10 common medications that cause heart failure

Heart failure pervades American healthcare, and is the main discharge diagnosis in adults aged 65 years or older. This problem costs Medicare $31 billion a year, and is expected to increase to $53 billion per year in 2030, with associated hospitalization representing the lion’s share of costs.

Those with heart failure often take many medications with complex dosage regimens. On average, patients with heart failure take 6.8 prescription medications—or 10.1 doses—per day. And this estimate doesn't take into account over-the-counter (OTC) medications. It’s important for physicians to know which drugs, whether OTC or prescription, can worsen heart failure.

“It is likely that the prevention of drug-drug interactions and direct myocardial toxicity would reduce hospital admissions, thus both reducing costs and improving quality of life,” according to the authors of a scientific statement from the American Heart Association (AHA) on drugs that may cause or exacerbate heart failure (HF).

The AHA guidance, which provides a comprehensive list of common drugs that cause heart failure, and their underlying mechanisms, was established in 2016 and is still cited as current by AHA.

Here are 10 examples of drugs that could precipitate or exacerbate heart failure.

NSAIDs

Nonsteroidal anti-inflammatory drugs (NSAIDs) can lead to major heart failure. These analgesics inhibit prostaglandin, thus leading to sodium and water retention, heightened systemic vascular resistance, and blunted diuretic response, which are all factors that underlie heart failure. Such effects have an immediate onset. 

α1-blockers

Urological agents such as doxazosin, prazosin, tamsulosin, and terazosin can cause moderate heart failure with delayed onset. These drugs cause stimulation of trigger β1 receptors, which increases renin and aldosterone levels.

Antimalarial agents

The antimalarial medications hydroxychloroquine and chloroquine act as intracellular inhibitors of lysosomal enzymes, which can precipitate major heart failure that is intermediate or delayed. Heart failure manifests with long-term exposure at higher doses to these antimalarial agents and can be reversed. Diagnosis can entail endomyocardial biopsy with electron microscopy.

TNF-α inhibitors

Rheumatologic agents known as TNF-α inhibitors can cause major cytokine-mediated heart failure with intermediate onset. Importantly, infliximab should not be administered to patients with moderate to severe heart failure.

Albuterol

With higher levels of exposure, this asthma medication decreases β-receptor responsiveness, thus leading to moderate/major heart failure of intermediate/delayed onset. The effects are dose-dependent on inhalation, and risk rises with systemic use.

Antineoplastic agents

Anticancer agents, such as the antimetabolites 5-FU and capecitabine, can cause moderate/major heart failure of immediate onset. The underlying mechanism is unknown but could be due to coronary vasospasm. Heart failure can be reversible. Of note, Takotsubo cardiomyopathy has been observed with administration of these agents, which resolves in weeks.

The alkylating agents cyclophosphamide and ifosfamide can cause moderate/major heart failure of immediate onset, which is mediated by oxidative stress. This heart failure is reversible, and usually resolves in 3-4 weeks.

Antifungal medications

Itraconazole has negative inotropic effects, which can lead to major heart failure of immediate/intermediate onset.  This agent should only be used to treat life-threatening fungal infections and not to treat onychomycosis. Effects are reversible on discontinuation of the agent.

Amphotericin B can cause moderate/major heart failure of intermediate onset and by unknown mechanisms. These effects are reversible on discontinuation, which is evidenced by some amelioration in left ventricular ejection fraction.

Minoxidil

This hair-regrowth agent is a peripheral vasodilator, which can lead to moderate heart failure of intermediate onset. The mechanism underlying heart failure is unknown.

Calcium-channel blockers

Agents to treat hypertension and irregular heart rhythms, such as diltiazem and verapamil, are both negative inotropes that can cause severe heart failure of immediate/intermediate onset. The calcium-channel blocker nifedipine can similarly lead to moderate heart failure.

Antidiabetic medications

The biguanide metformin can cause major heart failure that ranges from immediate to delayed onset secondary to fluctuations in renal function. The mechanism of action underlying heart failure involves increased anaerobic metabolism and elevated lactic acidosis. 

Thiazolidinediones, another type of biguanide, can cause major heart failure of intermediate onset. These effects can be reversible on discontinuation, and this drug is not meant for patients already diagnosed with symptomatic heart failure. The underlying mechanism may involve calcium channel blockade.

The dipeptidyl peptidase-4 inhibitors saxagliptin and sitagliptin can cause major heart failure of intermediate to delayed onset by unknown mechanisms.

Bottom line

The AHA cautioned against polypharmacy in their guidance on heart failure.

“Polypharmacy is a significant concern in patients with HF [heart failure] because of the burden of both cardiovascular and noncardiovascular conditions,” they wrote. “It is not unusual to have medications ordered and adjusted by different clinicians, many times with minimal consideration for drug-drug or drug-condition interactions, or to have prescriptions filled at different pharmacies. The following strategies may be helpful in detecting inappropriate and potentially hazardous medications that could exacerbate HF.”

They advised healthcare providers to conduct comprehensive medication reconciliation at every clinical visit and admission. They also advised clinicians to carefully consider the risks and benefits of each medication before prescribing a new agent, and to discontinue any medications that have no indication or are contraindicated. When justified and affordable, combination medications that treat more than one condition can also be considered to reduce polypharmacy. Importantly, clinicians should avoid prescribing medications that treat adverse effects, and only prescribe drugs as needed.