Annual MeetingSeptember 14, 2019
Is Less More? Deprescribing Pearls For The Older Adult
Melissa Green, PharmD, BCACPClinical Pharmacist
University of Utah Geriatric Clinic
Johanna Thompson, PharmD, BCPS, BCGPAdvanced Clinical Pharmacist
Intermountain Healthcare/Cottonwood Senior Clinic
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Disclosure
No conflicts of interest to disclose.
We will be discussing off-label use of aspirin.
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Learning Objectives
At the conclusion of this activity, pharmacists should be able to successfully:
1. Justify use or non-use of low-dose aspirin and statin medications for older adults.
2. Create a plan to de-prescribe proton pump inhibitors in older adults.
3. Identify patient-, provider- and system-level prescribing forces leading to polypharmacy.
4. Explain the SHARE Approach to deprescribing medications.
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Learning Objectives
At the conclusion of this activity, pharmacy technicians should be able to successfully:
1. Identify reasons a patient may or may not be eligible for low dose aspirin.
2. List risks and benefits of statin medications for older adults.
3. Discuss risks of proton pump inhibitor use.
4. Identify patient-, provider- and system-level prescribing forces leading to polypharmacy.
5. Identify opportunities to invite patients to discuss discontinuing a medication with their pharmacist.
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DefinitionsPolypharmacy: 5 – 9 medications
Hyperpolypharmacy: 10 or more medications
Potentially Inappropriate Medication (PIM): ◦ Medications where the potential risks outweigh the potential benefits
Deprescribing◦ Process of planned and supervised tapering or safe withdrawal of PIM that can cause harm, is no longer indicated, or beneficial to the current therapy
Lown Institute. Medication Overload: America’s Other Drug Problem. 2019 April.SalahudeenMS. Drugs Today. 2018;54(8):489 6
An Aging Population: By the Numbers
2018 Profile of Older Americans 7
An Aging Population: Disease Burden
Ncoa.org8
An Aging Population: Medication Use
Community‐Dwelling Nursing Home Residents
Moore KL, et al. PLoS ONE. 2018;13(4):1‐149
Prescribing Forces
Lown Institute. Medication Overload: America’s Other Drug Problem. 2019 April. 10
PolypharmacyIn 2018, associated with◦ 5 million outpatient visits for ADEs◦ 280,0000 hospitalizations ◦ Cost of $3.8 billion
Clinical Outcomes◦ ADEs◦ Delirium◦ Falls◦ Mortality
Lown Institute. Medication Overload: America’s Other Drug Problem. 2019 April. 11
“Older adults are hospitalized for adverse drug events at a greater rate than the general population is hospitalized for opioids.”
‐ Lown Institute
Lown Institute. Medication Overload: America’s Other Drug Problem. 2019 April. 12
The Deprescribing Toolbox Consensus‐based Lists◦ Beer’s Criteria (2019)◦ STOPP/START (2014)◦ PRISCUS list (2010)
Risk Assessment Tool◦ Medication Appropriateness Index (1992)
Harm vs Benefit
Time to Benefit
Goals of Care
Adherence
Medication regimen considered as a whole
Niehoff KM, et al. Ther Adv Drug Saf. 2019;10:1 13
Deprescribing Details
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Polypharmacy: Drug‐drug interactions, poor compliance
Uncertain Benefit
Potential Harms
Why Deprescribe ASA, Statins, PPIs?
ASABleeding
PPIsDiarrhea, impaired B12
absorption, hypomagnesemia, C. difficile infections, hip fractures,
pneumonia
STATINMyalgias, liver injury, diabetes, cognition
Farrell B, et al. Can Fam Physician. 2017;63:354.15
Aspirin in the Older Adult
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Current ASA 1° Prevention Guidelines
U.S. Preventative Services Task Force. April 2016.Arnett et al. 2019 ACC/AHA Guideline on the Primary Prevention of CVD. 2019Cardiovascular Disease and Risk Management. Standards of Medical Care in Diabetes. Diabetes Care 2019. American Geriatrics Society 2019 Beers Criteria Updated Expert Panel. J Am Geriatr Soc. 2019.Vandvick PO, et al. CHEST 2012;141(2).
