Statin combination therapies reduce LDL cholesterol at least as well as high-intensity statins
Patients at high risk of atherosclerotic cardiovascular disease respond just as well to certain statin combination therapies as they do to high-intensity statin monotherapy in terms of LDL cholesterol reduction, US researchers say in a paper published yesterday (Annals of Internal Medicine online 11 February 2014). Combination therapy could therefore be considered for patients who cannot tolerate or who do not respond to high-intensity statins, they conclude.
Sotiris Antoniou, consultant pharmacist in cardiovascular medicine at Barts Health NHS Trust, pointed out that current UK clinical guidance recommends prescribing a high-intensity statin for anyone admitted to hospital with an acute cardiovascular event. This strategy creates a “clinical conundrum” for high-risk patients who cannot tolerate higher intensity statins because of adverse effects or who have a poor response to statins, he said. “This study tries to address that by highlighting that combination therapy provides similar or better LDL reduction than high-intensity statin. However, as the authors point out, the data are not supported by outcomes such as improved mortality,” he added.
After reviewing 36 randomised controlled trials the researchers conclude that combination therapy with a lower-intensity statin and either a bile acid sequestrant or ezetimibe could be effective alternatives to high-intensity statin monotherapy.
The pooled results from five trials indicate that a low-dose statin combined with a bile acid sequestrant reduced levels of LDL cholesterol by 0–14 per cent more than a mid-intensity statin alone. If this combination is chosen, the researchers suggest that patients are advised to separate drug administration to maximise the effect of each medicine.
For combination therapy with ezetimibe, the evidence consisted of data from twelve trials that indicated that a mid-intensity statin combined with ezetimibe reduced LDL cholesterol 5–15 per cent more than a high-intensity statin alone. However, the researchers point out some limitations of the data; the trials did not specifically examine patients with statin intolerance and many of these patients were excluded. Furthermore, they point out that the trials were short so long-term outcomes from combination therapy cannot be assessed.
Finally, the researchers report that there was insufficient evidence to support combination therapy with a fibrate, niacin or omega-3 fatty acids.
The researchers point out that up to 14 per cent of patients either have no response to statin therapy or an inadequate response and that statin users have a 50 per cent greater adjusted odds of reporting musculoskeletal pain than non-statin users.
PCSK9 inhibitors in the pipeline
Mr Antoniou revealed that there is a new class of cardiovascular medicines in the pipeline. He told PJ Online: “Fortunately, an alternative approach may be on the horizon with the development of PCSK9 inhibitors (proprotein convertase subtilisin kexin type 9 inhibitor) that boost recycling of the LDL receptors and allow them to move more cholesterol out of circulation, with early studies showing promising results in reducing LDLs by over 50 per cent.” He added that outcome studies are under way and that the results are eagerly awaited.
Citation: The Pharmaceutical Journal DOI: 10.1211/PJ.2014.11134263
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