How often do you take inclisiran?

After the first injection, you get a second at three months, and then one every six months. So the first year involves three injections, and every year after that is two. It is given by a healthcare provider rather than self-injected at home, which is one difference from the older PCSK9 inhibitors.

How much does inclisiran cost?

Inclisiran is expensive, roughly $3,000 or more per injection, which works out to around $6,500 a year at the twice-yearly maintenance schedule and more in the first year with the extra dose. It is usually billed through your medical benefit because a provider administers it. Insurance coverage varies, so the out-of-pocket cost depends on your plan.

In the trials, inclisiran was well tolerated. The main distinctive side effect is a reaction at the injection site, such as redness or soreness, and it is usually mild. Otherwise the side effects looked similar to placebo, with no signal of liver, kidney, or muscle problems. Because it is a newer type of drug, long-term safety data are still being collected, but the picture so far is reassuring.

How often do you take inclisiran?

After the first injection, you get a second at three months, and then one every six months. So the first year involves three injections, and every year after that is two. It is given by a healthcare provider rather than self-injected at home, which is one difference from the older PCSK9 inhibitors.

How much does inclisiran cost?

Inclisiran is expensive, roughly $3,000 or more per injection, which works out to around $6,500 a year at the twice-yearly maintenance schedule and more in the first year with the extra dose. It is usually billed through your medical benefit because a provider administers it. Insurance coverage varies, so the out-of-pocket cost depends on your plan.

In the trials, inclisiran was well tolerated. The main distinctive side effect is a reaction at the injection site, such as redness or soreness, and it is usually mild. Otherwise the side effects looked similar to placebo, with no signal of liver, kidney, or muscle problems. Because it is a newer type of drug, long-term safety data are still being collected, but the picture so far is reassuring.

Inclisiran (Leqvio): The Twice-a-Year Cholesterol Shot | Philadelphia

TL;DR30-second take

Inclisiran (brand name Leqvio) is a newer cholesterol-lowering injection given by your provider just twice a year after two starter doses. It uses small interfering RNA to lower the liver's production of PCSK9, a protein that limits how much LDL your liver clears, and it lowers LDL cholesterol by about half. That makes it a strong option for people who cannot get their LDL or ApoB low enough on a statin alone. The important caveat is that the trials so far have proven it lowers cholesterol, but the studies testing whether it prevents heart attacks and strokes are still ongoing. It is well tolerated, with injection-site reactions the main side effect, and it is expensive.

TL;DR: Inclisiran, sold as Leqvio, is a cholesterol-lowering injection that uses RNA interference to lower the liver's production of PCSK9, which drops LDL cholesterol by about half. After two starter doses, it is given only twice a year, which solves the everyday burden of a daily pill. It is a strong option for people whose LDL or ApoB stays too high on a statin. The catch is that its cholesterol-lowering is proven while its heart-attack and stroke prevention is not yet: the large outcome trials are still running, with the first results expected around 2026. It is added on top of a statin rather than used in its place, it is well tolerated apart from injection-site reactions, and it is expensive.

What is inclisiran, and how does it work?

Inclisiran, sold as Leqvio, is a cholesterol-lowering medicine that works in a way no pill does. It is a small interfering RNA, or siRNA, a type of drug that silences a specific gene. In this case it silences the liver's production of a protein called PCSK9. PCSK9 acts like a brake on your body's cholesterol removal: it breaks down the LDL receptors your liver uses to pull LDL cholesterol out of the blood. Fewer receptors means higher LDL. By telling the liver to make less PCSK9, inclisiran leaves more of those receptors in place, and your LDL falls.

The injection is engineered to be absorbed mostly by the liver, which is what lets it work for months from a single dose. After two starter injections, one at the beginning and one at three months, it is given twice a year. That is the headline that draws people in: a cholesterol treatment you handle at a couple of visits a year rather than a daily pill.

How well does it lower cholesterol?

