Alirocumab and evolocumab are prescription medications designed to lower cholesterol levels in the blood. These therapies are considered for individuals who struggle to reach their cholesterol goals through traditional treatments, such as statins, or for those who cannot tolerate them. Both medications serve a similar purpose in managing high cholesterol, particularly in patients at increased risk for cardiovascular events.
Understanding PCSK9 Inhibitors
Proprotein Convertase Subtilisin/Kexin type 9 (PCSK9) is a protein that plays a role in regulating cholesterol levels in the body. PCSK9 binds to low-density lipoprotein (LDL) receptors on the surface of liver cells, leading to their degradation. When these receptors are destroyed, the liver’s ability to remove LDL-cholesterol, often called “bad” cholesterol, from the bloodstream is reduced, resulting in higher circulating LDL-C levels.
Alirocumab and evolocumab are classified as PCSK9 inhibitors. These medications are fully human monoclonal antibodies that bind to free PCSK9, preventing it from attaching to and degrading LDL receptors. By inhibiting PCSK9, these drugs increase the number of available LDL receptors on liver cells, thereby enhancing the liver’s capacity to clear LDL-C from the blood and effectively lowering cholesterol levels.
Approved Conditions and Administration
Alirocumab and evolocumab are approved for adults with primary hyperlipidemia, including heterozygous familial hypercholesterolemia (HeFH), and for those with established atherosclerotic cardiovascular disease (ASCVD) who require additional LDL-C reduction beyond diet and maximally tolerated statin therapy. Evolocumab also has an indication for homozygous familial hypercholesterolemia (HoFH) in adults and pediatric patients aged 10 years and older.
Both alirocumab and evolocumab are administered as subcutaneous injections. Alirocumab is given as a 75 mg or 150 mg injection every two weeks. For the 300 mg dose, two 150 mg injections are administered consecutively at different injection sites.
Evolocumab can be administered at a dose of 140 mg every two weeks or 420 mg once monthly. The 420 mg dose can be given as three consecutive 140 mg injections within 30 minutes, or via a single-use on-body infusor with a prefilled cartridge. Injection sites should be rotated among the thigh, abdomen, or upper arm, avoiding tender, bruised, red, or indurated areas.
Distinctions in Clinical Use
While alirocumab and evolocumab share a similar mechanism of action and many approved indications, differences exist in their clinical use. Both drugs have demonstrated LDL-C reductions, often ranging from 26% to 67% over various treatment durations. Clinical trials have shown that both agents are effective in reducing major adverse cardiovascular events like myocardial infarction and stroke.
One consideration is dosing flexibility; alirocumab offers a 75 mg starting dose that can be adjusted to 150 mg if a greater LDL-C reduction is needed. Evolocumab provides convenient monthly dosing options, which some patients may prefer over bi-weekly injections. While both drugs have similar safety profiles, some studies suggest alirocumab may be associated with a slightly increased risk of injection site reactions compared to evolocumab, though these are mild.
Differences in evidence exist regarding specific populations. Alirocumab’s evidence base may be stronger for patients at high cardiovascular risk who have not reached their LDL-C targets with statin therapy. Evolocumab has stronger evidence for patients with heterogeneous familial hypercholesterolemia and those with varied cardiovascular risk who have not met LDL-C goals. The choice between these medications depends on individual patient factors, including dosing preference, insurance coverage, and the patient’s response to therapy.
Safety Considerations
Alirocumab and evolocumab have a favorable safety profile, with most adverse events being mild to moderate in severity. Common side effects reported in clinical trials and real-world settings include injection site reactions, such as pain, redness, or bruising at the injection site. These reactions are temporary and rarely lead to treatment discontinuation.
Patients may also experience general systemic side effects, including nasopharyngitis, upper respiratory tract infections, influenza-like illness, myalgia (muscle pain), back pain, arthralgia (joint pain), and headache. While muscle-related events are recognized side effects, PCSK9 inhibitors have shown a favorable safety profile in this regard compared to statins. Serious allergic reactions, though rare, can occur, and patients should seek medical attention if symptoms like angioedema develop.
There is no consistent evidence suggesting an increased risk of new-onset diabetes or neurocognitive events with either alirocumab or evolocumab. Patients should discuss any new or worsening symptoms with their healthcare provider to determine if they are related to the medication and to receive appropriate guidance.