30 HOW TO TREAT: ISCHAEMIC HEART DISEASE IN WOMEN
30 HOW TO TREAT: ISCHAEMIC HEART DISEASE IN WOMEN
20 JUNE 2025 ausdoc. com. au
PAGE 27 either calcium channel or beta blockers. 112 Dyslipidaemia contributes to coronary endothelial dysfunction. 113 Statins are beneficial in non-obstructive CAD and their anti-inflammatory properties may be effective in patients with reduced CFR and vascular spasm. 114, 115 Statins reduce exercise induced ischaemia, improve flow-mediated dilation in INOCA, improve CFR and coronary microcirculation. 116-18 Patients with diabetes often have impaired coronary vasodilation and flow regulation, and insulin resistance and metabolic syndrome
119, 120 are associated with CMD. The US WARRIOR( Women’ s Ischemia Trial to Reduce Events in Non-Obstructive CAD) is an ongoing prospective randomised trial of 4422 women with INOCA investigating intensive medical therapy, including high-intensity statins and ACE-I or ARB versus usual care and will provide further insight into the management of INOCA. 121
ANTIANGINAL THERAPY Microvascular angina can be treated with a beta blocker( particularly with vasodilatory effects such as nebivolol), calcium channel blockers, nicorandil and lifestyle modifications. 24 Start with a low dose and increase according to tolerance and symptom relief. In women with CMD, ACE-I improves CFR and anginal frequency. 112 Statins and ACE-I / ARB therapy improve microvascular function.
In perimenopausal women without obstructive CAD, a combination of a low-dose alpha / beta blocker or selective beta blocker( nebivolol, bisoprolol) with a calcium antagonist( diltiazem) can be highly effective in reducing anginal symptoms, as oestrogen loss can induce autonomic dysfunction with a fast rise in heart rate during exercise. 122 Long-acting nitrates may aggravate symptoms in MVA because of a stealing effect. 123
Nicorandil, a vasodilatory agent acting via nitrate and potassium channel activation, can also be effective, although side effects are common. 124
Treat coronary artery spasm( either epicardial or microvascular) with calcium channel blockers( CCB) as first-line. 24 These reduce angina and are cardioprotective, with their cessation associated with an increased risk of MACE. 125, 126 The choice of CCB depends on heart rate, BP and drug interactions. Patients with severe VSA may require high doses of a CCB or a combination of a hydropyridine with a dihydropyridine CCB. Long-acting nitrates are used, given the pain is responsive to nitrates, with short-acting nitrates on
24, 127 demand for chest pain.
Nicorandil and cilostazol also have data as antianginal agents in vasospastic angina
128, 129
.
OTHER THERAPIES Ranolazine, a late sodium channel inhibitor, is effective in obstructive CAD with potential benefit in patients with low CFR shown in one study. 130
Ivabradine, a selective inhibitor of the sinoatrial current that decreases heart rate without affecting contractility, may be effective in patients with persistent anginal symptoms. 131
Adapted from Beltrame JF et al 2021 81
Figure 5. Common causes of chest pain in patients with non-obstructive coronary arteries.
Dr Ru-Dee Ting
Myocardial bridge
Myocardial bridging is a congenital anomaly of the coronary artery where the overlying myocardium partially or completely encases a segment of the coronary artery. 132 This is most commonly asymptomatic and an incidental finding. In a minority, the obstruction may lead to myocardial ischaemia / angina / ACS, arrhythmia and sudden cardiac death. The condition is diagnosed invasively( coronary angiography with or without intravascular ultrasound [ IVUS ]) or non-invasively( CTCA / cardiac MRI).
