HYPERTENSION MANAGEMENT IN ELDERLY POPULATIONS Michael J. Scalese, PharmD, BCPS, CACP Assistant Clinical Professor Auburn University Harrison School of Pharmacy July 14, 2018
DISCLOSURE/CONFLICT OF INTEREST I, Michael J. Scalese, have no actual or potential conflict of interest in relation to this program
OBJECTIVES 1. Discuss the impact of antihypertensives in older persons 2. Compare and contrast current guideline recommendations for the treatment of hypertension in adults 60 years of age 3. Develop an evidence-based treatment plan for older persons with hypertension
HYPERTENSION IN THE ELDERLY Elderly population is the largest growing demographic Large economic implications Expected to make up 50% of population by 2060 As of 2018, more than 80% of people 65 years have hypertension
CV DEATHS IN ALABAMA Alabama CVD deaths 294 deaths/100k people 2 nd highest in the US (rank 51/52) Alabama Stroke related deaths 48.6 deaths/100k people Highest in the US (rank 52/52) Impacts men more than women Circulation. 2017;135:00 00 https://nccd.cdc.gov/dhdspatlas/
HYPERTENSION IN THE ELDERLY May present differently than younger populations Psuedo-resistant or resistant HTN Noncompliance with medications Isolated systolic hypertension Much more common in elderly population Tight vs Lenient BP control Fall risk and Frailly
Goal Blood Pressure for the Elderly
PATIENT CASE-KM KM is a 71 year old Chinese female with no significant medial history. She was diagnosed with essential hypertension 6 months ago and has implemented lifestyle modifications. KM has been referred to your clinic today for pharmacologic management of her high blood pressure after incomplete success of diet, exercise, and other life style changes. Her BP readings at her visit today are 156/92 and 152/90 What is KM s blood pressure goal? A. <120/80 B. <130/80 C. <140/90 D. <150/90
JNC8 RECOMMENDATIONS General population > 60 years Blood pressure target < 150/90 mmhg reduces stroke, HF, CHD SBP < 140 mmhg not recommended No additional benefit vs higher goal 2 underpowered Japanese studies JATOS, VALISH JAMA 2014;311(5):507-520 NEJM 2008;358(8):1887-1898 Lancet 1997;350(9080):757-764 JAMA 1991;265(24):3255-3264.
JNC8 EVIDENCE: ELDERLY BP TARGET Trial Age Intervention Primary Endpoint Result HYVET 2008 Syst-Eur 1997 SHEP 1991 > 80 years > 60 years > 60 years Indapamide vs. placebo Nitrendipine vs. placebo Chlorthalidone vs. placebo Indapamide reduces fatal stroke Nitrendipine reduces fatal and nonfatal stroke Chlorthalidone reduces fatal and nonfatal stroke Mean SBP (mmhg) 2 years: 144 vs. 159 2 years: 150 vs. 160 5 years: 143 vs. 155 JAMA 2014;311(5):507-520 NEJM 2008;358(8):1887-1898 Lancet 1997;350(9080):757-764 JAMA 1991;265(24):3255-3264.