Guideline Age Statement
USPSTFAge 60 ‐ 69 years Consider if ASCVD ≥ 10% AND life expectancy > 10 years AND not at increased risk of
bleed
Age ≥ 70 years Insufficient evidence to assess balance of benefits and harms
ACC/AHAAge 40 ‐ 70 years Might consider ASA for those at high ASCVD risk but not at increased bleed risk
Age > 70 years Should not be administered on routine basis
ADA Age >70 years ASA may be considered after risk‐vs‐benefit discussion in high risk patients but generally not in older adults
2019 BEERs Adults ≥ 70 years Use with caution
ACCP (CHEST) Adults > 50 years Eligible for ASA. Acknowledge small benefit.
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The U.S. Food and Drug Administration recently DENIED a manufacturer’s request to add primary prevention of MI as an indication for aspirin use in any risk group. In a consumer bulletin, it noted the risks for GI and intracranial bleeding and suggested that the benefits of primary prevention have not been well‐established.
FDA Statement
U.S. Food and Drug Administration. Docket ID: FDA‐1977‐N‐001818
Question: Did 5 years of daily low‐dose aspirin therapy extend disability free life in healthy older adults?
ASPREE – ASA in Healthy Older Adults
Trial Patients Outcome Results
ASPREE 19,114 patientsMedian age: 74
No CVD, dementia or physical disability
Primary:Disability‐free survival (composite of death, dementia or persistent physical disability)
Secondary: ‐individual components‐major hemorrhage
ASA did NOT prolong disability free survival HR 1.01 (0.92‐1.11; p=0.79)
ASA INCREASED rate of major hemorrhage 3.8% vs 2.8% (HR 1.38 (1.18‐1.62; P<0.001)
McNeil, et al. NEJM 2018;379(16):1499 19
ARRIVE and ASCENDTrial Patients Outcome Results
ARRIVE Moderate CVD risk (ASCVD 10‐20%)
Composite of time to first occurrence CV death, MI, unstable angina, stroke or TIA
Hemorrhagic events
No difference in composite endpointHR 0.96 (0.81‐1.13); p=0.6
MORE bleeding (mostly mild GIB)HR 2.11 (0.36‐3.28); p=0.0007 NNH 66
ASCEND Diabetes(no CVD)
1st serious vascular event or death from any vascularcause
1st major bleeding event
LESS vascular eventsRate ratio 0.88 (0.79‐0.97) p=0.01 NNT = 90
MORE bleedingHR 1.29 (1.09‐1.52) p=0.003 NNH = 111
Gaziano, et al. Lancet 2018:392:1036McNeil, et al. NEJM 2018;379(16):1499
More studies of low dose ASA
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OBJECTIVE:‐ assess the association of aspirin use for primary prevention with cardiovascular events and bleeding
POPULATION:‐13 trials comparing ASA to no ASA‐164,225 patients (median age 62, ASCVD 9.2%) with no known CV disease
OUTCOMES AND RESULTS:‐ASA use associated with significant reduction in composite CV outcomes ◦ HR 0.89 (0.84‐0.95), absolute risk reduction 0.38% (0.20‐0.55%), NNT 265‐ASA use associated with increased bleed ◦ HR 1.43 (1.3‐1.56) absolute risk increase 0.47% (0.34‐0.62%), NNH 210
Association of Aspirin Use for Primary Prevention of CV Events and Bleed
Zheng, et al. JAMA 2019;321(3):277 21
Patients > 70 years old and ASAJohanna’s Conclusions
Generally ASA for primary prevention can be discontinued in those > 70 years of age
Consider use if age 50‐70 years:‐Low bleed risk‐High CV risk
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A 72 year old man came to see the pharmacist today to review medications. His primary care provider was concerned about polypharmacy and wanted to know what changes could be made to simplify and optimize his therapy.
Mr. B has a history of Parkinson's, HTN, T2DM, GERD and hypothyroidism. He lives at home with his wife. He is starting to struggle managing his medications. You suspect he is missing doses as he frequently comes up on your medication non‐adherence reports.
