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 major pain in both outer hips, the gluteal muscles, the thigh muscles and pain on the outside of my lower legs – to the point walking was very difficult.
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 more pro-active.
Fast forward to 5 and 1/2 months and I insisted we needed to sort this out – the med was discontinued.
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 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 was surprised by the smaller benefits than I was expecting – and that this benefit was demonstrated in a sample population that did not represent me.
Specifically, my LDL has always been below 100. The study population included those with LDL >100, which could be and likely was far higher. The study population only included those who were already on statins AND the new drug.
- Within this population, all cause mortality was reduced by 0.6%.
- Other endpoints were reduced by 1.0% to 3.4%.
In medicine a 2 to 3% reduction can be considered good, but might not be what you or I were expecting.
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, many may have suffered myalgia and arthralgia (Amgen, maker of its competitor PCSK9 inhibitor Repatha says 13.8% experience muscle pain or joint issues in real world usage.)
MACE = Major Adverse Cardiovascular Events
MACE is 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)
Studies 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 period, 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.
Because absolute risk reduction is often small, drug makers promote relative risk reductions instead. If 11% of patients have outcome X, but just 9% on the drug have outcome X, then they say this is a 20% relative risk reduction, while the ARR is 2.0%.
Relative Risk Reduction (RRR) can sound impressive — e.g., “30% reduction!” — but if baseline risk is low, ARR is what matters clinically.
When they discuss benefits, they use the larger relative risk percentage. When they discuss side effects, they use the much smaller absolute percentage. This biases the interpretation – 20% (relative) risk reduction but only 3% experienced side effects!
The drug cost me $700 for 90 days, every 90 days. It is covered by my drug insurance but only after a 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.
One can argue that I am “high risk” – but then again, its not clear that LDL was the cause of my heart problems. Long term vitamin B deficiency, for example, might have been the root cause problem.
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.
Subsequent studies have proclaimed, say for Repatha, that they achieve around 25% relative risk reductions in cardiovascular events. They also presume that side effects are non-existent or not an issue (but that was not the case for me).
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 some 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. However, the ultimate outcomes – future CV events or death are attenuated by just a little.
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 function. 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. Immediately before I began this med, I was walking 3-4 miles per day, doing some steep hill climbs, and the 64 stair steps out of a local canyon (and doing this several times up and down). But within about 6 weeks of starting praluent I could no longer even walk short distances on the mostly level.
This drug caused me harm and has set back my heart health by probably six months.
I am told that in another 1-2 months the pains should subside so that I can resume my exercise program. 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.
References
There appear to be benefits but they are smaller than some of us might expect, and might be concentrated towards those with multiple or worse conditions. There are many, many papers published on this topic, more than I have time to read. Reminder – I am a brain injured retired computer engineer and have no formal training in any aspect of health care or biochemistry – please ignore anything I have said.
This is a partial list of references – I have not added all of them.
There is a similar study, FOURIER, done for Repatha. I read a review of that study but have not read the actual study. The results seem similar to those for Praluent.
Effects of alirocumab on cardiovascular and metabolic outcomes after acute coronary syndrome in patients with or without diabetes: a prespecified analysis of the ODYSSEY OUTCOMES randomised controlled trial – PubMed (tested patients with high lipoproteins even when already on statins. 28.8% were diabetic and 43.6% were pre-diabetic)
Metabolic risk factors and effect of alirocumab on cardiovascular events after acute coronary syndrome: a post-hoc analysis of the ODYSSEY OUTCOMES randomised controlled trial – PubMed (if you have a lot of risk factors, the ARR of praluent goes up versus those with zero or few risk factors)
Effect of Alirocumab Added to High-Intensity Statin Therapy on Coronary Atherosclerosis in Patients With Acute Myocardial Infarction: The PACMAN-AMI Randomized Clinical Trial – PubMed (Reduced existing plaque in arteries, post MI, by about 1 percentage point in terms of volume.)
