Pharmacological Aspects of Cardiovascular Disease in the Elderly

1. Pharmacological Aspects of Cardiovascular Disease in the Elderly Erin Beth Hays, PharmD White River Medical Center Batesville, AR

2. Objectives • Discuss blood pressure goals and first-line treatment recommendations in the geriatric population for orthostatic hypotension and hypertension. • Discuss the benefits vs. risks in managing hyperlipidemias in elderly patients. • Discuss the barriers and issues regarding medications for heart failure in the geriatric population. • Describe the benefits vs. risks of anticoagulation in elderly patients for stroke prevention and venous thromboembolism prevention and management. • Discuss barriers to treating cardiovascular disease in the elderly population as they relate to medications

3. Orthostatic Hypotension • Definition • Decrease in SBP of ≥ 20 mmHg or • Decrease in DBP of ≥ 10 mmHg • Within 3 minutes of standing

4. Prevalence of OH in Relationship to Age

5. Orthostatic Hypotension- Epidemiology • Prevalence • Increasing age • Increasing vascular stiffness • Diminishing baroreflex sensitivity • Decreasing β-adrenoreceptor-mediated responses • Risk Factors • Acute illness • # of medications • Types of medications • Hypertension • Diabetes • Smoking • Carotid artery stenosis/carotid artery intimamedia thickness • Neurologic diseases

6. Orthostatic Hypotension • Causes • Sicknesses: Dehydration, diarrhea, extreme heat, MI, adrenal insufficiency, vomiting, sepsis • Medications: short-acting, vasodilators, or volume depleting • Centrally acting α-receptor agonist, peripheral α-antagonists, nitrates, hydralazine, minoxidil, loop diuretics. • Others: antipsychotic, dopamine agonists, levodopa, marijuana, narcotics, sedatives, sildenafil, and tricyclic antidepressants

7. Orthostatic Hypotension • Treatment • Discontinue causative agent • Non-pharmacologic treatments • Pharmacologic treatments • Fludrocortisone • Midodrine

8. Fludrocortisone • Synthetic mineralocorticoid • MOA: • Promotes increased reabsorption of sodium and loss of potassium from renal distal tubules promoting fluid retention • 0.1-0.3 mg daily • Adverse effects: • Suprine hypertension, ankle edema, headache, hypokalemia, heart failure

9. Midodrine • Peripheral selective α-receptor agonist • 2.5-10 mg TID • Adverse effects: suprine hypertension, pruritus, paresthesias, piloerection, bradycardia, and urinary retention • Avoid in patients with hx of CAD, HF, urinary retention, acute kidney disease or thyrotoxicosis

10. Hypertension • Goals • General population: <140/90 mmHg • Diabetes or CKD: <130/80 mmHg • Study: mortality of 140/90 vs 180 • Initial treatment (no compelling indications): • 140-159/ or 90-99 mmHg: thiazide diuretic • ≥ 160/ or ≥ 100 mmHg: thiazide + ACEI/ARB/ β-blocker/calcium channel blocker

11. HTN Tx for Compelling Indications

12. HTN Medication Concerns for the Elderly • Elderly are predisposed to orthostatic hypotension • Alpha blockers • Central alpha agonists • Diuretics • Overall treatment should be the same as with younger adults except with lower starting doses

13. HTN Medication Concerns for the Elderly • Renal function • Concern only when initiating and titrating therapy • Increased monitoring • i.e. ACEI more vulnerable in developing hyperkalemia • Thiazides lose efficacy when Clcr < 40 mL/min

14. Hyperlipidemias

15. Hyperlipidemias • Concern in the Elderly • May be at increased risk of developing statin-induced myopathy. • Polypharmacy, reduced renal function, and female sex • Should be counseled regarding the symptoms of statin-induced myopathy • Palliative-only interventions are often a reason to defer or discontinue drug therapy

16. Simvastatin • New Safety and Dosing Information – FDA June 2011 • Amiodarone, diltiazem or verapamil: Simvastatin dose should not exceed 10 mg/day • Amlodipine or ranolazine: Simvastatin dose should not exceed 20 mg/day • Limited Dosing: 80 mg use only in patients that have taken for > 12 months w/o evidence of myopathy

17. Contraindicated with simvastatin: Itraconazole Ketoconazole Posaconazole (New) Erythromycin Clarithromycin Telithromycin HIV protease inhibitors Nefazodone Gemfibrozil * Cyclosporine * Danazol * Do not exceed 10 mg simvastatin daily dose with Amiodarone † Verapamil † Diltiazem ¶ Do not exceed 20 mg simvastatin daily dose with Amlodipine (New) Ranolazine (New) Simvastatin – Updated Labeling * Moved from 10 mg max simvastatin dose to contraindicated † Moved from 20 mg max simvastatin dose to 10 mg max ¶ Moved from 40 mg max simvastatin dose to 10 mg max

18. Heart Failure • β-blockers • Decrease mortality and hospitalization • Well-tolerated • ACE Inhibitors • Use if tolerated • ARBs may be tried if ACEIs are not tolerated

19. Heart Failure • Digoxin • Reduces hospitalization (independent of age) • Age is a predictor of hospitalization for digoxin toxicity and withdrawal of digoxin therapy • Does not reduced mortality • Should only be used in patients with left ventricular systolic dysfunction who remain symptomatic despite maximally tolerated doses of a β-blocker, ACE inhibitor, and diuretic.

