Cholesterol Basics
Cholesterol is a waxy substance your body needs to build cells and make hormones. The problem isn't cholesterol itself, it's how much LDL cholesterol you have circulating.
- LDL ("bad" cholesterol): deposits in artery walls. Too much builds plaque, narrows arteries, and raises heart attack and stroke risk.
- HDL ("good" cholesterol): helps clear LDL from circulation by carrying it back to the liver.
Cardiovascular disease is one of the leading causes of death in Canada, and roughly 40 percent of Canadian adults have unhealthy cholesterol levels. High LDL over the long term is one of the biggest modifiable contributors.
Statins
How They Work
Statins block HMG-CoA reductase, an enzyme your liver uses to make cholesterol. With less cholesterol coming from the liver, LDL levels in your bloodstream drop. Statins also have anti-inflammatory effects on artery walls, which appears to help stabilize plaque and reduce the risk of plaque rupture.
Common Statins in Canada
- Atorvastatin (Lipitor): a strong LDL-lowering statin, often used in higher-risk patients.
- Rosuvastatin (Crestor): even more potent at the milligram level. Commonly used in familial hypercholesterolemia.
- Simvastatin (Zocor): moderate strength, generally well tolerated.
How Well They Work
Statins typically lower LDL by 30 to 50 percent depending on the drug and dose. Decades of randomized trials show they reduce heart attacks, strokes, and overall cardiovascular mortality across a wide range of patient populations, including people with diabetes, hypertension, and existing heart disease.
Side Effects
- Muscle pain: the most common reason people stop taking them. Ranges from mild aches to disabling pain. Most resolve with a switch to a different statin or a lower dose.
- Liver enzyme changes: usually mild, occasionally requires monitoring or a switch.
- Small increase in diabetes risk: especially in people already at risk. The cardiovascular benefit usually outweighs this.
PCSK9 Inhibitors
How They Work
PCSK9 is a protein that breaks down LDL receptors on the liver. Fewer LDL receptors means less LDL gets pulled out of the blood. Block PCSK9, more LDL receptors stay on the liver, and more LDL gets cleared. The result is a much steeper drop in LDL than statins alone deliver.
These are biologic drugs given as injections, usually every two to four weeks.
Common PCSK9 Inhibitors in Canada
- Alirocumab (Praluent): used for familial hypercholesterolemia and for people who haven't reached their LDL target on max-dose statins.
- Evolocumab (Repatha): similar profile. Used in high cardiovascular risk patients and for FH.
How Well They Work
On top of statins, PCSK9 inhibitors typically drop LDL another 50 to 60 percent. Some patients see reductions over 70 percent. Major cardiovascular event reduction is real, with trials in The New England Journal of Medicine confirming benefit in high-risk patients with existing heart disease.
Side Effects
Generally well tolerated because they don't act systemically the way statins do:
- Injection site reactions: redness, swelling, or itching at the injection spot.
- Flu-like symptoms: occasional fatigue or muscle aches.
- Cognitive effects: rare reports, still under investigation.
How They Compare
Cost
This is the biggest practical difference. Statins are cheap. Generic atorvastatin or rosuvastatin runs $10 to $50 a month in Canada. PCSK9 inhibitors run $600 to $800 a month. Some provincial drug plans and private insurers cover PCSK9 inhibitors for high-risk patients who meet specific criteria, but coverage isn't automatic.
How You Take Them
Statins are a daily pill. PCSK9 inhibitors are a subcutaneous injection every two to four weeks. Some people prefer the less frequent dosing, others don't want anything to do with needles.
Who They're For
- Statins: first-line treatment for almost everyone who needs cholesterol-lowering medication.
- PCSK9 inhibitors: typically reserved for familial hypercholesterolemia, people who can't tolerate statins, or high-risk patients whose LDL stays too high despite max-dose statin therapy.
LDL Lowering
Statins drop LDL 30 to 50 percent. PCSK9 inhibitors on top of statins drop it another 50 to 60 percent. Both classes reduce major cardiovascular events. Statins have 30+ years of trial data, PCSK9 inhibitors about a decade.
Long-Term Safety
Statins are extremely well characterized. PCSK9 inhibitors have less long-term data, but data from people born with natural PCSK9 mutations (essentially genetic PCSK9 inhibition over a lifetime) suggests the approach is safe. Ongoing surveillance will continue to refine the picture.
