Atherosclerotic CVD: efficacy and safety of alirocumab and evolocumab

Takeaway

• In patients with hyperlipidaemia and atherosclerotic cardiovascular disease (ASCVD), alirocumab and evolocumab were associated with a lower risk for myocardial infarction (MI), stroke and coronary revascularisation with favourable safety profile.

Why this matters

• Findings support the use of proprotein convertase subtilisin-kexin type 9 (PCSK9) inhibitors in clinical practice to reduce the residual ASCVD risk or low-density lipoprotein-cholesterol (LDL-C) level in patients who cannot tolerate statin therapy.

Study design

• 39 randomised controlled trials (RCTs; n=66,478) that compared the effects of PCSK9 inhibitors (14,639, alirocumab; 21,257, evolocumab) vs control group (n=30,582) in patients with hyperlipidaemia and ASCVD were identified.
• Funding: None disclosed.

Key results

• PCSK9 inhibitors vs control group were associated with a lower risk for:
  • MI (risk ratio [RR], 0.80; 95% CI, 0.74-0.86; P<.0001),
  • ischaemic stroke (RR, 0.78; 95% CI, 0.67-0.89; P=.0005) and
  • coronary revascularisation (RR, 0.83; 95% CI, 0.78-0.89; P<.0001).
• PCSK9 inhibitors vs control group did not differ in the risk for all-cause (P=.15) and cardiovascular (P=.34) mortality.
• Compared with the control group, PCSK9 inhibitors were not associated with an increased risk for:
  • neurocognitive adverse events (P=.91),
  • liver enzymes elevations (P=.34),
  • allergic reactions (P=.29),
  • haemorrhagic stroke (P=.68),
  • rhabdomyolysis (P=.58) and
  • new-onset diabetes mellitus (P=.97).

Limitations

• Time-to-event analyses not performed to evaluate the efficacy and safety of PCSK9 inhibition across different levels of baseline patient risk.