy, she said. In subgroup analyses, significantly longer time to decompensation was observed in Child-Pugh A and Child-Pugh B/C patients. Overall mortality was significantly lower in the statin group, at 37.0%, than in the control group, at 50.6%, said Dr. Kumar.
Statin use remained significantly associated with decreased mortality in multivariate analysis, with an odds ratio of 0.36. Coronary artery disease and hepatocellular carcinoma were associated with increased mortality, with respective odds ratios of 3.6 and 4.9.
There were no statistically significant differences in cause of death between the two groups, “however it is important to note that cause of death was not documented for approximately one-third of the study patients, so we cannot make definitive statements about whether patients on statins were less likely to die of liver- related or cardiovascular causes than patients in the control group,” said Dr. Kumar.
The apparent hepatoprotective effect of statin therapy in cirrhosis patients may be a function of previously observed hemodynamic and molecular effects of statins, Dr. Kumar hypothesized. Sinusoidal endothelial dysfunction with decreased nitric oxide production contributes to increased hepatic resistance in cirrhosis, she explained. Just as statins improve endothelial dysfunction in the peripheral vasculature, they may also improve the vascular disturbances that contribute to portal hypertension in cirrhosis by selectively increasing nitric oxide availability in the liver, thus reducing pressures, she said.
The retrospective design of the study limits the conclusions that can be drawn. Specifically, “we can’t say that all patients with liver disease should be prescribed statins,” Dr. Kumar said. “What we can say is that statin therapy is safe in this population, it may be beneficial for its effects on the liver as well as the cardiovascular system, and clinicians should not hesitate to prescribe it for appropriate cardiovascular indications in cirrhosis patients.”
The findings also indicate that prospective studies are warranted to clarify the role of statins in advanced liver disease, she stressed. Dr. Kumar disclosed no relevant financial conflicts of interest.
Published on Jun 13, 2012 by ElsGlobalMedicalNews
May 22, 2012
From Medscape Medical News
Statins Shown to Be Safe in Patients With Cirrhosis
Caroline HelwickSan Diego, California) — Statin therapy is not only safe for people with cirrhosis, it might be potentially beneficial, according to research presented here at Digestive Disease Week 2012.
"We found less progression of liver disease in patients taking statins, and a lower mortality rate. This is contrary to prior beliefs that statins may not be safe in patients with cirrhosis; in fact, they may be beneficial," said lead investigator Sonal Kumar, MD, from Brigham and Women's Hospital in Boston, Massachusetts.
Patients with cirrhosis have decreased hepatic clearance, and thus could be at increased risk for complications, specifically hepatic decompensation. Statins lower portal pressure and, therefore, might be protective of the liver, she explained.
Dr. Kumar and colleagues conducted a study to determine the effect of statin therapy on the risk from hepatic decompensation in 82 people with biopsy-proven cirrhosis who had taken statins for at least 3 months for the treatment of dyslipidemia. This group was compared with 162 control subjects who had cirrhosis but were not taking statins and who were matched in a 2:1 ratio by age, sex and Child-Pugh class.
In each group, 70.4% of patients were Child-Pugh A and 29.6% were Child-Pugh B/C. Other relevant disease-related factors were not different between the groups. Median duration of statin use was 25 months. Median follow-up was 36 months for the statin group and 30 months for the control group.
The primary outcomes were hepatic decompensation (defined as the development of ascites, jaundice, hepatic encephalopathy, or variceal hemorrhage) and time to decompensation.
Statins Cut Decompensating Events in Half
In a multivariate analysis, the use of a statin was associated with a 56% reduction in risk for hepatic decompensation (95% confidence interval [CI], 0.27 to 0.71). There were fewer decompensating events in the statin group than in the control group (39.5% vs 55.6%; P = .01), Dr. Kumar reported.
The largest difference was observed for patients who developed jaundice (7.4% vs 20.9%; P = .001) or ascites (20.9% vs 37.0%; P = .009).
Time to decompensation was significantly longer in the statin group. In the control group, half had decompensated at 2.3 years; in the statin group, median time to decompensation was not reached. In Child-Pugh A patients, median time to decompensation was 8.1 years in the control group; again, it was not reached in the statin group.
