# Evolocumab Versus Statins and Placebo in Patients With Cardiovascular Disease and Comorbidities: A Systematic Review and Meta-Analysis

## TL;DR

Evolocumab, a cholesterol-lowering drug, is more effective than statins and placebo in reducing LDL-C and cardiovascular events in high-risk patients.

## Contribution

This meta-analysis compares evolocumab, statins, and placebo, highlighting evolocumab's superior LDL-C reduction and cardiovascular benefits.

## Key findings

- Evolocumab significantly reduces LDL-C levels compared to placebo and statins.
- It lowers the risk of major adverse cardiovascular events like heart attack and stroke.
- Evolocumab works effectively as monotherapy or in combination with statins.

## Abstract

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.