Leuven, Belgium—Patients with high levels of LDL cholesterol who are at elevated risk of heart disease should be offered additional cholesterol-lowering drugs, such as ezetimibe and proprotein convertase subtilisin/kexin 9 (PCSK9) inhibitors, an international panel recommends.

This is according to an article in The BMJ, where experts from more than a dozen countries, including the United States, say their advice is for patients with LDL of 70 mg/dL or higher who are already taking the maximum dose of statins or are intolerant to statins.

The guidelines were a result of The BMJ's "Rapid Recommendations" initiative, which seeks to produce rapid and trustworthy guidance based on new evidence. The advice is a shift from current guidelines which prioritize lowering cholesterol levels because it focuses on reducing a patient's overall cardiovascular risk.

In addition to questioning whether another lipid-lowering drug should be added—either a PCSK9 inhibitor or ezetimibe—to reduce the risk of major cardiovascular events, the panel also looked at the issue of which drug is preferred and whether the other lipid-lowering drug should be added (if it was decided to use one).

In current practice, according to the study, LDL cholesterol targets are used to determine whether PCSK9 inhibitors and/or ezetimibe should be prescribed in adults at high risk of experiencing a major adverse cardiovascular event.

"However, to achieve these goals in very high-risk patients with statins alone is almost impossible, so physicians are increasingly considering other lipid-lowering drugs solely for achieving LDL cholesterol treatment goals rather than for achieving important absolute cardiovascular risk reduction," the panel noted. "Most guidelines do not systematically assess the cardiovascular benefits of adding PCSK9 inhibitors and/or ezetimibe for all risk groups across primary and secondary prevention, nor do they report, in accordance with explicit judgments of assumed patients' values and preferences, absolute benefits and harms and potential treatment burdens."

In explaining why the recommendations were mostly "weak," the panel said they relied on shared decision-making with patients. For adults already using statins, the group suggested adding a second lipid-lowering drug for those at very high and high cardiovascular risks but not for those at lower risk. Adults who are intolerant to statins should use a lipid-lowering drug if they are at very high and high cardiovascular risk but not if they are at lower cardiovascular risk, the panel added.

The recommendations advised clinicians to use ezetimibe in preference to PCSK9 inhibitors, although they counseled that a PCSK9 inhibitor should be added to ezetimibe for adults already taking statins at a very high risk and those at very high and high risk who are intolerant to statins.

Among the reasons for preferring ezetimibe is that PCSK9 inhibitors require injections that sometimes result in injection-site reactions and are more expensive than ezetimibe and statins, according to the study.

The recommendations take into account new evidence from 14 trials involving 83,660 patients. Those trials suggested that ezetimibe and PCSK9 inhibitors reduce heart attacks and strokes in patients with very high and high cardiovascular risk but not in patients with moderate and low cardiovascular risk.

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