In addition, overall mortality was significantly lower in the statin group (37.0% vs 50.6%; P = .043). On multivariate analysis, statin use was significantly associated with a 51% reduction in mortality (95% CI, 0.29 to 0.81), Dr. Kumar reported.
Strikingly, in Child-Pugh A patients, time to death was significantly longer in the statin group than in the control group (7.0 vs 14.4 years; P = .005).
Although 29 patients in the control group underwent liver transplantation, only 2 patients in the statin group did, she added.
There were no differences in cause of death, although for one third of patients, cause of death could not be ascertained.
The study has a number of limitations, Dr. Kumar acknowledged. It is a retrospective study of a heterogeneous population with varied duration of statin therapy; compliance with statin use was not well documented; and investigators could not account for a number of potentially contributing factors, including obesity, use of aspirin or other nonsteroidal anti-inflammatory drugs, and active alcohol consumption.
Bruce Sands, MD, MS, the Dr. Burrill B. Crohn professor of medicine at Mount Sinai Medical Center in New York City, moderated a press briefing during which the results were discussed. "This is a wonderful study, but it is retrospective and hypothesis-generating. I would like to see a prospective randomized controlled trial showing there are actually benefits to statin use," he said.
Zobair Younossi, MD, vice president of research and chair of medicine at the Inova Health System in Falls Church, Virginia, explained that his own research has shown that disease-related mortality is similar among statin users and nonusers. "Statins are safe," he maintained. "Don't worry about further liver toxicity."
Dr. Kumar said that this information should be reassuring to physicians, many of whom discontinue statin use in their patients, which puts them at risk for worsening cardiovascular disease.
Dr. Kumar, Dr. Sands, and Dr. Younossi have disclosed no relevant financial relationships.
Digestive Disease Week (DDW) 2012: Abstract 595. Presented May 21, 2012.
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One of the changes regards interactions between certain statins and hepatitis C virus (HCV) and HIV protease inhibitors. Taken together, statins and protease inhibitors may raise the blood levels of statins and increase the risk for muscle injury. One statin in particular, lovastatin, has been updated with new contraindications and dose limitations when it is taken with certain other drugs that can increase the risk for myopathy and rhabdomyolysis, including the HCV protease inhibitors boceprevir and telaprevir.
The FDA also approved labeling changes regarding the potential for statins to increase levels of blood sugar and glycosylated hemoglobin, signs of incipient type 2 diabetes. This decision was based on accumulating studies linking statins with the development of type 2 diabetes, the agency said. These included the Justification for the Use of Statins in Primary Prevention: an Intervention Trial
Evaluating Rosuvastatin trial, which reported a 27% increase in investigator-reported diabetes in patients who received rosuvastatin compared with those who took a placebo (Ridker PM et al. N Engl J Med 2008;359:2195-2207); the Pravastatin or Atorvastatin Evaluation and Infection Therapy—
Thrombolysis In Myocardial Infarction 22 substudy, which found an association between high-dose atorvastatin and worsening glycemic control (Sabatine MS et al. Circulation 2004;110:S834); and meta-analyses such as one by Sattar et al (Lancet 2010;375:735-742), which found that statin therapy was associated with a 9% increased risk for incident diabetes.
The potential for cognitive side effects, such as memory loss and confusion, in patients taking statins also was noted by the FDA. These side effects are generally reversible and not serious. The FDA stressed that “the cardiovascular benefits of statins outweigh these small increased risks.”
Additionally, statin labels have been revised to eliminate the need for routine periodic monitoring of liver enzymes in patients taking these drugs. Instead, statin labels now recommend the use of liver enzyme tests before starting the drugs and as clinically indicated afterward. Serious liver injury with statins is rare and unpredictable, according to the FDA, and routine periodic monitoring does not seem effective in detecting or preventing the problem.
Protease inhibitors and statins taken together may raise the blood levels of statins and increase the risk of myopathy, kidney damage, and kidney failure, which can be fatal.
FDA Drug Safety Communication: Interactions between certain HIV or hepatitis C drugs and cholesterol-lowering statin drugs can increase the risk of muscle injury
Additional Information for Healthcare Professionals
Statin Dose Limitations
Facts about statins and protease inhibitors
The labels for both the HIV protease inhibitors and the affected statins have been updated to contain consistent information about the drug-drug interactions.
