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How Should We ACCOMPLISH Good Disclosures Control In Our VETS? No conflicts of interest to disclose Updates in the Management of In the Elderly

Antoine T. Jenkins, Pharm.D., BCPS Assistant Professor of Pharmacy Practice Chicago State University‐‐‐College of Pharmacy Internal Medicine Pharmacy Specialist Roseland Community Hospital, Chicago, IL

Learning Objectives Hypertension: Nationwide Dilemma • Effects 1 in 3 US adults • Identify key recommendations from the • Serves as a “gateway” ACCF/AHA 2011 Consensus Statement on condition for more Hypertension in the Elderly. serious CV aliments • Discuss the key clinical trials specific to this • Direc t and idiindirec t costs population of hypertensive patients. associated with HTN were • Define the role of the pharmacist in managing ~ $73 billion hypertension in patients of advanced age. • Prevalence increases with aging – Ethnicity Circulation 2010;121:e1-e170. – Gender Circulation 2009.; 119:e21-181.

Hypertension in the Elderly: Hypertension In the Elderly: Specific Concerns What’s Currently Recommended? • Isolated systolic hypertension Recommendations from Internationally Published Guidelines – ↑ pressure Source Target BP Drug Selection Other Comments – Pseudohypertension JNC‐VII None •Same as younger Treatment should – Labile hypertension specifically individuals. not be withheld in stated •Two drugs required for the elderly; therapy • White coat hypertension most patients should not be • Weight loss and ↓ Na+ withheld on the • Orthostasis beneficial basis of age. • Postprandial hypotension AHA/ACC ‐‐‐‐ ‐‐‐‐ ‐‐‐‐‐

• Secondary causes JNC-VII Complete Report 2003 NIH Publicatio • Drug‐Induced causes Circulation 2007;115:2761-2788.

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Hypertension In the Elderly: Hypertension in the Elderly: What’s Currently Recommended? Review of Major Trials Recommendations from Internationally Published Guidelines Major Hypertensive Trials Involving Elderly Patients Trial Mean Age Starting BP Treatment ( Mean Outcomes Source Target BP Drug Selection Other Comments (Age Range) (Goal BP) Duration) ESC/ESH < 140/90 mm Hg •Thiazides, CCBs, Although benefits of STOP 76 yrs (70‐ 195/102 mm Pindolol, ↓ Stroke, MI, (if tolerated) ACEs/ARBs, BBs treatment in those ≥80 (Swedish 84 yrs) Hg (<160/95 metoprolol, and CV death • Two drug needed yrs old are inconclusive, TiTria l in Old mm H)Hg) atenolllol or HCTZ + (p= 0. 0031) and↓ for most successful treatment Patients with amiloride or stroke morbidity/ should not be stopped HTN) placebo (65 mos) mortality CHEP < 140/90 mm Hg •Thiazides, CCBs, Caution in frail individuals n=1627 (p=0.0081) ACEs/ARBs, BBs and those with SHEP 72 yrs (60 to 170/77 mm Hg Cholrothialidone ± ↓ fatal/nonfatlal • Two drug needed orthostasis (Systolic HTN > 80 yrs) (SBP< 160 or < atenolol or stroke for most in the Elderly 20 mm Hg from placebo (4.5 yrs) (p=0.0003). ↓ CV • Avoid BBs (> 60 yrs as Program) baseline) morbidity/ first line) n=4736 mortality European Heart Journal (2007) 28, 1462–1536 Lancet 1991; 338: 1281-85 www.hypertension.ca JAMA 1991; 265: 3255-64

Hypertension in the Elderly: Questions That Still Need Review of Major Trials Answering? Major Hypertensive Trials Involving Elderly Patients • What is an “ideal BP goal” for the elderly? Trial Mean Age Starting BP Treatment Outcomes (Age Range) (Goal BP) (Mean – < 80 yrs old? Duration) Sys‐Eur 70 yrs (≥ 60 174/86 mm Hg Nitrendipine ± ↓ total stroke – ≥ 80 yrs old? ((ySystolic HTN yy)rs) (SBP < 150 or < enalapril ±HCTZ by 42% in the Elderly) 20 mm Hg or placebo (2 (p=0.003). ↓ • Do the bbfitenefits of lliowering BP outtihweigh the n=4695 from baseline) yrs) fatal/nonfatal CV endpoints by potential risks? 31% (p=0.001) • When can BP lowering potentially cause harm MRC (Medical 70 yrs (65‐74) 184/91 mm Hg HCTZ or atenolol ↓ total stroke Research (SBP ≤ 150 or ± amiloride or and all CV in the elderly? Council Trial) 160 mm Hg) placebo (5.8 yrs) events (all stat. n= 4396 sig) • What is the best treatment regimen for this Lancet 1997; 350: 757-64 BMJ 1992; 304: 405-12 population?

