1. Search for the Fountain of Youth: Cardiovascular Disease Management in the Geriatric Patient Kevin Overbeck, DO Assistant Professor, NJISA

2. Learning Objectives Apply knowledge of Aging Physiology to JNC 8 + SPRINT to optimize strategy for HYPERTENSION management Understand the benefits of STATINS in aging in the context of 2013 guidelines for HYPERLIPIDEMIA Apply 2014 AHA/ACC/HRS guidelines for ATRIAL FIBRILLATION to decision-making for ANTICOAGULATION and RATE CONTROL in the elderly

3. HYPERTENSION & THE ELDERLY

4. Increased thickness of the intima and the media  INCREASED VASCULAR STIFFNESS Aging Physiology

5. Pearson, J.D., Morrell, C.H., Brant, L.J., Landis, P.K., and Fleg, J.L. (1997). Age- associated changes in blood pressure in a longitudinal study of healthy men and women. Journal of Gerontology, 52, M177–83.

6. Aging Physiology Increased BP variability Impaired BP homeostasis –Hypertension –Postural (orthostatic) hypotension –Post-prandial hypotension 1.Huang CC, et al. Effect of age on adrenergic and vagal baroreflex sensitivity in normal subjects. Muscle Nerve. 2007;36(5):637-42. 2.Jansen RW, et al. Postprandial hypotension: epidemiology, pathophysiology, and clinical management. Ann Intern Med. 1995;122(4):286 Consequences of Baroreceptor Changes 1

7. HTN & The Elderly Orthostatic BP Measurement Sitting-Standing vs. Laying-Standing After standing wait 1 minute vs. 3 minutes vs. 5 minutes At least a 20 mmHg fall in systolic pressure At least a 10 mmHg fall in diastolic pressure Symptoms of cerebral hypoperfusion Parkinson’s / Lewy Body Dementia Decreased Baroreceptor Sensitivity 1

8. HYVET Becket, NS, Peters, R, Fletcher, AE, et al. Treatment of hypertension in patients 80 years of age or older. N Engl J Med. 2008; 358(18): 1887-1898.

9. HYVET Becket, NS, Peters, R, Fletcher, AE, et al. Treatment of hypertension in patients 80 years of age or older. N Engl J Med. 2008; 358(18): 1887-1898.

10. JNC 8: Clinical Practice Guidelines individuals >60 years old Life style Modification (LSM) Laboratory 2014 Evidenced-Based Guideline for Management of High Blood Pressure in Adults: Reported from the Panel Members Appointed to the Eight Joint National Committee (JNC 8). JAMA FEB 2014. BP ClassificationSystolic (mmHg) Diastolic (mmHg) Initial Therapy Pre-HypertensionDeleted / Omitted DM<140<90LSM + No Anti-Hypertensive Drug Indicated CKD** (<70)<140<90Previous less than 130/80 Goal<150<90LSM + ACE or ARB or DIURETIC or Calcium Channel Blocker ** “based on evidence the committee cannot make a recommendation for individuals 70 and older” Ambulatory BP Monitoring Self Measuring BP Assess Risk Factors

11. SPRINT 1. Williamson JD, et al. Intensive vs Standard Blood Pressure Control and Cardiovascular Disease Outcomes in Adults Aged >75 years: A Randomized Clinical Trial. JAMA 2016: 315(24):2673-2682.

12. SPRINT NNT Data:Older (aged>75) Overall Study Group Primary Composite Outcome 2761 All Cause Mortality 4190 1. Williamson JD, et al. Intensive vs Standard Blood Pressure Control and Cardiovascular Disease Outcomes in Adults Aged >75 years: A Randomized Clinical Trial. JAMA 2016: 315(24):2673-2682. 2. The SPRINT Research Group. A Randomized Controlled Trial of Intensive versus Standard Blood Pressure Control. NEJM 2015: 373(22): 2103-2116.

13. SPRINT EXCLUSION CRITERIA DIABETES Previous history of STROKE Dementia / Memory Loss or MOCA < 19 SBP < 110mmHg following 1 MINUTE of STANDING Residents of a NURSING HOME / ASSISTED LIVING Symptomatic HF within 6 months (or EF < 35%) 1.Williamson JD, et al. Intensive vs Standard Blood Pressure Control and Cardiovascular Disease Outcomes in Adults Aged >75 years: A Randomized Clinical Trial. JAMA 2016: 315(24):2673-2682.

