Deprescribing: Principles and Practice

Educational Objectives

The goal of this program is to improve deprescribing of medications in older individuals. After hearing and assimilating this program, the clinician will be better able to:

1. Demonstrate the efficacy of statin therapy for primary and secondary prevention.
2. Consider risks for long-term prescription of proton-pump inhibitors.
3. Modify prescription of psychotropic and sleep medications.
4. Minimize risk for bleeding through deprescribing anticoagulant and antiplatelet medications.
5. Counsel patients regarding use of supplemental vitamins.

Summary

Background: deprescribing involves adjusting medication therapy to the minimum need by retaining medications that improve morbidity or mortality and stopping medications which do not improve morbidity or mortality; prioritize medications that are of proven benefit on an ongoing basis, while considering changes in circumstances, body morphology, and medical evidence; in the United States, ≈50% of older adults take ≥5 medications; the number of prescribed medications has tripled in the past 30 yr; in Italy, the average 70-yr-old individual takes 2 medications and enjoys longer lifespan and higher quality of life (QOL)

Reasons for deprescribing: financial considerations — though patients may be under the mistaken impression that a change in medication is undertaken for physician kickbacks, lowering patient cost is an important reason for conservative prescribing; layering — additive effects of multiple medications; trials are often conducted in a controlled setting, where patients do not receive other concurrent medications; however, when prescribing additional medications, clinicians often extrapolate the results with the hope of deriving similar benefits, ignoring drug interactions; body morphology — body morphology changes with regard to, eg, age, weight, renal and hepatic function, cognitive status; thus, no prescription should be permanent; goals of care — changes in patient needs and goals are not restricted to end-of-life care; patient goals change at different stages of life, necessitating reassessment of prescriptions

Approach to deprescribing: draw attention to evidence changes which indicate a medication is no longer necessary; mention that some medications may no longer be safe as the patient ages (eg, anti-inflammatory drugs negatively affect the kidneys); gently approach deprescribing, help patients set future goals rather than suddenly stopping or changing medications; challenge patients to research their medications

Statins

Primary prevention: Corti et al (1997) found that death from coronary artery disease (CAD) increases at serum cholesterol levels ≤160 mg/dL in elderly individuals; LaRosa et al (2005) demonstrated increased rate of noncardiovascular mortality (primarily from cancer) among patients with stable CAD prescribed high-dose atorvastatin, compared with low-dose atorvastatin; the US Preventive Services Task Force states that evidence is insufficient to recommend statin therapy for primary prevention of cardiovascular diseases (CVD) in individuals ≥75 yr of age; per the National Cholesterol Education Program (1993), “Patients with a limited lifespan from a concomitant illness are probably not candidates for drug therapy”; Ramos et al (2018) demonstrated no reductions in incidence of CVD or all-cause mortality with statin use in patients ≥75 yr of age without CVD or diabetes mellitus (DM), though benefitted patients ≤84 yr of age with DM; the ALLHAT-LLT trial (Han et al [2017]) demonstrated no improvements in CAD or mortality in patients 65 to 74 yr of age, but showed a trend toward increased mortality in patients ≥75 yr of age; a meta-analysis by the Cholesterol Treatment Trialists’ Collaboration (2019) suggests benefit at any age

Reasons for deprescribing: myalgias can occur in 5% to 10% of all patients, though in ≤50% of elderly individuals (in whom etiology of myalgias is difficult to discern); consider deprescribing in patients who experience muscle aches and fatigue after exercise; statins can cause elevated liver function testing, nausea, and weakness

Secondary prevention: the PROSPER trial (Shepherd et al [2002]) demonstrated reductions in incidences of myocardial infarction (MI) and stroke, but no change in overall mortality, during the first 3 yr of administration of a statin in patients 70 to 82 yr of age with history of CAD; no differences in CV events (CVEs) or mortality were observed after 8 yr

Medications for DM: studies show that most elderly patients are overtreated for DM; one trial demonstrated increased incidence of stroke and MI in patients whose DM was too intensely controlled; the hemoglobin A_1C (HbA_1C) goal for fit patients with 10-yr life expectancy is 7%, but ≥8% for frail, elderly patients with multiple comorbidities; Seidu et al (2019) demonstrated success with motivational interviewing, physical activity, diet changes, stress management, and ability to reduce or stop medications for DM; metformin is the preferred treatment, with clear mortality benefit; newer medications may produce weight loss (especially GLP-1 receptor agonists) and provide benefits with regard to CV and renal function; the SELECT trial (Ryan et al [2020]) demonstrated 20% fewer CVEs among patients with overweight and CVD who take semaglutide, compared with placebo

