Table A1.

Drugs and food supplements that can worsen HF prognosis.

Drugs [99]	Possible Mechanism Involved	Results	References
NSAIDs	Inhibition of cyclooxygenase enzyme Inhibition of renal prostaglandin synthesis	Sodium and water retention Higher systemic vascular resistance Reduction in renal perfusion, glomerular filtration rate, sodium excretion	[100,101,102,103,104,105,106]
Alpha-1 blockers (e.g., doxazosin)	Beta-1 receptor stimulation Stimulation of renin and aldosterone release Chronic alfa1 antagonism Stimulation of heart fibrosis factor galectin-3 expression	Edema Tachyphylaxis Cardiomyocyte apoptosis Myocardial hypertrophy	[107]
Calcium channel blockers (e.g., verapamil, diltiazem)	Negative inotrope Calcium channel blockade	Cardiac depression Atrioventricular conduction block	[103,106]
Moxonidine (centrally acting α-adrenergic drug)	Possible sympathetic withdrawal	Myocardial depression Hypotension Rebound norepinephrine increase	[108]
Class I antiarrhythmic (e.g., flecainide, disopyramide)	Negative inotrope Pro-arrhythmic stimulation	Myocardial infarction Premature ventricular beats Myocardial depressant effects	[106,109]
Class III antiarrhythmic (e.g., sotalol)	Beta inhibition Pro-arrhythmic stimulation Potassium channel blockade	Bradycardia Prolonged QT interval Torsades de pointes T-wave abnormalities	[109,110,111]
Inhibitors of dipeptidyl peptidase 4 (e.g., sitagliptin, saxagliptin)	Dipeptidyl peptidase 4 enzyme interference Direct interaction in myocytes Calcium channel interference Interference in substance P degradation Sympathetic nervous system stimulation	Myocardial infarction Stroke	[103,112,113,114,115]
Thiazolidinediones (e.g., rosiglitazone, pioglitazone)	Possible calcium channel blockade Interference with mitochondrial respiration or oxidative stress	Sodium and water retention Peripheral edema Myocardial infarction Stroke Transient ischemic attacks	[106,115,116,117]
Itraconazole	Negative inotropic effect Mitochondrial dysfunction Inhibition of 11 beta-hydroxysteroid dehydrogenase 2 Cytochrome P450 inhibition	Peripheral edema Hypertension Prolonged QT interval Cardiac depression Excess mineralocorticoid Myofibroblast damage	[118,119,120]
Amphotericin B	Unknown	Cardiotoxicity Dilated cardiomyopathy	[121]
Carbamazepine(overdose)	Negative inotropic and chronotropic effects Depression of phase 2 repolarization Direct toxic effect on myocardial fibers Anticholinergic action Increased automaticity of ectopic pacemakers Sodium channel blockade	Left ventricular dysfunction Suppressed sinus nodal activity Atrioventricular conduction disturbances Hypotension	[122,123,124]
Pregabalin	Alterations in cardiac renin angiotensin system (RAS) L-type calcium channel blockade	Peripheral edema Decreased calcium influx in cardiomyocytes Left ventricular deterioration	[125,126,127]
Tricyclic antidepressants	Negative inotrope Pro-arrhythmic stimulation Norepinephrine and serotonin reuptake blockade Sodium channel blockade Suppression of potassium channels in myocytes Vasoconstriction of cerebral arteries	Arrhythmias Impaired heart conduction Prolonged intraventricular conduction Prolonged QT interval Hemorrhagic stroke Ischemic stroke	[128,129]
Citalopram	Inhibition of depolarizing current mediated by L-type calcium channels Antagonistic effects on myocardial potassium channels	Prolonged QT interval Episodes of torsades de pointes Arrhythmias	[130,131]
Pergolide, cabergoline, pramipexole	Potent agonists at cardiac myocyte 5- HT2B serotonin receptors Induction of fibroblast activation	Valvular damage Cardiac valvular regurgitation Pulmonary arterial hypertension Peripheral edema	[132,133,134]
Clozapine	Calcium channel blockade Ig-E mediated hypersensitivity Reduced left ventricular function	Myocarditis Cardiomyopathy Prolonged QT interval Elevated troponin	[135,136,137,138]