These labels also have been updated to include dosing recommendations for those statins that may safely be co-administered with HIV or HCV protease inhibitors (see Statin Dose Limitations below).
Healthcare professionals should refer to the current drug labels for protease inhibitors and statins for the latest recommendations on prescribing these drugs.
Patients should contact their healthcare professional if they have any questions or concerns about taking protease inhibitors and statins.
- Human immunodeficiency virus (HIV) and hepatitis C virus (HCV) protease inhibitors can interact with cholesterol-lowering statins to increase the risk of muscle injury.
- Patients should inform their healthcare professional about all medicines that they are taking or plan to take prior to starting an HIV or HCV protease inhibitor or statin.
- HIV and HCV protease inhibitors should never be taken (are contraindicated) with lovastatin (Mevacor) and simvastatin (Zocor) (see Statin Dose Limitations below).
- Patients should contact their healthcare professional if they have any questions or concerns about HIV or HCV protease inhibitors or statins.
- Patients should report side effects from the use of HIV or HCV protease inhibitors and/or statins to the FDA MedWatch program, using the information in the "Contact FDA" box at the bottom of the page.
- Co-administration of human immunodeficiency virus (HIV) or hepatitis C virus (HCV) protease inhibitors with certain statins can increase the risk of myopathy/rhabdomyolysis.
- Healthcare professionals should follow the recommendations in the drug labels when prescribing HIV or HCV protease inhibitors with statins (also see Statin Dose Limitations below).
- Healthcare professionals should report adverse events involving HIV or HCV protease inhibitors and/or statins to the FDA MedWatch program using the information in the "Contact FDA" box at the bottom of this page.
Statin Dose Limitations
Interacting protease inhibitor(s)
Use with caution and use with the lowest atorvastatin dose necessary
Do not exceed 20 mg atorvastatin daily
Do not exceed 40 mg atorvastatin daily
No data available
No dose limitations
No dose limitations
Limit rosuvastatin dose to 10 mg once daily
- Lees RS, Lees AM. Rhabdomyolysis from the coadministration of lovastatin and the antifungal agent itraconazole. N Engl J Med. 1995;333:664-5.
Statins and HIV or Hepatitis C Drugs: Drug Safety Communication - Interaction Increases Risk of Muscle Injury
AUDIENCE: Infectious Disease, Family Practice, Patients
ISSUE: FDA notified healthcare professionals of updates to the prescribing information concerning interactions between protease inhibitors and certain statin drugs. Protease inhibitors and statins taken together may raise the blood levels of statins and increase the risk for muscle injury (myopathy). The most serious form of myopathy, called rhabdomyolysis, can damage the kidneys and lead to kidney failure, which can be fatal.
BACKGROUND: Statins are a class of prescription drugs used together with diet and exercise to reduce blood levels of low-density lipoprotein (LDL) cholesterol (“bad cholesterol”). HIV protease inhibitors are a class of prescription anti-viral drugs used to treat HIV. HCV protease inhibitors are a class of prescription anti-viral drugs used to treat hepatitis C infection.
RECOMMENDATION: Healthcare professionals should follow the recommendations in the prescribing information ( drug labels ) when prescribing HIV or HCV protease inhibitors with statins. See the FDA Drug Safety Communication for additional information, including a data summary.
Healthcare professionals and patients are encouraged to report adverse events or side effects related to the use of these products to the FDA's MedWatch Safety Information and Adverse Event Reporting Program:
Complete and submit the report Online: www.fda.gov/MedWatch/report.htm1
Download form2 or call 1-800-332-1088 to request a reporting form, then complete and return to the address on the pre-addressed form, or submit by fax to 1-800-FDA-0178
[03/01/2012 - Drug Safety Communication 3 - FDA]
- Friday, January 20, 2012
- Posted by HCV New Drugs
- File Under HCV-Statins
Journal of Hepatology
Volume 56, Issue 2 , Pages 305-307, February 2012
However, in contrast to fatty liver disease, the author is unaware of any long-term cardiovascular prevention trials with statins in patients with HBV or HCV; such trials have usually excluded patients with liver disease. Nonetheless, there is no reason to suspect that statins would have any diminished efficacy.
Does monitoring with ALT tests help to predict this rare injury? No.
