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  STATINS

Oxford, UK - New data from an individual patient meta-analysis of 27 large statin trials shows that statin treatment is clearly beneficial in much lower-risk patients than are currently recommended for such therapy in most guidelines [1].

And authors of an accompanying comment suggest that with this new data, everyone over 50 should now be eligible for statin treatment.

The meta-analysis, published online May 16, 2012 in the Lancet, was conducted by the Cholesterol Treatment Trialists' (CTT) Collaborators. They analyzed data from 175 000 individuals and grouped participants into five baseline categories of cardiovascular risk. Outcomes were studied in trials comparing statin with no statin treatment and of more vs less intensive statin regimens.

Results showed that statins reduced the risk of serious vascular events by around 21% for each 1-mmol/L reduction in LDL cholesterol in each of the five baseline risk groups, including those people with the lowest risk of vascular disease.

One of the senior authors on the paper, Prof Colin Baigent (Clinical Trial Service Unit, Oxford, UK), commented to heartwire: "Last year Cochrane published a review of statins in primary prevention that was somewhat unclear in its conclusions. They showed that although there was a clear reduction in mortality with statins, they were uncertain about adverse effects. We wanted to clarify the situation, so we looked at all the available individual patient data from all trials that included low-risk patients. As well as all the primary-prevention trials, these include some trials where both primary- and secondary-prevention patients were included, such as the Heart Protection Study. This was a much more thorough analysis than the Cochrane review, which only had access to the overall trial results."

Baigent continued: "We found the relative reduction in risk of cardiovascular events with a statin is just as good in the lowest-risk group as in higher-risk groups. Even in the very lowest-risk group studied (those with a risk below 10% in 10 years), the benefits greatly exceeded the harms."

"Half of cardiac deaths happen in people who have not previously had heart disease, so there is a limit to what can be achieved just with secondary prevention. So primary prevention is obviously needed. The question is where we set the threshold. And our data suggest this should be lowered to a risk of 10% over 10 years."

Baigent believes the decision on whether to take a statin needs to be made on the basis of risk of the patient rather than on their cholesterol level. "Typically, at the moment, the public and many doctors think that statins are necessary only if a patient has high cholesterol. But the preferable view would be that a statin is needed if you are at any increased risk of heart disease."

He added that everyone is supposed to have a vascular check in middle age, and the current recommendation in the UK is that if they are found to have a risk of a cardiovascular event of more than 20% over 10 years they should be offered a statin. "But we found in this current meta-analysis that the benefits of statins are still obvious at a risk level of 10% over 10 years, and even below that."

At present in the UK, five million patients take statins, and another five million are eligible to take them but are not receiving them, Baigent reported. "If the threshold were reduced to a cardiac risk of 10% over 10 years, an additional five million people would be eligible to receive these drugs. Simvastatin is off patent and atorvastatin is now coming off patent, so this will not be an expensive exercise. It is right and proper that there is an assessment of safety, but we have now done that and shown the benefits to greatly outweigh the risks. If the threshold were lowered to 10%, we could avoid 10 000 events, including 2000 deaths every year."

Asked if everyone should just receive a statin at a certain age, Baigent said this was one possibility. "It is up to the guidelines committees to decide on the strategy. We have called for NICE to reconsider the threshold they recommend for statin treatment. All we are saying is that we should at least treat everyone with a risk of 10% or more over 10 years. But we actually showed benefit in patients with a lower risk than this. People can be educated about risk. Everybody knows their age and if they are overweight, smoke, or don't exercise enough. It's not difficult to find out your cholesterol, blood pressure, family history, or whether you are diabetic. These things then should then trigger the thought that you might be able to benefit from a statin."

In the comment article, Drs Shah Ebrahim and Juan P Casas (London School of Hygiene and Tropical Medicine, UK) suggest that as most people older than 50 years are likely to be at a >10% 10-year risk of a cardiovascular event, it would be more pragmatic to use age as the only indicator for statin prescription, which would avoid the costs of vascular screening checks.

Major results for the new meta-analysis showed that statin treatment reduced the risk of major vascular events by 21% per 1.0-mmol/L reduction in LDL, and this was largely irrespective of age, sex, baseline LDL cholesterol, previous vascular disease, and baseline cardiovascular risk. The proportional reduction in major vascular events was at least as big in the two lowest-risk categories as in the higher-risk categories.

There was no evidence that reduction of LDL cholesterol with a statin increased cancer incidence (RR per 1.0-mmol/L LDL-cholesterol reduction 1.00, 95% CI 0.96-1.04), cancer mortality (RR 0.99, 95% CI 0.93-1.06), or other nonvascular mortality.

In terms of side effects, the data show that there was a small increased risk of myopathy (excess incidence of about 0.5 per 1000 over five years) and rhabdomyolysis (excess incidence of about 0.1 per 1000 over five years). There was also an increase of hemorrhagic strokes per 1.0-mmol/L LDL-cholesterol reduction of about 0.5 per 1000 people treated over five years. But the authors write that "this was outweighed by the reduction in ischemic stroke (as well as the reduction in other occlusive vascular events and deaths) even in individuals whose five-year risk of major vascular events is lower than 5%."

They also report an absolute excess of diabetes associated with statin treatment of about 0.1% per year. But they estimate that the increased risk of cardiovascular events associated with this excess in diabetes is more than 50 times smaller than the absolute benefit observed with statin therapy in low-risk patients.