A bold new study could alter the orbit of elective PCI

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Robert Yeh (L) and Yuri Pride (R)

The ORBITA (Objective randomised blinded investigation with optimal medical therapy of angioplasty in stable disease) study, recently presented at 2017 Transcatheter Cardiovascular Therapeutics (TCT) meeting (29 October–2 November, Denver, USA) and published simultaneously in The Lancet, caused a stir in the interventional cardiology community and also in the greater medical, device, and evidence-based medicine communities. Yuri Pride and Robert Yeh review whether the study will change the management of stable angina.

In brief, the ORBITA investigators randomised 200 patients with single-vessel coronary artery disease who had been optimised on medical therapy to either percutaneous coronary intervention (PCI) or a sham procedure. After six weeks, there was no significant difference in increase in exercise tolerance between the groups.

The results were met with astonishment from the majority of the lay press, with headlines splashed across the pages of the New York Times and many other media outlets. This was driven predominantly by a vocal minority among cardiologists who thought the study confirmed what they had long suspected—that PCI was nothing but a very expensive placebo in the era of modern medical therapy for angina. Our assessment, however, is a bit more tempered.

The investigators are to be commended for conducting a bold, original and rigorous sham controlled study of an intervention that is performed in more than 500,000 patients per year worldwide. The angiograms available for review in the manuscript’s appendix are representative of patients who undergo PCI in every institution in the developed world every day.

Implications

To be sure, there are significant lessons to be gleaned from the study:

  • Optimal medical therapy is exceptionally effective at reducing angina in a large proportion of patients with single vessel coronary disease and stable symptoms
  • Performing PCI on stable patients with few or no symptoms on optimal medical therapy is likely of little meaningful benefit, even if the angiogram appears concerning
  • Uptitration of antianginal medication should be aggressive. Given that PCI, while safe, is not without potentially serious complications, doing less than that is a disservice to patients with life-limiting angina.

However, inappropriately overextending the findings of ORBITA may do an equal disservice. The ORBITA trial had a number of features that suggest that its results may not be directly applicable to the management of many patients with stable coronary artery disease. First, the escalation of optimal medical therapy in the run-in phase of the trial was incredibly intense, facilitated by tailored management via phone with an on-call cardiologist one to three times per week and supported by home monitoring equipment given to patients as part of the study. Such rigorous medical management simply may not feasible in most clinical settings.

Next, the majority of patients enrolled had only Class I or II angina and low risk stress tests, and more than a quarter had a fractional flow reserve (FFR) of >0.8 at the time of PCI or sham procedure. There will be keen interest to see whether symptom improvement was greater among those patients with physiologically significant lesions by FFR. This was a trial of angiographic assessment of coronary lesions, and one of the unintended lessons of ORBITA may be that our visual assessment of stenosis is flawed. Physiologic assessment with FFR or instantaneous wave-free ratio (iFR) occurs in only a small minority of patients undergoing PCI in most settings today. ORBITA puts an even greater onus on interventional cardiologists to truly demonstrate both a symptomatic and physiologic need for PCI.

Important caveats of the study remain.  We at this point do not know whether the placebo response observed in the sham arm can be sustained for longer than a six-week period.

Furthermore, whether similar results would be observed in stable patients with more diffuse disease or more severe angina at baseline is unknown. It is probable that there will be many patients who have angina and but have a preference to avoid three antianginal medications or who cannot tolerate them because of headaches, hypotension, bradycardia or other intolerable side effects. PCI can be life changing for such patients, and should and will continue to be offered, with full knowledge that some of the perceived benefit may be related to a placebo effect.

Finally, though this was a study of PCI for stable angina, the lay press and many patients have had a difficult time discerning the difference between stable and unstable patients. Many patients see the words “stents bad” in a headline and wonder what their doctor might have done to them. There is clear and robust evidence that PCI saves lives, prevents myocardial infarction, improves quality of life and is cost effective in patients with acute coronary syndrome. ORBITA does not alter this.

Conclusion

The ORBITA trial put some of our most deeply held notions about the benefits of PCI to the test. The trial has sparked vigorous and important discussions that will ultimately improve how we treat patients with stable coronary artery disease. The results remind us that medical therapy should remain the first approach to alleviate angina for stable single vessel disease, and that the angiographic appearance of lesions alone should not dissuade us from pursuing this approach. Yet, there will continue to be stable patients with physiologically important single vessel disease for whom PCI is the right choice due to the severity of their symptoms or tolerability of medications. In such patients, offering PCI remains the most evidence-based, patient-centred approach.

Yuri B Pride is a practicing interventional cardiologist in the CardioVascular Group in Lawrenceville, GA, USA, and Robert W Yeh is at Cardiovascular Division, Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, USA.

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