Proton-pump inhibitors (PPIs): designed for short-term use and are generally not meant for long-term use (with few exceptions); long-term use of PPIs has been linked with osteoporosis-related fractures, Clostridioides difficile infection, pneumonia, and aspiration pneumonitis; possible associations include dementia, kidney disease, and stroke; prolonged acid suppression causes atrophic gastritis, chronic Helicobacter pylori infection, and development of precancerous gastric polyps; Laheij et al (2004) found that patients using PPIs are ≈4-fold more likely to acquire pneumonia, compared with patients who do not use PPIs, regardless of the reason for therapy; risk for pneumonia was dependent on PPI dose and prescription duration; studies have demonstrated decreased cytotoxicity of white blood cells with use of PPIs

Donepezil: not suitable for patients with advanced dementia and should not be used or marketed to patients and families as a treatment for dementia; indicated for mild to moderate Alzheimer disease (AD; ie, functional assessment staging tool score <7); compared with placebo, Courtney et al (2004) demonstrated no benefits from donepezil with regard to institutionalization, debility, or assistance with activities of daily living, in addition to improvement in cognitive testing by <1 point; per Raina et al (2008), “Treatment of dementia…can result in statistically significant, but clinically marginal, improvement in measures of cognition and global assessment of dementia”; Birks (2006) demonstrated improvement in cognitive function with recommended dosing of donepezil, galantamine, or rivastigmine in patients with mild, moderate, or severe AD; however, the average improvement was -2.7 points on the 70-point Alzheimer Disease Assessment Scale-cognitive Subscale scale, with limited evidence for efficacy in severe AD; no differences were noted with regard to overall quality of life, behavioral issues, or institutionalization; ≈33% of patients discontinued the medications because of adverse events (AEs; eg, syncope with falls, gastrointestinal [GI] upset)

Antidepressants and psychotropic medications: psychotropics are overused in the US; physicians should target prescription for clinical depression, rather than lifestyle use; psychotropics top the American Geriatrics Society’s “Beers list” of drugs to avoid; psychotropic drugs are often classically layered in symptom-based management, rather than considering other modalities of treatment; reevaluate selective serotonin reuptake inhibitors (SSRIs) after 3 to 6 mo; fluoxetine is not addictive and can be flexibly prescribed; benzodiazepines (eg, lorazepam) increase confusion and falls; SSRIs are a common cause of falls and hip fracture; older tricyclic antidepressants are on the Beers list; while appropriate for acute delirium and commonly used as adjunct treatment for depression, antipsychotics double the risk for early mortality in otherwise stable nursing home residents; prescription recommendations — start with a low dose and gradually increase the dose; always set a review or stop date; avoid prescribing new medications for every symptom (ie, layering); consider patient goals and priorities; carefully review medications, considering drug interactions and AEs

Oral anticoagulation agents: warfarin was commonly used to prevent clotting in patients with atrial fibrillation (AF), thromboembolic disease, or artificial heart valves; currently, direct oral anticoagulants (DOACs; eg, rivaroxaban, apixaban) are increasingly used; the 1-yr risk for stroke in a patient with AF and treated with anticoagulation is 2%, vs 4% if untreated; scoring tools for anticoagulation — the Stroke Prevention in Atrial Fibrillation Risk Calculator provides risk for stroke vs risk for major bleed; CHA₂DS2-VASc calculates stroke risk; HAS-BLED calculates bleeding risk; barriers for deprescribing — patients and their families often hesitate to stop anticoagulation medication because of fears of a stroke; discuss risks for hemorrhagic stroke vs major bleed; despite what specialists have done for the patient, healthcare providers should identify the need for change and work with patients and families toward a more effective deprescribing approach

Antiplatelet medication (APMs): clopidogrel is recommended for patients for 1 to 6 mo following coronary stent placement; although some data suggest efficacy of APMs for patients with stable CAD or recent acute coronary syndrome, the risk for bleeding renders APMs inappropriate for most patients; many elderly patients are inadvertently left on clopidogrel because of lack of follow-up with their stenting physician, and the medication is indefinitely renewed (ie, legacy prescribing); Bhatt et al (2006) demonstrated no benefit with regard to CAD, with 2-fold increased risk for GI bleeding in patients prescribed clopidogrel and aspirin, compared with aspirin alone

