A recent study published in The Lancet found that when treating chest pain and “severe coronary stenosis,” percutaneous coronary intervention (PCI) did not “increase exercise time” any more than the placebo procedure did. The findings were somewhat surprising to many in the medical community. Doximity asked some of those in cardiology what they thought about the study and if they saw it impacting their practice at all. Here is what they had to say.
“The ORBITA study is remarkable as the first blinded, placebo-controlled trial of percutaneous coronary intervention (PCI) for stable angina. After optimal medical treatment including dual antiplatelet therapy, all patients underwent invasive physiological assessment with fractional flow reserve (FFR) and instantaneous wave-free ratio (iFR). The patients were enrolled with ischemic symptoms, and severe stenosis in a single coronary artery (left anterior descending in 69 % of cases) based on anatomic (84 % area reduction) and haemodynamic (on-treatment FFR 0.69 and iFR 0.76) assessment. Objective relief of anatomical stenosis was confirmed by invasive and non-invasive indices.
“In conclusion, PCI did not improve exercise time relief of angina beyond the effect of the placebo. Needless to say, the study raises eyebrows in several aspects. First, placebo-controlled randomised trials are needed to rule out the placebo effects of the invasive procedures. Second, the ossified assumption of PCI relieves symptoms in stable coronary artery disease should be revisited with the current medical therapy. Obviously, the study cannot address the situation in multi-vessel disease or long-term myocardial infarction and mortality endpoints. We are all looking forward to seeing the results of ongoing ISCHEMIA trial. The medical community, policy makers, and patient interest groups should call for placebo-controlled randomised trials of PCI in stable angina.”
"Full disclosure — I am a cardiac electrophysiologist and I have never done an angioplasty or cardiac stent procedure. I have always left the plumbing procedures (angioplasties, or PCIs) to my colleagues. My 30-year career in cardiology has seen the development of balloon angioplasty from its infancy all the way to the mature stent technology of today with just about every development in the field in between.
“I marvel at the technological sophistication of interventional cardiology and the skill with which it is practiced. Yet, I have been deeply skeptical about elective or non-acute coronary stenting procedures. I am not a true believer who feels that all cardiac ischemia should be addressed with an invasive approach. I guess I just have a different perspective.
“After all, studies back to 2007 have not shown any long-term decrease in death or in MI in patients receiving PCI procedures. My belief has always been that PCIs are for relief of angina, period. Should stenting be preferentially selected over medical therapy to treat angina since there is no hard evidence for prevention of future cardiac events with an invasive approach? Let’s also factor in that elective PCIs are far from free of potential complications even in skilled hands.
“A wise former colleague once stated to me that ‘the cardiac cath lab is a great place to be if you are having a heart attack — it is not such a good place to be if you are not having a heart attack”.
“ORBITA certainly begins to scratch the surface of my concerns. Yes, larger numbers of study patients are needed, and certainly patients with more complex and multi-vessel CAD need to be included in future studies. The study follow up duration was only for 6 weeks. Pre- vs. post-procedure exercise treadmill times is certainly a pretty soft study endpoint. No study is ever perfect. The work advancing medical knowledge and improving treatments is never complete. Deeper digging into this issue will be needed.
“However, ORBITA is unique in many ways. Finally we have a cardiac study with a placebo group getting sham procedures. (Just like the standard for drug trials!) Also, both the patients and the researchers were blinded to treatments received. Wow! At the very least the investigators have begun to pry open a window allowing us more clearly to see that very powerful biases in treatment choices may have been led by placebo effect more so than measurable changes in physiology. So I say kudos to the investigators.
“A final observation: The 95 study subjects who underwent sham procedures had seven complications (7.3%).
“Three (3.1%) were major bleeding and four (4.2%) had “wire” problems causing the patients to cross over stent implantation. This seems high and starts to concern me as to whether further studies with a sham arm will or even ethically should be done.
“Will practice patterns change? I doubt it. Cardiologists will likely pass this off as just a small study with patients whose disease burden was relatively low. But who knows…. stock valuations for several of the stent manufacturers declined on the release of this study. Never dismiss where the smart money is placed….”
“My initial response to the trial was mixed. On one hand, I was very excited (and amazed) to see the first of its kind, sham-controlled trial in stable coronary artery disease. Not only does this bring to the table the many ethical issues raised by a sham-controlled trial, but it also highlights the dramatic placebo effect, which can result in improvements in endpoints such as quality of life and perception of angina, even with a sham procedure alone. This study sets the bar for (and frankly, brings into question) data from other clinical trials of medical interventions, begging the question of whether all studies of PCI for stable CAD should have had sham-controlled arms. From this perspective, this study was “game changing.”
“However, I want to approach the impact this has on our clinical practice with a “healthy skepticism.” Some of my colleagues are asking after this study, “what have we been doing all this time with PCI in stable CAD if not improving angina and quality of life?” I believe this may be an overstatement of the conclusions. There are many limitations to this study that warrant consideration: (1) The sample size was small (~200 patients) and therefore power to detect differences may have been limited (and of the 95 placebo patients, four ended up getting PCI due to procedural complications). (2) Some patients were already angina free going into the randomization for the trial due to the 6-week medication optimization period. (3) The patients were those with single-vessel CAD. (4) The time point of the trial was short (6 weeks) and the placebo effect may have had attrition over a longer period of time (5) there was an improvement in ischemic burden by dobutamine stress echo (an objective measure of ischemia).
“Keeping these in mind, for my practice, I think the ORBITA study continues to remind me that for my patients with stable CAD and single vessel disease with normal LVEF, shared decision making about the merits of medical therapy +/- PCI continue to be important.”
“I think this trial is interesting from the standpoint that it is comparing an interventional procedure to a placebo in the setting of trying to figure out the efficacy of a procedure. On first glance, there does not seem to be a difference between a PCI and placebo regarding exercise outcomes. However, I was wondering more about the baseline characteristics of the patients in the study (baseline exercise capacity, ejection fraction, location of lesion, etc…) that could potentially affect exercise tolerance in the subjects. Looking more at these characteristics could give more insight into what was behind the lack of difference between PCI and placebo noted in this study.
“Another question is whether there was any difference in symptoms between the two groups; this would be important since the primary concern that patients in this study (and I would argue any cardiac patient with stable angina) would have is whether their pain is relieved from a quality of life standpoint. I think more data is needed before there is a significant change in how often we use PCI for patients with stable angina, but this trial does raise important questions.”