14. RECOMMENDATIONS ADMINISTER COGNITIVE TEST – MOCA ROUTINELY measure STANDING BLOOD PRESSURE TARGET SBP 140mmHg – once reached could consider 130mmHg If standing BP < 110mmHg at ANY TIME raise the target from 140mmHg back to 150mmHg MORE FREQUENT VISITS WOULD NOT treat to a target of 120mmHg AVOID DIASTOLIC below 60mmHg

15. Applied Geriatrics A 85 year old with community dwelling male with CKD stage 3 (eGFR 55) presents to the office for routine evaluation of his chronic medical conditions ACTIVE MED LIST: 1.Aspirin 81mg daily 2.Metoprolol XL 50mg daily 3.Amlodipine 2.5mg daily 4.HCTZ 12.5mg daily 5.KCL 10meq daily 6.Losartan 50mg daily 7.Atorvastatin 10mg daily 8.Tamsulosin 0.4mg daily BP [sitting + standing]: 120/80mmHg HR 68 MOCA: 26/30 What is the next best step in the management of this patient’s condition? (A)Stop Amlodipine (Norvasc®) (B)Stop Hydrochlorothiazide (HCTZ) (C)Reduce Metoprolol XL (Lopressor XL ®) (D)Reduce Losartan (E)Continue current medication regimen

16. Applied Geriatrics A 85 year old with community dwelling male with previous TIA (>5 years ago) and CKD stage 3(eGFR 55) presents to the office for routine evaluation of his chronic medical conditions ACTIVE MED LIST: 1.Aspirin 81mg daily 2.Metoprolol XL 50mg daily 3.Amlodipine 2.5mg daily 4.HCTZ 12.5mg daily 5.KCL 10meq daily 6.Losartan 50mg daily 7.Atorvastatin 10mg daily 8.Tamsulosin 0.4mg daily BP [sitting + standing]: 120/80mmHg HR 68 MOCA: 26/30 What is the next best step in the management of this patient’s condition? (A)Stop Amlodipine (Norvasc®) (B)Stop Hydrochlorothiazide (HCTZ) (C)Reduce Metoprolol XL (Lopressor XL ®) (D)Reduce Losartan (E)Continue current medication regimen

17. Applied Geriatrics A 85 year old with community dwelling male with previous TIA (>5 years ago) and CKD stage 3 (eGFR 55) presents to the office for an evaluation of his increasing lower extremity edema ACTIVE MED LIST: 1.Aspirin 81mg daily 2.Metoprolol XL 50mg daily 3.Amlodipine 2.5mg daily 4.HCTZ 12.5mg daily 5.KCL 10meq daily 6.Losartan 50mg daily 7.Atorvastatin 10mg daily 8.Tamsulosin 0.4mg daily PHYSICAL EXAM BP [sitting + standing]: 120/80mmHg HR: 68 CARDIO: (+) regular (+) 2+ bilateral pitting lower extremity edema (-) S3 (-) JVD MOCA: 26/30 What is the next best step in the management of this patient’s condition? (A)Stop Amlodipine (Norvasc®) (B)Increase Hydrochlorothiazide (HCTZ) (C)Reduce Metoprolol XL (Lopressor XL ®) (D)Reduce Losartan (E)Continue current medication regimen

18. Medications Known To Increase BP Steroids Sympathomimetic Drugs Decongestants NSAIDS Erythropoietin Venlafaxine (Effexor®) Mirabegron (Myrbetriq®)

19. Applied Geriatrics An 80 year old male with PARKINSON’S DISEASE presents for an evaluation of deterioration in his GAIT evidence by FIVE FALLS in the home WITHOUT INJURY during the past SIX MONTHS despite strict adherence to utilization of TWO WHEELED ROLLING WALKER in the home CAD with previous MI (2008), Lower Extremity Edema, Barrett’s Esophagus MOCA: 21/30 BP / HR (laying): 154/70 -- 66 BP / HR (standing): 120/60 [asymptomatic] -- 70 Lower Extremity 1++ bilateral edema BUN 20 / Creat 1.2 / eGFR > 60 CURRENT MED LIST: 1.Aspirin 81mg daily 2.Losartan 50mg daily 3.Carvedilol 6.25mg BID 4.HCTZ 12.5mg daily 5.Omeprazole 20mg daily 6.KCL 10meq daily 7.Vitamin D 1000 IU daily 8.Pravastatin 40mg qHS What is the next BEST step in the management of this patient’s condition?

20. STATINS, DYSLIPIDEMIA & THE ELDERLY

21. Dyslipidemia Primary Prevention: CARDS Study Neil HA, et al. Analysis of efficacy and safety in patients aged 65-75 years at randomization: Collaborative Atorvastatin Diabetes Study (CARDS). Diabetes Care. 2006;29(11):2378. Age 45-75 yrs Atorvastatin 10mg v. Placebo 4 years NNT Data: OlderYounger 1 st major cardiovascular even 2232

22. Dyslipidemia Secondary Prevention: The LIPID Trial Hunt D, et al. Benefits of pravastatin on cardiovascular events and mortality in older patients with coronary heart disease are equal to or exceed those seen in younger patients: Results from the LIPID trial. Ann Intern Med. 2001;134(10):931. NNT Data: OlderYounger All Cause Mortality 2246 CAD Death 3571 Fatal / Non- Fatal MI 3036 Stroke 79170 Age 40-75 yr olds; Pravastatin v. Placebo

23. ATRIAL FIBRILLATION & THE ELDERLY

24. Atrial Fibrillation Patient Centered Care / Goals of Care Incidence increases with Age Stroke Risk Rate Control January CT, et al. 2014 AHA/ACC/HRS guideline for the management of patients with atrial fibrillation: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines and Heart Rhythm Society. J Am Coll Cardiol 2014; 64:e1-76.

