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Additional cholesterol-lowering drugs should be offered to patients with high levels of "bad" (LDL) cholesterol (70 mg/dL or higher), an international panel of experts and patients in the BMJ They are also at high risk for heart disease
The drugs evaluated by the panel were ezetimibe and PCSK9 inhibitors
These recommendations apply to adults already taking maximum doses of statins or those who cannot tolerate statins and the BMJ's "Rapid Recommendations" program - based on new evidence to produce fast and trustworthy guidance to help physicians and patients make better decisions
The panel considered the benefits to balance the burden and potential harms of starting a new drug based on a patient's risk level, values and preferences, and their recommendations represent a shift from a traditional focus on lowering cholesterol levels to a focus on reducing an individual's overall cardiovascular risk
New evidence from 14 trials involving 83,660 patients suggests that ezetimibe and PCSK9 inhibitors may reduce heart attack and stroke in very high and high cardiovascular risk patients, but not in intermediate and low cardiovascular risk patients
These relative benefits are consistent, but their absolute magnitude varies based on individual patient cardiovascular risk (eg, for 1000 people treated with PCSK9 inhibitors in addition to statins over five years, benefits ranged from 2 to the lowest risk of stroke reduction up to less than 21)
No significant side effects were found, although PCSK9 inhibitors require injections and sometimes lead to injection site reactions, which experts say are a burden and harm that could affect patients
PCSK9 inhibitors are also more expensive than ezetimibe and statins
Therefore, the panel favored ezetimibe over PCSK9 inhibitors, but stated that "both inhibitors would provide important benefits for adults in high-risk and very high-risk groups, but little benefit for adults in low-risk groups
The panel acknowledged some uncertainty in the evidence for this guideline, noting that clinicians need to identify patients' individual cardiovascular risk to apply these risk stratification recommendations
They said their recommendations could change as new evidence emerges