ACCF/AHA 2011 Expert Consensus Document on Hypertension in the Elderly

A Report of the American College of Cardiology Foundation Task Force on What is an “ideal BP goal” for the Clinical Expert Consensus Documents “old” and the “very old?”

Developed in Collaboration With the American Academy of Neurology, American Geriatrics Society, American Society for Preventive Cardiology, American Society of Hypertension, American Society of Nephrology, Association of Black Cardiologists, and European Society of Hypertension

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Hypertension In the Elderly: 2011 HYVET Consensus Recommendations (Hypertension in the Very Elderly Trial) • Uncomplicated vs. Complicated HTN? • 3,845 patients from global study sites • Age of the patient? – ≥ 80 yrs of age with sustained SBP ≥ 160 mm Hg – Patients 55‐79 yrs: BP goal < 140/90 mm Hg. Goal • Europe may differ depending on presence of compelling • Asia indications. • Australia – Patients ≥ 80 yrs: SBP of 140‐145 mm Hg, if tolerated, • Africa is acceptable . SBP ≥ 150 maybe acceptable in some cases. • Aggressive BP goals for compelling indications are still reasonable only if tolerated • Ensure usage of best clinical judgment Circulation 2011; 123: 2434-2506

HYVET: Study Population/Procedures HYVET: Endpoints 3845 patients randomized • to either active treatment Primary Outcomes or placebo – Total strokes

Indapamide ± • Secondary Outcomes Placeboacebo perindopril – Death from stroke (n=1933) (n=1912) – Death from any cause BP Target: <150/80 mm Hg – Death CV causes

Key Baseline Characteristics Mean Age 83 yrs Mean BP 173/90 mm Hg Presence of CVD/DM 12%/7%

HYVET: Results

Do elderly patients reap benefits from BP lowering therapy?

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ACCOMPLISH Trial ACCOMPLISH: Study Population/ (Avoiding Cardiovascular Events in Combination Procedures Therapy in Patients Living with Systolic 11, 506 Patients Received Hypertension) Combination BP Therapy • 11, 506 patients at high risk for CV events: – ≥ 60 yrs of age, with a SBP ≥ 160 mm Hg or Benazepril‐ Benazepril‐ currently on antihypertensive therapy, plus with Amlodipine Group HCTZ Group evidence of CV or renal disease or target organ (n=5744) (n=5762) damage. BP Targets: < 140/90 mm Hg or – 55‐59 yrs of age with evidence of two or more of < 130/80 mm Hg CV diseases or target organ damage present Key Baseline Characteristics Mean Age 68 yrs N Engl J Med 2008; 359: 2417‐28. Mean BP 145/80 mm Hg Am J Hypertens 2004; 17:793‐801. Predominate Study Region 70% sites in United States

ACCOMPLISH: Endpoints ACCOMPLISH: Results • Primary Outcomes – Composite of CV events and death from CV causes – Evaluation of individual components • Death from CV causes • Hosp. from unstable • TtlTotal MI • RlitiRevascularization • Total Stroke • Resuscitation from cardiac arrest – Prespecified subgroups (age, gender, diabetes) • Secondary Outcomes – Composite of death from CV events, nonfatal MI/stroke

SHEP Trial Follow‐Up SHEP Follow‐Up Trial (Association Between Chlorthalidone Treatment of Systolic Hypertension and Long‐Term Survival) • Recap of SHEP • Objective: To assess the “legacy effect” of – Active Group: Chlorthalidone ± atenolol active treatment 22 yrs after the conclusion of – Placebo Group the trial. – Length of Study: 4.5 yrs • Recap of SHEP Study: • Method of analysis – 4736 participants ≥ 60 yrs old with systolic HTN – Evaluation of National Death Index for mortality and cause of death through Dec 2006 – Baseline Characteristics: • Mean Age: 72 yrs old PMH: 5% had MI, ~1% had • Primary Outcomes • Mean BP: 170/76 mm Hg CVA, 10% had DM – CV Death • Smoking Status: 12% smoked JAMA 2011; 306 (23): 2588-93 – All‐Cause Mortality

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SHEP Follow‐Up Trial: Results SHEP Follow‐Up Trial: Results (Survival Free of CV Death) (Survival Probability of All‐Cause Mortality)

JAMA 2011; 306 (23): 2588-93 JAMA 2011; 306 (23): 2588-93

Hypertension In the Elderly: The J‐Curve

INVEST Study • 2011 Consensus Recommendations: When it comes to BP lowering, – SBP < 130 mm Hg and DBP < 65 mm Hg should how much is “too much”? be avoide d in patien ts ≥ 80 yrs old.

