1-Year Outcomes of Angina Management Guided by Invasive Coronary Function Testing (CorMicA)

Abstract

Objectives: The aim of this study was to test the hypothesis that invasive coronary function testing at time of angiography could help stratify management of angina patients without obstructive coronary artery disease.

Background: Medical therapy for angina guided by invasive coronary vascular function testing holds promise, but the longer-term effects on quality of life and clinical events are unknown among patients without obstructive disease.

Methods: A total of 151 patients with angina with symptoms and/or signs of ischemia and no obstructive coronary artery disease were randomized to stratified medical therapy guided by an interventional diagnostic procedure versus standard care (control group with blinded interventional diagnostic procedure results). The interventional diagnostic procedure-facilitated diagnosis (microvascular angina, vasospastic angina, both, or neither) was linked to guideline-based management. Pre-specified endpoints included 1-year patient-reported outcome measures (Seattle Angina Questionnaire, quality of life [EQ-5D]) and major adverse cardiac events (all-cause mortality, myocardial infarction, unstable angina hospitalization or revascularization, heart failure hospitalization, and cerebrovascular event) at subsequent follow-up.

Results: Between November 2016 and December 2017, 151 patients with ischemia and no obstructive coronary artery disease were randomized (n = 75 to the intervention group, n = 76 to the control group). At 1 year, overall angina (Seattle Angina Questionnaire summary score) improved in the intervention group by 27% (difference 13.6 units; 95% confidence interval: 7.3 to 19.9; p < 0.001). Quality of life (EQ-5D index) improved in the intervention group relative to the control group (mean difference 0.11 units [18%]; 95% confidence interval: 0.03 to 0.19; p = 0.010). After a median follow-up duration of 19 months (interquartile range: 16 to 22 months), major adverse cardiac events were similar between the groups, occurring in 9 subjects (12%) in the intervention group and 8 (11%) in the control group (p = 0.803).

Conclusions: Stratified medical therapy in patients with ischemia and no obstructive coronary artery disease leads to marked and sustained angina improvement and better quality of life at 1 year following invasive coronary angiography. (Coronary Microvascular Angina [CorMicA]; NCT03193294).

Keywords: coronary physiology; elective coronary angiography; microvascular angina; stable angina pectoris; stratified medicine; vasospastic angina.

Graphical abstract

Figure 1

CorMicA Trial Profile According to CONSORT Requirements The total number of patients randomized was 151 with analysis according to intention-to- treat. There was 98% completion of the primary efficacy endpoint assessment at 6 months and 94% at one year.

Figure 2

Primary Efficacy Endpoint: Quality of Life Mean Scores at Baseline and at 6 and 12 Months The estimated treatment effect in units is stated with 95% confidence intervals at 6 and 12 months (intervention group and control group). Repeated-measures linear mixed model adjusting for baseline differences between the groups. The relative percentage change represents the estimated treatment effect divided by the mean baseline score for the whole randomized population. (A) Primary efficacy endpoint (overall angina severity according to the Seattle Angina Questionnaire [SAQ] summary score). Higher scores represents better (less severe) angina. (B) EQ-5D index quality of life (higher scores represent better quality of life). (C) Illness perception according to the Brief Illness Perception Questionnaire (BIPQ; higher scores represent a more threatening patient perception of illness). (D) Global treatment satisfaction according to the global score of the Treatment Satisfaction Questionnaire for Medication 9 (TSQM-9) validated questionnaire.

Figure 3

Subgroups and Secondary Endpoints: Weight, BP, and Physical Activity Analyses (A) to (C) used linear regression adjusting for baseline value. Mean treatment effect is displayed for each groups with its 95% confidence interval and statistical significance. (A) Analysis of subgroup interaction with estimated treatment effect. (B) Estimated 1-year mean change from baseline in body weight and body mass index (BMI) between groups (intervention, green; control, blue). (C) Estimated 1-year mean change from baseline in systolic blood pressure (SBP), diastolic blood pressure (DBP), and pulse (intervention, green; control, blue). (D) Average functional capacity at 1 year in each group as measured using the Duke Activity Status Index (DASI). Bars represent mean score ± SD. Unpaired Student’s t-test for significant difference in DASI score between groups. The estimated difference between the groups and its 95% confidence interval are displayed. (E) Proportion of subjects in each group participating in cardiac rehabilitation or participating in “moderate” or “high” physical activity according to the International Physical Activity Questionnaire (IPAQ). BIPQ = Brief Illness Perception Questionnaire; BP = blood pressure; RR = relative risk as a measure of effect size with 95% confidence interval and statistical significance for each domain.

Central Illustration

Invasive Coronary Function Testing in Angina (CorMICA): 1-Year RCT Outcomes CAD = coronary artery disease; CorMICA = Coronary Microvascular Angina; RCT = randomized controlled trial.