The authors end their current report with wise counsel: “Responsible physicians should measure liver tests in patients taking statins with newly developed symptoms such as nausea, severe lethargy and abdominal pain.” I agree. This is the same approach shown useful in detecting severe cases of INH toxicity in early stages. ALT monitoring for statins does more harm than good by discovering the irrelevant finding of 1 in 10 patients who will elevate their ALT level; elevations that will return to normal even if the same statin is continued.
In summary, the elevation of ALT values that commonly occur at the start of statin therapy have no meaning in regard to hepatotoxicity. On the other hand, Bjornsson et al. present data that show drug idiosyncrasy due to statins probably exists, but is rare. ALT monitoring does not help to discover an idiosyncratic reaction. Patients started on statins should be counseled about possible symptoms of drug-induced hepatitis but told how rare this is.
Giving a statin to those patients with liver disease and cardiac risk factors may increase their lifespan more than any other therapy we offer. Writing this prescription would produce greater longevity, with far less risk, than liver transplantation for patients with fatty liver or peginterferon based triple therapy for hepatitis C. For liver patients with cardiac risk factors, the pen is mightier than the knife or needle!
- Bader T. The myth of statin-induced hepatotoxicity. Am J Gastroenterol. 2010;105:978–980
- Bjornsson E, Jacobsen E, Kalaitzakis E. Hepatotoxicity associated with statins: reports of idiosyncratic liver injury post-marketing. J Hepatol 2012;56:49-49.
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U.S. Food and Drug Administration Approves Gilead’s Harvoni® (Ledipasvir/Sofosbuvir), the First Once-Daily Single Tablet Regimen for the Treatment of Genotype 1 Chronic Hepatitis C
U.S. FDA Approves Gilead’s Harvoni® (Ledipasvir/Sofosbuvir)
Updated October 21, 2014
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AASLD annual meeting, held in Boston, Massachusetts, from November 7-12
AASLD - This Blog: Media Updates
Late-breaking abstracts now available
Special Issue: The 65th Annual Meeting of the American Association for the Study of Liver Diseases: The Liver Meeting 2014
View abstracts online, through the HEPATOLOGY App, or via download.
2014 Program Overview
Go to the AASLD Itinerary Planner to view invited speaker sessions, abstract titles, and create your own personalized itinerary.
Gilead has published both U.S. Prescribing Information and Patient Information, on their support website., In addition check out HCV Advocates new factsheet for; Genotype 1:Treatment: Harvoni (Sofosbuvir & Ledipasvir), other factsheets include; Sovaldi: Genotype 1 Triple Therapy, Sovaldi: Genotype 2 & 3 and Sovaldi: Genotype 4 Triple Therapy
In case you missed it; HCV Newsetters: Everything you need to know about Gilead's Harvoni
France uses tax to put pressure on hepatitis C drug prices
(CHMP), the scientific committee of the European Medicines Agency, has adopted a positive opinion on the company's Marketing Authorization Application (MAA) for Harvoni®, an investigational once-daily tablet combining the NS5A inhibitor ledipasvir (LDV) 90 mg and the nucleotide analog polymerase inhibitor sofosbuvir (SOF) 400 mg, for the treatment of chronic hepatitis C virus (HCV) infection in adults.
Ledipasvir/Sofosbuvir - Gilead Submits NDA to Japan’s PMDA
Bristol-Myers Squibb’s Daklinza (daclatasvir), Approved By European Commission - for use in combination with other medicinal products across genotypes 1, 2, 3 and 4 for the treatment of chronic hepatitis C virus (HCV) infection in adults.
Daklinza, when used in combination with sofosbuvir, is an all-oral, once daily regimen that yields cure rates of up to 100%
Daklinza + sofosbuvir offers potential cure for a broad range of EU HCV patients, including those with advanced liver disease, genotype 3 and protease inhibitor failures
PBAC decisions – a mixed bag for Australians living with Hepatitis C
Hepatitis Australia today welcomed the recommendation to add simeprevir (Olysio) to the Pharmaceutical Benefits Scheme (PBS) for the treatment of genotype 1 chronic hepatitis C.
Responding to the PBAC decision to reject an application to subsidise the antiviral medication sofosbuvir (Sovaldi), Ms Tyrrell said “it’s a sad day when access to game-changing therapy is denied. This is a bad outcome for people living with hepatitis C”.