Case
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Medication List:
ASA 81 mg daily
Atorvastatin 40 mg daily
Metformin ER 500 mg BID
Glipizide 5 mg BID
Pantoprazole 40 mg daily
Levothyroxine 50 mcg daily
Losartan 25 mg daily
Amlodipine 10 mg daily
Carbidopa‐levodopa 25‐100 mg tablets – 3/2/3 tablets TID
Selegiline 5 mg BID
Vitamin D 1000 IU daily
MTV daily
Glucosamine‐Chondroitin BID
Vitamin C 500 mg daily
Case
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YES
Keep the aspirin?
NO
Active learning for pharmacists and technicians 25
Statins in the Older Adult
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Statin treatment for secondary prevention of CVD
Primary Prevention for those < 65 years and older
What We Don’t KnowPrimary Prevention for those ≥ 75 years of age
What We Know
What about 65‐75?
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Patients > 75 years old and StatinsWhat do the guidelines say?
• Moderate intensity MAY be reasonable• May be reasonable to measure CAC to help determine therapy (CAC = 0 NO statin)
1° Prevention AND LDL 70‐189 mg/dL
• CONTINUING statin is REASONABLE • INITIATING statin may be reasonable after discussion of risks vs benefits
1° Prevention AND DM
• INITIATE moderate or high intensity• CONTINUE high intensity if toleratingClinical ASCVD
• Functional decline, multi‐morbidity, frailty or reduced life expectancy limits benefits of statinSTOPping Therapy?
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Landmark Trials: sub‐analysis of older adultsTrial Patients Results
JUPITERpatients ≥ 70 years (74)
Primary Prevention‐HLD and elevated CRP‐Low risk; low LDL
Morbidity: less
Mortality: no change
HOPE‐3Patients ≥ 65 years (70.8)
Primary Prevention‐Intermediate risk
Morbidity: less
Mortality: no change
ALLHAT‐LLT Patients ≥ 65 years
Primary Prevention‐HTN‐no atherosclerotic disease
Morbidity: no change
Mortality: no change
PROSPERPatients 70‐82 (75.3)
Primary Prevention group‐High risk for CVD
Morbidity: no change
Mortality: no change
Glynn RJ et al. Ann Intern Med. 2010;152(8):488.Yusuf S et al. NEJM. 2016;374:2021.Han BH et al. JAMA Int Med. 2017;177(7):955.Shepherd J et al. Lancet 2002;360:1623. 29
Older Data
Savarese G, et al. J Am Coll Cardiol. 2013;62(22):2090.Teng M, et al. Drugs Aging 2015;32:649.
2013 Meta‐AnalysisOlder adults
(73 yo; 1 RF or elevated CRP)
Primary Prevention
MI and Stroke
Mortality
2015 Meta‐Analysis
Older adults (> 65 yo)
Primary Prevention
CV events
Mortality
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New Data
Cholesterol Treatment Trialists’ Collaboration. Lancet 2019.
OBJECTIVE:‐ Compare the effects of statins at different ages
POPULATION:‐22 RCTs (134,537 patients) comparing statins to controls‐14,483 (8%) of patients > 75 years‐Median follow‐up 4.9 years
OUTCOMES:‐Major vascular events, cause‐specific mortality, cancer incidence
RESULTS:‐Overall: Significant reduction in major vascular events for ALL ages(RR 0.79, 95% CI 0.77‐0.81) ‐Primary Prevention: Age > 70‐75 and >75 years: nonsignificant difference in major vascular events (RR 0.92, 95% CI 0.73‐1.16)
Statins at Different Ages
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OBJECTIVE:‐ To assess whether statin treatment is associated with a reduction CVD and mortality in old and very old adults with and without DMPOPULATION:‐ 46,864 people aged ≥ 75 years (no CVD)‐Mean age 77 years‐Median follow‐up 5.6 yearsOUTCOMES:‐ Incidence of CVD and all cause mortality in patients 75‐84 and ≥ 85 yearsRESULTS:No DM Statin therapy was NOT associated with a reduction in CVD or mortality
DM 75‐84 years: associated with reduction in incidence of CVD and mortality in both age groups ≥ 85 years: effect decreased and disappeared after 90 years.
New Data
Ramos R et al. BMJ 2018;362:k3359.
