Parhofer Klaus G, Pittrow David, Birkenfeld Andreas L, Fraass Uwe, Hohenstein Bernd, Siegert Carsten, Klotsche Jens, Steinhagen-Thiessen Elisabeth, Dexl Stefan, Schettler Volker J J, Laufs Ulrich
Medizinische Klinik und Poliklinik IV, Ludwig-Maximilians-Universität, München, Deutschland.
Institut für Klinische Pharmakologie, Medizinische Fakulät, Technische Universität, Dresden, Deutschland.
Clin Res Cardiol. 2025 Aug 4. doi: 10.1007/s00392-025-02719-z.
In a cohort of patients with dyslipidemia at very high cardiovascular risk, we investigated differences in LDL-C lipid target achievement, clinical outcomes, and persistence rates between users and non-users of PCSK9 monoclonal antibodies (PCSK9-mAb) over a 3-year observation period. The prospective, multi-center observational study included 1695 patients with dyslipidemia. Eligible patients were adults with familial or non-familial hypercholesterolemia, mixed dyslipidemia, or other therapy-refractory lipid disorders in line with the G-BA reimbursement regulations. Treatment decisions, including PCSK9-mAb administration, were made at the discretion of the treating physician. At baseline, 804 (47.4%) patients received PCSK9-mAb therapy, and 891 (52.5%) did not. There were 42 (4.7%) new PCSK9-mAb receivers during the follow-up. Median propensity-score adjusted LDL-C levels in PCSK9-mAb non-receivers decreased over time from 106.0 to 68.4 mg/dL. LDL-C in PCSK9-mAb receivers dropped from 112.5 mg/dL at baseline to 58.0 mg/dL at 3 years, consistently outperforming non-receivers. Target LDL-C goal attainment (< 55mg/dL) after 3 years was higher in the PCSK9-mAb group (43.2% vs. 34.5%). Persistence with PCSK9-mAb therapy over 3 years since treatment initiation was high (91.5%). Higher discontinuation rates of PCSK9-mAb were associated with baseline statin intolerance (HR = 2.3, p = 0.012). The use of PCSK9-mAb was associated with numerically fewer cardiovascular events (9.3 versus 15.7 per 100 patient-years, p not significant) and lower hospitalization rates due to cardiovascular events compared to non-users (6.3 versus 12.4 per 100 patient years, p = 0.001). This study underscores the real-world efficacy and safety of PCSK9-mAb therapy in achieving sustained LDL-C reduction. Identifier: Clinicaltrials.gov NCT03110432.
在一组心血管风险极高的血脂异常患者中，我们调查了在3年观察期内，前蛋白转化酶枯草溶菌素9单克隆抗体（PCSK9 - mAb）使用者与非使用者在低密度脂蛋白胆固醇（LDL - C）血脂目标达成情况、临床结局及持续治疗率方面的差异。这项前瞻性、多中心观察性研究纳入了1695例血脂异常患者。符合条件的患者为患有家族性或非家族性高胆固醇血症、混合型血脂异常或其他符合德国联邦联合委员会（G - BA）报销规定的难治性血脂紊乱的成年人。治疗决策，包括PCSK9 - mAb的使用，由治疗医生自行决定。基线时，804例（47.4%）患者接受PCSK9 - mAb治疗，891例（52.5%）未接受。随访期间有42例（4.7%）新的PCSK9 - mAb使用者。未接受PCSK9 - mAb治疗者经倾向得分调整后的LDL - C水平中位数随时间从106.0降至68.4mg/dL。接受PCSK9 - mAb治疗者的LDL - C从基线时的112.5mg/dL降至3年时的58.0mg/dL，始终优于未使用者。3年后PCSK9 - mAb组达到目标LDL - C水平（<55mg/dL）的比例更高（43.2%对34.5%）。自开始治疗起3年的PCSK9 - mAb治疗持续率较高（91.5%）。PCSK9 - mAb停药率较高与基线时他汀不耐受相关（风险比[HR]=2.3，p = 0.012）。与未使用者相比，使用PCSK9 - mAb在数值上与较少的心血管事件相关（每100患者年9.3次对15.7次，p无统计学意义），且因心血管事件导致的住院率较低（每100患者年6.3次对12.4次，p = 0.001）。本研究强调了PCSK9 - mAb治疗在实现LDL - C持续降低方面的真实疗效和安全性。标识符：Clinicaltrials.gov NCT03110432
