The new guideline, issued by a panel of international experts and patients and published in The BMJ, was developed based on a systematic review and meta-analysis of 14 trials involving close to 84,000 patients. The recommendations are for adults who are receiving high doses of or are intolerant to statins with LDL cholesterol levels over 70 mg/dL, and who are considering newer lipid-lowering drugs to reduce cardiovascular risk.
Patients are categorized based on their risk of experiencing a MACE within five years: low (<5%); moderate (5%-15%); high (15%-20%); and very high (>20%).
"The choice to start these drugs...should be made based on risk of cardiovascular disease, and not on LDL-cholesterol threshold levels as proposed in some other guidelines," Dr. Nicolas Delvaux of KU Leuven in Belgium, told Reuters Health by email. "Using LDL-cholesterol levels to guide treatment decisions probably appeals more to physicians because this is easy to measure and monitor, but steers the attention away from what really matters to patients - the effect these drugs can have on the risk of heart attacks and stroke."
The evidence showed that both ezetimibe and PCSK9 inhibitors "probably" reduce heart attacks and strokes in patients at very high and high cardiovascular risk, but not in those at moderate and low cardiovascular risk.
Although the relative benefits were consistent, their absolute magnitude varied based on cardiovascular risk in individual patients. For example, for 1,000 people treated with PCSK9 inhibitors in addition to statins over five years, benefits ranged from two fewer strokes in the lowest risk to 21 fewer in the highest risk.
Two systematic reviews on potential harms found no important adverse events; however, PCSK9 may result in injection-site reactions (best estimate: 15 more per 1,000 in a five-year timeframe).
PCSK9 inhibitors are also more expensive than ezetimibe and statins, and are therefore are favored by the panel.
Overall, the guideline states, "Their comparative effectiveness - with absolute benefits carefully weighed against burdens and harms - should therefore inform clinicians and their patients whether and when they should consider adding ezetimibe or a PCSK9 inhibitor to reduce cardiovascular risk."
Dr. Delvaux added, "Use decision aids to discuss the anticipated effects a treatment can have on outcomes that matter to the patient considering these drugs. These decision aids are available through The BMJ website and allow a physician to discuss the potential benefits and harms of ezetimibe and/or PCSK-9 inhibitors based on their cardiovascular risk."
"A limitation to implementing this guideline is that every country has their specific tool to calculate cardiovascular risk, and the results from these tools may not always be consistent with the risk categories that we defined in these recommendations," he acknowledged.
"However," he said, "we do believe that it is possible to use our risk estimates in most cases and that the decision aids should prove useful in the discussion of the potential effects of treatment for an individual patient."
"Our goal is not that all patients with a high risk of cardiovascular should be taking these novel drugs, but that the choice to start these drugs should be driven by the effects it can have on cardiovascular risk and not on LDL-cholesterol levels," Dr. Delvaux concluded
Dr. Kulpreet Barn, Director of the Advanced Heart Failure Program at Deborah Heart and Lung Center in Browns Mills, New Jersey, said he agrees with the new guideline, noting that while "PCSK9s will be a great addition to the armamentarium in treatment of coronary artery disease, we have to be careful in selecting high risk patients where this drug is of benefit in addition to traditional treatments."
SOURCE: https://bit.ly/39FUqQM The BMJ, online May 4, 2022.
By Marilynn Larkin
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