Negative statin study labelled ‘irresponsible’

An Australian endocrinologist has called authors of a US study irresponsible for pedalling claims that statins provide no benefit for primary cardiovascular disease prevention in older patients.

Director of lipid services at the Austin Hospital in Melbourne, Professor Richard O’Brien has criticised the JAMA study widely publicised this week its ‘poor design’ and for using outdated treatment targets and drugs to reach its conclusions.

The post-hoc analysis of data from the almost 20-year old ALLHAT-LLT trial showed that pravastatin sodium at 40mg daily was not associated with any improvement over usual care for rates of coronary heart disease or all-cause mortality in patients over the age of 65.

The analysis found no statistically significant difference between the pravastatin and placebo groups in any of the outcomes measured.

There was a trend towards a decrease in heart attacks among people older than 75 and a non-significant trend towards higher all-cause mortality, the researchers say.

The authors speculate the effects of statins might be heterogeneous when used for primary prevention in the elderly.

“Elevated lipid levels are less predictive of cardiovascular risk with increasing age and low lipid levels in the oldest adults usually correlate with increased mortality,” they said.

“The use of statins may be producing untoward effects in the function or health of older adults that could offset any possible cardiovascular benefit,” they concluded.

But Professor O’Brien argues that the 17% reduction in LDL cholesterol seen in study patients on statins was ‘very inadequate’ given current guidelines recommend that statin therapy should achieve a minimum LDL reduction of 30% to be effective.

The treatment effect was also likely to be ‘a big dilution’ because people in the trial could be treated with a statin if their doctor wished – and many were, including in the placebo group.

He added that pravastatin was also an older drug that was no longer commonly used.

“A small difference in LDL cholesterol means the expected reduction in heart attacks and deaths from heart attack will be small.

Under these circumstances, it only takes a few excess deaths from other causes in the treatment group, and of course deaths are common in an elderly population, to confound the results and make it appear as if the drug has caused harm,” he said in an interview.

Adding to this, the trial was open label – doctors and patients knew what they were taking which could have led to treatment bias, he said.

“Doctors may treat their patients differently, perhaps not being as aggressive at treating other heart risk factors, if they know the person is taking a statin.”

Professor O’Brien also takes aim at an accompanying editorial by Gregory Curfman, which suggests the findings may be of concern and cites other potential problems with statins including multiple musculoskeletal problems and memory disturbance.

“The paper he cites on musculoskeletal problems has been criticised in the literature for its methodology … I am [also] unsure why he believes there are problems with cognitive function [because he includes no reference].  Large studies using statins and other cholesterol lowering agents, treating patients to very low cholesterol levels, have been totally reassuring in this respect.”

He says while studies with newer statins in elderly people without established cardiovascular disease are yet to demonstrate reductions in mortality they have shown ‘substantial’ reductions in heart attack and stroke, which can improve a person’s quality of life.

“A more responsible conclusion from this study is that statin therapy in older people without previous heart disease is unlikely to prolong life, but may reduce heart attack and stroke risk. Therefore, whether or not to take a statin may depend on a patient’s individual philosophy, and should be a choice a person takes after discussion with their doctor.”

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