Statins in Primary Prevention
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Patients > 75 years old and StatinsJohanna’s Conclusions
Primary PreventionLikely will not initiate if age only risk factor (CAC?)If currently on a statin and tolerating then evaluate risk/benefit
Primary Prevention with DiabetesLikely continue the statinConsider initiating a moderate intensity
Secondary PreventionUse a moderate or high intensity statin
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Medication List:
ASA 81 mg daily
Atorvastatin 40 mg daily
Metformin ER 500 mg BID
Glipizide 5 mg BID
Pantoprazole 40 mg daily
Levothyroxine 50 mcg daily
Losartan 25 mg daily
Amlodipine 10 mg daily
Carbidopa‐levodopa 25‐100 mg tablets – 3/2/3 tablets TID
Selegiline 5 mg BID
Vitamin D 1000 IU daily
MTV daily
Glucosamine‐Chondroitin BID
Vitamin C 500 mg daily
Case
34
YES
Keep the statin?
NO
Active learning for pharmacists and technicians 35
Proton Pump Inhibitors in the Older Adult
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Mild to moderate esophagitis
GERD treated x 4‐8 weeks
PPI Treatment
PUD treated x 2‐12 weeks
ICU stress ulcer prophylaxis
Uncomplicated H. pylori treated x 2 weeks and asymptomatic
Barrett’s esophagus
Chronic NSAID users with bleeding risk
Severe esophagitis
Bleeding GI ulcer or idiopathic ulcer
Farrell B, et al. Can Fam Physician. 2017;63:354.Laine et al. Am J Gastroenterol 2012.
Continue therapy
Stop/Taper off
Stop/Taper offOn‐Demand therapy
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1. STOPPING◦ Abrupt discontinuation◦ Taper
2. STEPPING DOWN◦ Stop or taper PPI and replace with an H2
blocker
3. REDUCING◦ Lower dose◦ On‐Demand
PPI Deprescribing Methods
ON‐DEMANDTake daily until symptoms resolve
and then STOP. Repeat as necessary.
Farrell B, et al. Can Fam Physician. 2017;63:354.
TAPERBID Daily
Daily Lowest dosage strengthDaily every other day
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Medication List:
ASA 81 mg daily
Atorvastatin 40 mg daily
Metformin ER 500 mg BID
Glipizide 5 mg BID
Pantoprazole 40 mg daily
Levothyroxine 50 mcg daily
Losartan 25 mg daily
Amlodipine 10 mg daily
Carbidopa‐levodopa 25‐100 mg tablets – 3/2/3 tablets TID
Selegiline 5 mg BID
Vitamin D 1000 IU daily
MTV daily
Glucosamine‐Chondroitin BID
Vitamin C 500 mg daily
Case
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YES
Keep the PPI?
NO
Active learning for pharmacists and technicians 40
Option 1Step 1:
Reduce dose to 20 mg daily Step 2:
Every other daySTOP
How would you taper?
Option 2Step 1:
Reduce dose to 20 mg daily Step2:
Remove 1 dose per week until offSTOP
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Evidence-based Medications for Ischemic Heart Disease in the Older Adult
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Gnjidic D, et al.Objectives:◦ Investigate the use of evidence‐based medications (EBMs) for ischemic heart disease (IHD) in older men with and w/out geriatric syndromes (GS) and impact of adherence on adverse outcomes
Population:◦ Subgroup of 462 community‐dwelling Australian men > 70 yrs w/IHD enrolled in CHAMP ◦ Mean age 78 years◦ Average follow‐up 4 years◦ 226 (49%) reported > 1 geriatric syndrome
Outcomes:◦ Prevalence of EBM adherence ◦ Determine associations between EBM adherence and AEs◦ Determine if any combinations of specific EBM associated with AEs
Gnjidic D, et al. Int J Cardiol. 2015;192:49 43
ResultsDeath◦ w/IHD vs w/out IHD, HR 1.71 (1.42‐2.06)◦ Use of 3 (HR 0.54, 95% CI 0.32‐0.84) or 4 (HR 0.40, 95% CI 0.21‐0.95) EBM medications reduced risk◦ Combinations NOT assoc w/reduced risk:
◦ ACEI/ARB + statin◦ ACEI/ARB + beta‐blocker
Institutionalization◦ No difference between those w/IHD or those w/out IHD◦ Use of 2 (HR 0.34, 95% CI 0.10‐0.83), 3 (HR 0.30, 95% CI 0.04‐0.73), or 4 (HR 0.32, 95% CI 0.09‐0.81) EBM medications reduced risk◦ Combinations associated w/reduced risk:
◦ ACEI/ARB + statin◦ ACEI/ARB + beta‐blocker◦ ACEI/ARB + statin + beta‐blocker◦ ACEI/ARB + statin + beta‐blocker + antiplatelet
Gnjidic D, et al. Int J Cardiol. 2015;192:4944