Am J Med 2010; 123: 719-296 Circulation 2011; 123: 2434-2506

Hypertension In the Elderly: 2011 Consensus Recommendations • Interdisciplinary Approach How should hypertensive elderly – “This management is fostered by behavioral interventions that focus on re‐enforcement patients be managed? techniques to enhance engagement of elderly individuals in their own care employing a team” – “The team should ideally be composed of clinical pharmacists, nurses, physician assistants, clinical psychologists, and others (as necessary).”

Circulation 2011; 123: 2434-2506

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Hypertension In the Elderly: 2011 Hypertension In the Elderly: 2011 Consensus Recommendations Consensus Recommendations • Nonpharmacologic Recommendations • Prior to initiating pharmacotherapy, consider: – – Weight reduction QOL and cognitive function – Age related physiologic changes – DASH eating plan – Other meds the patient may be currently taking – Dietary sodium restriction • Initiation of drug therapy – Increased physical activity – Initial drug should be started at the lowest dose and – Moderation of alcohol consumption gradually ↑ depending on the BP response to the – Smoking cessation maximum tolerated dose. • If BP ↓ response to the inial drug is inadequate aer reaching full dose, a 2nd drug from another class should be added, provided Circulation 2011; 123: 2434-2506 JNC-VII Complete Report 2003 NIH Publication the initial drug is tolerated. Circulation 2011; 123: 2434-2506

Hypertension In the Elderly: 2011 Hypertension In the Elderly: 2011 Consensus Recommendations Consensus Recommendations • Initiation of drug therapy • Adjustments to meds should not be made – If no therapeutic response or significant adverse effects, a until the following are assessed: drug from another class should be substituted. If a diuretic – Compliance nd is not the initial drug, it’s usually indicated as the 2 drug. – Volume status – If BP ↓ response is inadequate aer reaching the full dose – Drug interactions of 2 classes of drugs, a 3rd agent from another class should – Other drugs/secondary conditions that can exacerbate be added. HTN – If BP is >20/10 mm Hg above goal, drug therapy should – Lifestyle factors generally be initiated with 2 agents one of which should be a thiazide diuretic; however, in the elderly, treatment – Adverse effect profile must be individualized. – Pseudoresistance Circulation 2011; 123: 2434-2506 Circulation 2011; 123: 2434-2506

Hypertension In the Elderly: 2011 Hypertension In the Elderly: 2011 Consensus Recommendations Consensus Recommendations

Patients ≥ 80 yrs, SBP 150 mm Hg may be acceptable for dx HTN and treatment target If SBP ≥ 150 mm Hg If SBP with one of the <150 mm Hg following: can be safely -Regimen of 4 drugs achieved: -Intolerable adverse -effects May consider -DBP < 65 SBP < 140 mm Hg. Also SBP 140‐145 mm Hg is Lowest safely achieved reasonable. SBP ≥ 150 mm Hg is acceptable

Circulation 2011; 123: 2434-2506

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TG is an 85 y/o male with a long standing h/o Which RCT illustrated CV benefits of a thiazide/ACE HTN. He takes lisinopril/HCTZ 10 /25 mg daily and his SBP inhibitor combination in an population of 80+ yr old usually ranges between 142‐145 mm Hg and DBP 70‐75 mm Hg. Which BP goal is the most appropriate? patients with systolic HTN? 1. SHEP Trial 1. < 140/90 mm Hg 2. HYVET 2. < 130/80 mm Hg 3. ACCOMPLISH Trial 3. < 120/80 mm Hg 4. STOP Study 4. His BP measurements are acceptable

KW is an 85 yr female with newly dx HTN. She was started on amlodipine 5 mg /day 6 wks ago. The medical resident How Should We ACCOMPLISH Good wishes to ↑ to 10 mg daily for beer control . Prior to Blood Pressure Control In Our VETS? changing the dose, what should be considered?

1. Compliance Updates in the Management of 2. Able to perform Hypertension In the Elderly lifestyle modifications Antoine T. Jenkins, Pharm.D., BCPS 3. Other meds that she Assistant Professor of Pharmacy Practice takes Chicago State University‐‐‐College of Pharmacy 4. All of the above Internal Medicine Pharmacy Specialist Roseland Community Hospital, Chicago, IL

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