Avoiding Inappropriate Medication Use In Older Adults

1. Avoiding Inappropriate Medication Use In Older Adults Jason Stein, MD Emory Reynolds Faculty Scholar Emory Hospital Medicine Service

2. Scope of the Problem If medication related problems were ranked as a disease by cause of death it would be the: 5th leading cause of death in the U.S. Updating the Beers Criteria

3. Demographic Trends: the Elderly DEMOGRAPHIC TRENDS • 20th century • U.S. population < 65 tripled • U.S. population > 65 increased by factor of 11 • grew from 3.1 million (1900) to 33.2 million (1994) • Will more than double by middle of 21st century • to 80 million people, with most of this growth b/t 2010-30. Hobbs, FB, Damon BL. Sixty-Five Plus in America. Current Population Reports, Special Studies, P23–P190. Washington, DC: US Department of Commerce, Economics, and Statistics Administration, Bureau of the Census; 1996. National Center for Health Statistics. Health, United States, 1999 With Health and Aging Chartbook. Hyattsville, MD: US Department of Health and Human Services, National Center for Health Statistics; 1999. DHHS Pub. No. (PHS) 99–1232.

4. Educational Trends: the Elderly Educational Trends: High School Diploma • 1970: 28% • 1998: 67% • 2030: 83% Bachelor’s Degree(or higher) • 1998: 15% • 2030: 24% Education = closely related to lifetime economic status Education = associated with better health and lower risk of disability than those with low levels of educational attainment Education ~ more activist health care consumers, more demanding of the health care system (speculation about better-educated elderly baby boomers) American Association of Retired People (AARP) and Administration on Aging (AOA), US Department of Health and Human Services. Profile of Older Americans. 1999. Hobbs, FB, Damon BL. Sixty-Five Plus in America. Current Population Reports, Special Studies, P23–P190. Washington, DC: US Department of Commerce, Economics, and Statistics Administration, Bureau of the Census; 1996. National Center for Health Statistics. Health, United States, 1999 With Health and Aging Chartbook. Hyattsville, MD: US Department of Health and Human Services, National Center for Health Statistics; 1999. DHHS Pub. No. (PHS) 99–1232.

5. Health Trends: the Elderly Health Trends: • 79% of persons > 70 have at least one of the 7 chronic conditions most common among elderly: • Arthritis • Hypertension • Diabetes mellitus • Heart disease • Stroke • Respiratory disease • Cancer Hobbs, FB, Damon BL. Sixty-Five Plus in America. Current Population Reports, Special Studies, P23–P190. Washington, DC: US Department of Commerce, Economics, and Statistics Administration, Bureau of the Census; 1996. National Center for Health Statistics. Health, United States, 1999 With Health and Aging Chartbook. Hyattsville, MD: US Department of Health and Human Services, National Center for Health Statistics; 1999. DHHS Pub. No. (PHS) 99–1232.

6. Functional StatusTrends:the Elderly Functional Status Trends: • Functional disability increases with age • Functional disability is associated with chronic disease • majority < 85 yo have no difficulty in ADLs or instrumental activities of daily living (iADLs) • 72% of those 65 – 74 yo • 53% of those 75 - 84 yo • majority > 85 do report difficulty • 78% !! Hobbs, FB, Damon BL. Sixty-Five Plus in America. Current Population Reports, Special Studies, P23–P190. Washington, DC: US Department of Commerce, Economics, and Statistics Administration, Bureau of the Census; 1996. National Center for Health Statistics. Health, United States, 1999 With Health and Aging Chartbook. Hyattsville, MD: US Department of Health and Human Services, National Center for Health Statistics; 1999. DHHS Pub. No. (PHS) 99–1232.

7. Hospital Diagnosis Trends:the Edlerly Discharge Diagnosis Trends: • Heart Disease • Heart Disease + Stroke • Malignant neoplasms • Pneumonia • Bronchitis Leading discharge diagnosis Account for > 25% of all hospital discharges among men and women > 85 American Association of Retired People (AARP) and Administration on Aging (AOA), US Department of Health and Human Services. Profile of Older Americans. 1999. Hobbs, FB, Damon BL. Sixty-Five Plus in America. Current Population Reports, Special Studies, P23–P190. Washington, DC: US Department of Commerce, Economics, and Statistics Administration, Bureau of the Census; 1996. National Center for Health Statistics. Health, United States, 1999 With Health and Aging Chartbook. Hyattsville, MD: US Department of Health and Human Services, National Center for Health Statistics; 1999. DHHS Pub. No. (PHS) 99–1232.

