Efficacy and Safety of Oral PCSK9 Inhibitors in Adults With Hypercholesterolemia: An Updated and GRADE Assessed Systematic Review and Meta-Analysis of Randomised Controlled Trials.
Muhammad Huzaifa Khattak, Sohana Memon, Humaira Bibi et al.
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In 30 seconds
This systematic review and random-effects meta-analysis assessed oral PCSK9 inhibitors versus placebo in adults with hypercholesterolemia. It included five randomised controlled trials with 4268 participants. Treatment was associated with lower LDL-C (MD -49.49 mg/dL; 95% CI -54.81 to -44.18; p < 0.00001) and triglycerides (MD -11.65 mg/dL; 95% CI -15.53 to -7.78; p < 0.00001), alongside reductions in several other lipid measures. Overall adverse events and mortality did not differ significantly; discontinuation due to adverse events was lower with treatment.
Key findings
- LDL-C was lower with oral PCSK9 inhibitors (MD -49.49 mg/dL; 95% CI -54.81 to -44.18; p < 0.00001).
- Triglycerides were reduced (MD -11.65 mg/dL; 95% CI -15.53 to -7.78; p < 0.00001).
- Non-HDL cholesterol, apolipoprotein B, lipoprotein(a), and total cholesterol also decreased, with greater reductions at higher doses.
- Mortality and overall adverse events did not differ significantly; adverse-event-related discontinuation was lower with treatment.
Why it matters
The findings suggest oral PCSK9 inhibitors can improve several lipid measures in adults with hypercholesterolemia, with no detected increase in overall adverse events in the included trials. However, lipid changes are surrogate outcomes, and the evidence does not establish whether these agents reduce cardiovascular events or clarify their longer-term safety.
What to keep in mind
Evidence came primarily from short-term randomised trials assessing surrogate lipid outcomes; longer follow-up and cardiovascular outcome data were lacking.