Efficacy of PCSK9i on Lipid Residual Risk Lipid Real Registry

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.

MAT-KW-2300056/V1/FEB2023