20. Heart Failure Barriers • Diagnosis of HF • Hesitation to attempt titration of HF medications due to risk for adverse effects • Start at lowest dose • β-blockers: titrate every 2-4 weeks • ACE Inhibitors: titrate every 1-2 weeks • Monitoring of SCr and potassium with dose increases • Diuretics can cause volume depletion and kidney function may reduce diuretic efficacy • Digoxin toxicity • Drug interactions – counsel against use of NSAIDs

21. Anticoagulation • Stroke prophylaxis in patients with AFib • VTE prophylaxis

22. Atrial Fibrillation • CHAD2 Score • Congestive heart failure = 1 point • Hypertension = 1 point • Age ≥ 75 years = 1 point • Diabetes = 1 point • Stroke or TIA history = 2 points

23. Atrial Fibrillation

24. Atrial Fibrillation – a new option • Dabigatran • Indication: VTE and stroke prophylaxis in nonvalvular AFib • 150 mg BID • Renally adjusted • 15-30 mL/min: 75 mg BID • Adverse Rxns • Dyspepsia 11% • Bleeding (8% to 33%; major: ≤6%)

25. VTE Prophylaxis • Mechanical methods • Medications • Total Knee & Hip • LMWH, fondaparinux, warfarin • Hip fracture • LWMH, fondaparinux, warfarin, LDUH • Medically ill patients • LWMH, fondaparinux, LDUH • No evidence for use of prophylaxis in NH or homebound geriatrics

26. VTE Treatment • LMWH, fondaparinux, heparin • Bridge with warfarin • Target INR = 2-3

27. Enoxaparin • LMWH • Prophylaxis doses • 40 mg daily • 30 mg BID for hip and knee patients • Renal adjustment • <30 mL/min = 30 mg daily • Treatment doses • 1 mg/kg BID • Renal Adjustment • <30 mL/min = 1 mg/kg daily

28. Dalteparin • LMWH • Prophylaxis doses • 2500-5000 int. units daily • Renal adjustment • Treatment doses • Cancer patient • Initial: 200 int. units/kg daily for 30 days • Maintenance (after 30 days): 150 int. units daily • Renally adjustment • if Clcr <30 mL/minute: monitoring anti-Xa levels

29. Fondaparinux • Factor Xa Inhibitor • Prophylaxis doses • 2.5 mg once daily • Treatment doses • <50 kg: 5 mg once daily • 50-100 kg: 7.5 mg once daily • >100 kg: 10 mg once daily • Renal adjustment • Clcr 30-50 mL/minute: Use caution • Clcr <30 mL/minute: Contraindicated

30. Warfarin • Initial dose ≤5 mg daily • Pros • Well studied • Cons • Monitoring burden • Drug-drug and drug-food interactions • Compliance • High sensitivity • Hypoalbuminemia • Decreased dietary vitamin K intake

31. Counsel patients and caregivers/family about signs & symptoms of stroke

32. Medications in the Elderly • Start LOW and titrate SLOW • More frequent monitoring • Polypharmacy concerns • Drug-drug interactions • Compliance • Do all medications have an indication? • Are the directions practical? • Renal function • Nutrition status

33. Medication Appropriateness Index Questions to Ask About Each Individual Medication • Is there an indication for the medication? • Is the medication effective for the condition? • Is the dosage correct? • Are the directions correct? • Are the directions practical? • Are there clinically significant drug–drug interactions? • Are there clinically significant drug–disease/condition interactions? • Is there unnecessary duplication with other medication(s)? • Is the duration of therapy acceptable? • Is this medication the least expensive alternative compared with others of equal utility?

34. Medication Adherence • Simplify regimen • Medication appropriateness • Dosing intervals • Reduce cost • Dosage forms • Pill boxes, calendars, etc • Family involvement

35. Questions? Contact information ebhays@wrmc.com 870-262-1509

36. References • Beckett NS, Peters R, Fletcher AE, Staessen JA, Liu L, Dumitrascu D, et al. Treatment of hypertension in patients 80 years of age or older. N Engl J Med 2008;358(18):1887-98. • Benvenuto LJ, Krakoff LR. Morbidity and Mortality of OH: Implications for Management of Cardiovascular Disease. Am J of Hypertension. 2011; 24: 135-144. • Cohen DL, Townsend RR. Update on Pathophysiology and Treatment of Hypertension in the Elderly. Curr Hypertens Rep. Pub online June 18, 2011. DOI 10.1007/s11906-011-0215-x • Connolly SJ, Ezekowitz MB, Yusuf S, et al. Dabigatran versus Warfarin in Patients with Atrial Fibrillation. N Engl J Med. 2009; 361(12):1139-1152. • Cook K, Tisdale JE. Cardiovascular. In L. Hutchison & R.B. Sleeper (eds), Fundamentals of Geriatric Pharmacotherapy: An Evidence-Based Approach, 1st edn, American Society of Health-System Pharmacists: Bethesda, Maryland, 2010, pp. 121-161 • FDA Drug Safety Communication: New restrictions, contraindications, and dose limitations for Zocor (simvastatin) to reduce the risk of muscle injury. Accessed online Jun 27, 2011. http://www.fda.gov/Drugs/DrugSafety/ucm256581.htm • All drug dosing and adverse effects were obtained from Lexicomp Online. Accessed Jun 26, 2011.