Medications for pain disorders: physicians rely on subjective reports and pain scales (as objective evidence is difficult to obtain); gabapentin — used off-label for diabetic neuropathy and chronic back pain; gabapentin is currently considered a controlled substance in many states, as Cairns et al (2019) demonstrate misuse, abuse, and risk for death which approaches other common controlled substances; a meta-analysis by Wiffen et al (2017) found that 38% of patients on gabapentin reported substantial improvement in neuropathic pain (≥50% improvement from baseline) and ≥50% reported moderate improvement in neuropathic pain (≥30% improvement from baseline); however, the number needed to treat was 7 (owing to high placebo effect); common AEs include dizziness, somnolence, and gait disturbance (experienced by ≈20% of patients); confirm that medications provide pain relief for patients

Sleep agents: zolpidem is a controlled substance which may induce sleepwalking; trazodone and mirtazapine have been associated with high fall risk; benzodiazepines are addictive and dangerous; quetiapine is an antipsychotic; haloperidol has been associated with early mortality in nursing home residents; the speaker favors melatonin (has proven benefits for circadian sleep; early-evening administration is recommended) and zolpidem; short-term use of sleep medications is beneficial, but long-term use should be reconsidered; cognitive behavioral therapy is effective in treating chronic insomnia

Pulmonary inhalers: the Global Initiative for Asthma (GINA) and the Global Initiative for Chronic Obstructive Lung Disease (GOLD) have published specific guidelines; Canadian Thoracic Society guidelines recommend step-up or step-down therapy based on disease control (Ebell [2024]); if a short-acting β-agonist is insufficient for treatment of asthma, step up to a steroid inhaler, avoiding a combination inhaler with a long-acting β-agonist; well-managed patients may benefit from a step-down trial; GOLD and GINA warn that all patients are not capable of using the devices; 30% of medications are wasted by lack of use or inappropriate technique

Vitamins: vitamin D has been associated with fall prevention; evidence lacks which supports the benefits of vitamins; some high-quality studies demonstrate harm with vitamin E, vitamin A, and β-carotene; supplemental vitamin E can cause cancer; high doses of vitamins have not been proven to improve QOL or longevity; many vitamins taken by elderly individuals provide little or no benefit; the speaker occasionally recommends iron (when appropriate), zinc (short-term use may improve wound healing), and vitamin C (in patients with complications from prolonged Foley catheter use); some natural products (eg, kava, St John's wort, goldenseal, green tea extract) are known to cause more harm than benefit; help people transition from vitamins to a healthy diet and exercise