25. CHA 2 DS 2 -VASc SCOREAdjusted Stroke Rate (%/year) 00 11.3 22.2 33.2 44.0 56.7 69.8 79.6 86.7 915.2 With CHA2DS2- VASc > 2, oral anticoagulants are recommended With CHA2DS2- VASc = 0, it is reasonable to omit antithrombotic therapy With CHA2DS2- VASc = 1, no antithrombotic therapy or treatment with oral anticoagulation or aspirin may be considered

26. Atrial Fibrillation Stroke Prophylaxis We underutilize anticoagulation in the elderly with atrial fibrillation

27. Anticoagulation Clinician Concerns Compliance Monitoring “Fall Risk 1,2 ” Cognitive Impairment Drug-Drug Interactions Bleeding Risk 1. Man-Son-Hing M, Nichol G, Lau A, et al. Choosing antithrombotic therapy for elderly patients with atrial fibrillation who are at risk for falls. Arch Intern Med 1999; 159: 677-685 2. Kappor J. Management of Atrial Fibrillation. The Lancet, Volume 370, Issue 9599, Page 1608, 10 November 2007

28. Anticoagulation Clinician Concerns 1. Staerk L, et al. Stroke and recurrent haemorrhage associated with antithrombotic treatment after gastrointestinal bleeding in patients with atrial fibrillation nationwide cohort study. BMJ 2015; 351:h5876.

29. Anticoagulation Increased risk of ICH > 85 but not statistically significant INRs less than 2.0 as compared to INRs 2-3 were not associated with lower risk of ICH INRs > 3.5 associated with increased risk as should be avoided Fang MC, et al. Advanced age, anticoagulation intensity, and risk for intracranial hemorrhage among patients taking warfarin for atrial fibrillation. Ann Intern Med. 2004;141(10):745

30. Warfarin vs Aspirin in the Elderly 973 patients > 75 years old (mean 81.5 years old) Randomly assigned to Aspirin 75mg or Warfarin INR 2-3 The primary endpoint was fatal or disabling stroke (ischemic or hemorrhagic) or intracranial hemorrhage or significant emboli Warfarin Group – 24 events (21 strokes, 2 ICH, 1 embolism) Aspirin Group – 48 events (44 strokes, 1 ICH, 3 emboli) Mant J, et al. Warfarin versus aspirin for stroke prevention in an elderly community population with atrial fibrillation (the Birmingham Atrial Fibrillation Treatment of the Aged Study, BAFTA): a randomised controlled trial. Lancet. 2007;370(9586):493.

31. Warfarin vs Aspirin + Clopidogrel CHADS2 Score of 2 Randomly assigned to receive Warfarin (target INR 2.0-3.0) or the combination of Clopidogrel 75mg plus Aspirin 75mg-100mg Trial Terminated Early due to WARFARIN superiority Connolly S, et al. Clopidogrel plus Aspirin versus oral anticoagulation for atrial fibrillation in the Atrial fibrillation Clopidogrel Trial with Irbesartan for prevention of Vascular Events (ACTIVE-W): a randomized controlled trial. Lancet 2006; 367:1903-12.

32. Anticoagulation & The Elderly Setting% in Range Self-Monitoring72% Randomized Trials 55-66% Anti-Coagulation Clinics 66% Community Physicians 57% 1. van Walraven C, et al. Effect of study setting on anticoagulation control: a systematic review and metaregression. Chest. 2006;129(5):1155. * Simple Finger Stick required

33. NOVEL ANTICOAGULATION 1.Shama, et al. Efficacy and harms of direct oral anticoagulants in the elderly for stroke prevention in atrial fibrillation and secondary prevention of venous thromboembolism systemic review and meta-analysis. Circulation 2015; 132(3): 194-204.

34. ATRIAL FIBRILLATION RATE CONTROL

35. An 88 year old male with systolic cardiomyopathy with an EF < 35% presents with complaints of fatigue and palpitations due to ATRIAL FIBRILLATION with HR 110-130 bpm. He is euvolemic, BP 130/70, and presently taking CARVEDIOLOL 25mg BID. Which of the following strategies is the best next step in the management of his heart rate? (A)Prescribe Diltiazem (B)Prescribe Verapamil (C)Prescribe Digoxin (D)Prescribe Amiodarone (E)Consult Cardiology

36. Recommendations for Rate Control Control ventricular rate with Beta-Blocker or Non-Dihydropyridine Calcium Channel Antagonist for AF A heart rate control (resting heart rate < 80 bpm) strategy is reasonable for symptomatic management in AF A lenient rate-control strategy (resting heart rate < 110bpm) maybe reasonable when patient asymptomatic & LV systolic function preserved Non-Dihydropyridine Calcium Channel Antagonists should NOT be used in decompensated HF

37. Craig T. January et al. Circulation. 2014;130:e199-e267