The number of patients being diagnosed with heart failure (HF) is increasing worldwide, and thus we need to know which medications to avoid or be cautious with prescribing that may cause or exacerbate this medical condition. So, we decided to talk about these medications, how they cause these adverse events in these patients, and their mechanism of action.
How these medications cause adverse events in HF patients?
Overall, these medications might cause these adverse effects by one of the following mechanisms: 1) causing direct myocardial toxicity; 2) by negative inotropic effect; 3) chronotropic effects; 4) by exacerbating hypertension; 5) by delivering a high sodium load; or 6) by drug-drug interactions that limit the beneficial effects of HF medications.
Here, we will talk briefly about the common medication classes that should be avoided in heart failure and their mechanism of causing these adverse events.
1. Non-dihydro Calcium Channel Blockers (CCB):
Including (diltiazem and verapamil) è have a negative inotropic effect, thus might increase adverse outcomes [1].
2. Nonsteroidal Anti-Inflammatory Drugs (NSAID) : Diclofenac , indomethacin , ketorolac ..etc AND COX-2 selective inhibitors (Celecoxib) :
Commonly Dispensed as over the counter drugs or as anti-inflammatory prescribed drugs è these medications are associated with increased risk of HF exacerbation, causing decline in renal function, and peripheral vasoconstriction; as such they can attenuate the efficacy and enhance the toxicity of diuretics and angiotensin converting enzyme inhibitors [2].
US Boxed Warning regarding Serious cardiovascular risk: (NSAIDs) cause an increased risk of serious cardiovascular thrombotic events, including myocardial infarction (MI), and stroke, which can be fatal. This risk may occur early in the treatment and may increase with duration of use. Celecoxib is contraindicated in the setting of coronary artery bypass graft (CABG) surgery [2].
3. Some Oral Hypoglycemic Agents:
Thiazolidinediones such as Pioglitazone è are associated with fluid retention
US Boxed Warning: Thiazolidinediones may cause or exacerbate heart failure è closely monitor for signs and symptoms of HF particularly after initiation or dose increases. If HF develops, treat and consider dose reduction or discontinuation of pioglitazone. Initiation of therapy is contraindicated in patients with NYHA class III or IV HF [3].
Dipeptidyl Peptidase-4 (DPP-4) Inhibitors: Sitagliptin, saxagliptin, and linagliptin
In a scientific statement from American Heart Association (AHA) , saxagliptin has been determined to be an agent that may exacerbate underlying myocardial dysfunction , 2016 . The ADA recommends avoiding the use of saxagliptin in patients with HF, 2020) [4].
Bies ( Metformin ) is associated withguanid lactic acidosis, which can be fatal in patients with CHF
US Boxed Warning regarding Lactic acidosis: Risk factors include renal impairment, ≥65 years and hypoxic states, e.g: acute congestive heart failure. Metformin may be used in patients with stable heart failure, ADA 2020 [5].
4. Tumor Necrosis Factor alpha inhibitors (Anti-TNF-alpha):
Including infliximab, etanercept, and adalimumab.
Use with caution in patients with mild HF (NYHA class I, II) or decreased left ventricular function. Infliximab doses >5 mg/kg are contraindicated with moderate to severe HF (NYHA class III/IV). In a scientific statement from AHA, TNF blockers have been determined to cause either direct myocardial toxicity or exacerbate underlying myocardial dysfunction, 2016 [6,7].
5. Antiarrhythmic medications:
Class I: Flecainide, disopyramide [8]
Class III: Dronedarone, Sotalol [8]
6. Anti- Cancer medications:
Anthracyclines: doxorubicin, Daunorubicin, Mitoxantrone
US Boxed Warning: Myocardial damage (including acute left ventricular failure) can occur with doxorubicin with incidences from 1% to 20% for cumulative doses from 300 mg/m2 to 500 mg/m2 when administered every 3 weeks è monitor LVEF before, during and after treatment [9]
Targeted therapy: Bevacizumab, Lapatinib, Trastuzumab
US Boxed Warning: Trastuzumab is associated reductions in left ventricular ejection fraction (LVEF) and heart failure; the incidence is highest in patients receiving trastuzumab with an anthracycline-containing chemotherapy regimen è Evaluate LVEF in all patients prior to and during treatment; discontinue for cardiomyopathy [10]
7. Cilostazol
This is a selective inhibitor of phosphodiesterase type 3, antiplatelet and vasodilatory agent used primarily in patients with intermittent claudication and peripheral arterial disease [11].
US Boxed Warning: Cilostazol is contraindicated in patients with heart failure of any severity è causing decreased survival in patients with class III to IV heart failure [11].
8. Anti-depressant drugs:
Citalopram, Tricyclic antidepressants (TCA) such as amitriptyline, Imipramine … etc.
- TCAuse with extreme caution in patients with a history of CVD or family history of sudden death, dysrhythmias, or conduction abnormalities. In a scientific statement from AHA, TCA has been determined to exacerbate underlying myocardial dysfunction,2016 è monitor EKG [12]
- Citalopram risk of dose-dependent QT prolongation ECG and torsade de pointes (TdP) . Risk factors include Structural heart disease, e.g: MI or HF [12]
9. α1 -Blockers:
Such as prazosin and doxazosin
In a scientific statement from the AHA, -Zosin has been determined to exacerbate underlying myocardial dysfunction , 2016 [13].
10. Pregabalin
Peripheral edema may occur in patients with or without a prior history of heart failure, which may result in acute decompensated heart failure. Risk factors: Pre-existing heart failure (NYHA Class III or IV) (cautious use recommended due to limited data in this patient population [14]
11. Beta-blockers (except those approved for HF treatment: Metoprolol, Bisoprolol, Carvedilol) [15]
12. Selected Intravenous and Oral Medications High in Sodium content:
- Oral meds: Alendronate effervescent tablet, Sodium polystyrene sulfonate suspension, Polyethylene glycol powder for solution, erythromycin
- Injection meds: Piperacillin/tazobactam, Metronidazole, Ticarcillin/clavulanate, azithromycin
