I was put on an LDL lowering drug which unfortunately had severe side effects causing significant swelling on the tops of my feet and much swelling in my lower legs. It also caused pain in both outer hips, the gluteal muscles, the thigh muscles and pain on the outside of my lower legs.
I was on this for six months and by month two, I could no longer do my multi-mile walks/hikes, hill and stair climbs. In another month, I had to use hiking poles just to walk inside my home due to extreme pain.
During this time I brought this up to my health care team (2 doctors, PAs, etc) but was told that lots of patients have this medication and they had no problems …. I have since learned that I need to be assertive and far more pro-active.
Fast forward to 5 and 1/2 months and I told them I would discontinue my meds if we didn’t sort this out. That got attention and they told me to discontinue the medication.
At 2 and 1/2 weeks since the last injection, the swelling in the lower legs is down by 95%, the swelling in the left foot is down by 90%, and the swelling in the right foot is down by 75 to 80%. This is inline with reported recovery from this side effect – 1-4 weeks for the swelling to end, and then an additional 1-2 months for the pain to gradually subside. Recovery takes a long time because the half life of the drug is up to 3 weeks. That means it takes about 3 weeks for half of it to clear out – and 4 to 5 half lives to be considered out of your system (12-15 weeks).
I am now able to walk again without using hiking poles – albeit, there is still pain and while I can now walk outside without a hiking pole, doing so for any distance ends up being sore afterwards.
I pulled up the drug’s background information and what surprised was how low the benefit of the drug is – and that this benefit was only demonstrated in a sample population that did not represent me.
Specifically, my LDL has always been below 100. The study population only included those with LDL >100, which could be far higher. The study population only included those who were already on statins AND the new drug; I am unable to take statins (of the 2 that were tried).
- Within this population, all cause mortality was reduced by 0.6%.
- Other endpoints were reduced by 1.0% to 3.4%.
The first reduction – 0.6% – means that for every 1000 patients taking this medication, there were 6 fewer deaths. However not shown in the sales pitch, up to 15% or 150 patients likely suffered myalgia and arthralgia (in real world data from their competitor, and based on real world data collected by some reputable online databases). Up to 30% likely experienced at least one side effect, but most were mild and short lived.
MACE = Major Adverse Cardiovascular Events
It’s a composite endpoint commonly used in cardiovascular trials, typically including:
- Cardiovascular (CV) death
- Non-fatal myocardial infarction (MI)
- Non-fatal stroke
- Sometimes unstable angina or hospitalization for ACS (acute coronary syndrome)
They measure what percent experienced a “MACE”.
1. Small Absolute Risk Reduction (ARR)
- All-cause death ARR = 0.6% → That means for every 1000 patients treated for a time, 6 fewer deaths.
- CV events overall ARR = 1.0–3.4% → 10–34 fewer CV events per 1000 patients.
These are small absolute benefits, when weighed against cost, side effects, and long-term adherence.
Relative Risk Reduction (RRR) can sound impressive — e.g., “30% reduction!” — but if baseline risk is low, ARR is what matters clinically.
The drug cost me $700 for 90 days, every 90 days. It is covered by my drug insurance but only after a fairly large deductible has been reached.
2. Study Population Bias
- Baseline LDL >100 + on statins → This is a high-risk, already-treated group.
- But the drug is being used in broader populations (e.g., statin-naïve) → Generalizability is questionable.
This is a classic case of “efficacy vs. effectiveness” — the trial shows benefit in a controlled, selected group, not necessarily in real-world, unselected patients.
3. Confounding by Statin Use
- Statins themselves reduce MACE.
- If the new drug is added on top of statins, the incremental benefit may be small. Indeed, the study compared the test group (drug + statins + prior high LDL) to a group taking only a placebo.
- Giving it to statin-naïve patients? The benefit might be smaller or nonexistent — unless the drug works differently.
The benefits appear modest, and the trial design limits real-world applicability.
In addition to being disabled for months, the experience of this drug was costly.
I spent $1000s out of pocket on the drug and on physical therapy services trying to address the pain. I was diagnosed at various times with trochanteric bursitis and gluteal tendinopathy – which is something that was reported by in the trial studies (said online search).
I now have $700 worth of the drug in my refrigerator that will be thrown out.
I may as well have set my wallet on fire!
The drug, by the way, is a PCSK9 inhibitor named Praluent, made by Regeneron and Sanofi.
It is similar to their competitor Repatha, which has similar side effects.
Both are very effective at dramatically lowering LDL numbers. Unfortunately, medicine is treating numbers and not health, as seen by the small absolute risk reductions, above.
At the end of this six months, I am worse off than before I started on this “medication”. Unable to exercise, I was unable to improve my heart functions. Frequently unable to stand for more than a few minutes, I was unable to prep “hearth healthy” meals of the type I’ve long done.
This drug caused actual harm – in another 1-2 months the pains should have subsided so that I can resume my exercise program. It expect it will take another 2 months, at least, to get back where I was last September and be able to fully resume my exercise program.
During this period – 4 days after I started the drug – I experienced a systemic bacterial infection (very unlikely it was related) that put me in the hospital on IV antibiotics and later oral antibiotics. I did not learn until days ago what antibiotics they gave me – BOTH were already listed in my records as causing allergic reactions. But no one told me what they were giving me, nor that they were giving me antibiotics to which I had a known allergic reaction!
What do you suppose happened after I was discharged? A severe allergic reaction that took 4 weeks to recover from. My entire body from head to toes was covered in raised, red, itchy welts – and eventually my face swelled up. Since I have food allergies, I had the medications on hand to address this and did not have to go to the ER – which is the only option for most people.
May be they had to give me those specific antibiotics – but they should have informed me of what they were doing and what was likely to happen.
The experience has left me disillusioned.
Reference: ODYSSEY OUTCOME Presentation
