Coronary Microvascular Resistance as a Predictor of the Placebo-Controlled Response to Percutaneous Coronary Intervention: Microvascular-Stratified Analysis of ORBITA.

BACKGROUND

The first placebo-controlled trial of percutaneous coronary intervention (PCI), ORBITA (Objective Randomised Blinded Investigation With Optimal Medical Therapy of Angioplasty in Stable Angina; NCT02062593), showed minimal symptom benefit with PCI. No placebo-controlled data describing the relationship between microvascular resistance (MVR) and PCI exist. The authors hypothesized that patients with low MVR would derive the greatest benefit from PCI.

OBJECTIVES

The aims of this study were to compute MVR in patients recruited for ORBITA and to evaluate interactions with prespecified endpoints.

METHODS

Hyperemic MVR was calculated using computational fluid dynamics (CFD) and compared against placebo-controlled changes in treadmill exercise time, patient-reported symptoms, physician-assessed symptoms, and dobutamine stress echocardiography scores at 6-week follow-up.

RESULTS

MVRCFD was computed for 131 patients (66 undergoing PCI and 65 placebo). Median MVRCFD was 1.38 mm Hg · min/mL (Q1-Q3: 0.89-2.09 mm Hg · min/mL). Baseline exercise time correlated with MVRCFD (ordinal correlation coefficient = 0.20; 95% credible interval [CrI]: 0.18-0.22). For patients with low (20th centile) MVRCFD, PCI increased exercise time by 48 seconds vs placebo (95% CrI: 6-92 seconds; Pr = 98.5%). Exercise time did not improve for patients with high (80th centile) MVRCFD (16 seconds; 95% CrI: -29 to 61 seconds; probability of significant difference [Pr] = 75.2%), but evidence for an interaction was modest (Printeraction = 83.1%). Low MVRCFD was also associated with a placebo-controlled benefit of PCI for likelihood of complete freedom from angina (Pr = 98.8%) and improvements in angina frequency (Pr = 97.8%) and stress echocardiography scores (Pr = 99.9%).

CONCLUSIONS

The placebo-controlled benefit of PCI was greater in patients with lower MVRCFD, but interactions with symptom-based endpoints were modest. For patients with severe single-vessel disease taking optimal medical therapy, microvascular dysfunction may attenuate the functional and symptomatic benefits of PCI.