Polypharmacy and comorbidity in heart failure

The care of patients with heart failure has become increasingly complex. For some patients treatment based on evidence and recommended by guidelines now includes agents that prolong life, alleviate symptoms, and reduce admissions to hospital.¹,² Simultaneously, the treatment of underlying causative factors, including hypertension, coronary artery disease, and dyslipidaemia has evolved rapidly, increasing the number of pharmacological agents that are considered necessary for many patients with heart failure. The characteristics of the typical patient further complicate management. The burden of heart failure falls disproportionately on elderly people, who often are simultaneously afflicted with many other conditions.³,⁴ In a recent study of older Americans admitted to hospital with heart failure, diabetes (38%), chronic lung disease (33%), atrial fibrillation (30%), and prior stroke (18%), were remarkably common.⁵ Thus practitioners typically face the challenge of managing not a single condition but multiple conditions requiring multiple medications. As the population ages this scenario will become more common.

Unfortunately little evidence is available to guide the inevitable polypharmacotherapy in patients with heart failure and multiple comorbidities. The strongest evidence supporting individual drug treatment derives primarily from randomised trials, which have typically either implicitly or explicitly excluded older patients and patients with multiple comorbidities.⁶ In addition, some trials implement run in periods to assess tolerance to regimens—an approach that may constrain the applicability of the results.

Given the paucity of data to inform the comprehensive management of the typical patient with heart failure, what can be recommended? Collaborative disease management programmes that include the careful review of medication lists have been shown to reduce hospital admission rates and reduce the costs of care.⁷,⁸ Whenever possible, patients with heart failure, particularly those with multiple competing comorbidities and polypharmacy, need to be enrolled in such programmes.

Regardless of the availability of disease management programmes, clinicians need to have systems in place to review medication lists carefully at every visit of a patient, with the goal of eliminating medications that are not known to provide a clear benefit. When initiating new medications, particular attention needs to paid to the possibility of adverse drug interactions—for example, adding spironolactone to a regimen that includes potassium supplements, or amiodarone to a regimen that includes coumadin.

In treating coexisting conditions many commonly used medications need to be avoided whenever possible in patients with heart failure, based on known pharmacological principles and recommendations from guidelines. For example, many antiarrhythmic drugs, particularly the class I agents, have cardio-depressant and proarrhythmic effects. Nondihydropyridine calcium channel blockers may also adversely affect left ventricular function. Thiazolidinediones are not recommended in patients with diabetes with advanced symptomatic heart failure because they cause fluid retention and may exacerbate heart failure. Metformin is contraindicated in patients with heart failure who require drug treatment or with renal insufficiency, owing to the risk of producing life threatening lactic acidosis. Non-steroidal anti-inflammatory drugs are not recommended because they antagonise the effects of angiotensin converting enzyme inhibitors and exacerbate hypertension. Finally, in patients with renal insufficiency drug dosages need to be adjusted appropriately for the estimated glomerular filtration rate, with the appreciation that serum creatinine may provide an overly optimistic estimate of renal function, particularly in women and elderly people.⁹

While the relevance of polypharmacy and comorbidity to the care for patients with heart failure has been noted before,¹⁰ more must be done to address these rapidly mounting challenges. Clinical research must adapt to ensure its relevance, and trials need to include not just young patients with systolic dysfunction and little comorbidity. Ongoing studies enrolling the often ignored group of patients with preserved systolic function are an encouraging development but only represent the beginning of a necessary trend.¹¹,¹² Future trials must also focus on optimal strategies for the comprehensive management of the patient with heart failure rather than the isolated effects of single drugs.

Where clinical trials are not possible community based studies could provide some answers to issues facing practitioners. The most urgent include the ideal dosing of medications, the appropriate use of potentially life saving drugs in patients with multiple competing comorbidities, and the treatment of coexisting illnesses in the context of heart failure. High quality registries of representative patients with heart failure could help generate new information about the safety and effectiveness of clinical strategies.

Currently barriers have prevented the widespread incorporation of disease management programmes into practice. In the United States, for example, “fee for service” Medicare has no mechanism to pay for disease management in heart failure. The current situation reflects the lack of adequate knowledge and systems to optimise outcomes for typical patients with heart failure. If we continue to ignore these deficiencies then we will fail to deliver the best care to the rapidly growing population of complex patients with heart failure.