When PCSK9 Inhibitors Make Sense
Statin Intolerance
The most common reason. Statin-related muscle pain can be mild or genuinely disabling. If switching statins and trying lower doses hasn't worked, PCSK9 inhibitors offer an alternative without the muscle side effect profile.
Familial Hypercholesterolemia
FH is a genetic condition that drives LDL extremely high from a young age. Statins help but often can't get LDL low enough. Adding a PCSK9 inhibitor often brings levels into safer range. For patients with severe FH (homozygous), PCSK9 inhibitors are sometimes the difference between treatable and not.
High Cardiovascular Risk
People who've already had a heart attack or stroke have very low LDL targets. If max-dose statin therapy doesn't get them there, PCSK9 inhibitors can close the gap. The cost is justified by the size of the risk reduction in this population.
Diabetes With Persistent High LDL
People with diabetes have higher baseline cardiovascular risk, and tight cholesterol control matters. If statins aren't getting LDL to target (or are worsening glycemic control), PCSK9 inhibitors are an option.
What Canadian Guidelines Say
The Canadian Cardiovascular Society (CCS) puts statins as first-line treatment for almost everyone with high cholesterol or significant cardiovascular risk. PCSK9 inhibitors come in when statins aren't enough or aren't tolerated.
The Stepwise Approach
- Start with a statin at a dose that aims for 30 to 50 percent LDL reduction. Higher-risk patients usually get atorvastatin or rosuvastatin at higher doses.
- Add ezetimibe if statin alone isn't enough.
- Escalate to a PCSK9 inhibitor if LDL is still above target on max-tolerated statin therapy, or if the patient genuinely can't take a statin.
- Combination therapy: PCSK9 inhibitors plus statins for very high-risk patients.
- Monitor regularly and adjust based on response.
Cost in Practice
Even where guidelines say PCSK9 inhibitors are appropriate, cost limits use. Insurance and provincial plans usually require documentation of FH, statin intolerance, or persistent high LDL despite maximum therapy.
The Bottom Line
For most people, statins are the right answer. They work, they're cheap, and the safety profile is well known. PCSK9 inhibitors fill the gap when statins can't get the job done or can't be tolerated, especially in FH or after a major cardiovascular event. Talking to your doctor about your specific risk profile is how you figure out which approach fits.
FAQ
Can PCSK9 inhibitors cause fatty liver?
There is no strong evidence that PCSK9 inhibitors, like Repatha, directly cause fatty liver disease. In fact, these drugs lower LDL cholesterol without significantly affecting liver fat in most cases. However, monitoring liver function during treatment is standard, particularly in patients with existing liver conditions.
Can Repatha replace a statin?
Repatha (a PCSK9 inhibitor) is typically used when statins alone are insufficient or not tolerated. It can replace a statin for people who can’t use statins due to side effects, but for most, it is prescribed alongside statins to further lower cholesterol levels.
Does Repatha remove plaque from arteries?
Repatha does not directly remove plaque from arteries. It significantly lowers LDL cholesterol, which can slow the progression of plaque buildup and may slightly reduce the amount of existing plaque over time, but it does not physically clear it out.
Who should not use Repatha?
People who should not use Repatha include those with a known hypersensitivity or allergic reaction to any component of the drug. Additionally, individuals with active liver disease or certain liver conditions should use it with caution. Pregnant or breastfeeding women should consult with their healthcare provider to weigh risks and benefits.
Do you stay on Repatha forever?
Repatha is typically used as a long-term therapy for managing cholesterol, meaning patients may stay on it indefinitely. However, this depends on individual health factors, cholesterol levels, and cardiovascular risk. Patients may be advised to continue using Repatha as long as it remains effective and no significant side effects occur.
Does Repatha raise A1c?
Repatha has not been shown to raise A1c levels. Unlike some other cholesterol-lowering drugs, such as statins, which may have a small impact on blood sugar levels, PCSK9 inhibitors like Repatha generally do not have a significant effect on A1c or the development of diabetes.
Is Repatha hard on the kidneys?
Repatha is not typically associated with kidney damage or being hard on the kidneys. Clinical studies have not shown a significant negative impact on kidney function, and it is generally considered safe for individuals with kidney disease. However, as with any medication, kidney function should be monitored in patients with pre-existing kidney conditions.
Disclaimer: This blog post is intended for educational purposes only and should not be taken as medical advice. Always consult your healthcare provider for personal health concerns.