On this measure, inclisiran is strong. In the two pivotal trials, ORION-10 and ORION-11, it lowered LDL cholesterol by about 50% compared with placebo in people already taking the highest statin dose they could tolerate.¹ In people with an inherited cholesterol disorder called familial hypercholesterolemia, a separate trial found a similar drop of roughly 48%.² An earlier dose-finding study set the twice-a-year schedule.³

That degree of lowering matters because LDL, and the ApoB particle count it travels with, is the main driver of plaque in the arteries. Cutting it in half on top of a statin brings many people to a target they could not reach otherwise.

Does inclisiran prevent heart attacks and strokes?

Here is the part that gets glossed over, and the part I care most about. Lowering LDL is not the goal in itself; the goal is fewer heart attacks and strokes. For statins and for the PCSK9 antibodies, we have large trials proving they lower that risk. For inclisiran, we do not have that proof yet. Every published inclisiran trial has measured cholesterol rather than events.

The trials that will answer the question are underway. ORION-4, a study of about 15,000 people with established heart disease, is expected to report around 2026, with two more outcome trials following over the next several years. Until they read out, the expectation that inclisiran prevents heart attacks rests on inference: it lowers LDL a great deal, and lowering LDL by other means lowers risk, so it very likely helps. That is a reasonable expectation, but it is not the same as proof, and I think patients deserve to know the difference.

How does it compare to statins and PCSK9 inhibitors?

A statin is still the foundation. It is proven to prevent events, it is inexpensive, and it does more than lower LDL. Inclisiran is not a replacement for a statin; in the trials it was added on top of one.

The closer comparison is to the PCSK9 inhibitors, evolocumab and alirocumab. Those are also injections that target PCSK9, and they are proven to lower cardiovascular events.⁴ The difference is how, and how often. The PCSK9 antibodies mop up the PCSK9 protein already in the blood, and are injected every two to four weeks, usually by the patient at home. Inclisiran works one step earlier, telling the liver to make less PCSK9 in the first place, which is what lets it last six months. The trade-off is that the antibodies have the outcome proof today, while inclisiran offers the convenience of twice-a-year dosing with that proof still pending.

For many people the deciding factors are practical: how often you want an injection, whether you would rather manage it yourself or have it done in the office, what your insurance covers, and how you weigh proven benefit against convenience.

Who is inclisiran for, and what does it cost?

Inclisiran fits a specific situation: someone whose LDL or ApoB is still too high despite a statin, or who cannot tolerate enough statin, and who needs substantial extra lowering. The FDA first approved it in 2021 for people with established heart disease or an inherited cholesterol disorder, and it has since been expanded to a broader group at high risk, including some who have not yet had a cardiovascular event.⁵

Two practical points shape the decision. First, it is given in a medical setting rather than self-injected, so it means a visit for each dose, which for most people is three in the first year and two a year after that. Second, it is expensive, roughly $3,000 or more per injection, on the order of $6,500 a year, usually billed through your medical benefit rather than the pharmacy. Whether that is worth it depends on how far your LDL needs to come down, what your other options are, and what your coverage looks like. This is a decision to make with a physician who knows your full risk picture.

Guidance from the Clinic

"Inclisiran is a clever piece of medicine, and the twice-a-year schedule solves a problem that daily pills create, because the hardest part of cholesterol treatment is often simply taking it every day. When a patient asks me about it, I give them the plain version: it lowers LDL powerfully, its safety looks good so far, and what we are still waiting on is proof that it prevents heart attacks, which the big trials should tell us soon. For the right patient, whose LDL will not come down any other way, I am comfortable using it now while we wait for that proof. For someone earlier in their risk, I would rather rely on the tools that already have the outcome data. It is a case-by-case call, made with your numbers in front of us."

Key Takeaways

Inclisiran (Leqvio) is a twice-a-year injection that uses RNA interference to lower the liver's production of PCSK9, cutting LDL cholesterol by about 50%.
After two starter doses (day one and month three), it is given every six months, so the first year is three injections and later years are two.
Its cholesterol-lowering is proven, but its heart-attack and stroke prevention is not yet, with the large outcome trials expected to report from about 2026 onward.
It is added on top of a statin rather than used as a replacement, and the closest comparison is the PCSK9 antibodies, which already have outcome proof but are injected far more often.
It is well tolerated, with injection-site reactions the main side effect, and it is expensive (roughly $6,500 a year), usually billed through the medical benefit.