CLINICAL CONTROVERSIES THE MINORITY VIEW JNC8 5 of 17 panel members disagreed with elderly BP goal JNC 8 recommendation missing sufficient evidence Concern for reducing intensity of antihypertensive therapy in high risk population Higher BP goal may reverse CVD and stroke benefit SBP goal of < 140 mmhg, especially in high risk population Supported by observational studies and RCT data Support SBP < 150 mmhg in frail patients > 80 years old Similar to European guideline recommendations Ann Intern Med. 2014;160(7):499-503
HYVET 3845 hypertensive patients > 80 years old and SBP > 160 mmhg Indapamide SR 1.5 mg vs placebo Perindopril 2-4 mg or placebo added if necessary to achieve SBP < 150 mmhg Median follow-up: 1.8 years Primary endpoint (fatal or nonfatal stroke) Lower but not significantly reduced with indapamide (12.4% vs. 17.7%) Fatal stroke was significantly reduced (p=0.046) Seated blood pressure after 2 years 143.5/77.9 mmhg indapamide vs 158.5/84 mmhg placebo NEJM 2008;358(8):1887-1898
JATOS (2008) & VALISH (2010) JATOS VALISH 2 year duration 3 year duration Patients 65-85 years of age Goal SBP <140mmHg vs <160mmHg No difference in CVD or renal outcomes (primary outcome) No difference in All-cause mortality (secondary outcome) Patients 70-84 years of age with isolated systolic hypertension Goal SBP <140mmHg vs <150mmHg No difference in CV morbidity or mortality Study underpowered Study underpowered Major type II error Major type II error Ann Intern Med. 2014;160(7):499-503 Hypertens Res. 2008;31:2115-27 Hypertension. 2010;56:196-202
FEVER (EXCLUDED FROM JNC-8) Investigator-designed, prospective, multicenter, double-blind, randomized, placebo-controlled, parallel group trial 9800 Chinese patients 50-79 years of age with BP 140-80/90-100mmHg 1-2 additional CV risk factors All patients on low dose thiazide Addition of low dose felodipine ER vs placebo Median 40 month follow up BP 137.3/82.5mmHg vs 142.5/85mmHg respectively Incidence of stroke reduced in felodipine group (P =0.001) (primary outcome) Secondary outcomes also significantly reduced (CV events, all cause mortality, coronary events, heart failure) J Hypertens. 2005 Dec;23(12):2157-72
JNC-8 ELDERLY PATIENT BOTTOM LINE Higher BP target in 65-80 age range not supported by evidence 2 Japanese only studies underpowered FEVER trial excluded Sufficient evidence to support rise in SBP target to <150 in patients 80 years old Especially in Isolated systolic hypertension Strong support from HYVET & SHEP In this case, majority doesn t rule Minority report highlights significant limitations to JNC-8 recommendations JAMA 2014;311(5):507-520 NEJM 2008;358(8):1887-1898 Lancet 1997;350(9080):757-764 JAMA 1991;265(24):3255-3264. Ann Intern Med. 2014;160(7):499-503 Hypertens Res. 2008;31:2115-27 Hypertension. 2010;56:196-202
PATIENT CASE REVISITED-KM KM is a 71 year old Chinese female with no significant medial history. She was diagnosed with essential hypertension 6 months ago and has implemented lifestyle modifications. KM has been referred to your clinic today for pharmacologic management of her high blood pressure after incomplete success of diet, exercise, and other life style changes. Her BP readings at her visit today are 156/92 and 152/90 Based on JNC-8 and the minority report, what is KM s blood pressure goal? A. <120/80 B. <130/80 C. <140/90 D. <150/90
ACP GUIDELINES 2017 HTN TREATMENT IN ADULTS > 60 YEARS Adults > 60 years History of stroke High CV risk SBP goal < 150 mmhg to reduce mortality, stroke, and cardiac events Consider SBP goal < 140 mmhg to reduce recurrent stroke Consider SBP goal < 140 mmhg to reduce stroke or cardiac events Ann Intern Med 2017 Mar 21;166(6):430-437
2017 GUIDELINES (ACC/AHA/AAPA/ABC/ACPM/AGS/APHA/ ASH/ASPC/NMA/PCNA) Joint guideline supported by many interdisciplinary organizations 24 member development panel reviewed >900 clinical studies Paradigm shift in blood pressure targets to much more strict goals BP >130/80 now stage I HTN prevalence of HTN in US by 14% Treat if elevated CV risk or history of CV event BP >140/90 now stage II HTN Treat all patients with 1 drug Consider 2 agents if significantly elevated or if 1 agent unlikely to get patient to goal Inclusion of ASCVD Risk Assessment to guide treatment strategies J Am Col Cardiol 2018 ;71(19):127-248
