Imagine a 78-year-old woman is transferred from an outlying emergency department for “recurrent transient ischemic attacks.” Her medical history is significant for multiple hospitalizations for congestive heart failure and atrial fibrillation due to idiopathic cardiomyopathy in the past year. Additional medical history includes colloid cyst of the third ventricle (treated with a ventriculoperitoneal shunt), severe osteoporosis (for which she wears a back brace), gastroesophageal reflux disease, one episode of fugue-like state, multiple falls, and progressive declining memory. She was recently treated at three different medical institutions, and her medications came from a mail-order pharmacy as well as a local pharmacy.
Over the past three decades, medical literature has focused on preventing medication errors in hospitals and clinical practices through redesigning care delivery systems upon admission and during hospitalization. Information technology and clinical decision support tools have resulted in a culture shift of clinicians' prescription behavior and major reductions in adverse events (11. Bates DW, Spell N, Cullen DJ, Burdick E, Laird N, Petersen LA, et al. The costs of adverse drug events in hospitalized patients. Adverse Drug Events Prevention Study Group. JAMA. 1997;277:307-11. [PMID: 9002493]).
However, modest effort has been made to explore what may be a more common medication misadventure: unforeseen adverse effects occurring after the appropriate prescriptions are made. Though hospitalists do their sincere best, they heavily rely on patients' understanding of and adherence to the medical regimen (22. Osterberg L, Blaschke T. Adherence to medication. N Engl J Med. 2005;353:487-97. [PMID: 16079372]). Although patients are instructed to bring all of their medications, it is uncommon for a patient to have all prescription bottles along at either the hospital or a physician appointment (33. Choudhry NK, Avorn J, Glynn RJ, Antman EM, Schneeweiss S, Toscano M, et al; Post-Myocardial Infarction Free Rx Event and Economic Evaluation (MI FREEE) Trial. Full coverage for preventive medications after myocardial infarction. N Engl J Med. 2011;365:2088-97. [PMID: 22080794] doi:10.1056/NEJMsa1107913). If not even the hospitalist is certain of the patient's home medication regimen, the patient may be at risk.
A simplified approach to adherence could spare patients information fatigue and lead to better outcomes. Prescribers of medications must consider the ability of the patient or the caregiver to understand and comply with complicated medication regimens. The duty of prescribing and dispensing the right medications should not end when the patient has the correct medication in hand. We therefore propose some additional steps for clinicians and the health care system to prevent adverse medication events in patients receiving multiple medications.
Scope of the problem
It's important to recognize that research on pharmaceuticals is typically conducted only in limited populations and that similar benefits and safety may not apply to wider populations. This problem becomes more significant as guidelines and quality assurance programs attempt to shift therapy toward greater uniformity. Polypharmacy is then applied to an aging populace in ways that are previously untested and may lead to clinical harm. Few could reasonably argue that a hypertensive septuagenarian with type 2 diabetes who is treated with three medications to control blood pressure, three more to control blood glucose, a statin, and aspirin will achieve the same benefit as a patient without such comorbidities. It remains unlikely that the combinations of medications being used have been tested for safety and efficacy together. Additionally, over-the-counter drugs, vitamins, and nutraceuticals—often publicly advocated and advertised, but never tested in the context of multiple prescription medications—increase the potential for drug-drug interactions.
In the past, the system to provide proper medication therapy included the physician, patient, and pharmacist. Local pharmacies usually carried the same medications from the same companies on a consistent basis. These relationships offered some checks and balances that are now dropped from our daily practice. Mail-order prescriptions, insurance restrictions, multiple generics, and production shortages have all led to increased potential confusion for the patient (44. Wiske CP, Ogbechie OA, Schulman KA. Options to promote competitive generics markets in the United States. JAMA. 2015;314:2129-30. [PMID: 26513309] doi:10.1001/jama.2015.13498).
The number of medications that an individual may be expected to take has increased with scientific advancement (55. Steinbrook R. Patients with multiple chronic conditions—how many medications are enough? [Editorial]. N Engl J Med. 1998;338:1541-2. [PMID: 9593796]). In the 1970s, the patient with chronic heart failure was properly prescribed digoxin and a diuretic. Today, standard of care for a similar patient requires consideration of an angiotensin-converting enzyme inhibitor, angiotensin-receptor blocker, sacubitril-valsartan combination, a beta-blocker, spironolactone, diuretics, and aspirin, a new oral anticoagulant, or warfarin.
No attempt has been made to standardize the color, size, shape, or markings on medications so as to decrease the likelihood of confusion from this polypharmacy (66. Greene JA, Kesselheim AS. Why do the same drugs look different? Pills, trade dress, and public health. N Engl J Med. 2011;365:83-9. [PMID: 21732842] doi:10.1056/NEJMhle1101722). Compounding the problem, it is not at all unusual for patients to receive one prescription to commence immediately from the local pharmacy and another from a mail-order pharmacy. Physicians besieged by calls when samples and pharmacy pills don't look alike are additionally confused by formulary and coverage changes.
