Efficacy of PCSK9 inhibitors on remnant cholesterol and lipid residual risk in real-world patients: Results from the LIPID-REAL registry

Treatment with proprotein convertase subtilisin/kexin type 9 inhibitors (PCSK9i) showed significant improvement in the lipid profile beyond substantial reduction in low-density lipoprotein cholesterol (LDLc) levels, which might help in strengthening the benefit of PCSK9i in patients with high or very high cardiovascular (CV) risk.

Key Takeaway

  • This multicenter, retrospective, observational study assessed the effect of PCSK9i on lipid residual risk and showed:
    • Significant improvement in the lipid profile, including cholesterol remnants (P = 0.017), triglycerides/high-density lipoprotein cholesterol (TG/HDL) ratio (P = 0.020), total cholesterol/HDLc (TC/HDL) ratio (P <0.001), and triglycerides-to-glucose index (TGGi; P <0.001), in addition to considerable reduction in LDLc levels (P <0.001)
    • Only 2.14% of patients reported side effects
  • These findings might assist in strengthening the benefits of PCSK9i therapy in individuals with high or very high CV risk.

Why This Matters

  • Residual risk is linked with numerous lipoproteins including remnants of cholesterol, very LDL or small and dense LDL. In addition, low levels of high-density lipoprotein cholesterol (HDLc), cholesterol remnants, or TG/HDL have been identified as crucial predictors of coronary heart disease rather than LDLc.
  • This study assessed the efficacy of PCSK9i on lipid residual risk in real-world settings.

Study Design

  • A multicenter, retrospective, observational study of real-world patients treated with PCSK9i from 18 different hospitals in Spain.
  • Lipid parameters were measured before and during PCSK9i therapy. All samples were obtained after overnight fasting.
  • The following parameters were used to calculate lipid residual risk: (i) Cholesterol remnants, (ii) TG/HDL, (iii) TC/HDL, and (iv) TGGi.

Key Results

  • Overall, 652 patients treated with PCSK9i were included in this study.
    • Age (years)* = 60.21 (9.63); women† = 161 (24.69)
    • Patients receiving statin plus ezetimibe before initiating PSCK9i‡ = 49.11
    • Use of PCSK9i†: i) Evolocumab = 394 (60.43); ii) alirocumab = 258 (39.57) (alirocumab 75 mg = 238 [92.25] and alirocumab 150 mg = 20 [7.75])
  • Significant improvement in all the lipid parameters were observed following initiation of PCSK9i treatment
Lipid parameters Before treatment On-treatment P value
LDLc (mg/dL)* 149.58 (50.42) 67.46 (45.84) <0.001§
&Cholesterol remnants (mg/dL)* 29.88 (20.29) 27.30 (17.25) 0.017
Cholesterol remnants >30‡ 34.6 30.07 <0.001
TG/HDL ratio* 3.86 (4.15) 3.35 (3.62) 0.020
TG/HDL ratio >2‡ 71.25 61.98 <0.001
TC (mg/dL)* 227.83 (61.61) 146.47 (55.12) <0.001
TC/HDL ratio* 4.87 (1.92) 3.01 (1.27)
TC/HDL ratio >3‡ 94.28 38.97
TGGi * 8.82 (0.60) 8.71 (0.65) <0.001

§ Before treatment to on-treatment saw a 55% reduction in mean LDLc levels

  • Approximately, 34.61% of patients had LDLc <55 mg/dL and cholesterol remnants <30 mg/dL, whereas 31.95% had cholesterol remnants <30 mg/dL but LDLc >55 mg/dL.
  • Interestingly, patients who had cholesterol remnant levels >30 mg/dL prior to starting PCSK9i therapy exhibited greater reduction in cholesterol remnants, TG/HDL ratio, TC/HDL ratio, and TGGi (P <0.001). 
    • Analysis of parameters for lipid residual risk based on the baseline LDLc, age, gender or obesity showed no differences
  • Safety†: 14 (2.14) patients reported side effects (skin reactions: 7 [1.07]; muscle pain (6 [0.92]); and cold-like symptoms: 1 [0.15])
    • Patients with remnants of cholesterol >30 mg/dL prior to treatment had the same incidence of side effects‡ (2.33 vs 2.22, P = 0.933)

Values presented in *mean (standard deviation [SD]); †n (%); and ‡%; For additional details, please refer the source publication Cordero A, et al.

Limitations

  • Retrospective observational study so might be hypothesis-generating.
  • Several confusing factors were not captured in the study protocol and were therefore not controllable.
  • Treatment adherence to lipid-lowering therapies was self-reported by patients, hence accuracy of use could not be assured.
  • Reimbursement requirements for PCSK9i in Spain did not entirely meet the recommendations of the guidelines.
  • Study was neither designed nor powered to evaluate the impact of CV events.

Values presented in *mean (standard deviation [SD]); †n (%); and ‡%; For additional details, please refer the source publication Cordero A, et al.

    Cordero A, Fernández Olmo MR, Cortez Quiroga GA, et al. Effect of PCSK9 inhibitors on remnant cholesterol and lipid residual risk: The LIPID-REAL registry. Eur J Clin Invest. 2022;52:e13863. doi: 10.1111/eci.13863. PMID: 36039486.

MAT-KW-2300056/V1/FEB2023