Table 2

Treatment of SCS endotypes

SCS endotypeInvestigationPathophysiologyTreatmentEfficacySide effects
Microvascular angina secondary to impaired vasodilationReduced CFR and/or increased microvascular resistanceAnatomical remodelling, vascular rarefaction, disturbed coronary regulationß-blockersReduction in myocardial oxygen consumptionFatigue, blurred vision,
cold hands
ACE inhibitorsImprove CFR, reduce workload, may improve microvascular remodellingCough, renal impairment, hyperkalaemia
RanolazineImproves MPRi in patients with MVA and reduced CFRNausea, dizziness, headache
Phosphodiesterase inhibitors↓cGMP degradation, ↑vascular smooth muscle relaxation and ↑ CFR for those with baseline CFR <2.5Flushing, tinnitus, headache
Microvascular angina secondary to abnormal vasoconstrictionHyper-reactivity to stimuli (eg, acetylcholine, exercise, stress)Endothelial dysfunction, inappropriate prearteriolar vasoconstrictionACE inhibitorsImproves endothelial vasomotor dysfunctionCough, renal impairment, hyperkalaemia
Calcium antagonistsVascular smooth muscle relaxation, reduction in myocardial oxygen consumptionConstipation, ankle swelling, flushing
NicorandilPotassium channel activator with coronary microvascular dilatory effectDizziness, flushing, weakness, nausea
StatinsImproved coronary endothelial function, pleiotropic effects including reduced vascular inflammationMyalgia, headache, cramps
ExerciseBeneficial effect on endothelium, ↓ resting blood flow and ↑ vasodilatory capacityMuscle fatigue, myalgia
Hormone replacement therapyOestrogen therapy improves endothelial function short term in CMD↑ Risk of breast cancer, marginally ↑ risk of CVD
Microvascular angina secondary to abnormal pain processingEnhanced nociceptionDysfunctional cortical pain processingTricyclic antidepressantsImproved symptom burden potentially through reduced visceral painBlurred vision, dry mouth, drowsiness, impaired coordination
Xanthine derivativesAntialgogenic effect (due to the direct involvement of adenosine in cardiac pain generation)Nausea and vomiting, palpitations
Epicardial and/or microvascular coronary vasospasmPropensity to coronary vasospasmVascular smooth muscle hyper-reactivityCalcium channel antagonists↓ Spontaneous and inducible coronary spasm via vascular smooth muscle relaxation and ↓ oxygen demandConstipation, ankle swelling, flushing
Nitrates↓ Spontaneous and inducible coronary spasm via large epicardial vasodilation, ↓ oxygen demand; lack of efficacy in microvascular angina with potentially deleterious effectHeadaches, dizziness, flushing
Rho-kinase inhibitors↓ Calcium sensitivity of smooth muscle by ↑ phosphatase activity reducing phosphorylated (active) myosin light chainsRash, dizziness; not licensed for use in Europe or USA
Adjunctive non-pharmacological interventionsMay be useful in all endotypesMetabolic syndrome, endothelial dysfunction, cardiovascular risk factors, anxiety/depressionSmoking cessation, exercise, cardiac rehabilitation, Mediterranean diet, cognitive behavioural therapy
  • CFR, coronary flow reserve; CMD, coronary microvascular dysfunction; MPRi, myocardial perfusion reserve index; MVA, microvascular angina; SCS, stable coronary syndrome; CVD, cardiovascular disease; cGMP, Cyclic guanosine monophosphate