Can PCI Ever Replace Optimal Medical Therapy in Treating“ Stable” Epicardial Coronary Stenosis?

Abstract

EditorialIn 2007, the COURAGE trial was published showing that in the 2287 randomized patients with stable coronary disease PCI was no better than medical therapy in altering outcome over a median followup period of 4.6 years [1]. The same mortality rate observed among the 2 randomized groups held true at late median follow-up of 6.2 years amongst the 1211 patients with available survival data [2]. One major criticism of COURAGE is that PCI (including the nature of the deployed stents and adjunctive pharmacological therapy) has evolved so rapidly in the last 10 years that the COURAGE findings are no longer applicable today. Modern drug eluting stents plus appropriately potent antiplatelet regimes have ensured almost 100% procedural successes with <1% stent thrombosis and low restenosis rates. Prior editorials in the Journal have discussed some of these aspects [3][4][5][6]. It is tempting for one to think that PCI with stenting will fix any stable epicardial coronary stenosis relieving myocardial ischemia with measurable clinical benefit. However, 2 recent trials have reported somewhat unexpected results.In the ORBITA trial [7], a double-blinded, multicentre randomised trial of real PCI versus "sham PCI" for angina relief at 5 UK study sites, symptomatic patients with severe (≥ 70% diameter narrowing) singlevessel stenosis were enrolled. They first received 6 weeks of medical therapy optimisation followed by cardiopulmonary exercise testing, symptom questionnaires, and dobutamine stress echocardiography. Then, they were randomised 1:1 to undergo PCI or a placebo procedure. In both groups fractional flow reserve (FFR) and instantaneous flow reserve (iFR) were measured. These FFR and iFR measurements required introducing special coronary wires across the coronary lesion so all patients actually needed the cath lab procedures. Patients were sufficiently sedated together with "auditory isolation" that they were unaware as to whether they received real or sham PCI. Six weeks after the procedure the aforementioned non-invasive assessments were repeated. The primary endpoint was difference in exercise time increment between groups.Of 230 patients enrolled, 200 were finally randomised in the period from January 2014 to August 2017 after completing the medication optimisation phase. The coronary lesions had mean area stenosis of 84·4%, FFR of 0·69 (FFR <0.75-0.8 generally considered significant indicating myocardial ischemia in the subtended territory), and iFR of 0·76 (iFR <~0.9 generally considered significant). All PCI procedures were successful but the primary endpoint, exercise time increment between groups (PCI minus placebo), was only non-significantly higher by 16·6 seconds (P=0.20).Intervention trials with "clinical procedures" are almost always confounded because of the absence of patient blinding unless sham procedures are performed in the control group with all their implications. In the hypertension field, there had been high hopes for renal denervation until it was refuted by the sham-procedure controlled S...