There is not enough evidence that statins, a class of drugs that lowers blood cholesterol, benefit patients at low risk of cardiovascular disease, and doctors should be cautious about prescribing them to this group, according to a new Cochrane Systematic Review.

Lead researcher Fiona Taylor, from the Cochrane Heart Group at the London School of Hygiene and Tropical Medicine in London, UK, said in a press statement that their review points out important shortcomings in the evidence about how statins affect people with no history of cardiovascular disease:

“The decision to prescribe statins in this group should not be taken lightly,” she added.

Nearly a third of deaths worldwide are due to cardiovascular disease, which is also the most common cause of death globally.

The researchers noted that statins, drugs that lower cholesterol by blocking the action of the enzyme HMG-CoA reductase in the liver that is necessary for making cholesterol, are first line treatments for heart patients and for this group the benefits are well established.

However, they say there is less evidence that statins help prevent heart problems in people with no history of cardiovascular disease and given there is evidence that low cholesterol can raise risk of death from other causes, the risks of giving statins to this group of patients may outweigh the benefits.

For their research, Taylor and colleagues reviewed evidence from 14 randomized controlled trials involving more than 34,000 patients that compared results from subjects given statins to those of subjects who had placebos or usual care.

Eight of the trials covered over 28,000 patients, and provided data on deaths from all causes. Pooled data from these showed that statins reduced risk of dying from 9 to 8 deaths per 1,000 people treated with statins every year. They showed statins also reduced fatal and non-fatal events, including heart attack, stroke and revascularization surgery, in addition to blood cholesterol levels.

But, Taylor and colleagues said they were impeded from drawing clear conclusions because of shortcomings in the reporting of the studies. They recommend that doctors give careful consideration to patients’ individual risk profiles before prescribing statins.

Taylor said:

“It is not as simple as just extrapolating the effects from studies in people who have a history of heart disease“.

The reviewers highlighted that all but one of the trials they reviewed was sponsored by industry:

“We know that industry-sponsored trials are more likely to report favourable results for drugs versus placebos, so we have to be cautious about interpreting these results,” said Taylor.

“The numbers eligible for treatment with statins are potentially great so there might be motivations, for instance, to stop trials earlier if interim results support their use,” she added.

Among the reviewers’ other concerns, reported by MedPage Today, were:

  • 8 of the 14 trials reviewed did not report on adverse events.
  • More than a third of the studies reported “selective rather than intent-to-treat outcomes”.
  • Two of the larger trials stopped early, when benefits may have been overestimated.
  • The subjects were mostly white, male and middle-aged, so the results may not apply to other groups such as females and the elderly.

They commented in their conclusions that any trials testing the benefit of using statins as a preventive measure are going to show better outcomes if they are influenced by “various biases” rather than “a real effect”.

The review has drawn criticism from other experts. For example, some cardiologists contacted by MedPage Today and ABC News said that while the reviewers’ concerns may be valid, they have missed the “big picture of clear benefit for primary prevention”.

Others point to the fact the review didn’t include the JUPITER trial that led to the first and only drug to be approved by the US Food and Drug Administration (FDA) for preventive use. The reason it wasn’t included was because the trial hadn’t finished by 2007, the cut-off date of the review.

The American Heart Association (AHA) guidelines now include statins as having a role in primary prevention. If lifestyle changes don’t work in reducing cholesterol in low risk patients, then the AHA guidelines suggest statins may help bring it down and reduce the risk of heart attack, stroke or vascular death, Ralph Sacco, president of the AHA told MedPage Today.

Cochrane Reviews

Sources: Wiley-Blackwell (press release, 18 Jan 2011), MedPage Today (Crystal Phend, “Review Questions Statins for Low-Risk People”, 18 Jan 2011).

Written by: Catharine Paddock, PhD