Alirocumab (sold as Praluent) and evolocumab (sold as Repatha) are close cousins: injectable drugs that lower LDL cholesterol far beyond what a statin alone usually reaches. They cut LDL by roughly 55 to 60 percent and lower the risk of heart attack and stroke by about 15 percent on top of a statin, so for most people the choice between them matters less than the decision to take one at all.1PubMed Central. Relative Efficacy of Alirocumab, Evolocumab, Inclisiran, and Bempedoic Acid on Lipids in Patients with Cardiovascular Disease or Familial Hypercholesterolaemia2PubMed. Evolocumab and Clinical Outcomes in Patients with Cardiovascular Disease3PubMed. Alirocumab and Cardiovascular Outcomes after Acute Coronary Syndrome They were proven in different groups of heart patients, so each has evidence that fits some histories a little more closely. In everyday life, dosing, insurance coverage and price often settle the question more than the drug itself.
How Both Drugs Work the Same Way
LDL cholesterol (LDL-C), the “bad” cholesterol on your lab report, is cleared from the blood by catchers called LDL receptors on liver cells. A protein called PCSK9 tags those receptors for destruction, so fewer are left to clear LDL.4PubMed Central. PCSK9 inhibitors – mechanisms of action Both alirocumab and evolocumab are antibodies that grab PCSK9 in the blood before it reaches the receptors.5PubMed Central. PCSK9 inhibitors – mechanisms of action The receptors are then recycled back to the liver surface and keep pulling LDL out of the blood.6PubMed Central. PCSK9 inhibitors – mechanisms of action
Statins work from the other side: they make the liver build more receptors, while PCSK9 drugs keep those receptors from being destroyed. That is why the two are usually taken together rather than one replacing the other. Most people are prescribed a PCSK9 drug when a top statin dose has not reached their LDL goal, or when statin side effects are intolerable.
These are lab-made antibodies, which are large protein molecules. Stomach acid and digestive enzymes would break them down like any food protein, so they cannot be made into a pill. Injected under the skin, the drug seeps slowly into the blood, which is why a dose every two weeks or every month keeps working. The body also breaks antibodies into small pieces rather than clearing them through the liver enzymes that process many pills, so they have few interactions with other medicines.
Which One Prevents More Heart Attacks and Deaths
In people with established heart disease already on a statin, evolocumab lowered the rate of heart attack, stroke, heart death and related hospital events from 11.3% to 9.8% over about two years.7PubMed. Evolocumab and Clinical Outcomes in Patients with Cardiovascular Disease That is roughly a 15% cut in risk, and about 1 or 2 fewer events for every 100 people treated.8PubMed. Evolocumab and Clinical Outcomes in Patients with Cardiovascular Disease The harder outcome of heart attack, stroke or heart death fell by about 20%.9PubMed. Evolocumab and Clinical Outcomes in Patients with Cardiovascular Disease In a longer follow-up the benefit held across groups and was largest in people with a recent heart attack, several past heart attacks, or blockages in many arteries.10American College of Cardiology. Further Cardiovascular Outcomes Research With PCSK9 Inhibition in Subjects With Elevated Risk
Alirocumab was tested in nearly 19,000 people within a year of a heart attack or unstable angina, all on a strong statin.11PubMed. Alirocumab Reduces Total Hospitalizations and Increases Days Alive and Out of Hospital in the ODYSSEY OUTCOMES Trial Major events fell from 11.1% to 9.5%, the same 15% relative cut seen with evolocumab.12PubMed. Alirocumab and Cardiovascular Outcomes after Acute Coronary Syndrome Fewer people also died from any cause, 3.5% versus 4.1%.13PubMed. Alirocumab and Cardiovascular Outcomes after Acute Coronary Syndrome About 87 people would need treatment for 4 years to prevent one death.14PubMed Central. Effect of Alirocumab on Mortality After Acute Coronary Syndromes That death finding came lower in the trial’s planned order of tests, so researchers treat it as encouraging rather than proven.15PubMed Central. Effect of Alirocumab on Mortality After Acute Coronary Syndromes Alirocumab also meant fewer total hospital stays.16PubMed. Alirocumab Reduces Total Hospitalizations and Increases Days Alive and Out of Hospital in the ODYSSEY OUTCOMES Trial
The two drugs have never been tested head to head for heart attacks or deaths. Differences like alirocumab’s death signal may reflect who was studied, people with a recent heart attack, rather than the drug itself. Each drug was proven in a different group of patients, so the trial results describe who was studied, not a ranking of the drugs.