Currently, a change in the color or shape of pills when a prescription is renewed is not uncommon. Medication toxicity in a patient receiving both a branded and generic form is unfortunately also not rare. As the number of medications required increases, the ability of the patient to recognize and deal with any change decreases. The disorganization of the health care system increases confusion that may lead to patient medication misadventures (77. Shortell SM, Gillies RR, Anderson DA, Mitchell JB, Morgan KL. Creating organized delivery systems: the barriers and facilitators. Hosp Health Serv Adm. 1993;38:447-66. [PMID: 10130607]).
If prescription medications were recognizable, and local pharmacies and mail-order pharmacies delivered the same tablets, little opportunity for confusion would exist. A coordinated system for drug identification needs to be considered either voluntarily by industry or by regulatory mandate.
The best currently available method to prevent and stop these medication problems may be to participate in “brown bag” medication review. Hospital systems, hospitalist groups, and pharmacies should sponsor “brown bag” days, providing (and advertising) an opportunity for pharmacists to sit down and go over all medications with at-risk patients or their families. Medicare, commercial insurers, and other payers should advocate and sponsor programs for disease management nurses to ascertain that patient safety is maintained. For the geriatric patient, simpler solutions may include daily blister packs of medications or a “polypill” to avoid confusion.
Another systematic approach would be to involve a pharmacist in team-based care; that model has resulted in meaningful improvement in compliance and outcomes among patients with hypertension and cardiovascular disease (88. Tsuyuki RT, Al Hamarneh YN, Jones CA, Hemmelgarn BR. The effectiveness of pharmacist interventions on cardiovascular risk: the multicenter randomized controlled RxEACH trial. J Am Coll Cardiol. 2016;67:2846-54. [PMID: 27058907] doi:10.1016/j.jacc.2016.03.528, 99. Weinrauch LA, Segal AR, D’Elia JA. Cardiovascular risk reduction and the community pharmacist [Editorial]. J Am Coll Cardiol. 2016;67:2855-7. [PMID: 27311524] doi:10.1016/j.jacc.2016.04.018). However, the popularity of mail-order delivery of medications makes it difficult to assure that pharmacists will have access to the complete profile of an individual patient. At some point, a linkage among pharmacy, payer, hospital, hospitalist, and outpatient physician will be required to preserve patient safety. Crosstalk between electronic health records of various institutions and offices, if correctly implemented, may help.
Another potential solution includes smart delivery devices and instantaneous feedback systems. For example, companies are working to develop real-time clinical monitoring of vital signs and give feedback to the patient, which may modify adherence as well as treatment decisions. Wireless pulmonary artery hemodynamic monitoring has helped reduce chronic heart failure hospitalizations by guiding early intervention (1010. Givertz MM, Stevenson LW, Costanzo MR, Bourge RC, Bauman JG, Ginn G, et al; CHAMPION Trial Investigators. Pulmonary artery pressure-guided management of patients with heart failure and reduced ejection fraction. J Am Coll Cardiol. 2017;70:1875-1886. [PMID: 28982501] doi:10.1016/j.jacc.2017.08.010). Smart delivery systems will increasingly enable us to detect whether a medicine has been taken—the first such tracker was recently approved by the FDA to be used in conjunction with aripiprazole.
To recommend that physicians simplify prescribing regimens seems obvious. Until the major task of changing how government and major industry regulate and produce medications is accomplished, clinicians will need to recognize the possibility of medication misadventures and design systems to avoid this endemic outpatient problem.
Within hospitals, barcoding for drug and device delivery has diminished error rates. This has not occurred, however, for the vast majority exposed to polypharmacy as outpatients. We must assure that understandable labeling and usage directions accompany medications to the point of use. Currently, there has not been sufficient effort placed upon delivery of a single set of instructions, adjusted for comprehensibility in the spoken language of the patient. The patient on polypharmacy may receive multiple pages of contradictory explanations and instructions that become a source of countless calls to physicians for explanations, which undermines the clinical relationship and generates confusion.
The individual medical practitioner is not equipped to determine whether or where a prescription has been filled. The electronic health record systems currently available do not quickly identify individuals at risk by virtue of using multiple pharmacies. We must enable our hospitalists to quickly identify situations in which polypharmacy creates unanticipated risk without parallel increase in benefit, such as the use of more than one medication from similar classes.
If we can accomplish this goal we will reduce health care errors. Hospitalists play a critical role in preventing medication errors and improving adherence by collaborating with a pharmacist-guided system.
Returning to our example patient, after multiple admissions, a local pharmacist alerted her clinicians that she was refilling her nitroglycerin at an alarming rate. Once she was helped to take her medications as intended, all symptoms resolved and her workup was objectively negative. Although the patient insisted that she never missed a scheduled dose or confused the medications, rectifying her medical regimen resolved the acute presentation.