Cognitive Function with PCSK9 Inhibitors: A 24-Month Follow-Up Observational Prospective Study in the Real World—MEMOGAL Study

IF 2.8 4区医学 Q2 CARDIAC & CARDIOVASCULAR SYSTEMS American Journal of Cardiovascular Drugs Pub Date : 2023-08-23 DOI:10.1007/s40256-023-00604-6

Jose Seijas-Amigo, Mª José Mauriz-Montero, Pedro Suarez-Artime, Mónica Gayoso-Rey, Ana Estany-Gestal, Antonia Casas-Martínez, Lara González-Freire, Ana Rodriguez-Vazquez, Natalia Pérez-Rodriguez, Laura Villaverde-Piñeiro, Concepción Castro-Rubinos, Esther Espino-Faisán, Moisés Rodríguez-Mañero, Alberto Cordero, José R. González-Juanatey, Investigadores MEMOGAL

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Abstract

Introduction

The cognitive safety of monoclonal antibody proprotein convertase subtilisin/kexin type 9 inhibitors (PCSK9i) has been established in clinical trials, but not yet in real-world observational studies. We assessed the cognitive function in patients initiating PCSK9i, and differences in cognitive function domains, to analyze subgroups by the low-density lipoprotein cholesterol (LDL-C) achieved, and differences between alirocumab and evolocumab.

Methods

This has a multicenter, quasi-experimental design carried out in 12 Spanish hospitals from May 2020 to February 2023. Cognitive function was assessed using the Montreal Cognitive Assessment (MoCA).

Results

Among 158 patients followed for a median of 99 weeks, 52% were taking evolocumab and 48% alirocumab; the mean change from baseline in MoCA score at follow-up was + 0.28 [95% CI (− 0.17 to 0.73; p = 0.216)]. There were no significant differences in the secondary endpoints—the visuospatial/executive domain + 0.04 (p = 0.651), naming domain − 0.01 (p = 0.671), attention/memory domain + 0.01 (p = 0.945); language domain − 0.10 (p = 0.145), abstraction domain + 0.03 (p = 0.624), and orientation domain − 0.05 (p = 0.224)—but for delayed recall memory the mean change was statistically significant (improvement) + 0.44 (p = 0.001). Neither were there any differences in the three stratified subgroups according to lowest attained LDL-C level—0–54 mg/dL, 55–69 mg/dL and ≥ 70 mg/dL; p = 0.454—or between alirocumab and evolocumab arms.

Conclusion

We did not find effect of monoclonal antibody PCSK9i on neurocognitive function over 24 months of treatment, either in global MoCA score or different cognitive domains. An improvement in delayed recall memory was shown. The study showed no differences in the cognitive function between the prespecified subgroups, even among patients who achieved very low levels of LDL-C. There were no differences between alirocumab and evolocumab.

Registration

ClinicalTtrials.gov Identifier number NCT04319081.

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PCSK9抑制剂的认知功能：一项24个月的现实世界随访前瞻性研究——MEMOGAL研究

引言单克隆抗体前蛋白转化酶枯草杆菌蛋白酶/可辛9型抑制剂（PCSK9i）的认知安全性已在临床试验中得到证实，但尚未在现实世界的观察性研究中得到证实。我们评估了启动PCSK9i的患者的认知功能，以及认知功能域的差异，以通过实现的低密度脂蛋白胆固醇（LDL-C）分析亚组，以及阿罗库单抗和埃沃洛单抗之间的差异。方法采用多中心准实验设计，于2020年5月至2023年2月在西班牙12家医院进行。使用蒙特利尔认知评估（MoCA）对认知功能进行评估。结果158名患者随访了99周，其中52%的患者服用了埃沃洛单抗，48%的患者服用阿洛单抗；随访时MoCA评分与基线相比的平均变化为+ 0.28[95%CI（− 0.17至0.73；p = 0.216）]。次要终点——视觉空间/执行域没有显著差异+ 0.04（p = 0.651），命名域− 0.01（p = 0.671），注意力/记忆域+ 0.01（p = 0.945）；语言域− 0.10（p = 0.145），抽象域+ 0.03（p = 0.624），方向域− 0.05（p = 0.224）——但对于延迟回忆记忆，平均变化具有统计学意义（改善）+ 0.44（p = 0.001）。根据最低LDL-C水平——0-54 mg/dL、55-69 mg/dL和≥ 70 mg/dL；p = 0.454——或在阿罗库单抗和埃沃洛单抗组之间。结论在24个月的治疗中，无论是在整体MoCA评分还是在不同的认知领域，我们都没有发现单克隆抗体PCSK9i对神经认知功能的影响。延迟回忆记忆得到改善。研究表明，即使在LDL-C水平非常低的患者中，预先指定的亚组之间的认知功能也没有差异。阿利罗库单抗和埃沃洛单抗之间没有差异。RegistrationClinicalTtrials.gov识别号NCT04319081。

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来源期刊

American Journal of Cardiovascular Drugs 医学-心血管系统

CiteScore

6.70

自引率

3.30%

发文量

审稿时长

>12 weeks

期刊介绍： Promoting rational therapy within the discipline of cardiology, the American Journal of Cardiovascular Drugs covers all aspects of the treatment of cardiovascular disorders, particularly the place in therapy of newer and established agents. Via a program of reviews and original clinical research articles, the journal addresses major issues relating to treatment of these disorders, including the pharmacology, efficacy and adverse effects of the major classes of drugs; information on newly developed drugs and drug classes; the therapeutic implications of latest research into the aetiology of cardiovascular disorders; and the practical management of specific clinical situations. The American Journal of Cardiovascular Drugs offers a range of additional enhanced features designed to increase the visibility, readership and educational value of the journal’s content. Each article is accompanied by a Key Points summary, giving a time-efficient overview of the content to a wide readership. Articles may be accompanied by plain language summaries to assist patients, caregivers and others in understanding important medical advances. The journal also provides the option to include various other types of enhanced features including slide sets, videos and animations. All enhanced features are peer reviewed to the same high standard as the article itself. Peer review is conducted using Editorial Manager®, supported by a database of international experts. This database is shared with other Adis journals.