Understanding the Mortality Link: Polypharmacy in Heart Failure
Polypharmacy, defined as the use of multiple medications, is common among patients with heart failure. A 2022 study found that polypharmacy is significantly associated with higher mortality, with a relative risk of 1.31 (95% CI 1.07–1.61). Notably, this risk appears most pronounced when multiple non-guideline-directed drugs are combined, while strictly guideline-concordant cardiovascular therapy can mitigate early death. The study’s DOI is 10.1038/s41598-022-24285-4. An accompanying ESC position paper from 2022 highlights the most relevant stumbling blocks to safe prescribing (doi: 10.1093/ehjcvp/pvaa108). These findings underscore the need for vigilant medication review in heart failure care.
Typical Stolpersteine: Real-World Drug Interactions
Beyond the disease itself, everyday prescribing and patient behavior create concrete risks. Here are illustrative examples often seen in clinical practice:
Self-medication with NSAIDs in heart failure
A 75-year-old woman with heart failure with reduced ejection fraction (HFrEF) treated with routine medications began taking ibuprofen purchased OTC for arthritis. NSAIDs promote sodium and fluid retention, worsening heart failure symptoms and outcomes. Clinicians should routinely ask about OTC medicines and offer safer analgesic alternatives such as acetaminophen (paracetamol) when appropriate.
Herbal supplements and anticoagulation: St John’s wort
A 68-year-old patient on edoxaban for atrial fibrillation (AF) treated depressive symptoms with St. John’s wort. Hyperforin in the herb induces P-glycoprotein, lowering the exposure of DOACs and increasing stroke risk. This case highlights the importance of explicitly asking about phytotherapy and ensuring anticoagulation remains therapeutic.
DOACs and antiarrhythmics: a bleeding risk
A 78-year-old AF patient with reduced kidney function on edoxaban and the antiarrhythmic amiodarone presented a higher bleeding risk. Reviews confirm that DOACs plus amiodarone can elevate GI bleeding risk, suggesting clinicians reconsider the antiarrhythmic strategy or adjust treatment rather than cycling through another DOAC.
Statins and macrolide antibiotics: a myopathy concern
A 72-year-old with coronary artery disease on atorvastatin developed pneumonia treated with clarithromycin. Macrolides inhibit CYP3A4, raising statin levels and the risk of statin-induced myopathy (creatine kinase elevations can occur). Older data already warned about this interaction; when possible, choose a non-CYP3A4-inhibiting antibiotic or pause the statin briefly if needed.
Economic and Clinical Consequences
Polypharmacy does not only affect patients clinically; it drives substantial costs. Adverse drug events lead to more doctor visits, new prescriptions, emergency department visits, and hospitalizations. In the United States, the aggregate cost of polypharmacy-related issues has been estimated at about $528 billion, representing roughly 16% of total health expenditures. These figures stress the value of routine medication reconciliation and deprescribing where appropriate.
Practical Takeaways for Safer Prescribing
To reduce mortality risk and improve quality of life for people with heart failure, clinicians should:
- Perform systematic medication reviews at every visit, including OTC drugs and phytomedicines.
- Favor guideline-directed medical therapy for heart failure and avoid unnecessary add-ons that lack evidence of benefit.
- Be vigilant about drug–drug and drug–disease interactions, especially with DOACs, statins, antiarrhythmics, and NSAIDs.
- When interactions are likely, consider alternative therapies (e.g., different antibiotics, analgesics, or antiarrhythmics) or temporary dose adjustments with careful monitoring.
- Educate patients about recognizing signs of adverse effects and when to seek medical attention promptly.
Conclusion
In heart failure care, polypharmacy is a double-edged sword: it can improve symptoms and outcomes when guided by evidence, but it also raises mortality risk and health costs when unmanaged. By integrating regular medication reviews, prioritizing guideline-based therapies, and avoiding dangerous combinations, clinicians can reduce early death and improve patient safety. The evidence from 2022 and the ESC position paper reinforce a simple clinical rule: ask, review, and tailor therapy to the individual, avoiding unnecessary polypharmacy whenever possible.
