Drugs-induced heart failure: Onset, mechanism, and safer alternatives
Onset of drugs induced heart failure
Acute Onset (Hours-Days)
Alpha blockers, e.g., doxazosin
Centrally acting alpha agonists
NSAIDs
Pramipexole, Carbergoline
Lithium (acute toxicity)
Amphotericin B
Early Onset Chronic (Weeks-Months)
Class I antiarrhythmics, e.g, flecainide, disopyramide
Class IV antiarrhythmics, e.g, verapamil, diltiazem
Sotalol, Dronedarone
Sulfonylureas
Thiazolidinediones
Itraconazole
DPP-4 inhibitor (Saxagliptin)
Antracyclines
HER2-targeted therapies
VEGF inhibitors
Multikinase TKIs
Alkylating agents
Late Onset Chronic (Months-Years)
Antracyclines (Delayed)
Long-term NSAIDs
HER2-targeted therapies (Delayed recurrence)
VEGF inhibitors and TKIs
Lithium (chronic toxicity)
Mechanism of drugs induced heart failure
Drugs | Fluid retention | Negative inotropy | Arrhythmia | Myocardial toxicity |
|---|---|---|---|---|
Antidiabetics | ||||
TZDs | High | |||
DPP4i (saxagliptin) | Moderate | Moderate | ||
sulfonylurea | Moderate | |||
Antiarrhythmic drugs | ||||
Class Ic | Moderate | High | ||
Sotalol | High | Moderate | ||
Dronedarone | Moderate | High | ||
CCB | Moderate | High | ||
Antihypertensives | ||||
Doxazosin | High | |||
Moxonidine | High | |||
Minoxidil | High | |||
Anti-infectives | ||||
Itraconazole | Moderate | High | ||
fluoroquinolones | QT prolong | |||
piperacillin-tazobactam | Sodium content loading | |||
Bactrim | Hyperkalemia | |||
Amphotericin B | High | |||
Analgesics | ||||
NSAIDs | High | |||
Neurological and psychiatric | ||||
Pramipexole | High | |||
Cabergoline | High | |||
Lithium | Moderate | Moderate | ||
Anticancer | ||||
Anthracyclines | High | High | ||
Alkylating agents | High | |||
Antimetabolites | High | |||
HER2-targeted therapies | Moderate | High | ||
VEGF inhibitors and multikinase TKIs | Moderate | High | ||
Taxanes | High |
Safer alternatives of drugs induced heart failure
Drugs | Safer alternatives | Evidence of strength |
|---|---|---|
Analgesic | ||
Ibuprofen, diclofenac, celecoxib | Paracetamol, topical NSAIDs | Strong |
Antidiabetic | ||
Pioglitazone, rosiglitazone | SGLT2 inhibitors or metformin | Strong |
Saxagliptin | Sitagliptin, linagliptin | Strong |
Glimepiride, glibenclamide | SGLT2 inhibitors or metformin | Strong |
Antiarrhythmics | ||
Class Ic (flecainide, disopyramide) | Amiodarone (with monitoring) | Strong |
Sotalol, dronedarone | Amiodarone (with monitoring) | Moderate (sotalol), strong (dronedarone) |
Verapamil, diltiazem | Amlodipine, felodipine | Moderate |
Antihypertensives | ||
Doxazosin, prazosin | Other antihypertensives per HF guidelines | Strong |
Moxonidine, clonidine | Other antihypertensives per HF guidelines | Strong |
Anti-infectives | ||
Clarithromycin, erythromycin | Azithromycin | Moderate |
Itraconazole | Fluconazole | Moderate |
Neurological and psychiatric | ||
Pramipexole, cabergoline | Ropinirole, pergolide | Moderate |
Pramipexole, cabergoline | Valproate, lamotrigine | Moderate |
Anticancer | ||
Doxorubicin, epirubicin | Liposomal formulations, dexrazoxane | Strong |
Sunitinib, bevacizumab | Use only if essential; monitor closely | Moderate |
Trastuzumab, pertuzumab, lapatinib | Use only if essential; monitor closely | Strong |
Cyclophosphamide, ifosfamide, mitomycin c | Use only if essential; monitor closely | Moderate |
Reference
Abdin A, Bauersachs J, Abdelhamid M, Aktaa S, Al Ghorani H, Bayes-Genis A, Biegus J, Böhm M, Butler J, Girerd N, Metra M, Mullens W, Skouri H, Vaduganathan M, El Hadidi S, Rosano GMC, Savarese G. Pharmacologic pitfalls in heart failure: A guide to drugs that may cause or exacerbate heart failure. A European Journal of Heart Failure expert consensus document. Eur J Heart Fail. 2025 Dec;27(12):2671-2690. doi: 10.1002/ejhf.70087. Epub 2025 Dec 11. PMID: 41382384; PMCID: PMC12803569.