The lipid lowering efficacy of PCSK9 inhibitors alone vs. statins alone: a meta-analysis

Background PCSK9 inhibitors (PCSK9is) have been developed as an add-on therapy to maximally tolerated statin therapy. To date, high prices have precluded their use as first-line agents but, in the near future, PCSK9is will go off patent protection, reducing cost barriers and making them first-line agent candidates before statins. This study's objective was to evaluate the lipid lowering efficacy of PCSK9i monotherapy compared with high intensity statin monotherapy as a first line agent. Methods This meta-analysis adhered to PRISMA guidelines. A systematic literature review identified all RCTs of: 1) PCSK9i vs. control in which data were available on a patient subgroup receiving PCSK9i monotherapy (predominantly due to total statin intolerance); and 2) high-intensity statins vs. control, with high-intensity statins defined as atorvastatin 40 or 80 mg daily or rosuvastatin 20 or 40 mg daily. The primary outcome was mean percent change in serum low density lipoprotein cholesterol (LDL-C). Secondary outcomes evaluated high density lipoprotein cholesterol (HDL-C), total cholesterol (TC), triglycerides (TG), and apolipoprotein B (ApoB). Results Five trials (766 patients) were identified for PCSK9is and 49 trials (19,603 patients) for statins. The mean age (±SD) was 57.5 ± 5.1 years in PCSK9i trials and 60.2 ± 2.3 years in statin trials, with a higher proportion of women enrolled in the PCSK9i group (54.3% vs. 39.9%). Compared to all high-intensity statin regimens combined, PCSK9is showed significantly greater reductions in LDL-C (−52.4% vs. −46.6%, p = 0.03), ApoB (−43.3% vs. −32.8%, p = 0.004), and increases in HDL-C (8.0% vs. 4.4%, p = 0.02). Statin agent subgroup analysis found PCSK9is were superior to atorvastatin and comparable to rosuvastatin in increasing HDL-C and reducing LDL-C, ApoB, and TC, and inferior to atorvastatin and rosuvastatin in reducing TG. Conclusions PCSK9i monotherapy is superior to atorvastatin and comparable to rosuvastatin in improving LDL-C, HDL-C, TC, and ApoB, though inferior in reducing TG. These findings confirm that PCSK9is are currently highly useful second-line agents in patients with total statin intolerance and in the near future, after expiration of patent protection, will be useful first line agents for hyperlipidemia.