Discontinuing Medications at the End of Life

1. Discontinuing Medications at the End of Life Jennifer Good MD Hospice Medical Director, Home Nursing Agency Altoona, Pennsylvania Mary Mihalyo BS, PharmD, RPh Duquesne University Pittsburgh , Pennsylvania

2. Objectives • To understand that many medications that patients are on for chronic illnesses may not be helpful late in life. • To understand that decisions for discontinuation must be individualized and take into consideration the patient’s goals of therapy, life expectancy and risk/benefits of discontinuation (will depend on comorbidities). • To understand that there is little experimental data dictating discontinuing medications in palliative care patients.

3. Elizabeth N. • Elizabeth N. is a 90 y/o woman who has been referred to hospice following three hospitalizations in the last 2 months for refractory congestive heart failure. She is short of breath with minimal exertion. She has decided that she does not want to be readmitted to the hospital. • Her current medications include furosemide, lisinopril, carvedilol, spironolactone, warfarin, simvastatin, ASA, alendronate and morphine sulfate PRN. • Would it be appropriate to discontinue any of these medications?

4. Specific considerations in discontinuing medications • Life-expectancy • What is patient’s life expectancy? • How long does it take to see a benefit from a given drug? • Risk/benefit ratios • For general population • For given patient • Patient’s goals of therapy • Treatment targets (what is the treatment for)

5. Life-expectancy? • Palliative Care vs. Hospice Care • Expected life expectancy in hospice is < 6 months • Expected life expectancy in palliative patients with multiple chronic co-morbidities might be 12 months or more

6. How long to see effect from prescribed medication? • How long does it take for medication to render effect? • Analgesics—minutes to hours • Bisphosph0nates for osteoporosis—months to years • Tight glucose control in DM—years • Statins?

7. Risk-benefit ratio? • Benefits for general population • NNT • Benefits for given patient • Controls symptoms • Harms for general population • NNH • Harms for a given patient • Adverse drug reactions • Cost • Treatment is not in line with overall goals of care

8. Patient’s goals of therapy? • Prolong life • Prevent morbidity • Slow disease progression • Prevent decline • Comfort

9. Treatment targets? • Primary prevention • Secondary prevention • Control chronic diseases • Treat acute diseases • Control symptoms

10. Medications to consider discontinuing • Cholesterol lowering therapy • Anti-platelet agents • Anti-coagulants • Dementia medications • Osteoporosis medications

11. Discontinuing statins • What is risk of ACS or CVA upon discontinuing? • ACS • Prevent 5 MIs in 100 patients treated for 5 years (secondary prevention) • Decreased risk of death by 20 – 30% over 5 years • Patients have increased mortality if statin discontinued during ACS (5% vs. 11%) • Immediate risk reduction—1 less MI in 100 patients treated for one month after MI. • CVA

12. Recommendations for discontinuing statin • Continue: • Recent MI • Recent CVA • ? Symptoms of myocardial ischemia • Discontinue: • Patients on statin for primary prophylaxis

13. Anti-platelet Agents • Aspirin • Clopidogrel (Plavix ®)/Prasugrel (Effient®) • ASA/Dipyridamole (Aggrenox ®)

14. Discontinuing anti-platelet agents • Continue clopidogrel/ASA if: • Bare metal stent in last 3 months • Drug-eluting stent in last 12 months • Recent TIA/CVA (if occurred while patient on ASA) • Continue Aggrenox® if: • Recent TIA/CVA (if occurred while patient on ASA) • Continue ASA if: • Used for secondary prevention in patients with h/o ACS or CVA • Used for primary prevention in high risk patient • Recommend 81 mg/d

15. Anticoagulants • Warfarin—most common indications: • Chronic Atrial Fibrillation to prevent thromboembolic complications • Mechanical heart valves to prevent valve thrombosis and thromboembolic complications • Patients with history of venous thromboemboli (VTE) • Dabigatran—a new oral direct thrombin inhibitor • Non-valvular chronic Atrial Fibrillation • Low molecular weight heparins • Most commonly used long term in patients with VTE and concomitant malignancy

16. Risk of Embolic Events in AF • Risk is 2 – 18% year • Risk based on CHAD2 score: • Low risk = 0 • Moderate = 1 • High risk= ≥ 2 1 Gage BF. JAMA 285(22):2864 – 70.

