Evolocumab 140mg/1ml solution for injection pre-filled disposable devices

INTRODUCTION: The PCSK9 enzyme is present mainly in the liver and is responsible for the degradation of LDL-C receptors. Currently, there are some drugs that inhibit this enzyme, such as alirocumab and evolocumab. Consequently, these drugs reduce serum LDL-C levels. Therefore, a systematic review and a meta-analysis were carried out in order to compare alirocumab against evolocumab in reducing cardiovascular outcomes. METHODS: This systematic review was carried out in accordance with PRISMA and was registered in PROSPERO (CRD42024573217). The following databases were searched on July, 9, 2024: PubMed, Web of Science and Scopus. Randomized clinical trials with a control group were included and meta-analyses were performed to assess relative risk (RR). The random effects model was used in heterogeneous samples. The articles were distributed into 2 subgroups: use of alirocumab and evolocumab. RESULTS: Initially, 2,213 articles were found, of which 6 were included. In total, 62,119 patients participated. The RR values were significant for alirocumab in the following outcomes: myocardial infarction (MI) 0.85 (95% CI 0.77-0.93), stroke 0.75 (95% CI 0.60-0.94) and hospitalization for unstable angina 0.58 (95% CI 0.39-0.86), while for evolocumab they were significant for MI 0.75 (95% CI 0.68-0.83) and coronary revascularization 0.81 (95 CI % 0.75-0.88). There was a statistically significant difference between the drugs for hospitalization for unstable angina (p=0.02). DISCUSSION: This study highlights the benefits of PCSK9 inhibitors, especially alirocumab, in reducing major cardiovascular events. Alirocumab significantly lowered hospitalizations for unstable angina, with a 42% reduction, and showed favorable outcomes in reducing myocardial infarction, coronary revascularization, and stroke. These reductions are clinically meaningful, as they lower morbidity, improve patient quality of life, and reduce healthcare costs. Both alirocumab and evolocumab are effective and safe, offering important therapeutic options for high-risk cardiovascular patients. CONCLUSION: The use of alirocumab is preferable if the focus is to avoid hospitalizations for unstable angina or stroke, while evolocumab may be an option if one wants to avoid coronary revascularization. Both drugs are effective in reducing cardiovascular outcomes, but alirocumab was superior to evolocumab.

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Evolocumab is a PCSK9 inhibitor designed to significantly reduce low-density lipoprotein cholesterol (LDL-C) levels. Unlike statins, which work by inhibiting 3-hydroxy-3-methylglutaryl coenzyme A reductase to reduce cholesterol synthesis in the liver, evolocumab enhances LDL receptor recycling, leading to more efficient clearance of LDL-C from the bloodstream. Compared to placebo, evolocumab shows a profound LDL-C lowering effect while also offering incremental benefit over statins, especially in high-risk patients or those with statin intolerance. In this meta-analysis, the primary focus was on lipid-lowering efficacy and cardiovascular outcomes, making direct comparisons among evolocumab, statins, and placebo essential. Evolocumab consistently demonstrated a statistically significant reduction in LDL-C and, in several large-scale trials (such as Further Cardiovascular Outcomes Research With PCSK9 Inhibition in Subjects With Elevated Risk (FOURIER)), also showed a reduction in cardiovascular events, including myocardial infarction and stroke. It is important to specify that the most significant outcomes were both the substantial LDL-C reduction and the associated reduction in major adverse cardiovascular events (MACE). For our meta-analysis, we generated three graphical models using Review Manager (RevMan) version 5.4 (Cochrane Collaboration, Copenhagen, Denmark) based on the selected studies. To conduct our systematic review, we extensively examined a total of 10 articles. The subgroup analyses in these studies looked at how well evolocumab worked on its own, with statins, and as an extra treatment for people who were already taking low or high doses of statins. Additionally, we compared the effectiveness of evolocumab vs. placebo in both individuals with and without cardiovascular conditions. Our findings indicated that evolocumab, whether used as monotherapy or alongside statins, demonstrated statistical significance (p = 0.01). Moreover, all reviewed studies reported statistically significant results (p < 0.05). According to our analysis, there is an urgent need for more research to build on this body of evidence and carry out larger randomized controlled trials (RCTs) to find the best timing and dose for each patient and avoid any possible long-term side effects.

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BACKGROUND: Cardiac allograft vasculopathy is characterized by increased coronary intimal thickness and is a leading cause of death in heart transplant (HTx) recipients despite the routine use of statins. The experience with inhibitors of proprotein convertase subtilisin-kexin type 9 in HTx recipients is limited. Our hypothesis was that lowering cholesterol with the proprotein convertase subtilisin-kexin type 9inhibitor evolocumab would reduce coronary intimal thickness in these patients without compromising safety. OBJECTIVES: This double blind, randomized trial was conducted to test whether evolocumab reduces the burden of cardiac allograft vasculopathy. METHODS: Patients who had received a cardiac allograft at 1 of the Nordic transplant centers within the prior 4 to 8 weeks were randomized to monthly subcutaneous injections of evolocumab 420 mg or matching placebo. The primary endpoint was the baseline-adjusted maximal intimal thickness as measured by intracoronary ultrasound after 12 months' treatment. RESULTS: The trial enrolled 128 patients between June 2019 and May 2022. Matched pairs of coronary ultrasound images were available for 56 patients assigned to evolocumab and 54 patients assigned to placebo. At 12 months, the adjusted mean difference in the maximal intimal thickness between the 2 arms was 0.017 mm (95% CI: -0.006 to 0.040; P = 0.14). The mean reduction in low-density lipoprotein cholesterol with evolocumab compared with placebo was 1.11 mmol/L (95% CI: 0.86-1.37 mmol/L). The use of evolocumab was not associated with an increase in adverse events. CONCLUSIONS: Twelve months of treatment with evolocumab substantially reduced low-density lipoprotein cholesterol but did not reduce maximal coronary intimal thickness in HTx recipients. (Cholesterol Lowering With EVOLocumab to Prevent Cardiac Allograft Vasculopathy in De-novo Heart Transplant Recipients [EVOLVD]; NCT03734211).

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