5MinuteConsult Journal Club

PCSK9 Inhibitors are Equally Effective… But are they Better than Just a Statin?

Reference

Heart 2022 Jan; 108:14. (https://doi.org/10.1136/heartjnl-2021-319629

Study Summary

This systematic review evaluated 18 trials (>60,000 high risk patients) of the PCSK9 inhibitors alirocumab and evolocumab vs each other (assuming all patients were on a statin with or without ezetimibe) on total cardiovascular disease (CVD) events (urgent coronary revascularization, unstable angina, myocardial infarction, stroke, and coronary heart disease death), all-cause mortality, myocardial infarction, and stroke. A secondary analysis of a smaller number of studies compared PCSK9 inhibitor vs statin/ezetimibe.

Outcomes

When compared to placebo, statistically significant odds ratios for alirocumab and evolocumab were: 0.87 and 0.84 for total CVD events; 0.86 and 0.72 for myocardial infarction; and 0.73 and 0.79 for stroke respectively. For all-cause mortality, odds for alirocumab 0.83 which was significant, but for evolocumab the odds ratio was 1.04 and not significant. In all the categories, the absolute risk reduction was between 1-2%.

In 6 trials, PCSK9 inhibitors vs. with statin ± ezetimibe was evaluated; these were considered low-quality. The odds ratios and absolute risk reductions were not significant, but because of their quality, it was determined no conclusion could be made about their efficacy.

Conclusion

Adding PCSK9 monoclonal antibodies to statins plus/minus ezetimibe reduces cardiovascular outcomes and sometimes mortality. There is insufficient data to state they are more effective than statins plus/minus ezetimibe.

Discussion

This paper provides a wealth of information… but nothing clinically useful. Yes, PCSK9 inhibitors, when combined with statins plus/minus ezetimibe, lower cardiovascular outcomes. But are they better than just statins? We don’t know this from the papers included here.

Publication bias occurs when the available data for analysis is not all the research on a subject. The motivation to NOT publish is great when you have results that don’t support your hypothesis, or your drug development and marketing. There were likely well-done studies comparing PCSK9 + statins vs statins alone. But the Cochrane, a diligent searcher for all the data, could not find it. So, based upon the best, current data, there is no known benefit of PCSK9 inhibitors over statins alone.

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