17. Recommendation for Discontinuing Warfarin/Dabigatran • Continue in Atrial Fibrillation if: • CHADs2 score of 5 – 6 • Prior CVA • Mechanical valve (particularly if mitral/tricuspid position) • Continue in VTE if: • VTE in last 3 – 6 months • History of recurrent VTE • VTE with concomitant malignancy (LMWH is probably first choice as more efficacious)

18. Dementia medications • Cholinesterase inhibitors—indicated for mild to moderate dementia • Donepezil (Aricept®) • Rivastigment (Exelon®) • Galantamine (Razadyne®) • NMDA receptor antagonist—indicated for moderate to severe dementia • Memantine (Namenda®)

19. Recommendations for discontinuing dementia medications • Patients in hospice have dementia more severe than what drug therapy is indicated for • Expensive • $200 – 300/month • May be safer to taper • Can see more agitation when medication discontinued • Alternative, cheaper agents for agitation exist

20. Osteoporosis Medications • Bisphosphonates • Alendronate (Fosamax ®) • Risedronate (Actonel®) • Ibandronate (Boniva®) • Zoledronic Acid (Reclast®) • Teriperatide (Forteo®) • ≈ $1000/month

21. Recommendations for discontinuing osteoporosis medications • Continue bisphosphonates if: • Known metastatic bone disease • Breast CA, prostate CA or multiple myeloma • Paget’s disease of bone (usually high dose) • Discontinue all other osteoporosis medications: • Teriperatide • Denosumab (Prolia®) • Calcitriol • Calcitonin?

22. Drugs to taper if discontinuing • Anti-epileptic medications • Opioids • Anti-depressants • Benzodiazepines • Beta blockers • Clonidine • Corticosteroids

23. Barriers to discontinuing medications • Psychological attachment • Concern that discontinuation implies “giving up” • Uncertain of risks with discontinuation • Physical dependence • Clinical inertia • Poor communication

24. Elizabeth N. • Elizabeth N. is a 90 y/o woman who has been referred to hospice following three hospitalizations in the last 2 months for refractory congestive heart failure. She is short of breath with minimal exertion. She has decided that she does not want to be readmitted to the hospital. • Her current medications include furosemide, lisinopril, carvedilol, spironolactone, warfarin, simvastatin, ASA, alendronate and morphine sulfate PRN. • Would it be appropriate to discontinue any of these medications?

25. Elizabeth N. • Discontinue: • Warfarin • Simvastatin • Alendronate • Continue: • Lisinopril • Carvedilol • Spironolactone • ASA • Morphine sulfate

26. David E. • David E. is a 53 y/o referred to hospice with newly diagnosed metastatic pancreatic cancer. At the time of presentation his tumor was non-resectable due to hepatic metastases and a biliary stent was placed percutaneously because of obstructive jaundice. His comorbidities include COPD, BPH and a DVT which occurred during his recent hospitalization. • His current medications include warfarin, tamsulosin, ipratropium, salmeterol/fluticasone, saw palmetto, iron sulfate and oral meperidine for pain.

27. David E. • Discontinue • Saw palmetto • FeSO4 • Meperidine (substitute alternative opioid) • Continue • Tamsulosin • Ipratropium • Salmeterol/fluticasone • Warfarin (consider change to LMWH)

28. Lola P. • Lola P. is a 89 y/o woman with endstage dementia who has been referred to hospice. She is nonambulatory, nonverbal, is unable to assist in any activities of daily living. She is incontinent and has contractures of her hands and knees. Her comorbidities include COPD, CAD (with prior MI and CHF), HTN and hypercholesterolemia. • Her current medications include furosemide, lisinopril, salmeterol/fluticasone, simvastatin, alendronate, vitamin D, calcium carbonate, omeprazole, donepezil, memantine and aspirin

29. Lola P. • Discontinue • Vitamin D • Calcium carbonate • Salmeterol/fluticasone (substitute PRN nebulized beta agonist) • Donepazil • Memantine • Simvastatin • Alendronate • Continue • Furosemide • Lisinopril • (? Omeprazole)

30. Questions? Jennifer Good, MD jgood@altoonafp.org Mary Mihalyo, BS, PharmD Mihalyo@duq.edu