Saturday, June 09, 2007
statines
Statins ‘well tolerated’ by most patients
8 June 2007
MedWire News: Statins are well tolerated in the majority of patients, according to a comprehensive review of their safety published in The Lancet.
The main adverse effects of statins on muscle – rhabdomyolysis and myopathy – are rare at standard doses and those on the liver are “unusual,” writes the review’s author Jane Armitage (University of Oxford, UK).
“For most people, statins are safe and well-tolerated, and their widespread use has the potential to have a major effect on the global burden of cardiovascular disease,” she concludes.
Armitage reports that collective results from large randomized controlled trials of statin therapy show that maintaining low cholesterol for at least 5 years is “not only safe but beneficial.”
Neither overall, nor in any individual trial, was there an increase in non-vascular deaths suggested by observational data, she writes.
Furthermore, a meta-analysis of 14 controlled statin trials including more than 90,000 patients revealed similar rates of non-vascular deaths in statin-treated versus control-treated patients (3.8% vs 4.0%). This applied both overall and for specific types of non-vascular death such as cancer, hepatic, or respiratory disease.
Three trials of standard-doses of statins (producing 30-45% reduction in LDL-cholesterol) with more extended follow-up have provided reassuring long-term safety information. Meanwhile trials so far of more intensive statin therapy have shown no adverse effect associated with sustained substantial reductions in LDL-cholesterol to below 2.0 mmol/l (77 mg/dl).
Armitage finds that all statins occasionally cause myopathy that can progress to rhabdomyolysis but says it is rare with standard doses, and, although it seems to increase with higher doses, remains very low with atorvastatin 80 mg.
She adds that both myopathy and rhabdomyolysis are usually reported in association with concomitant use of interacting drugs, especially fibrates.
Data from randomized trials do not indicate that statins are hepatoxic, and it is not clear whether cases of hepatitis and liver failure reported simultaneously with staitns are causally related or whether the risk is higher than background risk of sporadic liver failure.
Furthermore, the review indicates that only minor and non-significant numbers of patients with raised liver enzymes – specifically alanine or aspartate transaminases – have been reported in large randomized trials. These increases in transaminase are reversible with dose reduction, usually occurring in the first few months of randomization, and there is no convincing evidence that they are associated with liver damage.
In contrast to myopathy, the increased likelihood of raised transaminases with increasing doses of statin could be tied to the degree of cholesterol lowering, Armitage notes.
“With a few caveats, and while awaiting good-quality randomized data for the newer drugs, statins seem to be a remarkably safe group of drugs when used at their usual doses,” she concludes.
Lancet 2007; Advance online publication
© Copyright Current Medicine Group Ltd, 2006
8 June 2007
MedWire News: Statins are well tolerated in the majority of patients, according to a comprehensive review of their safety published in The Lancet.
The main adverse effects of statins on muscle – rhabdomyolysis and myopathy – are rare at standard doses and those on the liver are “unusual,” writes the review’s author Jane Armitage (University of Oxford, UK).
“For most people, statins are safe and well-tolerated, and their widespread use has the potential to have a major effect on the global burden of cardiovascular disease,” she concludes.
Armitage reports that collective results from large randomized controlled trials of statin therapy show that maintaining low cholesterol for at least 5 years is “not only safe but beneficial.”
Neither overall, nor in any individual trial, was there an increase in non-vascular deaths suggested by observational data, she writes.
Furthermore, a meta-analysis of 14 controlled statin trials including more than 90,000 patients revealed similar rates of non-vascular deaths in statin-treated versus control-treated patients (3.8% vs 4.0%). This applied both overall and for specific types of non-vascular death such as cancer, hepatic, or respiratory disease.
Three trials of standard-doses of statins (producing 30-45% reduction in LDL-cholesterol) with more extended follow-up have provided reassuring long-term safety information. Meanwhile trials so far of more intensive statin therapy have shown no adverse effect associated with sustained substantial reductions in LDL-cholesterol to below 2.0 mmol/l (77 mg/dl).
Armitage finds that all statins occasionally cause myopathy that can progress to rhabdomyolysis but says it is rare with standard doses, and, although it seems to increase with higher doses, remains very low with atorvastatin 80 mg.
She adds that both myopathy and rhabdomyolysis are usually reported in association with concomitant use of interacting drugs, especially fibrates.
Data from randomized trials do not indicate that statins are hepatoxic, and it is not clear whether cases of hepatitis and liver failure reported simultaneously with staitns are causally related or whether the risk is higher than background risk of sporadic liver failure.
Furthermore, the review indicates that only minor and non-significant numbers of patients with raised liver enzymes – specifically alanine or aspartate transaminases – have been reported in large randomized trials. These increases in transaminase are reversible with dose reduction, usually occurring in the first few months of randomization, and there is no convincing evidence that they are associated with liver damage.
In contrast to myopathy, the increased likelihood of raised transaminases with increasing doses of statin could be tied to the degree of cholesterol lowering, Armitage notes.
“With a few caveats, and while awaiting good-quality randomized data for the newer drugs, statins seem to be a remarkably safe group of drugs when used at their usual doses,” she concludes.
Lancet 2007; Advance online publication
© Copyright Current Medicine Group Ltd, 2006
# posted by roodbont @ 2:29 PM 
