Suspicions over statin status


Giving over-65s a statin to help prevent heart attack and death may not be useful, new research suggests—but one expert disagrees

A new study published by JAMA Internal Medicine analysed an older subgroup of people in a previous study on adults with high blood pressure.

The new analysis showed no benefit of a statin for all-cause mortality or coronary heart disease events when a statin was started for primary prevention in older adults with hypertension and moderately high cholesterol.

While many older patients take statins for primary cardiovascular prevention, data are limited on the risks and benefits of statins for primary prevention in this age group. Improving the understanding of preventive interventions in older patients has implications for health care and its costs.

Benjamin H. Han, of the New York University School of Medicine, and coauthors analysed data from older adults in the Lipid-Lowering Trial (LLT) component of the Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial (ALLHAT-LLT), which was conducted from 1994 to 2002.

The authors used an analytical sample that included 2,867 adults with hypertension but without baseline atherosclerotic cardiovascular disease.

Of the 2,867 adults, 1,467 were in the pravastatin sodium group (40 mg per day) and 1,400 received usual care from their primary care physician to lower cholesterol.

The authors report no benefit of pravastatin for the main outcome of all-cause mortality or secondary outcomes of coronary heart disease events and cause-specific mortality.

More deaths occurred in the pravastatin group than in the usual care group (141 compared to 130) among adults 65 to 74, and among adults 75 and older (92 deaths versus. 65).

There were 76 CHD events in the pravastatin group compared with 89 in the usual care group among adults 65 to 74, and 31 CHD events compared with 39 among adults 75 and older, the results show.

Stroke, heart failure and cancer rates were similar in the two treatment groups for both age groups.

The authors noted that the current study had limitations including its design as a post hoc secondary analysis of a trial of a subgroup of patients.

“No benefit was found when a statin was given for primary prevention to older adults. Treatment recommendations should be individualized for this population,” the article concludes.

But further limitations have been pointed out by Professor Richard O’Brien, clinical dean of medicine at the Austin Clinical School at the University of Melbourne, and director of Lipid Services at the Austin Hospital.

“The drug used was pravastatin, a weak and older statin not commonly used today,” he pointed out.

“The trial was open label – the doctors and patients knew what they were taking. This is a potential source of bias as 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.

“People in the trial could be treated with a statin if their doctor wished, and many were, including in the ‘placebo’ group.

“This led to a big dilution in the effect of the study treatment, so that the difference in LDL ‘bad cholesterol’ was only 17%. 

“This would be considered very inadequate today: guidelines suggest that effective statin therapy should achieve a minimum LDL reduction of 30%.”

Prof O’Brien says that 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 says.

“Studies with newer statins have demonstrated substantial reductions in heart attack and stroke in elderly people without cardiovascular disease, but not reductions in mortality. 

“Preventing a non-fatal heart attack or stroke in an elderly person may dramatically improve potential quality of life, even if it does not prolong life. Statins have been shown to achieve this.”

Prof O’Brien also criticises an accompanying editorial in JAMA Internal Medicine by Gregory Curfman, which suggests the analysis data could indicate concerns including multiple musculoskeletal problems and memory disturbance.

“This is incorrect. The paper he cites on musculoskeletal problems has been criticized in the literature for its methodology, and I am unsure why he believes there are problems with cognitive function (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.
 
“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.”

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