Community‐dwelling men > 70 years with IHD + Geriatric Syndrome(s)Continuing 3 or 4 EBM medications provides mortality benefit
In a palliative approach, continuing 2 to 4 evidence‐based medications may prevent institutionalization◦ Consider ACEI/ARB + statin and/or beta‐blocker
Melissa’s Conclusions
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Withdrawal of EBMs in Recovered Dilated Cardiomyopathy
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Purpose Examine the effect of treatment withdrawal in patients with clinical, imaging, and biochemical evidence of recovery from dilated cardiomyopathy (DCM)
Design Single center, open‐label, randomized, pilot study with one arm cross‐over
Population Inclusion Criteria• Previous dx of DCM
LVEF 40% or lowerCurrently asymptomatic
• TakingLoop diuretic, beta‐blocker, ACEI/ARB, MRA, or any combination of these medications
• Current LVEF > 50%• LVEDVi within normal range on CMR• Plasma NT‐pro‐BNP < 250 ng/L
Exclusion Criteria• Uncontrolled hypertension
Clinic blood pressure > 160/100 mmHg• Valvular disease > moderate severity• eGFR < 30 mL/min/1.73 BSA• Atrial, supraventricular or ventricular arrhythmia
requiring beta‐blockade• Pregnancy• Angina• Age < 16
Outcomes PrimaryRelapse of DCM w/in 6 mon
SecondarySafety composite (CV mortality, MACE, unplanned hospital admission)Occurrence of sustained atrial/ventricular arrhythmias
TRED‐HF
Halliday BP, et al. Lancet. 2019;393:61. 47
TRED‐HFPhased Medication Withdrawal◦ Starting doses above threshold reduced by 50% every 2 weeks until at/below threshold to discontinue
◦ a
Follow‐up and Monitoring during Phased Medication Withdrawal◦ Clinic visit every 4 weeks
◦ Clinical assessment◦ NT‐pro‐BNP
◦ Interim telephone follow‐up◦ Med adjustment q2wk until all withdrawn◦ Treatment re‐established if patient met any primary endpoint criteria
Development of non‐study‐defined AEs◦ Arrhythmias: case‐by‐case assessment◦ HTN: treated with indapamide and/or amlodipine
ACEI/ARB(< 25% max daily recommended dose)
Beta‐blocker(< 25% max daily recommended dose)
MRA(< 50mg spironolactone/day)
Loop Diuretic(< 40mg furosemide/day)
Halliday BP, et al. Lancet. 2019;393:61. 48
TRED‐HF: BaselineAt enrollment◦ 34 men (67%)◦ Median age 55 (IQR 20‐33)◦ Median LVEF, 60% (IQR 55‐64%)◦ NT‐pro‐BNP, 72 ng/L (39‐135)
Previous Cardiovascular History◦ Median LVEF at initial diagnosis, 25% (IQR 20‐33)◦ Median time since dx, 57 mon (25‐98)◦ Time since LVEF recovery > 50%, 24 mon (6‐43)
Nominal Differences, withdrawal vs continued treatment group◦ Idiopathic DCM, 20 vs 15 (80 vs 58%)◦ Previous Afib, 8 vs 4 (32 vs 15%)◦ Previous unplanned HF admission, 18 vs 14 (72 vs 54%)
Halliday BP, et al. Lancet. 2019;393:61. 49
TRED‐HF: ResultsRelapse of DCM at 6 months◦ Randomized phase: 11 of 25 (44%) vs 0 of 25 ◦ Single‐arm crossover phase: 9 of 26 (35%)◦ Overall
◦ 20 of 50 (40%)◦ 13 relapsed w/in 8 wks of taking their last med◦ 4 restarted w/out meeting 1o outcome
◦ Two for HTN refractory to other tx◦ Two for episode of Afib◦ One for episode of non‐sustained SVT
◦ 25 of 50 (50%) successfully completed 6 months of follow‐up without relapse
Of the 20 patients who relapsed:◦ 10 met more than one criterion
◦ 9 of the remaining 10 had deterioration in another variable, but did not reach the pre‐specified threshold
Halliday BP, et al. Lancet. 2019;393:61. 50
Phased Med Withdrawal in Patients with DCMPhased withdrawal of medications in patients with recovered DCM is generally not advised
In a palliative approach, the study protocol provides a relatively safe roadmap to approach phased withdrawal of medications◦ Requires frequent follow‐up◦ Consider monitoring NT‐pro‐BNP for evidence of relapse
Melissa’s Conclusions
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“[Deprescribing is a] systematic process of identifying and discontinuing drugs in instances in which existing or potential
harms outweigh existing or potential benefits within the context of an individual patient’s care goals, current level of
functioning, life expectancy, values and preferences.”