8. Prescription Medication Trends:the Elderly Prescription Medication Trends: • 80% of elderly use > 1 prescription medication • 93% of elderly with low functional status (dependent for 3-5 ADLs) use > 1 prescription medication • Medicate beneficiaries spend more out-of-pocket for prescription medications than physician care, vision services, and medical supplies combined. • Medicare beneficiaries spend more than 5x more on prescription drugs than for outpatient and inpatient hospital care combined American Association of Retired People (AARP) and Administration on Aging (AOA), US Department of Health and Human Services. Profile of Older Americans. 1999. Hobbs, FB, Damon BL. Sixty-Five Plus in America. Current Population Reports, Special Studies, P23–P190. Washington, DC: US Department of Commerce, Economics, and Statistics Administration, Bureau of the Census; 1996. National Center for Health Statistics. Health, United States, 1999 With Health and Aging Chartbook. Hyattsville, MD: US Department of Health and Human Services, National Center for Health Statistics; 1999. DHHS Pub. No. (PHS) 99–1232.

9. The Elderly and Hospital Medicine Differential diagnosis of every problem in a geriatric patient includes a drug side effect

10. Inappropriate Medication definition: “inappropriate” medication → greater potential to harm than benefit patient May be due to: • Lack of proven effect • High likelihood of ADE • Potential for severe ADEs • High potential for interaction with another drug or class of drugs Chutka D, Takahashi P, Hoel R. Inappropriate Medications in Elderly Patients. Mayo Clin Proc. 2004; 79:122-139.

11. Use of Inappropriate Medications • Evidence: physicians often prescribe medications with increased potential of harm to elderly patients • Evidence: physicians treat certain conditions aggressively despite patient’s age and functional status • Evidence: adverse reactions up to 7x more common in 70-79 yo compared with 20-29 yo • Evidence: Increasing number of meds increase risk of serious drug interaction Chutka D, Takahashi P, Hoel R. Inappropriate Medications in Elderly Patients. Mayo Clin Proc. 2004; 79:122-139.

12. Adverse Drug Events (ADEs) definition: “adverse drug event” → when injury or illness occurs as a result of drug use Majority of occur in older adults – likely d/t 3 primary reasons: • increased polypharmacy (# medications = single most important factor) • altered pharmacodynamics/kinetics (75% of geriatric adverse drug effects occur at manufacturer recommended doses) • increased prevalence of disease with advancing age

13. Polypharmacy definition: “polypharmacy” → >5 medications • Increases risk of drug interactions (which likely contributes to increased adverse effects in older adults) • Increases complexity and cost of medication regimens

14. Why Consider the Elderly? • Quantity of the Elderly • Demographics • Quality of the Elderly • Age Related Physiological Changes • Other Age Related Factors • Multiple medical conditions • Multiple medications

15. Why Consider the Elderly? ADEs, drug-drug interactions, and drug toxicities are more likely in elderly patients due to: • Age related changes in pharmacokinetics • Age related changes in pharmacodynamics • Reduced organ reserve capacity (tends to increase the severity of ADEs) • Multiple medical conditions • Number of medications taken Chutka D, Takahashi P, Hoel R. Inappropriate Medications in Elderly Patients. Mayo Clin Proc. 2004; 79:122-139.