Lifestyle modification, such as mindfulness-based stress reduction, and risk factor management
Adapted from Kunadian V et al 2020 24, Beltrame JF et al 2021 81, Reynolds HR et al 2022 90
Chest pain without obstructive coronary artery disease
Coronary angiography
Pressure wire and adenosine- Exclude obstruction( FFR > 0.8)- Coronary microvascular dysfunction( CFR < 2, IMR ≥ 25)
Coronary macrovascular dysfunction
Vasoreactivity- acetylcholine provocative spasm test
Cardiac causes
Non-cardiac causes
are appropriate for patients with mild symptoms / asymptomatic. Beta blockers relieve symptoms by lowering heart rate and increasing diastolic filling time, thus lowering the artery’ s contractility and compression. 25 If vasospasm is present, beta blockers should not be used in isolation. Nitrates worsen symptoms by vasodilating both the proximal and distal portions of the vessel adjacent to the bridge, increasing systolic compression of the bridged segment, and are contraindicated. 133 Surgical myotomy and stent placement are reserved for those with persistent symptoms or significant myocardial ischaemia. 132
1. No or < 90 % reduction in diameter 2. No chest pain 3. No ischaemic ECG changes
Non-cardiac chest pain
Figure 6. Coronary angiography. Left: Coronary angiogram visualising epicardial arteries, resolution to 0.3mm. Right: Ex vivo arteriogram demonstrating coronary microvasculature, resolution 0.03mm.
FFR > 0.8 CFR≥2 IMR < 25 No coronary microvascular dysfunction present
MANAGEMENT OF SUSPECTED IHD
THE management of suspected IHD appears in box 5.
MYOCARDIAL INFARCTION
THE diagnosis and treatment of women with IHD targets the prevention of MACE, including MI.
In 2021, there were 57,300 acute coronary events( MI and unstable angina) in Australia, with 171 events per 100,000 population in women, and 386 per 100,000 population in men. 134 Compared with men, women tend to be older at the time of first MI, have more associated symptoms
1. > 90 % reduction in diameter 2. + Chest pain 3. + Ischaemic ECG changes
Epicardial vasospastic angina
Non-ischaemic disorders: * Pericarditis * Myocarditis * Valvular heart disease * Cardiomyopathies
Ischaemic disorders( INOCA) * Coronary macrovascular disorders( vasospastic angina) * Coronary microvascular disorders( microvascular angina, microvascular spasm)
Musculoskeletal( eg, costochondritis) Gastro-oesophageal disorders( eg, GORD) Biliary disorders( eg, biliary colic) Psychological disorders( eg, panic attack) Pulmonary
Coronary angiography No obstrucive coronary arteries(< 50 %)
1. No or < 90 % diameter reduction 2. No angina 3. No ischaemic ECG changes
Microvascular angina
( though chest pain is still the most common symptom), are more likely to present more than six hours after onset of symptoms of MI, are less likely to undergo invasive coronary angiography within 24 hours for non-ST segment elevation myocardial infarction( NSTEMI), have longer door to device times in STEMI, have less GDMT for MI, and greater MI
135 – 39 mortality. The pathophysiology of MI in women is diverse and can be broadly stratified based on the presence or absence of obstructive CAD and coronary dissection at the time of coronary angiogram. Obstructive atherosclerotic CAD is the most common aetiology of MI in women. Spontaneous coronary artery dissection( SCAD) as a cause of MI may be obstructive or non-obstructive, and MINOCA may be a result of coronary vasospasm( epicardial or microvascular), thromboembolism, plaque rupture or plaque erosion. Elevated troponin in women can also be caused by non-MI aetiologies such as takotsubo syndrome, myocarditis and non-ischaemic cardiomyopathy( see figure 9).
MI with obstructive coronary artery disease
Most women with MI have obstructive CAD from atherosclerosis. 140 Atherosclerotic MI may be due to plaque rupture or erosion. Management of MI from obstructive atherosclerotic CAD is per ACS guidelines. Women may be candidates for coronary revascularisation such as percutaneous coronary intervention( PCI) and stent or coronary artery bypass grafting( CABG). Women with ACS have less GDMT, less invasive management and revascularisation, increased in-hospital mortality, rehospitalisation, decreased health status, more vascular complications post-PCI and postoperative complications post-CABG. 141-43
MI with no obstructive coronary arteries
To make a diagnosis of MINOCA, the usual criteria for MI need to be met, and coronary angiography needs to show no stenosis greater than 50 % in a major epicardial artery. The diagnosis indicates there is an ischaemic
FFR > 0.8 CFR < 2.0 IMR≥ 25 Coronary microvascular dysfunction present
1. No or < 90 % or > 90 % diameter reduction 2. + Angina 3. + Ischaemic ECG changes
Microvascular and epicardial vasospastic angina
REFRACTORY ANGINA Consider the issues in box 4 in INOCA with refractory angina( ie, requiring two or more antianginal agents).
Figure 7. Invasive evaluation of INOCA with functional coronary angiography.
INOCA ENDOTYPES