Stepping up the intensity of statin therapy can reduce the rate of major vascular events such as heart attack and ischaemic stroke by an extra 15%, a meta-analysis by researchers from the UK and Australia has found.

The results of the study by members of the Cholesterol Treatment Trialists’ Collaboration from the Clinical Trial Service Unit and Epidemiological Studies Unit at the University of Oxford and the National Health and Medical Research Council Clinical Trial Centre at the University of Sydney were published in The Lancet.

They suggest “that the primary goal for patients at high risk of occlusive vascular events should be to achieve the largest LDL cholesterol reduction possible without materially increasing myopathy risk”, the authors commented.

The meta-analysis took in data from five trials involving 39,612 patients who were on more or less intensive statin regimens and from 21 trials involving 129,526 patients who were taking statins or were in control groups (placebo or usual care).

In the trials of more versus less intensive statin therapy, the weighted mean extra reduction in LDL cholesterol at one year on the more intensive regimens was 0.51 mmol/L. 

That translated, the researchers reported, into a “highly significant” 15% further reduction in major vascular events, comprising 13% fewer coronary deaths or non-fatal myocardial infarctions, 19% fewer coronary revascularisations and 16% fewer ischaemic strokes.

For each 1.0 mmol/L cut in LDL cholesterol, the further reductions in risk were similar to the proportional reductions observed in the statin versus control trials.

When all 26 trials were combined, similar proportional reductions in major vascular events per 1.0 mmol/L decrease in LDL cholesterol were found in all types of patients studied, including those with LDL cholesterol under 2 mmol/L who were on less intensive statin or control regimens.

All-cause mortality in the combined trials was reduced by 10% per 1.0 mmol/L reduction in LDL cholesterol, largely reflecting significantly fewer deaths due to coronary heart disease and other cardiac causes but no significant effect on deaths due to stroke or other vascular causes, the authors noted.

Safe further reductions

Further reductions in LDL cholesterol using statin therapy can safely produce “definite further reductions” in the incidence of heart attack, revascularisation and ischaemic stroke, with each 1.0 mmol/L decrease lowering the annual rate of these major vascular events by just over a fifth, they concluded.

There was no evidence of any threshold within the cholesterol range studied, suggesting that cutting LDL cholesterol by 2-3 mmol/L would reduce risk by 40-50%, the researchers added.

Current therapeutic guidelines on cholesterol levels tend to emphasise the need to reach a particular LDL target, the authors pointed out. By contrast, “our results suggest that lowering of LDL cholesterol further in high-risk patients who achieve such targets would produce additional benefits, without an increased risk of cancer or non-vascular mortality”.

Some guidelines have proposed using high doses of generic statins (e.g., 80mg simvastatin daily) for this purpose, but these regimens may be associated with a higher risk of myopathy, the researchers cautioned.

Instead, they suggested relying on newer, more potent statins (e.g., 80mg atorvastatin or 20mg rosuvastatin daily) and, potentially, combining standard doses of generic statins (e.g., 40mg simvastatin or pravastatin daily) with other LDL cholesterol-lowering therapies.