UK Recommends Covering Sovaldi Hepatitis C Pill
PegLambda Discontinued by BMS
Vertex to stop selling hepatitis C drug Incivek
To learn more about Hepatitis C virus clinical trials or to find out if a study is enrolling patients in your area, please click here.
ClinicalTrials.gov: updated in the last 30 days
Hepatitis C Clinical Trials - FDA Approved And Investigational Drugs
News, Research And Clinical Trials
See **Clinical Trials @ HCV Advocate For Enrollment Information
AbbVie is a new, independent biopharmaceutical company composed of Abbott’s former proprietary
News and Research
ABT-450/ritonavir/ombitasvir/dasabuvir with or without ribavirin,
r = ritonavir
**Clinical Trials @ HCV Advocate-AbbVie
News and Research
**Clinical Trials @ HCV Advocate-Achillion
News and Research
In January 2014 Boehringer Ingelheim announced the development of deleobuvir would not be continued since recent findings from phase III trials did not suggest sufficient efficacy.
Faldaprevir - On June 20 2014 Boehringer Ingelheim announced it will withdraw all regulatory filings for faldaprevir, which had been granted accelerated assessment by the European Medicines Agency, and will discontinue further development of the protease inhibitor.
**Clinical Trials @ HCV Advocate-Boehringer Ingelheim
News and Research
**Bristol-Myers withdraws FDA NDA for asunaprevir
**Clinical Trials @ HCV Advocate-Bristol-Myers Squibb (BMS)
FDA Approved News and Research
(Sofosbuvir) now Sovaldi
Before FDA Approval
GS-7977 sofosbuvir /GS-5885 ledipasvir,
GS-0938 and Sofosbuvir
Sofosbuvir/Ledipasvir plus GS-9451
Sofosbuvir/Ledipasvir plus GS-9669
GS-7977 now Sofosbuvir and simeprevir (TMC435)
**Clinical Trials @ HCV Advocate-Gilead
News and Research
**Clinical Trials @ HCV Advocate-Idenix
News and Research
Simeprevir now Olysio
Before FDA Approval
Simeprevir now Olysio and Daclatasvir
New - OLYSIO™ (Simeprevir) and Sovaldi (Sofosbuvir)
GS-7977 now Sofosbuvir and simeprevir (TMC435)
Simeprevir (TMC435)-Before FDA Approval
**Clinical Trials @ HCV Advocate-Tibotec / Janssen
News and Research
FDA Approved - Victrelis (Boceprevir)
**Clinical Trials @ HCV Advocate-Merck
News and Research
**ClinicalTrials.gov - Danoprevir
News and Research
**ClinicalTrials.gov - Miravirsen
FDA Approved News and Research
**Vertex to stop selling hepatitis C drug Incivek
..Vertex said it will license an experimental hepatitis C drug called VX-135 to Alios BioPharma..As a reminder (VX-135) is still on partial clinical hold by the FDA in the U.S.
**Clinical Trials @ HCV Advocate-Vertex
Prescribing and patient information, financial assistance, research and news
Sovaldi is approved in HCV genotypes 1 and 4, treatment-naïve adults in combination with PEG-IFN and ribavirin and the first approved interferon-free treatment regimen for people with HCV genotypes 2 and 3. Overall cure rates are at 80%, response rates and treatment duration varies, depending on genotype, viral and host factors.
Prescribing and patient information, articles and important updates
Johnson & Johnson's protease inhibitor OLYSIO (Simeprevir) is approved for the treatment of HCV genotype 1, in combination with peginterferon alfa and ribavirin in adults with compensated liver disease, including cirrhosis, who are treatment-naïve or who have failed previous interferon therapy (pegylated or non‑pegylated) with ribavirin.
'Mix-and-match` approach to new hepatitis C drugs
The European Association for the Study of the Liver has issued new guidelines for the treatment of hepatitis C which recommend that wherever possible, patients should be treated with the newest direct-acting antivirals.
EASL is also encouraging European physicians to combine products from different pharmaceutical companies to achieve the most potent interferon-free regimens, often in advance of full phase III trial data, in its new hepatitis C treatment guidelines issued in April at the International Liver Congress in London.
Lucinda K. Porter, RN, the author of "Free from Hepatitis C" has graced the HCV community with a second book "Hepatitis C Treatment One Step at a Time" available now on Amazon.
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