Updates on Pharmacologic Management of Microvascular Angina
Table 2
Classification of drugs for management of microvascular angina and their proposed mechanisms; (a) first line therapy or synergistic combination therapy; (b) effective treatments with lower level of evidence; (c) less effective drugs.
(a) First-line therapy or synergistic combination therapy
Medication class
Example
Mechanism of action
Beta-blockers
(i) Propranolol (ii) Atenolol (iii) Carvedilol (iv) Nebivolol
(i) Lowering heart rate, myocardial contractility, blood pressure, and oxygen consumption (ii) Endothelium-dependent vasodilatory effects through increasing plasma NO (endothelium-dependent)
Statins
(i) Pravastatin (ii) Fluvastatin
(i) Improving endothelial function through increasing NO bioavailability (endothelium-dependent and anatomical)
ACEI/ARBs
(i) Enalapril (ii) Quinapril (iii) Irbesartan (iv) Eplerenone
(i) Vasoconstriction through increasing superoxide production by its effect on nicotinamide adenine dinucleotide phosphate -NADPH- and nicotinamide adenine dinucleotide (endothelium-dependent) (ii) Stimulating NO production by lowering bradykinin degradation
Calcium channel blockers
(i) Amlodipine (ii) Nifedipine (iii) Verapamil (iv) Diltiazem
(i) Negative inotropic and vasodilatory effects (reducing microvascular tone and relieving spasm), therefore, reducing afterload (endothelium-dependent) (ii) Protecting endothelium against free radical injuries (endothelium-independent) (iii) Increasing nitrate
Antiplatelet
(i) Aspirin
(i) Inhibition of thromboxane A2 (TXA2) (endothelium-dependent)
(b) Effective treatments with lower level of evidence
Medication class
Example
Mechanism of action
Nitric oxide modulators
(i) L-arginine (ii) Sildenafil (iii) Cilostazol (iv) Tetrahydrobiopterin
(i) Vasodilation induced by nitrates through activation of the guanylyl cyclase signaling pathway (endothelium-dependent)
Hormonal drugs
(i) Estrogen
(i) Accelerating reendothelialization (endothelium-independent) (ii) Inhibiting endothelial cell apoptosis
(ii) Vitamin D
(iii) Decreased vascular inflammation and improving endothelial function (endothelium-independent)
Novel antianginal
(i) Ivabradine
(i) Lowering heart rate and reducing myocardial oxygen demand
(ii) Fasudil
(ii) Mediates vascular smooth muscle, endothelial, and inflammatory cell function
Miscellaneous
(i) PPI
(i) Inhibiting esophagocardiac reflex which leads to coronary vasoconstriction (endothelium-dependent)
(ii) Metformin
(ii) Significant improvement in acetylcholine-stimulated flows (endothelium-dependent)
(iii) SGLT inhibitors
(iii) Action on endothelium-not know yet (endothelium-dependent)
(iv) Endothelin receptor antagonist
(iv) Decreasing vascular tone and causing vasodilation (endothelium-dependent)
(v) Nicorandil
(v) Arterioles’ smooth muscle relaxation (vi) Vasodilation through nitrate
(vi) Imipramine
(vii) Elevating pain threshold
(vii) Omega-3
(viii) Modifying inflammatory cytokine expression and inhibiting oxidative stress (endothelium-independent)
(viii) Incretin
(ix) Endothelial nitric oxide synthase (eNOS) phosphorylation and increasing NO
(ix) NAC
(xi) Modifying NO half-life and potentiates the activity of NO
(c) Less effective drugs
Medication class
Example
Mechanism of action
Nitric oxide modulators
(i) Nitrates
(i) Vasodilation induced by nitrates through activation of the guanylyl cyclase signaling pathway (endothelium-dependent)
Alpha-blockers
(i) Doxazosin
(i) Sympatholytic capacity which causes a reduction in the microvascular tone (endothelium-dependent)
Novel antianginal
(i) Ranolazine
(i) Inhibiting late sodium current in cardiomyocytes (ii) Improving endothelial function (endothelium-dependent)
Miscellaneous
(i) Trimetazidine
(i) Inhibiting the long-chain of 3-ketoacyl coenzyme A thiolase
(ii) Thiazolidinediones
(i) Improving endothelial dysfunction through modulation of oxidative processes (endothelium-independent)
(iii) Xanthine derivatives
(i) Vasodilation (endothelium-dependent) (ii) Mediating ischemic pain perception