Lithium	Altered acetylcholinesterase activity Direct myofibril degeneration Induction of oxidative stress Interference with calcium ion influx	Cardiac fibrosis Cardiomyocyte apoptosis Rhythm disturbances Edema, ascites Complete heart block and first-degree AV block	[139,140,141,142,143]
β2 adrenergic agonists (e.g., salbutamol)	Decreased β-receptor responsiveness Small positive inotropic and chronotropic effects Activation of Gs/cAMP/PKA Inhibition of Gi/PDE	Arrhythmias Prolonged QT interval	[144,145]
Tumor necrosis factor-α (TNF-α) inhibitors	Cytokine mediation Sympathetic excitation Inflammation and renin-angiotensin system upregulation	Peripheral inflammation Cardiac dysfunction	[146,147,148]
Topical beta-blockers (e.g., timolol)	Hemodynamic effects due to beta blockade	Arrhythmias Myocardial ischemia Hypotension Pulmonary edema	[99]
Food supplements [149]	Possible mechanism involved	Results	Reference
Aconitum spp. (Monkshood)	Alkaloids block potassium channels	Ventricular fibrillation Bradycardia Hypotension	[150]
Aesculus hippocastanum L. (Horse chestnut)	Antiplatelet effect	Increased risk of bleeding when associated with anticoagulant drugs	[151]
Allium sativum L. (Garlic)	Inhibition of platelet aggregation (dose-dependent)	Increased risk of bleeding when associated with anti-thrombotic drugs	[152]
Aloe barbadensis Mill. (Aloe vera)	Laxative effect	Risk of hypokalemia with increased toxicity of cardiotonic glycosides or antiarrhythmia drugs	[153]
Angelica sinensis (Oliv.) Diels (Angelica)	Antiplatelet and anticoagulant effect	Increased anticoagulant effect	[154]
Cassia senna L. (Senna)	Laxative effect	Risk of hypokalemia with increased toxicity of digitalis or antiarrhythmia drugs	[153]
Citrus paradisi Macfad. (Grapefruit)	Inhibition of CYP3A4 enzyme	Increased effects (therapeutic or toxic) of co-administered drugs (e.g., calcium channel blockers, antiarrhythmia drugs) Inefficacy of pro-drugs metabolized by CYP3A4	[155,156]
Cratageus spp. (Hawthorn)	Increases digitalis toxicity (incompletely elucidated)	Risk of digitalis intoxication if co-administered	[157,158]
Ephedra sinica Stapf (Chinese ephera)	Alkaloids stimulate adrenergic receptors Indirect agonist stimulation and noradrenaline release	Tachycardia Hypertension Arrythmias Heart attack Stroke	[159]
Ginkgo biloba L. (Ginkgo)	Antiplatelet effect	Increased risk of bleeding when co-administered with antithrombotic drugs	[160,161]
Glycyrrhiza glabra L. (Licorice)	Hypokalemia Reduced sodium and water excretion	Increased toxicity of digitalis or antiarrhythmic drugs Decreased effect of diuretics	[153]
Harpagophytum procumbens Burch. (Devil’s claw)	Inhibition of CYP1A2 and CYP2D6	Increased effects of diuretics, antihypertensives, statins, and anticoagulants	[162,163]
Hypericum perforatum L. (St. John’s Wort)	Induction of CYP3A4 isoenzyme activity	Decreases plasma levels of co-administered drugs metabolized by this enzyme	[164,165,166]
Leonurus cardiaca L. (Motherwort)	Antiplatelet effect	Increased risk of bleeding when co-administered with antithrombotic drugs	[152]
Oenothera biennis L. (Evening primrose)	Inhibition of platelet activating factor	Increased risk of bleeding when co-administered with antithrombotic drugs	[167,168]
Panax ginseng C.A. Meyer (Asian ginseng)	Decreased prothrombin time	Decreased warfarin effect and increased risk of thrombo-embolic events	[152]
Stephania tetrandra S. Moore	Calcium channel blockade	Cardiac depression	[169]
Zingiber officinale Roscoe (Ginger)	Thromboxane synthase inhibition Prostacyclin agonist	Increased risk of bleeding when co-administered with antithrombotic drugs Increased effects of antihypertensive drugs	[170]