POOLED COHORT EQUATIONS ASCVD RISK ESTIMATOR Developed from 5 major cohorts ARIC, CHS, CARDIA, Framingham Cohort, and Offspring Validated in MESA & REGARDS studies Age 40-79 years with No ASCVD, AF, or HF at baseline Designed for primary prevention patients NOT on drug therapy Very few patients in cohorts were on lipid lowering therapy Provides 2 different risk assessments 10 year risk of hard ASCVD Lifetime risk for someone age 50 yrs
ASCVD CALCULATION-KM KM is 71 year old Chinese female with no significant past medical history Vitals: BP 154/91 (average of todays readings), HR 74, RR 16 Medications: Daily Multi-vitamin Social History: denies tobacco, occasional alcohol, no illicit drugs Family history: Mother had a stroke at age 79 Labs: TC=190 mg/dl TG=205 mg/dl HDL=30 mg/dl LDL-C =119 mg/dl What is KM s 10-year ASCVD risk? A. 15.0% B. 15.9% C. 16.2% D. 21.1%
POOLED COHORT EQUATIONS ASCVD RISK ESTIMATOR Incorporates ASCVD Risk Factors: Age Sex Race Systolic blood pressure Total Cholesterol HDL Diabetes Smoking status Current hypertension treatment
POOLED COHORT EQUATIONS ASCVD RISK ESTIMATOR Applies best to AA or C of either sex Limitations Overestimates risk for Eastern Asian (Chinese, Japanese, Vietnamese, or Korean), Hispanics Underestimates risk for: Native Americans, Pacific Islanders, and individuals of South Asian ancestry, defined as those of Indian, Pakistani, or Bangladeshi descent If applied should classify these individuals as Caucasian or other Only incudes data for people aged 40-79 (10 yr); 20-59 (lifetime)
2017 GUIDELINES- ELDERLY POPULATION (ACC/AHA/AAPA/ABC/ACPM/AGS/APHA/ ASH/ASPC/NMA/PCNA) Goal to CV/stroke risk & prevent harm (falls, AE s, orthostasis, etc) No evidence of orthostasis or injury in community dwelling older adults in multiple trials renal injury with tighter control but risk was the same as in younger populations Use caution if frequent falls, cognitive impairment, or multiple comorbidities BP recommendation parallels general population (BP <130/80) focus on ASCVD risk assessment 88% of patients 65 years have >10% ASCVD risk or clinical ASCVD 100% of patients 75 years have >10% ASCVD risk or clinical ASCVD Recommendation relied heavily on HYVET and SPRINT trials J Am Col Cardiol 2018 ;71(19):127-248
SPRINT Randomized, controlled, multicenter, open-label trial 9361 patients with SBP > 130 mmhg, high CV risk, no diabetes Intervention SBP < 120 mmhg vs. SBP < 140 mmhg Primary outcome MI, other ACS, stroke, heart failure, CV death NEJM 2015;373(22):2103-2116
SPRINT Mean follow-up: 3.26 years (terminated early) Intensive treatment significantly reduced primary endpoint (5.5% vs. 6.5%, p<0.001) Mean SBP achieved 121.5 mmhg vs. 134.6 mmhg respectively Mean number of medications: 2.8 vs. 1.8 Subgroup analysis Potentially better results in those > 75 years, mean 79.9 years NEJM 2015;373(22):2103-2116
SPRINT-ELDERLY SUBGROUP Primary outcome MI, other ACS, stroke, heart failure, CV death 7.74% (intensive) vs. 11.2% (standard), p=0.001(nnt=29) Significant reduction in HF and all-cause mortality No difference in adverse effects Hypotension Syncope Electrolyte abnormalities AKI/renal failure JAMA 2016;315(24):2673-2682
2016 SYSTEMATIC REVIEW AND META-ANALYSIS Evaluated safety & efficacy of intensive BP in high risk patients 19 RCTs comparing BP targets or intensity of treatment Intensive lowering (mean BP 133/76 mmhg vs. 140/81 mmhg in less intensive groups) Reduces major CV events, MI, stroke, albuminuria, retinopathy Minimal difference in serious adverse events Sub-group of 7 trials with mean age > 62 years significant reduction in major CV events Lancet 2016; 387: 435 43
2017 SYSTEMATIC REVIEW AND META-ANALYSIS -RESULTS High-strength evidence from 9 trials BP < 150/90 mmhg reduces mortality, cardiac events, and stroke Low- to moderate-strength evidence from 6 trials BP < 140/85 mmhg Reduces cardiac events and stroke No reduction in mortality Results largely weighted by SPRINT No increase in falls or cognitive impairment Ann Intern Med. 2017;166(6):430-437
PATIENT CASE REVISITED.AGAIN KM is a 71 year old Chinese female with no significant medial history. She was diagnosed with essential hypertension 6 months ago and has implemented lifestyle modifications. KM has been referred to your clinic today for pharmacologic management of her high blood pressure after incomplete success of diet, exercise, and other life style changes. Her BP readings at her visit today are 156/92 and 152/90 Based on everything we now know, what is KM s blood pressure goal? A. <120/80 B. <130/80 C. <140/90 D. <150/90
