The CorMicA Trial: Medical therapy guided by invasive coronary function testing offers symptomatic improvement of angina for patients with nonobstructive coronary artery disease

1. In this blinded, randomized controlled trial, medical therapy guided by invasive coronary function testing offered greater improvements in angina severity compared with standard medical therapy alone.

2. There were no differences in major adverse cardiac events after 6 months.

Evidence Rating Level: 1 (Excellent)

Study Rundown: Coronary artery disease (CAD) and angina are two of the most common medical conditions in North America, and coronary angiography is regularly utilized in part to diagnose and manage obstructive coronary artery disease. However, about half of patients will not have any obstructive coronary artery disease found despite anginal symptoms. Invasive coronary function testing provides higher sensitivity in assessing for microvascular angina (MVA) and vasospastic angina (VSA). This study was the first randomized control trial to assess if invasive coronary function testing linked to stratified medical therapy can provide symptomatic improvement.

The British Health Foundation Coronary Microvascular Angina (BHF CorMicA) study found that use of results from invasive coronary function testing improved recognition of MVA and VSA, reduced symptoms of angina, lowered rates of diagnosis of noncardiac chest pain, and increased rates of anti-anginal therapy as well as secondary preventative therapies such as ace-inhibitors and statins. There were no serious adverse effects secondary to invasive coronary function testing and rates of major cardiovascular/cerebrovascular adverse effects were the same across groups. Although the randomized control trial methodology was a strength of this study, there were some limitations. Firstly, the sample size was small, with only 151 patients randomized across two groups. Secondly, there were several significant differences between the control and intervention group, including more history of stroke/transient ischemic attack (17.1% vs 9.3%), lower rates of definite angina (55.5% vs 73.3%), and lower rates of abnormal myocardial perfusion imaging (43.3% vs 60.7%). In addition, the follow up time was short at only six months. Finally, the primary outcome was patient reported and therefore subjective, and in light of the inability to blind participants/attending cardiologists, there may have been some bias affecting responses.

Click to read the study, published today in JACC

Relevant Reading: Prevalence of Coronary Microvascular Dysfunction Among Patients With Chest Pain and Nonobstructive Coronary Artery Disease

In-Depth [randomized controlled trial]: This was a small, randomized, parallel group, sham-controlled trial with blinded outcome assessment. Inclusion criteria included adult patients referred for elective invasive coronary angiography at two large regional hospitals in the West of Scotland with definite/probable angina based on the Rose angina questionnaire. Exclusion criteria included noncardiac indication for angiography, inability to give informed consent, and obstructive coronary artery disease (CAD) (defined as at least 50% diameter stenosis or fractional flow reserve (FFR) < 0.80. There were 391 patients recruited between November 2016 and November 2017, of whom 151 had nonobstructive coronary artery disease and were randomized. The primary outcome was angina severity using the Seattle Angina Questionnaire summary score (SAQSS) score (scale 0 – 100). Secondary outcomes included health status using the EQ-5D-5L score, a widely used standardized instrument for measuring quality of life (scale -0.59 – 1.00), as well as diagnostic utility (frequency, certainty, and change in diagnosis, missed diagnoses), and clinical utility (impact on management). Outcomes were measured at 6 months. Safety was also assessed based on rate of major adverse cardiac and cerebrovascular events (MACE) including cardiovascular death, nonfatal myocardial infarction, hospitalization for heart failure, nonfatal stroke/transient ischemic attack, and resuscitated cardiac arrest.

All patients had invasive coronary function testing (invasive diagnostic procedures, or IDP) of fractional flow reserve (FFR), coronary flow reserve (CFR), and index of microcirculatory resistance (IMR). This was performed on a single major coronary artery to limit time added to the procedure (left anterior descending artery used unless technical factors precluded this). Patients were randomly assigned 1:1 to either the intervention group (medical therapy stratified according to IDP by attending cardiologist) or the control group (IDP performed but results not disclosed). In the intervention group, IDP results were used to classify patients as either having microvascular angina (MVA), vasospastic angina (VSA), both, or none. This classification was linked to guideline-based treatment for these patients. Attending cardiologists were provided with IDP results as well as information on guideline based management. Letters were also sent to general practitioners of patients in the intervention group with advice on tailoring and optimizing treatment in line with IDP results.

There were 148 patients (98%) who completed the primary outcome assessment (SAQ) at six months. There was greater reduction in angina severity in the intervention group (SAQSS improvement 14.4 vs 3.1, for treatment effect of -11.68 units [95% CI, -4.99 to -18.37, p=0.001]). Change in quality of life score was also higher in the treatment group (0.02 vs -0.07, treatment effect 0.10 [95% CI 0.01-0.18, p=0.024]). In terms of diagnostic utility, frequency of diagnosis of angina due to coronary artery function was 88.0% in the intervention group compared with 46.1% of the control group. Frequency of diagnosis of noncardiac chest pain was lower in the intervention group (16.0% vs 64.5%). In terms of clinical utility, physicians were more likely to include anti-anginal therapy for the intervention group (87.8% vs 48.7%). Secondary preventative therapies (including ace-inhibitors/statins) were also more commonly prescribed at 6 months in the intervention group (58.7% vs 36.8% for ace-inhibitors, 88.0% vs 53.9% for statins). No serious adverse events occurred secondary to the IDP, and rates of MACE were equivalent (2.6% vs 2.6%).

Image: PD

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