16. The Elderly: Pharmacokinetics Body composition changes:  body fat (relative) • lean body mass • decreased total body water • Changes in drug distribution, metabolism, and elimination increases susceptibility to ADEs (but minimal changes in absorption) • Water soluble medications: concentrations increased at any given dose relative to younger adults • Fat soluble medications: half-lives prolonged

17. The Elderly: Pharmacodynamics Elderly more sensitive so greater drug effects (both beneficial and adverse) may occur at a given serum level relative to younger adults. e.g. altered pharmacodynamics with aging include opiates, benzodiazepines, warfarin, and theophylline

18. The Elderly and Medication Compliance Altered Compliance • Under-utilization (taking less than prescribed dose frequency or strength) • Over-utilization (taking more than prescribed doses) • Enforced Adherence

19. The Elderly and Medication Compliance Under-utilization (taking less than prescribed dose frequency or strength) • Common and increases with polypharmacy • Associated with complex dosing regimens • Associated with expensive medications • May be “appropriate” if due to drug side effects • May occur if difficulty obtaining or taking drugs (e.g., functional impairments, cognition, dexterity, vision problems)

20. The Elderly and Medication Compliance Over-utilization (taking more than prescribed doses) • Occurs often in patients with cognitive impairment • Increases the potential for adverse drug events • Suspect if medication refills needed early, too frequently

21. The Elderly and Medication Compliance Enforced Compliance • Occurs when administering an “assumed” outpatient dose (when in fact patient has not been taking that dose) • Common occurrence in hospital or nursing home setting • High potential for overdose/adverse drug effects

22. Elderly Patients and Hospital Medicine Risk Factors • Hospitalized patients with lower admission MMSE scores may have higher rates of ADEs • More newly prescribed inpatient medications Frequency • 1 in 6 hospitalized elderly patients (>70 yo) may experience an ADE Inevitable? • Over half of ADEs are potentially preventable Gray S, Sager M, Lestico M, Jalaluddin M. Adverse Drug Events in Hospitalized Elderly. Journ of Gerontology. 1998; 1: M59-M63.

23. Elderly Patients and Hospital Medicine ADEs and Functional Decline • 50% of hospitalized patients who experience an ADE deteriorate in ADL function during the hospitalization (25% of non-ADE patients) Gray S, Sager M, Lestico M, Jalaluddin M. Adverse Drug Events in Hospitalized Elderly. Journ of Gerontology. 1998; 1: M59-M63.

24. Elderly Patients and Hospital Medicine Which Drug Can We Eliminate to Make the Problem Go Away? • No single drug accounts for a high % of ADEs • But there are high risk drug classes (those most often a/w preventable ADEs) → meds with CNS effects: • narcotics • sedatives • antidepressants Gray S, Sager M, Lestico M, Jalaluddin M. Adverse Drug Events in Hospitalized Elderly. Journ of Gerontology. 1998; 1: M59-M63 54%

25. Elderly Patients and Hospital Medicine LOS and Costs • In one study 60/190 ADEs preventable • Additional LOS assoc with ADE=2.2 d • Additional cost assoc with ADE=$3,244 • Based on cost data and incidence of ADEs: • estimated annual attributable cost to in a 700 bed teaching hospital was… $5.6 million (attributable to all ADEs) $2.8 million (attributable to preventable ADEs) Bates D, Spell N, Cullen D, et al. The Costs of Adverse Drug Events in Hospitalized Patients. JAMA. 1997; 277(4): 307-311.

26. Elderly Patients and Hospital Medicine Scope of the Problem • As many as 30% of hospital admissions of elderly patients are due to ADEs • 35% of ambulatory older adults experience an ADE (29% require health care services: physician, ED, or hospitalization) • Symptoms of ADEs in elderly can be: • non-specific, or • subtle • Temptation is to “treat” an ADE with another drug Chutka D, Takahashi P, Hoel R. Inappropriate Medications in Elderly Patients. Mayo Clin Proc. 2004; 79:122-139. confusion, falls, hip fractures, functional decline, poor PO intake, urinary retention, or constipation

27. Identifying the Medications to Avoid for Elderly Patients:Beers Criteria – the Why How do we formulate Clinical Guidelines? • Controlled studies • Systematically review the evidence-based literature

28. Beers Criteria – the Why What if # of controlled studies is limited? • For “Medication Use in Elderly Patients” that’s the problem – elderly excluded from many studies • One approach is to ask the opinion of those considered experts • Consensus Criteria • Types of Bias this introduces • Recognize the Bias…and Move On

