One-year outcomes of angina management guided by invasive coronary function testing (CorMicA)

Selected in JACC: Cardiovascular Interventions by N. Ryan , D. Milasinovic

CorMicA was a randomised control trial comparing medical therapy guided by invasive coronary function testing (CFR, IMR and acetylcholine provocation) versus standard care in 151 patients with symptoms and/or signs of ischaemia with no obstructive coronary artery disease (INOCA).

References

Authors

Ford TJ, Stanley B, Sidik N, Good R, Rocchiccioli P, McEntegart M, Watkins S, Eteiba H, Shaukat A, Lindsay M, Robertson K, Hood S, McGeoch R, McDade R, Yii E, McCartney P, Corcoran D, Collison D, Rush C, Sattar N, McConnachie A, Touyz RM, Oldroyd KG, Berry C

Reference

JACC Cardiovasc Interv. 2019 Nov 8

Published

November 2019

Link

Read the abstract

Reviewers

Nicola Ryan

@NicolaRyanI1

Interventional cardiologist / Cardiologist

Aberdeen Royal Infirmary - Aberdeen, United Kingdom

Dejan Milasinovic

@MilasinD18

Interventional cardiologist / Cardiologist

Clinical Centre of Serbia - Belgrade, Serbia

Our Comment

This joint review is part of the PCRonline GLOBAL Journal Club Initiative by selected members of the EAPCI/PCR Journal Club and PCR NextGen, and is based on the underlying idea of “Bringing peers together, exchanging ideas, towards a common standard of care”.

Why this study – the rationale/objective?

Myocardial ischaemia may arise from microcirculatory and endothelial dysfunction, both of which are predictors of poorer clinical outcomes therefore important considerations in the appropriate clinical scenario.

The CorMicA trial demonstrated the feasibility of an interventional diagnostic procedure (IDP) to diagnose or exclude microvascular angina (MVA), vasospastic angina (VSA) and mixed (MVA and VSA) in patients with non-obstructive CAD. At six-month follow-up there was a greater reduction in angina severity in the intervention group, mean improvement in Seattle Angina Questionnaire summary score (SAQSS) (11.7 units 95% CI: 5.0-18.4, p=0.001), with no differences in major adverse cardiac events (MACE) (2.6% vs. 2.6%, p=1.00).

Targeting anginal therapy based on coronary microvascular and endothelial function testing is potentially attractive however, longer-term effects on patient-reported outcomes and MACE are unknown. In this paper, the authors report the extended follow-up to one year.

How was it executed – the methodology?

CorMicA was a randomised control trial in patients undergoing coronary angiography for symptoms and/or proven ischaemia on non-invasive testing. Patients with no evidence of obstructive CAD were randomised in a 1:1 fashion to an IDP (CFR, IMR and Acetylcholine provocation) with the results disclosed to the treating cardiologist (intervention group) or an IDP with the treating cardiologist blinded to the results (control). Treatment was determined by the treating cardiologist based on current guidelines.

The primary endpoint was angina severity according to the Seattle Angina Questionnaire (SAQ) at one year.
Secondary endpoints were 1) health status including quality of life, 2) lifestyle factors: smoking, weight, blood pressure, attendance at cardiac rehabilitation, 3) physical activity and functional capacity, and 4) MACE (all-cause death, non-fatal MI, stroke, unstable angina or heart failure requiring hospitalization).

What is the main result?

CorMicA randomised 151 patients, 75 to the intervention arm and 76 to control. Amongst these patients the majority (73.5%) were female with a mean age of 61 years, 64.2% had typical angina, stress ECG was performed in 62.9% with 47.4% abnormal and 39.0% inconclusive. Of those who underwent radionuclide myocardial perfusion scanning (38.4%), 51.7% were abnormal with the remainder negative or inconclusive. At one year no patients were lost to follow-up with 94% completing the SAQ. Two patients, both in the intervention group died – one from heart failure and one of a malignancy.

Diagnosis following IDP was MVA in 52%, VSA in 17%, Mixed in 20%, non-cardiac chest pain in 11%.
The intervention group had a 27% higher SAQSS (Adjusted mean difference of 13.6 units, 95%CI 7.3-19.9, p<0.001) – this correlates to an improvement of one grade in the Canadian Cardiovascular Society (CCS) classification.
Improved angina related quality of life, reduced angina limitation and reduced angina frequency were seen in the intervention group.
Patient reported quality of life and global treatment satisfaction were higher in the intervention arm with reduced illness perception scores.
Interestingly, blood pressure control was better in the intervention group and the utilization of cardiac rehabilitation more frequent, whereas weight control was similar between the study groups.
There were no statistically significant differences in physical activity between the groups.
There was no difference in MACE or its subgroups between the intervention and control groups at one year (12% vs. 11%, p=0.803).

Critical reading and relevance for clinical practice

The results of this study show that therapy guided by invasive coronary function testing provides a clinically relevant improvement in angina symptoms compared to standard of care; it is likely that this improvement in anginal symptoms is multifactorial. Given the reduced illness perception scores in the intervention arm, it is plausible that simply having a diagnosis for their symptoms provided significant reassurance to patients as well as motivation to comply with medication and lifestyle recommendations. The increased participation in cardiac rehabilitation in the intervention group along with increased prescription of antianginals, ACEi and statins likely reduced symptoms given that control of traditional cardiovascular risk factors along with tailored anti-anginal therapy is the mainstay of treatment in microvascular and vasospastic angina.

A note of caution when interpreting the results, one must bear in mind that this was a single centre study with relatively small numbers in each arm. IDP added 20 minutes to the procedural time, that along with the use of pressure wires increase procedural cost, thus potentially warranting cost-effectiveness studies, given the increased healthcare utilisation in patients with INOCA.

In summary, CorMicA provides randomised control data showing the benefit of individualised therapy based on invasive coronary function testing in patients with angina and non-obstructive coronary disease, in terms of symptoms and quality of life improvement. The one-year MACE rate of 12% further emphasises that microvascular and vasospastic angina, in the absence of obstructive epicardial disease (median FFR was 0.88 in the CorMicA trial), are not benign diagnoses, thus warranting research into the mechanisms of association of microvascular/vasospastic angina with hard endpoints.