Scott IA, et al. JAMA Intern Med. 2015;175(5):827 52
Shared Decision Making
AHRQ. The SHARE Approach (Workshop Curriculum: Tool 2). April 2014 53
SEEK your patient’s participationCommunicate and invite to participate◦ Acknowledge a decision can be made ◦ Requires input from patient and provider
Encourage family/caregiver involvement◦ Lend support in clarifying the patient’s values and preferences
◦ Serve as legal proxy for children, elderly, and seriously ill
Triggers◦ Number of medications◦ A new symptom◦ Identify high risk, ineffective or unnecessary medication(s)
◦ Apparent non‐adherence◦ Changed treatment priorities◦ Life transitions
◦ Hospital admission◦ New diagnosis◦ Seeing a new doctor
AHRQ. The SHARE Approach (Workshop Curriculum: Tool 2). April 201454
HELP your patient explore/compare treatment optionsDiscuss the benefits and risks of each treatment option
Use evidence‐based decision‐making resources to compare treatment options
Help patient understand the deprescribingprocess
TIPS◦ Explain limitations of what is known about the options
◦ Summarize by listing the options◦ Use teach‐back to verify understanding
AHRQ. The SHARE Approach (Workshop Curriculum: Tool 2). April 2014 55
ASSESS your patient’s goals and valuesAim: Help patients identify their preferences, goals and priorities
Explore what outcomes are most important to the patient◦ Quality of life and independence vs adding years to life
TIPS◦ Use open‐ended questions◦ Listen actively; show empathy and interest◦ Acknowledge what matters to the patient◦ Agree on what is important to the patient
AHRQ. The SHARE Approach (Workshop Curriculum: Tool 2). April 2014 56
REACH a decision with your patientDecide together on the best option
Arrange follow‐up to achieve the preferred treatment
TIPS:◦ Ask the patient if ready to make a decision◦ Ask the patient if they need more information/time◦ Schedule another visit if pt not ready to make decision◦ Confirm the decision with the patient
AHRQ. The SHARE Approach (Workshop Curriculum: Tool 2). April 2014 57
EVALUATE your patient’s decisionSupport your patient to obtain a positive impact on health outcomes
For management of chronic illnesses, revisit decision after a trial period
TIPS:◦ Monitor implementation of treatment decision(s)◦ Assist the patient in managing barriers to implementation◦ Revisit the decision if desired health outcome not achieved
AHRQ. The SHARE Approach (Workshop Curriculum: Tool 2). April 201458
A. Seek
B. Help
C. Assess
D. Reach
E. Evaluate
Using evidence‐based decision aides to facilitate discussion regarding treatment options is an example of . . .
59Active learning for pharmacists
A. Life transitions
B. A new symptom
C. Apparent non‐adherence
D. Number of medications
E. All of the above
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Which of the following are opportunities to invite and inform a patient of the option to deprescribemedication(s)?
