Could the ORBITA trial’s enduring value be in prompting the cardiology community to rethink how it diagnoses, treats and even defines angina?
Rethinking old paradigms
The firestorm touched off by the release of ORBITA 40 years after the first PCI was performed in Switzerland was wholly predictable. Presented at TCT.17, the study, which found PCI to be no more effective than asham procedure at six weeks for treating patients with stable angina, was derided by some cardiologists as patently flawed and inconclusive, while others lauded it as courageous, far reaching and a blow to the long-held primacy of PCI (Lancet 2018;391:31-40). Still others, though, preferred to read between the lines of the first placebo-controlled trial of angioplasty for stable angina. They found in ORBITA the seeds for a meaningful new discussion around coronary angina and some of the medical community’s cherished beliefs about how to recognize and treat it.
“Times change, technologies change, medicines change, and something we thought was extraordinarilyeff ective 20 years ago may be less effective today,” observes Robert Yeh, MD, MSc, director of the Total Chronic Occlusion PCI Program at Beth Israel Deaconess Medical Center in Boston. “I think we need to be willing to subject our beliefs to the rigors of testing, and that’s what ORBITA did.”
That broad discussion may have already begun. “For me, one of the most important messages from ORBITA is that angina and ischemia are very complex and multifactorial, and that we need to take a step back as physicians and think about our patients much more holistically,” says Rasha Al-Lamee, MBBS, principal investigator of ORBITA and an interventional cardiologist at Imperial College in London, U.K. “It has certainly changed how I practice, and I hear from others that they feel the same way.”
To many in the field, no clinical fi nding provides a greater rationale for rethinking angina and ischemia as its proximate cause than the fact angioplasty fails to relieve symptoms in so many patients who complain of chest pain. As reported by Joshua D. Mitchell, MD, and David L. Brown, MD, cardiologists at the Washington Universiy School of Medicine in St. Louis, the percentage of patients treated with PCI who continued to have angina at one year ranged from 45 percent in the MASS-II study to 60 percent in BARI 2D to 68 percent in COURAGE (J Am Heart Assoc, online Nov. 13, 2017).
“There are clearly enough people with persistent chest pain for us to step back and try to fi gure out what’s going on,” Brown says. What’s going on in his opinion is something apart from what he calls the centuries-old paradigm that links obstructive coronary artery disease to angina in a one-to-one relationship, eventually leading to myocardial infarction (MI) and death. Instead, he sees ischemia as resulting from multiple mechanistic failures along the vascular conduit, including microvasculature, endothelial dysfunction, flow obstruction or coronary spasm.
Thanks to research and general clinical observation, the notion that not all chest pain is attributable to obstructive coronary artery disease is rapidly gaining currency. Increasingly, microvascular disease—more common in women and people with diabetes or high blood pressure—is believed to be among the causes. As an associate professor of medicine at NYU Langone Health in New York and a cardiologist with a large referral practice involving women with chest pain, Harmony Reynolds, MD, deals with microvascular disease routinely. “I do think it makes sense to rethink this sort of male-centric, obstructive coronary disease way of looking at angina,” she asserts, noting that about half of her patients have open rather than blocked arteries. “We use the term ischemic heart disease to recognize it can be a problem of blood fl ow anywhere from the larger arteries we can see on an angiogram to the tiny branches we can’t see.”
If microvascular disease has failed in the past to get much attention, some in the cardiovascular community profess to see a reason why. “It’s much harder for us to say. ‘That’s a microvascular obstruction’ because we don’t have great tools to diagnose it and we don’t have great treatments for it,” Yeh says. “As doctors, we want to be able to treat or fix something, and epicardial coronary stenosis is something we can see and something we can fix. There are many different cognitive biases that go into wanting to attribute the chest pain we hear about to the obstruction we can see.”
In pursuit of medical therapy
Any revisionist notion of angina and ischemia raises pointed questions about stenting—why it works for some patients and not others, whether it’s too often the more comfortable (or more profitable) default for physicians who might instead be paying more attention to optimal medical therapy for their patients. “We shouldn’t look at studies like ORBITA and think that PCI is in some way ineffective or sham therapy,” maintains Kirk Garratt, MD, MSc, medical director of Christiana Care Health System’s Center for Heart & Vascular Health and president of the Society for Cardiovascular Angiography and Interventions (SCAI). “What we need to be taking away is that if we work really hard to optimize medical therapies before we reach for the balloon and stent, we may find that we can skip the invasive therapy in a lot of patients.”
Therein lies what many in the field believe could be the linchpin of any new model for treating angina—striving for a more aggressive brand of medical therapy coupled with lifestyle changes like healthy eating and regular exercise before proceeding to the cath lab. In ORBITA, patients were enrolled in a six-week medical optimization phase that included antianginal therapy and an assessment of fractional flow reserve (FFR) and instantaneous wave-free ratio (iFR) prior to randomization to PCI or placebo.
Al-Lamee believes that even more important than the stent vs. medical therapy decision should be an upfront commitment by the physician to better manage patient expectations. “Two-thirds of what I do as an interventional cardiologist is stenting patients having heart attacks, so I’m certainly not going to stop stenting,” she notes. “But for the one-third that remains—and I think this is the impact of ORBITA—I’ve changed how I talk to my patients. For those with stable angina and a severe coronary stenosis, I tell them that treatment with a stent might make their symptoms go away, but it might not for a variety of other reasons. And I’ve also started to offer my patients more intensive medical therapy—much more than I did before.”
Critics of ORBITA point out that aggressive medical therapy has limitations. “I don’t have very many patients who are really keen on taking three antianginal tablets one to three times daily so they can play nine holes of golf,” offers Garratt. Given those strictures, the belief is growing that more exhaustive screening and diagnosis to determine which patients are most likely to benefit from optimal medical therapy or from stenting could be the most powerful component of any new treatment paradigm.
“This is about more than interventionalists needing to be more judicious with stents,” insists Yeh. “It really has to do with changing the way patients get to the cath lab in the first place.” That pathway, he elaborates, should be replete with more assiduous history-taking by physicians (an art Yeh feels has been lost), improved stress testing and increased use of FFR, which was shown in the FAME and FAME 2 trials to significantly reduce the number of stents used while improving clinical outcomes (N Engl J Med 2009;360:213-24; N Engl J Med 2012;367:991-1001). FFR is in fact helping to drive the movement well underway toward greater physiologic assessment to determine if an artery is ischemic enough to warrant a stent. Yeh subscribes to what he calls “the Goldilocks principle,” that is, the “judicious use of PCI where it appears to be physiologically relevant” instead of “the indiscriminate use of PCI based on anatomical characteristics.”
Reynolds says she’s already witnessed a more thoughtful approach when it comes to assessing patients with angina. “The trend I’ve been seeing with a lot of physicians is going back to the more old-fashioned way of diagnosing their patients, and really paying attention to long-term risk and not as much to the testing,” she says. “Sometimes that means not going directly from an abnormal stress test to an angiogram. I think we’re beginning to realize that testing less can mean doing more for patients with stable angina.”