A 15% relative cut means 15% of the events that would have happened are prevented, not that 15% of people benefit. The benefit builds over time, so the gain over many years is larger than the two-year numbers suggest. And the higher your starting risk, such as repeated heart attacks or blockages in many arteries, the more events the same percentage prevents.
If your heart attack was recent, alirocumab’s trial matches your situation closely; if it was years ago, evolocumab’s trial does. That match is a reason to lean one way, not a rule, because guidelines accept both for either history.
How Much Each Lowers LDL and Lp(a)
Over a year in people with heart disease or inherited high cholesterol, alirocumab lowered LDL about 62% and evolocumab about 58%.17PubMed Central. Relative Efficacy of Alirocumab, Evolocumab, Inclisiran, and Bempedoic Acid on Lipids in Patients with Cardiovascular Disease or Familial Hypercholesterolaemia In the first weeks after a heart attack, both cut LDL by about 60%, with no real difference.18Kosin Medical Journal. Early effects of PCSK9 inhibitors: evolocumab versus alirocumab Pooled comparisons of standard doses, though, found evolocumab lowered LDL more than alirocumab.19PubMed Central. Systematic Review and Network Meta‐Analysis on the Efficacy of Evolocumab and Other Therapies for the Management of Lipid Levels in Hyperlipidemia The gap appears mostly when alirocumab is used at its lower 75 mg dose, which can be raised.
Lower appears to keep helping. In evolocumab users, the lower LDL went, the fewer heart events occurred, even below about 8 mg/dL.20PubMed. Clinical efficacy and safety of achieving very low LDL-cholesterol concentrations with the PCSK9 inhibitor evolocumab: a prespecified secondary analysis of the FOURIER trial Pushing LDL very low did not raise safety problems over about two years.21PubMed. Clinical efficacy and safety of achieving very low LDL-cholesterol concentrations with the PCSK9 inhibitor evolocumab: a prespecified secondary analysis of the FOURIER trial
Lp(a) is an inherited cholesterol particle linked to heart disease that statins do not lower; it may appear on a specialist lipid panel. PCSK9 drugs lower it by about a quarter on average, with no difference between the two.22PubMed. Lipoprotein(a) reduction with inclisiran, alirocumab, evolocumab, enlicitide, and lerodalcibep: A systematic review and meta-analysis of randomized controlled trials In inherited high cholesterol, both reduced Lp(a) by about 20%.23PubMed. Impact of alirocumab/evolocumab on lipoprotein (a) concentrations in patients with familial hypercholesterolaemia: a systematic review and meta-analysis of randomized controlled trials
Your first repeat lipid test usually comes a few weeks to about three months after starting, once the effect has settled. Many people at very high risk are given an LDL goal near 55 mg/dL or lower, though the exact target depends on your doctor and guideline. If your LDL barely dropped, check for missed doses, a pen that was not fully injected, or a dose that needs raising before assuming the drug failed.
Doses and Injection Schedules
Evolocumab is injected under the skin as 140 mg every 2 weeks or 420 mg once a month.24U.S. Food and Drug Administration. REPATHA (evolocumab) injection If LDL hasn’t dropped enough after 12 weeks, the dose can be raised to 420 mg every 2 weeks.25U.S. Food and Drug Administration. REPATHA (evolocumab) injection People who have their blood filtered to remove cholesterol can inject right after each session.26U.S. Food and Drug Administration. REPATHA (evolocumab) injection
Alirocumab is given at 75 mg or 150 mg every 2 weeks, or 300 mg monthly. A doctor can start lower and step up, or stay low if a smaller cut is enough.