Active learning for technicians
Is Less More? Deprescribing Pearls For The Older Adult
Melissa Green, PharmD, BCACPClinical Pharmacist
University of Utah Geriatric Clinic
Johanna Thompson, PharmD, BCPS, BCGPAdvanced Clinical Pharmacist
Intermountain Healthcare/Cottonwood Senior Clinic
61
1. Lown Institute. Medication Overload: America’s Other Drug Problem. https://lowninstitute.org/wp‐content/uploads/2019/04/medication‐overload‐lown‐web.pdf. Published April 2019. Accessed June 2019.
2. Salahudeen MS. Deprescribing medications in older people: a narrative review. Drugs Today (Barc). 2018;54(8):489‐498.
3. Administration for Community Living. 2018 Profile of Older Americans. https://acl.gov/sites/default/files/Aging%20and%20Disability%20in%20America/2018OlderAmericansProfile.pdf. Published April 2018. Accessed June 2019.
4. National Council on Aging Center for Healthy Aging. 10 Common Chronic Conditions for Adults 65+. https://d2mkcg26uvg1cz.cloudfront.net/wp‐content/uploads/10‐Common‐Chronic‐Conditions‐Older‐Adults‐ncoa.png. Published Feb 2017. Accessed July 2019
5. Moore KL, Patel K, Boscardin WJ, et al. Medication burden attributable to chronic comorbid conditions in the very old and vulnerable. PLoS ONE. 2018;13(4):1‐14
6. Niehoff KM, Mecca MC, Fried TR. Medication appropriateness criteria for older adults: a narrative review of criteria and supporting studies. Ther Adv Drug Saf. 2019;10:1‐9.
7. Farrell B et al. Deprescribing proton pump inhibitors. Evidence Based Practice Guideline. Can Fam Physician. 2017;63:354‐64.
8. U.S. Preventive Services Task Force. Final recommendation statement. Aspirin to prevent cardiovascular disease and colorectal cancer: preventive medication. April 2016. https://www.uspreventiveservicestaskforce.org/Page/Document/RecommendationStatementFinal/aspirin‐toprevent‐cardiovascular‐disease‐and‐cancer. (Accessed May 3, 2019).
9. Arnett DK, et al. 2019 ACC/AHA Guideline on the Primary Prevention of Cardiovascular Disease. Circulation. 2019.
10. American Diabetes Association. 10. Cardiovascular disease and risk management: Standards of Medical Care in Diabetesd2019. Diabetes Care 2019;42(Suppl. 1): S103–S123.
11. American Geriatrics Society 2019 Beers Criteria Updated Expert Panel. American Geriatrics Society updated Beers Criteria for potentially inappropriate medication use in older adults. J Am Geriatr Soc. 00:1‐21, 2019.
12. Vandvik PO et al. Primary and Secondary Prevention of Cardiovascular Disease. CHEST 2012;141(2)(Suppl):e637S‐e668S.
13. U.S. Food and Drug Administration. Citizen Petition Denial Response From FDA to Bayer Healthcare LLC. Docket ID: FDA‐1977‐N‐0018. Silver Spring, MD: U.S. Food and Drug Administration; 2014. Accessed at www.regulations.gov/#!documentDetail;D=FDA‐1977‐N‐0018‐0101This link goes offsite. Click to read the external link disclaimer on 13 March 2019.
14. McNeil JJ et al. Effect of Aspirin on Disability‐free Survival in the Healthy Elderly. NEJM 2018;379(16):1499‐1508
15. Gaziano JM et al. Use of Aspirin to reduce risk of initial vascular events in patients with moderate risk of cardiovascular disease (ARRIVE): a randomized, double‐blind, placebo‐controlled trial. Lancet 2018:392:1036‐46.
16. Zheng, et al. Association of Aspirin Use for Primary Prevention with cardiovascular events and bleeding events. JAMA 2019;321(3):277‐287.
17. Glynn RJ et al. Rosuvastatin for the primary prevention of older persons with elevated C‐reactive protein and low to average low‐density cholesterol levels: exploratory analysis of a randomized trial. Ann Intern Med. 2010;152(8):488‐96.
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28. Halliday BP, Wassall R, Lota AS, et al. Withdrawal of pharmacological treatment for heart failure in patients with recovered dilated cardiomyopathy (TRED‐HF): an open‐label, pilot, randomized trial. Lancet. 2019;393:61.
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