29. Consensus Criteria for Medication Use in Older Adults – 2 such sets Beers Criteria Canadian Criteria

30. Beers Criteria – the What • “Criteria” = Statements: • Specific medications (or classes of medications)… • Should generally be avoided in any person > 65yo • Should not be used routinely > 65 yo with a specific medical condition • Risk for ADE too high when safer alternative exists • Problematic in excessive dosages • Problematic in extended duration of use (when initially intended for limited time)

31. Beers Criteria – the How? • The process – Delphi Method • Analysis Concurrent with Data Collection • 1) Literature Review -> 1st Questionnaire • 2) Experts complete 1st Questionnaire • 3) Analysis of 1st Questionnaire -> 2nd Questionnaire • 4) Experts complete 2nd Questionnaire (Using Feedback Provided by Investigators - allowed to see answers from 1st Questionnaire plus Face-to-Face discussion)

32. Delphi Method • Set of procedures for formulating group judgment for subject matter where precise info is lacking • Procedures consist of obtaining individual answers to pre-formulated questions, e.g. by questionnaire • Iterating questionnaire one or more times where information feedback b/t rounds is carefully controlled by exercise manager

33. Delphi Method • Taking as the group response a statistical aggregate of the final answers • Leads to increased accuracy of group responses more often than not

34. Who Were the Experts? • 12 of them (13 in 1991, 6 in 1997) • “nationally recognized experts in geriatric care, clinical pharmacology, and psychopharmacology”

35. What Made Them “Experts?” • Published extensively • Senior academic rank • Represented acute care, long-term care, and community practice setting • Geographically diverse • 12 of 16 invited experts completed all rounds of survey (dropout, intention to survey)

36. Response Standardization • Likert Scale • Rate agreement or disagreement with a statement from • <1> strongly agree • <3>expresses equivocation • <5>strongly disagree

37. Response Open-ended • If expert didn’t feel qualified to reply, could opt not to answer • If expert wanted to add own statement provision for that (this is good because…)

38. Literature Review • 4 Investigators -> 1st questionnaire from systematic review of the literature: • Identified literature published in English 1/1994-12/2000 analyzing medication use in older adults living in the community and living in NH’s • Note: did not include medication use in hospitals

39. Literature Review • Searched MEDLINE using terms: • Adverse drug reactions • Adverse drug events • Medication problems • Medications and elderly

40. Literature Review • Hand searched & identified additional references from bibliographies of relevant articles • All panelists invited to add references to the literature review

41. Literature Review-> 1st Questionnaire • Each publication was reviewed by 2 (of the 4) principal investigators • Each investigator used a table to outline: • Study design • Sample size • Medications reviewed • Summary of results and key points • Quality, type, and category of medication addressed • Severity of drug related problem

42. 1st Questionnaire • Experts Respond • Parts 1 and 2 reviewed 1997 criteria • Parts 3 and 4 new for 2002 • Part 3 – Medications Independent of Disease or Condition • Part 4 – Medications Considering Disease or Condition • Provision for Expert to add open-ended input (44)

43. 1st Questionnaire Analyzed • Building the 2nd Questionnaire – Trashing Questions • Calculated mean rating (Likert 1-5) • Calculated corresponding 95% CI for each “statement or dosing question” • Where lower limit of the 95% CI was > 3 those statements & dosing questions were excluded • Included statements & dosing questions whose upper limit of 95% CI < 3

44. 1st Questionnaire • Building the 2nd Questionnaire – Adding Questions • Any statement added by an expert in the open-ended included in 2nd Questionnaire

45. 2nd Questionnaire • Experts received it 10 days before meeting face-to-face • Opportunity to reconsider own responses • After given information on their previous answers plus anonymous answers of other experts

46. Severity Rating • Potential medication problems • 5 point scale

47. Results • Final Criteria • Table 1 • 48 individual medications (or classes) to avoid in older adults • Table 2 • 20 diseases or conditions plus medications to avoid • Table 3 • Sensitivity of the Process Poor?

48. Example

49. Example

50. Critiques of this Method • Simplistic – misses other prescribing problems such as underuse or interactions of drugs in older patients • Limiting – clinical judgment • Lack of prospective, controlled studies that show criteria make a difference in outcomes • May not reflect best practice for the oldest old (sig > 65 yo) • Same limitations previously documented regarding use of Delphi technique