PATIENT CASE REVISITED.AGAIN KM is a 71 year old Chinese female with no significant medial history. She was diagnosed with essential hypertension 6 months ago and has implemented lifestyle modifications. KM has been referred to your clinic today for pharmacologic management of her high blood pressure after incomplete success of diet, exercise, and other life style changes. Her BP readings at her visit today are 156/92 and 152/90 What medication should we initiate for KM? A. Atenolol 25mg by mouth daily B. Chlortalidone 12.5mg by mouth daily C. Fosinopril 10mg by mouth daily D. Verapamil SR 120mg by mouth twice daily
Medications in the Elderly
GENERAL CONSIDERATIONS FOR MEDICATION SELECTION Presence of comorbidities Isolated Systolic Hypertension (ISH) vs combined hypertension Orthostatic risk with medications & patient frailty One medication vs multiple Use combination products when possible/available First line options to consider Thiazides Long-acting calcium channel blockers ACE/ARB s Medication choice less important than reaching BP goal
THIAZIDES/THIAZIDE-LIKE DIURETICS Most effective BP lowering in elderly Drug of choice in isolated systolic hypertension Strong evidence from SHEP/HYVET May be preferred over ACE/ARB in essential hypertension Reduction of CV events in post-hoc subgroup of ALLHAT Well tolerated in older population Lancet 1997; 350:757 JAMA 2002; 288:2981 Lancet 1999; 354:1751 NEJM 2008;358(8):1887-1898
CALCIUM CHANNEL BLOCKERS Dihydropyridine preferred over non-dihydropyridines Effective antihypertensive in the older population Especially in isolated systolic hypertension Supported by elderly subgroups in FEVER, ALLHAT, Syst-Eur trial, STOP Hypertension-2, Syst-China, & ACCOMPLISH trials Good evidence for use as part of combo therapy regimen Limited side effects in elderly as compared to general population Low risk of orthostasis Lancet 1997; 350:757 J Hypertens 1998; 16:1823 JAMA 2002; 288:2981 Lancet 1999; 354:1751 N Engl J Med 2008; 359:2417
ARB/ARB First line agent but less preferred than CCB s and thiazides May be slightly less potent antihypertensives Some side effects more common in elderly 1 st dose hypotension Orthostasis Caution with renal function Especially with lower BR target in new guidelines Use cautiously in AA population May not be as big of a deal as we once thought JAMA 2002; 288:2981 Lancet 1999; 354:1751 NEJM 2008;358(8):1887-1898
MEDICATIONS TO AVOID (IN ABSENCE OF COMPELLING INDICATION) Beta-blockers High orthostasis risk May increase CV outcomes and increase adverse effects Just say NO to atenolol Clonidine High dizziness & fall risk Rebound hypertension Alpha-2 Class (ex-doxazosin) May increase CV outcomes (Alpha-2 arm terminated early in ALLHAT) Significant orthostasis risk
PATIENT CASE REVISITED...AGAIN...AGAIN KM is a 71 year old Chinese female with no significant medial history. She was diagnosed with essential hypertension 6 months ago and has implemented lifestyle modifications. KM has been referred to your clinic today for pharmacologic management of her high blood pressure after incomplete success of diet, exercise, and other life style changes. Her BP readings at her visit today are 156/92 and 152/90 What medication should we initiate for KM? A. Atenolol 25mg by mouth daily B. Chlortalidone 12.5mg by mouth daily C. Fosinopril 10mg by mouth daily D. Verapamil SR 120mg by mouth twice daily
TAKE HOME POINTS JNC-8 recommended a more lenient BP goal of <150/90 for patients >60 years Minority of panel disagreed citing unpowered nature of studies and excluded trials Goal <150/90 appropriate for patients> 80 years, unclear target for patients 60-80 years 2017 multidisciplinary guidelines support stricter goal of <130/80 in elderly population Lower goal reduced CV outcomes and did not increase risk of AE s Emphasis on CV history & ASCVD-10 year risk assessment When treatment is indicated, thiazides, CCB s, and ACE/ARB are preferred agents in elderly patients without compelling indications Individualize treatment plan based on patient-specific risk/benefit
HYPERTENSION MANAGEMENT IN ELDERLY POPULATIONS Michael J. Scalese, PharmD, BCPS, CACP Assistant Clinical Professor Auburn University Harrison School of Pharmacy July 14, 2018