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Pharmacological Aspects of Cardiovascular Disease in the Elderly

Pharmacological Aspects of Cardiovascular Disease in the Elderly. Erin Beth Hays, PharmD White River Medical Center Batesville, AR. Objectives. Discuss blood pressure goals and first-line treatment recommendations in the geriatric population for orthostatic hypotension and hypertension.

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Pharmacological Aspects of Cardiovascular Disease in the Elderly

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  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.

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