It’s understandable if you were otherwise occupied, as it seemed to be a busy news week, but last Saturday the American Heart Association met in Philadelphia where primary outcomes were presented from the much anticipated ISCHEMIA trial.
US taxpayers footed the $100 million bill and 10 years of research for “The International Study of Comparative Health Effectiveness With Medical and Invasive Approaches” the goal of which was to “establish whether a strategy of revascularization with percutaneous coronary intervention (PCI) or surgery, if feasible, results in fewer adverse cardiovascular events than optimal medical therapy alone in patients with stable moderate-to-severe ischemia.”
What did I pay for? In English please?
First, a couple of definitions:
1. PCI (percutaneous coronary intervention): a procedure used to open clogged heart arteries. A tiny balloon catheter is inserted in a blocked blood vessel to help widen it and improve blood flow to your heart.
2. Stent: made of metal or plastic, these are placed during PCI. Most stents used today are coated with a medication to help keep the artery open (drug eluting stents).
3. Statin: medications that can lower cholesterol. They work by lowering your body’s production of cholesterol.
4. Sham surgery: also termed placebo surgery and it is an intervention that omits the step thought to be therapeutically necessary.
Now lets move to some history. Way back in 1999, the AVERT study (Cardiologists seem to have a knack for acronyms in addition to their clinical talents – Atorvastatin VErsus Revascularization Treatment) was published in the New England Journal of Medicine by Dr Bertram Pitt and colleagues, with the hypothesis that “aggressive lipid lowering with atorvastatin appears to be as safe and as effective as angioplasty and usual care in reducing the incidence of ischemic events.” (Note: the brand name of atorvastatin is Lipitor and it is a statin / cholesterol lowering medication). Here were the first data suggesting that opening up a clogged heart artery in patients with stable symptoms may not improve future health outcomes. Critics bemoaned the small sample size (341 patients) and the fact that some participants had such minor disease burden that they didn’t even have symptoms. (We will ignore the fact that in 2004, 85% of all stenting procedures were performed in patient with stable coronary artery disease).
Fast forward to 2007 (still eons ago – I was a medical resident), Boden et al published the COURAGE study (Clinical Outcomes Utilizing Revascularization and Aggressive Drug Evaluation). In this study they found that placing a stent (the small mesh tube defined above) in a narrowed artery of the heart to help keep it open did not work better than medications. It was known at that point that stenting reduced the incidence of death and subsequent heart attacks in patients who presented with acute coronary syndrome (i.e. active heart attack symptoms) but similar benefit had not been shown in patients with stable coronary artery disease
However, the study led to massive criticism, and proper use of stents has since then become one of the most heated debates in medicine. Why? As eloquently stated by Carolyn Y. Johnson of the Washington Post, it is because so much is at stake. “Coronary heart disease affects 17.6 million Americans; companies that make stents are multibillion-dollar enterprises; the procedures are a major income stream to interventional cardiologists and hospitals; and many people who have stents credit their good health to the procedure.” (https://www.washingtonpost.com/…/embargoed-drugs-are…/
One of my favorite studies in this field was published in 2017 by lead investigator Dr Rasha Al-Lamee (Imperial College London, UK) and colleagues. Called ORBITA (Objective Randomised Blinded Investigation with optimal medical Therapy of Angioplasty in stable angina), this UK based study sought to highlight the effect of stenting by adding a study group that had a ‘sham’ procedure. In other words, some patients underwent an apparent intervention but no stent was placed. Among patients with stable angina, even with severe coronary stenosis, exercise capacity and symptom relief were no better after PCI for single-vessel disease than a sham procedure. Dr. Robert Yeh seemed to echo the general reaction by saying, “To extrapolate that this means that elective PCI is not an indicated procedure is the furthest overreach that I can possibly imagine from a very small and I think hypothesis-generating trial with an interesting result.”
So last week’s ISCHEMIA results represent the “latest entry into a long and contentious argument over how to treat artery blockages, one that has pitted powerful factions of American heart specialists against each other” (Johnson; Washington Post). Check out #cardiotwitter
for the debate in real time. But at its essence, not much has changed since 1999 as PCI and medical management are not mutually exclusive. Either can be employed in the correct patient context and, now, there is a better defined framework to discuss risks and benefits.
The best summary and contextualization that I could find on these findings, actually was from 2007 relating to the COURAGE trial. Dr. Eric Topol (a true thought leader in Cardiology and Medicine from Scripps Translational Science Institute, La Jolla, CA) reflected that these types of findings are neither new nor unexpected. “PCI has never been shown to reduce death or MI compared with medical therapy, COURAGE really does not present anything new but simply reinforces that the basis for revascularization is for control of ischemia. There is no surprise with this trial.”
No real surprise either with ISCHEMIA. But, no doubt, the debate will rage on.