Both come as prefilled pens you press against the skin of the belly, thigh or upper arm, so no needle handling is needed. Pens are kept in the refrigerator; take one out and let it reach room temperature first, which usually takes some minutes and makes the injection less stinging. Change the spot each time and avoid skin that is bruised, tender or scarred. If you miss a dose, follow the timing rule on the package rather than doubling up. Monthly dosing means fewer injections to remember, while every-2-weeks uses a smaller single injection.
Side Effects and Safety Compared
The usual complaints are mild: cold-like symptoms, pain at the injection site, joint pain and back pain.27PubMed. Safety and tolerability of injectable lipid-lowering drugs: a review of available clinical data Rates of side effects bad enough to stop the drug, allergic reactions, and eye problems are the same for both.28European Heart Journal – Cardiovascular Pharmacotherapy. Indirect comparison of the efficacy and safety of alirocumab and evolocumab: a systematic review and network meta-analysis Both cause slightly more injection-site reactions than a placebo shot.29European Heart Journal – Cardiovascular Pharmacotherapy. Indirect comparison of the efficacy and safety of alirocumab and evolocumab: a systematic review and network meta-analysis30PubMed Central. A Systematic Review of PCSK9 Inhibitors Alirocumab and Evolocumab
About 5.5% of alirocumab users develop antibodies against the drug, versus 0.3% with evolocumab.31The Cardiovascular. PCSK9 inhibitors: evolocumab (Repatha) and alirocumab (Praluent) These antibodies are weak and do not make alirocumab work less well.32The Cardiovascular. PCSK9 inhibitors: evolocumab (Repatha) and alirocumab (Praluent) Their only noticeable effect is more injection-site reactions, 7.5% versus 3.6%.33The Cardiovascular. PCSK9 inhibitors: evolocumab (Repatha) and alirocumab (Praluent)
A typical injection reaction is redness, itching or soreness at the site that fades within a day or two. Hives, swelling of the face or lips, or trouble breathing is not a normal reaction and needs urgent medical care.
Some people fear very low cholesterol could affect the brain. Evolocumab users followed for up to about 7 years showed no decline in memory or thinking.34Circulation. Abstract 14714: Long-Term Neurocognitive Safety of LDL-C Lowering With Evolocumab: Open-Label Extension Data From FOURIER In two years of everyday use, thinking scores stayed steady on both drugs, and delayed recall improved slightly.35PubMed Central. Cognitive Function with PCSK9 Inhibitors: A 24-Month Follow-Up Observational Prospective Study in the Real World—MEMOGAL Study36PubMed Central. PCSK9 inhibitors in neurodegenerative disorders: mechanisms, therapeutic potential, and clinical implications
Unlike statins, PCSK9 drugs did not raise the risk of new diabetes in large trials.37PubMed. Proprotein Convertase Subtilisin/Kexin Type 9 Inhibitors and Ezetimibe on Risk of New-Onset Diabetes: A Systematic Review and Meta-Analysis of Large, Double-Blinded Randomized Controlled Trials Evolocumab did not raise diabetes risk even in people with prediabetes, and blood sugar stayed level.38PubMed. Cardiovascular safety and efficacy of the PCSK9 inhibitor evolocumab in patients with and without diabetes and the effect of evolocumab on glycaemia and risk of new-onset diabetes: a prespecified analysis of the FOURIER randomised controlled trial Reaching very low LDL did not increase diabetes, muscle problems, cataracts, liver problems or cancer.39PubMed Central. Safety and Efficacy of Achieving Very Low LDL Cholesterol Concentrations with PCSK9 Inhibitors
Many people are offered these drugs because statins made their muscles hurt, so they worry the same will happen again. PCSK9 antibodies work in the blood and are not taken up into muscle cells the way statins are, though aches can still happen for unrelated reasons.
