A New Mini-Series on the Study of the Week: What Does it Mean to Discover a Coronary Blockage?
Many people--including prominent podcasters--believe that discovering a coronary blockage is a great idea. Let's look at the actual studies. You will be surprised.
Coronary heart disease is a leading killer. Coronary heart disease can be silent until it presents with a severe heart attack or silent death.
The idea of using technology to find these partial blockages before they cause a severe event makes perfect sense. You can call this the clogged pipe frame of cardiology.
Many people, now including prominent podcasters, has joined the advocacy for early detection of atherosclerotic disease. Because, if you know there is a widow-maker-like lesion, a cardiologist can fix with it with a stent or a surgeon can bypass it.
Yet, one of the most fascinating parts of cardiology is that nearly all of the empirical evidence refutes the clogged pipe frame of atherosclerosis.
In a series of columns, using randomized controlled trials, I will show you why simple thinking fails. In the end, I hope to show the folly of “screening” for heart disease.
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Let’s start in 2007.
The New England Journal of Medicine published the COURAGE trial.
In many centers, patients with severe but stable coronary lesions and known ischemia on stress testing were randomized to two groups of initial therapy: one got percutaneous coronary intervention (PCI or stent) and medical therapy and the other group got medical therapy alone.
(Crucially, these were stable patients. Patients having acute heart attacks definitely benefit from urgent opening and stenting of the blockage.)
Either group could have further intervention if symptoms occurred. About 1 in 5 patients in the PCI group had additional revascularization (stents or bypass) while 1 in 3 patients in the medical arm eventually had revascularization.
The choice to name the trial COURAGE was apt as this was the heyday for PCI and stents. Rare was a cardiologist who did not stent any severe narrowings.
The primary endpoint of COURAGE was death or MI. Followup was nearly 5 years.
And boom. COURAGE sent shocks through the cardiology world: No difference. No difference in the composite, no reduction of death, and no reduction of MI.
COURAGE investigators did not rest.
Over the coming years, they published many sub-studies, looking for a group of patients who might benefit from the addition of PCI. Surely those with multi-vessel disease or LV dysfunction or those who crossed over from the medicine group to PCI would benefit.
Nope. None of them.
The COURAGE investigators even carried out their study to ten years. And again, they reported no difference in outcomes.
You might wonder how PCI remained so popular after such a definitive study. One reasons was the relief of angina or chest pain.
A year later, in 2008, COURAGE trialists published a follow-up paper looking at quality of life.
Here is the key graph.
In the first two years, there were more angina-free patients in the PCI arm. But by three years, there were no differences. The relief of angina was transient.
Of course, I know what you are thinking. Yes, COURAGE was an unblinded study.
Both groups knew they had bad blockages, and one group knew they were “fixed”with a stent and the other group knew they were not. And angina is pain, and pain is subjective, so of course it is hard to sort out the significance of these differences without blinding.
Short-term angina relief was not the only reason cardiologists largely ignored COURAGE—and pressed on with the use of stents.
One criticism was that COURAGE largely did not use drug-eluting stents, which are felt to be better. Except that is quite debatable.
Another criticism was patient selection.
Proponents of stents said that the worst patients were excluded from COURAGE. This is a reasonable critique because patients were randomized after the coronary angiogram. Doctors may have randomized only their best patients. Any patients who induced worry because of more complex disease may have been excluded from the trial.
Against this argument, however, are the multitudes of COURAGE substudies looking at the most severe patients. None showed an advantage to initial PCI.
COURAGE may not have immediately changed the practice of coronary angiography and stents and bypass, but it was a landmark study that started convincing cardiologists (and patients) that atherosclerosis was a diffuse disease.
The focal narrowings seen in the coronary vessels were one manifestation of the diffuse disease. Medical therapy treated the diffuse disease. Stents merely relieved the focal lesions. (Of course, at the cost of leaving a metal cage in the artery, and the need to take drugs that inhibit platelet function over the longterm.)
COURAGE found that in patients not having an acute heart attack, there was no need to initially open a narrowing. You could treat with medicines and lifestyle, and reserve stents for patients with symptoms.
Look at those death and MI curves. Absolutely no difference. Yet to took decades and many more millions invested in other trials to convince cardiologists to favor medical therapy over stents.
Future posts will consider the coming landmark studies in this field. Stay tuned.