Every once in a while, a medical research study is published that significantly alters clinical practice. The paper on percutaneous coronary intervention (PCI) in patients with stable coronary artery disease, published in the prestigious New England Journal of Medicine on March 26, 2007, is one such study. The results show that PCI plus optimal medical management (lifestyle changes and drugs) are no more effective than optimal medical management alone at preventing heart attacks and death in individuals with stable coronary artery disease.
In the NY Times’ story about the study, Steven E. Nissen, MD, President of the American College of Cardiology, describes the study as a blockbuster. And indeed, it could lead to some folks’ blocks being busted (particularly stent companies, such as Boston Scientific and the Cordis Cardiology division of Johnson and Johnson, as well as invasive cardiologists who perform these procedures).
The name of the study is COURAGE, an apt description for a study that is likely to be attacked vigorously by people who stand to lose in the high stakes arena of invasive cardiology. COURAGE stands for “Clinical Outcomes Utilizing Revascularization and Aggressive Drug Evaluation.”
In order to understand what these researchers were trying to determine, it is important to understand a bit about what causes heart attacks. Years ago, we used to think heart attacks were caused because one or more blood vessels supplying the heart became progressively more narrowed by atherosclerotic plaques, perhaps even closed off completely, thus, depriving the heart muscle of oxygen.
As we have learned more about the anatomy and physiology of coronary artery plaques, we have discovered that the plaques that cause heart attacks and other acute coronary syndromes, such as unstable angina, are prone to rupture, lead to clot formation, and, in that manner, block the coronary artery.
These vulnerable plaques, according to the NEJM article, tend to “have thin fibrous caps, large lipid cores, fewer smooth muscle cells, more macrophages [inflammatory cells], and less collagen” than stable plaques. They also tend to grow outward in the coronary artery wall. Thus, before they rupture, they actually cause less blockage (stenosis) of the coronary artery lumen than stable plaques.
Stable plaques can cause symptoms of shortness of breath and chest pain with exertion, but they are less likely than unstable plaques to cause a heart attack or the worst outcome, sudden death.
This is an important point so I will repeat it by quoting from the article:
“…unstable coronary lesions that lead to myocardial infarction are not necessarily severely stenotic, and severely stenotic lesions are not necessarily unstable.”
The study is a well-designed randomized trial with enough participants, 2,287 in all, to detect small differences between the two groups. One thousand one hundred and forty-nine (1,149) patients were assigned to undergo PCI with optimal medical therapy and 1,138 to receive optimal therapy alone. The primary outcome was non-fatal heart attack or death from any cause. Participants were in the study between 2.5 to 7 years (median 4.6 years).
There were 211 of the above described primary events in the PCI group and 202 in the medical therapy group. This translated to a 4.6-year cumulative primary-event rate of 19% in the PCI group and 18.5% in the medical therapy group. There were no significant differences between the PCI group and the medical-therapy group in the composite of death, heart attack, and stroke, nor in the percent hospitalized for an acute coronary syndrome, such as unstable angina, nor in the percent that had myocardial infarctions.
The PCI group did have a greater decrease in symptoms (shortness of breath or chest pain) compared with the medical management group. But it is important to note that there was a substantial reduction in angina in both groups during follow up and, by 5 years, the percent free of angina was similar in both groups. Fewer individuals (21.1% vs 32.6%) had to undergo a subsequent revascularization for angina (chest pain) unresponsive to maximal medical therapy or when there was worsening ischemia (oxygen deprivation of heart muscle).
Advocates for PCI are going to try to find reasons why PCI should still be used to prevent heart attacks. In the NY Times article, Dr. David Kandzari of J&J’s Cordis Cardiology (stent company) points out that the individuals in the trial were largely from the Veterans Hospitals in the U.S. and Canada and, therefore, usually get their medications for free. Yeah, so that is a reason for a $25,000 procedure instead of finding a way to get those at risk the relatively inexpensive generic medications used in this study.
Others will point out that bare metal stents were used in most of the patients in the study. Drug-eluting stents were not available until the end of the study. Perhaps, there would have been a greater difference in symptoms if the drug-eluting stents were used. Maybe, but there is no evidence that drug-eluting stents prevent deaths or heart attacks in stable patients, and there is the recently described problem of late-forming clots that has led some cardiologists to switch back to bare stents.
Another important lesson from the study
I do think there is another very important takeaway lesson from this study. All you doctors out there should study Table 2 of this study carefully. These people were aggressively managed. This is not usual care. LDL levels were lowered from about 100 to the mid-70s after five years. Average blood pressure went from a 130/74 range to 122 to 124/70-72. HDLs increased slightly and Hemoglobin A1cs were maintained in the low 7s. There was a substantial increase in individuals following the American Heart Association diet and there was an increase in the percentage of people who participated in moderate physical activity.
Now, we all know that it is hard work for people with heart disease to take a bunch of medications and change their lifestyles. It is also hard work for doctors and other clinicians to provide support for people as they try to make these changes. On the other hand, if we could take even a portion of the $25,000 spent on each PCI and apply it to buy support for people trying to make these changes; we probably could help folks in the general population achieve the same remarkable adherence to an optimal medical regimen. How many hours of nutritional counseling and personal training could be bought for even a fraction of that amount…week after week, for years? Not only would it be affordable in the long haul, there probably would be enough money left over to buy or subsidize the generic medications as well.
Isn’t it time we to start paying for the right stuff in healthcare?