Beyond Statins: Other Ways to Lower Cholesterol and ApoB - where inclisiran fits among the options
PCSK9 Inhibitors (Repatha, Praluent) - the antibody cousins with proven outcome trials
ApoB and Heart Health - the particle count worth targeting
What Is a Preventive Cardiologist? - the decision layer around these choices
Nervous About Statins? - working through statin concerns first
Advanced Lipid Testing in Philadelphia - measuring ApoB and LDL properly

Scientific References

Ray KK, Wright RS, Kallend D, et al. "Two Phase 3 Trials of Inclisiran in Patients with Elevated LDL Cholesterol." New England Journal of Medicine. 2020;382(16):1507-1519.
Raal FJ, Kallend D, Ray KK, et al. "Inclisiran for the Treatment of Heterozygous Familial Hypercholesterolemia." New England Journal of Medicine. 2020;382(16):1520-1530.
Ray KK, Landmesser U, Leiter LA, et al. "Inclisiran in Patients at High Cardiovascular Risk with Elevated LDL Cholesterol." New England Journal of Medicine. 2017;376(15):1430-1440.
Sabatine MS, Giugliano RP, Keech AC, et al. "Evolocumab and Clinical Outcomes in Patients with Cardiovascular Disease." New England Journal of Medicine. 2017;376(18):1713-1722.
U.S. Food and Drug Administration. Leqvio (inclisiran) prescribing information and approval history. 2021, with label expansions in 2023 and 2025.

Fishtown Medicine | Cardiovascular risk

2418 E York St, Philadelphia, PA 19125(267) 360-7927 hello@fishtownmedicine.comHSA/FSA Eligible

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Frequently Asked Questions

Common Questions

Not proven yet. Inclisiran clearly lowers LDL cholesterol, but the trials testing whether it lowers the rate of heart attacks and strokes are still ongoing, with the first large results expected around 2026. Because lowering LDL by other means reduces cardiovascular risk, inclisiran is expected to help, but that benefit has not been demonstrated in an outcomes trial yet. Statins and the PCSK9 antibodies do have that proof.

Deep-Dive Questions

Both target the same protein, PCSK9, but in different ways. The PCSK9 inhibitors evolocumab (Repatha) and alirocumab (Praluent) are antibodies that bind and remove PCSK9 already circulating in the blood, and they are injected every two to four weeks. Inclisiran works one step upstream, using RNA interference to reduce how much PCSK9 the liver makes in the first place, which is why a dose lasts six months. The antibodies currently have proof that they lower cardiovascular events; inclisiran has proof that it lowers LDL, with the outcome trials still to report.

PCSK9 is a protein made by the liver that controls how many LDL receptors the liver keeps on its surface. Those receptors are what pull LDL cholesterol out of the blood, so they are the body's main way of clearing it. PCSK9 marks those receptors for destruction, so the more PCSK9 you have, the fewer receptors survive and the higher your LDL climbs. Lowering PCSK9, whether by antibody or by silencing its gene, lets the liver keep more receptors working, which drives LDL down. It is one of the most important discoveries in cholesterol treatment of the past two decades.

Because lowering a number and preventing a disease are not the same thing until a trial shows they are. The history of cardiology includes drugs that improved a lab value but did not help patients, and a few that caused harm. That is why we wait for outcome trials that count heart attacks, strokes, and deaths themselves, rather than trusting the cholesterol number alone. For inclisiran, the LDL effect is strong and the mechanism is shared with proven drugs, so the expectation is good, but the ORION-4 trial and the others are what will turn expectation into evidence.

Usually not as a switch. In the trials, inclisiran was added to a statin rather than used in place of one, because statins are proven, inexpensive, and do more than lower LDL. Inclisiran is for when a statin alone, at the highest dose you tolerate, does not bring your LDL or ApoB low enough, or when you cannot take much statin at all. For most people it is an addition to the foundation rather than a replacement for it. Your physician can tell you whether your numbers and risk make it a reasonable next step.

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