Are stents better than a placebo?
You would think it would be really easy to prove that putting a stent in a blocked artery reduces chest pain better than pretending to put a stent in a blocked artery.
But it turns out that it’s wasn’t until the end of 2023 do we have some clear evidence that this is actually the case.
ORBITA-2, which was presented at the 2023 AHA conference, asked the question: do patients with severe blockages in the arteries around their heart who have chest pain feel better by putting stents in and increasing bloodflow?
ORBITA-2 comes on the heels of the even-more-provocative ORBITA trial, which suggested that stents may not be better than pretending to put in stents.
ORBITA is one of the most gutsy clinical trials that’s even been run, and ORBITA-2 comes from the same investigators.
To understand ORBITA, you need to be familiar with the placebo effect
The placebo effect is one of the most powerful but most poorly understood phenomena in science.
The mind-body connection is real, but we don’t understand it anywhere near well enough to manipulate it.
It’s not good enough for a medical intervention to improve symptoms - a medical intervention needs to do that better than a placebo.
The challenge with a placebo is that it’s much harder to give somebody a fake procedure than it is to give them a fake medicine.
Harder, but not impossible.
It’s harder because you need to take patients to a procedure room and pretend to do something to them. This usually means breaking the skin and exposing a patient to some degree of procedural risk.
It’s important to use a a sham procedure if you want to show a benefit in a soft endpoint
If you’re studying something that’s obvious to measure - such as likelihood of death - you don’t necessarily need to use a placebo because the placebo effect doesn’t keep people alive who would have otherwise died (as far as we know).
But for soft outcomes like quality of life, pain, functional status, or anything that has room for interpretation, there’s probably value in proving that your non-life-saving intervention that is supposed to reduce symptoms actually reduces symptoms when it’s compared to a placebo.
A few years ago, a paper shocked the world by showing that for many patients with degenerative meniscus tears, surgery isn’t better than pretending to do surgery on functional outcome.
And that’s ultimately why the ORBITA investigators had their studied given the go-ahead by their IRB - there was a lack of clarity about whether stents actually made people feel better than just pretending to put in stents.
Enter the original ORBITA trial - stents aren’t better than placebo (in some patients, over 6 weeks, by some measurements)
The first ORBITA trial has been one of the most talked about trials in the last 20 years.
The investigators randomized patients with severe, single vessel heart disease to stent versus placebo procedure, followed them for 6 weeks while adjusting their medicines
They found that this group of patients (only one major coronary artery blocked) who had some symptoms of chest pain but not the worst symptoms, didn’t have a better outcome over a short period of time compared to the sham procedure.
It’s pretty crazy - some smart people suggested that ORBITA confirmed that stents are mostly bad if you aren’t having a heart attack:
Now comes ORBITA-2 - a different study asking a different question
ORBITA-2 had a really cool trial design that really tried to ensure that the patients in the study were having symptoms related to a blocked artery.
Make sure patients have a severe coronary blockage
Make sure patients have an abnormal stress test documenting that there is a bloodflow problem provoked with activity
Stop the medicines that are reducing their chest pain
Make sure they have angina when off medications
Randomize them to stents versus placebo
It’s a straightforward but rigorous enrollment process.
One of the reasons that we’re at this point - questioning whether stents have a benefit in stable patients - is that lots of patients get stents for bad reasons.
ORBITA-2 was designed to answer the question of whether stents help reduce symptoms of blocked arteries, and the design is pretty elegent.
ORBITA-2 shows us a positive result - when you correctly select patients for stenting, they seem to have a benefit
Look at the proportion of patients who had a reduction in chest pain from the procedure:
Stents seem quite a bit better in reducing the amount of chest pain that patients have compared to a placebo.
But it’s also pretty interesting to note that the placebo seems to reduce chest pain too!
So what does this trial tell us? Well, a few important conclusions can be drawn:
For the correctly selected patient, stents improve symptoms and may lead to a need for less medication
It’s reasonable to use stents as a first line treatment for a patient with symptoms from a blocked artery who prefers a procedure rather than medication
It’s really important to make an accurate diagnosis. The investigators in ORBITA-2 were rigorous about ensuring that patients enrolled in the study actually had chest pain that was due to a blocked artery - remember, they had anatomic information about the patients and evidence of reduced bloodflow from a functional test. They weren’t just grabbing people with an abnormal scan and sending them for stents.
That last part is really important. There’s a difference between stenting something because you *can* stent it versus stenting something because you *should* stent it.
Procedures aren’t risk free - most cardiologists have seen major, life changing or life threatening complications from these procedures.
And so in the case of patients with blocked arteries who aren’t having a heart attack, it’s an important caveat that a stent isn’t life saving.
As a result, ORBITA-2 tells us something really important: for stable patients who won’t have their lives saved with a procedure, stents can reduce symptoms of chest pain better than pretending to put in stents can.
This doesn’t mean that every patient with a blockage and some symptoms needs to rush to the cath lab - remember, these patients had their medications that were reducing chest pain stopped in the run-in phase - and medical management remains a reasonable strategy for these patients.
But ORBITA-2 tells us medical management is not the only reasonable strategy to reduce symptoms of heart disease. Stents work too.