Readings

Agwu NP, Umar AM, Oyibo UE. Review Article: Urethral catheters and catheterization techniques. Niger J Med. 2022;31(5):p497–508. DOI:10.4103/NJM.NJM_99_21. View Article; Amarenco P. Effect of statins in stroke prevention. Curr Opin Lipidol. 2005;16(6):614-618. DOI: 10.1097/01.mol.0000194127.99968.ca. View Article; Berry SD, Zhang Y, Lipsitz LA, et al. Antidepressant prescriptions: an acute window for falls in the nursing home. J Gerontol A Biol Sci Med Sci. 2011;66(10):1124-1130. DOI:10.1093/gerona/glr113. View Article; Bhatt DL, Fox KAA, Hacke W, et al. Clopidogrel and aspirin versus aspirin alone for the prevention of atherothrombotic events. N Engl J Med. 2006;354(16):p1706–1717. DOI:10.1056/NEJMOA060989. View Article; Corti MC, Guralnik JM, Salive ME, et al. Clarifying the direct relation between total cholesterol levels and death from coronary heart disease in older persons. Ann Intern Med. 1997;126(10):753–760. DOI:10.7326/0003-4819-126-10-199705150-00001. View Article; Grundy SM, Bilheimer D, Chait A, et al. Summary of the Second Report of the National Cholesterol Education Program (NCEP) expert panel on detection, evaluation, and treatment Of high blood cholesterol in adults (adult treatment panel II). JAMA. 1993;269(23):3015-3023. DOI:10.1001/jama.1993.03500230097036. View Article; Han BH, Sutin D, Williamson JD, et al. Effect of statin treatment vs usual care on primary cardiovascular prevention among older adults: the ALLHAT-LLT randomized clinical trial. JAMA Intern Med. 2017;177(7):p955–965. DOI:10.1001/jamainternmed.2017.1442. View Article; Hung A, Kim YH, Pavon JM. Deprescribing in older adults with polypharmacy. BMJ. 2024;385:e074892. DOI:10.1136/BMJ-2023-074892. View Article; Laheij RJF, Sturkenboom MCJM, Hassing RJ, et al. Risk of community-acquired pneumonia and use of gastric acid–suppressive drugs. JAMA. 2004;292(16):p1955–1960. DOI:10.1001/jama.292.16.1955. View Article; LaRosa JC, Grundy SM, Waters DD, et al. Intensive lipid lowering with atorvastatin in patients with stable coronary disease. N Engl J Med. 2005;352(14):1425-1435. DOI:10.1056/NEJMoa050461. View Article; Mangione CM, Barry MJ, Nicholson WK, et al. Statin use for the primary prevention of cardiovascular disease in adults: US Preventive Services Task Force recommendation statement. JAMA. 2022;328(8):p746–753. DOI:10.1001/JAMA.2022.13044. View Article; Moore A, Derry S, Wiffen P. Gabapentin for chronic neuropathic pain. JAMA. 2018;319(8):818-819. doi:10.1001/jama.2017.21547. View Article; Poole RM. PROSPER: pravastatin benefits elderly patients. Inpharma Weekly. 2002;1368:p11–12. View Article; Ramos R, Comas-Cufí M, Martí-Lluch R, et al. Statins for primary prevention of cardiovascular events and mortality in old and very old adults with and without type 2 diabetes: retrospective cohort study. BMJ. 2018;362:k3359. DOI:10.1136/BMJ.K3359. View Article; Ryan DH, Lingvay I, Colhoun HM, et al. Semaglutide effects on cardiovascular outcomes in people with overweight or obesity (SELECT) rationale and design. Am Heart J. 2020;229:p61–69. DOI:10.1016/J.AHJ.2020.07.008. View Article; Schneeweiss S, Wang P. Association between SSRI use and hip fractures and the effect of residual confounding bias in claims database studies. J Clin Psychopharmacol. 2004;24(6):632-638. DOI:10.1097/01.jcp.0000145344.76288.39. View Article; Seidu S, Kunutsor SK, Topsever P, et al. Deintensification in older patients with type 2 diabetes: a systematic review of approaches, rates and outcomes. Diabetes Obes Metab. 2019;21(7):p1668–1679. DOI:10.1111/DOM.13724. View Article; Tsuno N. Donepezil in the treatment of patients with Alzheimer's disease. Expert Rev Neurother. 2009;9(5):p591–598. DOI:10.1586/ERN.09.23. View Article.

Disclosures

For this program, members of the faculty and planning committee reported nothing relevant to disclose. Dr. Allen's lecture includes information related to the off-label or investigational use of a therapy, product, or device.

Acknowledgements

Dr. Allen was recorded exclusively for Audio Digest on July 19, 2024. Audio Digest thanks Dr. Allen for his cooperation in the production of this program.

CME/CE INFO

Accreditation:

The Audio- Digest Foundation is accredited by the Accreditation Council for Continuing Medical Education to provide continuing medical education for physicians.

The Audio- Digest Foundation designates this enduring material for a maximum of 2.00 AMA PRA Category 1 Credits™. Physicians should claim only the credit commensurate with the extent of their participation in the activity.

Audio Digest Foundation is accredited as a provider of continuing nursing education by the American Nurses Credentialing Center's (ANCC's) Commission on Accreditation. Audio Digest Foundation designates this activity for 2.00 CE contact hours.

Lecture ID:

FP723701

Expiration:

This CME course qualifies for AMA PRA Category 1 Credits™ for 3 years from the date of publication.

Instructions:

To earn CME/CE credit for this course, you must complete all the following components in the order recommended: (1) Review introductory course content, including Educational Objectives and Faculty/Planner Disclosures; (2) Listen to the audio program and review accompanying learning materials; (3) Complete posttest (only after completing Step 2) and earn a passing score of at least 80%. Taking the course Pretest and completing the Evaluation Survey are strongly recommended (but not mandatory) components of completing this CME/CE course.

Estimated time to complete this CME/CE course:

Approximately 2x the length of the recorded lecture to account for time spent studying accompanying learning materials and completing tests.

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