Table 1

Insights from recent randomised controlled trials specific to patients with NOCAD and CMD.

Trial, journal and yearPatients with NOCAD (n)Pertinent results in patients with NOCADTake home messages for NOCAD
FAME-2, NEJM, 201213 332/1220 (27%) of patients had an FFR >0.80
  • Similar CCS angina class compared with FFR <0.80.

  • Similar levels of silent ischaemia compared with FFR <0.80.

  • MACE rate of 9% in 2 years.

  • Patients with NOCAD have similar symptom burden to patients with CAD.

  • Patients with NOCAD have a high MACE rate.

PROMISE, NEJM, 201536 4477/4996 (90%) of patients in the CTCA group had a ‘negative’ result
  • 89% of patients had typical or atypical angina in both groups.

  • Only 10% of patients in the CTCA group had angina attributable to CAD.

  • A large proportion of anginal symptoms are attributable to NOCAD in patients with an intermediate PTP of CAD.

SCOT-HEART, Lancet, 201537 1326/1778 (75%) in the CTCA groups had anatomical NOCAD
  • CTCA-guided therapy resulted in a reduced diagnosis of angina due to CAD, prompting alteration of therapy in this group, and deterioration in QoL and symptoms.

  • Patients in the CTCA group with a change in diagnosis, either confirming obstructive CAD or excluding CAD had the greatest improvement in symptoms, while those with non-obstructive CAD had the least improvement in symptoms.

  • In a population with high predicted 10-year CHD risk, NOCAD is common.

  • Defining NOCAD anatomically (instead of with FFR) may explain the poorer outcomes in the non-obstructive CAD group.

  • Inappropriate cessation of antianginal therapy in patients with NOCAD with CMD may have attenuated symptom improvement derived by identifying CAD and revascularisation leading to symptom neutrality when adopting a CTCA-guided approach.

CE-MARC 2, JAMA, 2016 38 139/265 (52%) of patients who underwent angiography had NOCAD
  • All 1202 patients had angina with 401 (33%) having typical angina.

  • A minority of patients had a positive non-invasive test (12.4% in the CMR group, 18.2% in the MPS group and 13.4% in the NICE guideline group).

  • Adhering to NICE guidelines results in a frequent diagnosis of NOCAD.

  • The rate of ‘unnecessary angiography’ was nearly double in women, compared with the rate in men.

ORBITA, Lancet, 201739 57/200 (29%) of patients had an FFR >0.80
  • In a sham-placebo trial, PCI was found to be equivalent to OMT in providing symptom relief.

  • Patients with angina and FFR >0.80 also underwent PCI and may have diluted effects between the groups.

  • NOCAD is common among lesions judged to be visually severe.

  • Differences in microvascular physiology is postulated to have contributed to inconsistent benefits of PCI.

ISCHAEMIA and CIAO-ISCHAEMIA substudy, tba40 5179 patients with moderate ischaemic burden have been randomised to an invasive approach versus OMT (ISCHAEMIA trial)
  • A proportion of patients with moderate-to-severe ischaemia on stress testing have NOCAD (enough to justify forming the CIAO-ISCHAEMIA substudy).

INOCA is an increasingly recognised entity that warrants specific management.
  • CAD, coronary artery disease; CCS, Canadian Cardiovascular Society; CFR, coronary flow reserve; CMR, cardiovascular magnetic resonance; CTCA, CT coronary angiography; FFR, fractional flow reserve; INOCA, ischaemia with no obstructive coronary disease; MACE, major adverse cardiovascular events; MPS, myocardial perfusion scintigraphy; NICE, National Institute for Health and Clinical Excellence; NOCAD, non-obstructive coronary artery disease; OMT, optimal medical therapy; PCI, percutaneous coronary intervention; PTP, pretest probability.