Cost, Insurance, and Staying on Treatment
Whether these drugs are worth their price depends heavily on the price paid and how high your risk is.40PubMed Central. Fair pricing, fair access; a systematic review of cost-effectiveness of new hyperlipidemia injectable medication in developing countries41PubMed Central. Theoretical Cost-Effectiveness of PCSK9 Inhibitors in Stroke Due to Intracranial Atherosclerosis In one UK analysis alirocumab looked better value than evolocumab, though both cost well above usual thresholds.42PubMed Central. Cost-Effectiveness of Icosapent Ethyl, Evolocumab, Alirocumab, Ezetimibe, or Fenofibrate in Combination with Statins Compared to Statin Monotherapy In other countries alirocumab was not cost-effective in ordinary heart attack patients, only in those with blockages in several body areas.43PubMed Central. Fair pricing, fair access; a systematic review of cost-effectiveness of new hyperlipidemia injectable medication in developing countries
Most insurers require prior authorization, meaning your plan must approve the drug before it will pay. Plans commonly ask for proof of a maximum tolerated statin and often ezetimibe, along with your LDL result and heart history. Your doctor’s office submits the paperwork, so ask who is handling it and how long the decision usually takes. Many plans prefer one brand, so the covered drug is often the practical choice, and manufacturer copay cards and assistance programs can lower out-of-pocket cost. If coverage changes, switching from one to the other is usually straightforward.
In real life only about 57% of people still take either drug consistently after a year.44PubMed Central. Real-world treatment adherence and persistence among patients initiating inclisiran or PCSK9 mAbs Adherence, persistence and effect are the same for both drugs in practice.45PubMed. Efficacy, safety, adherence and persistence of PCSK9 inhibitors in clinical practice: A single country, multicenter, observational study (AT-TARGET-IT) Approval paperwork, repeat authorizations and cost push many people to stop; in one group about 40% stopped within 60 days for that reason.46PubMed Central. PCSK-9 Inhibitors in a Real-World Setting and a Comparison Between Alirocumab and Evolocumab in Heterozygous FH Patients After the last dose, LDL returns toward its old level within weeks, and heart protection depends on staying on treatment.
Kidney Disease and Other Special Cases
In chronic kidney disease, both drugs lowered LDL and Lp(a) similarly at every stage, including severe disease.47PubMed Central. Efficacy and safety of PCSK9 inhibitors in patients with chronic kidney disease Kidney function stayed stable and no serious muscle breakdown occurred.48PubMed Central. Efficacy and safety of PCSK9 inhibitors in patients with chronic kidney disease In older people with moderate kidney disease, LDL fell from about 148 to 63 mg/dL and stayed down for two years.49Nephrology Dialysis Transplantation. #4791 TREATMENT WITH PCSK9 INHIBITORS IN PATIENTS WITH CHRONIC KIDNEY DISEASE AT VERY HIGH CARDIOVASCULAR RISK
Because antibodies are not filtered out by the kidneys, reduced kidney function does not cause the drug to build up. The standard doses are therefore used at every stage. People on dialysis were studied less, so they should confirm the plan with their kidney doctor.
In people with inherited high cholesterol but no heart symptoms, alirocumab with a strong statin shrank and steadied artery plaque on scans over 18 months.50PubMed Central. Alirocumab and Coronary Atherosclerosis in Asymptomatic Patients with Familial Hypercholesterolemia: The ARCHITECT Study
How They Compare With Inclisiran
Inclisiran blocks PCSK9 by stopping the liver from making it, rather than catching it in the blood. It lowered LDL about 47% over a year, less than alirocumab or evolocumab.51PubMed Central. Relative Efficacy of Alirocumab, Evolocumab, Inclisiran, and Bempedoic Acid on Lipids in Patients with Cardiovascular Disease or Familial Hypercholesterolaemia In a comparison, evolocumab ranked most effective, followed by alirocumab, then inclisiran.52PubMed Central. Effects of Inclisiran, Alirocumab, Evolocumab, and Evinacumab on Lipids: A Network Meta-Analysis In six months of real-world use, apoB, a count of harmful cholesterol particles, was slightly lower with inclisiran, though not clearly different.53PubMed Central. Comparative effectiveness and safety of inclisiran versus evolocumab and alirocumab: a 180-day real-world study Real-world adherence was similar to the antibodies.54PubMed Central. Real-world treatment adherence and persistence among patients initiating inclisiran or PCSK9 mAbs
Inclisiran is given by a health professional at a clinic, at the start, at three months, and then every six months. This suits people who dislike self-injecting or tend to miss doses, since someone else handles the schedule. The tradeoffs are a smaller LDL cut than the antibodies and, unlike alirocumab and evolocumab, no completed trial yet showing fewer heart attacks.