Hypertension Pharmacotherapy: A Practical Approach Ronald Victor, MD Burns & Allen Chair in Cardiology Director, The Hypertension Center Associate Director, The Heart Institute Hypertension Center
1. 2. JNC 8 Relaxed drug Rx thresholds Office BP My Approach Pull the trigger on drug Rx Out-of-office BP 3. Higher drug doses as in RCTs Low-dose combination drug Rx
Daytime BP >135/85 Sleep BP > 125/75 MY APPROACH Initiate or intensify drug therapy if: Less intensive therapy for frail elderly More intensive therapy for high risk patients First-line combination drug therapy CCB plus ARB Add-on therapy Thiazide Aldosterone antagonist Vasodilating β-blocker Hypertension Center
Case #1: 79 y/o woman with no h/o CVD but family h/o stroke Healthy, robust, BMI 24 Office BP 200/85 mmhg Her home systolic BPs 132-149 Normal electrolytes, Cr 0.7 No diabetes, normal lipids No current medication Should we prescribe BP medication?
Relaxed Drug Therapy BP Thresholds JNC 8 (2014) JNC 7 (2003) Age > 60 Age < 60 Diabetes, CKD 150/90 140/90 140/90 140/90 130/80
Older Patients Evidence for Office SBP < 150 200 Systolic BP, mmhg 190 180 170 160 150 140 130 HYVET SCOPE SHEP SystEur Syst-China C & W STOP RCTs (1995-2008) Drug vs. placebo - HYVET: age 80+ - Others: ages 65-79 - Not designed to test different thresholds or goals of Rx 120 Initial Final STOP2
Hypertensive Patients in General Evidence for Office SBP < 140 Systolic BP, mmhg 180 170 160 150 140 130 120 Initial Final FEVER ELSA NORDIL CAPP CONVINCE VALUE ASCOT ACCOMPLISH ALLHAT ALLHAT2 ONTARGET LIFE INVEST (ECG-LVH) (CAD) RCTs (1995-2008) new vs. old drugs - Mean age 67 years - No data < age 50 - Not designed to test benefits of more vs. less intensive Rx
Systolic BP (mm Hg) 136 121 Standard Rx Intensive Rx Years
CVD Event Death Years
Subgroup Hazard Ratio, 95% CI Our Patient Elderly- 33% Woman- 16%% Untreated home SBP 132-149 24-30% Intensive Rx Better Standard Rx Better
Risks of more intensive Rx? (+) (-) No increase in: Injurious falls Symptomatic orthostatic hypotension Overall SAEs Increase in: Hyponatremia +76% Hypokalemia +50% Acute kidney injury +71%
1. 2. JNC 8 Relaxed drug Rx thresholds Office BP My Approach Pull the trigger on drug Rx Out-of-office BP 3. Higher drug doses as in RCTs Low-dose combination drug Rx
Pull the trigger on drug Rx? Blood pressure, mm Hg 250 200 150 100 50 0 15:00 24:00 Office visits sleep 15:00 Robust 79 y/o woman with: Stage 1 ISH (awake) White Coat Rkn Nocturnal HTN- SBP 142 (normal sleep BP < 120/70) Rx: Amlodipine 2.5 mg QHS Next, losartan 25 mg QHS Start low, go slow Avoid orthostatic BP
Blood pressure, mmhg Frail 69 y/o woman with on-treatment office SBP 160 Hour: lunch White coat reaction breakfast lunch bathroom ISH & white coat HTN Postprandial & orthostatic hypotension Less intensive Rx
1. 2. JNC 8 Relaxed drug Rx thresholds Office BP My Approach Pull the trigger on drug Rx Out-of-office BP 3. Higher drug doses as in RCTs Low-dose combination drug Rx
Case #2: 61 y/o woman with severe hypertension and palpitations BMI 29, OWNL exam Normal: CBC, lipids Normal ECG Normal 126! CBC 4.3 116 Normal 101 lipids 29 0.9 14
Her Initial Rx 1. Losartan HCT (Hyzaar) 100-25 QD 2. Lisinopril 40 mg QD 3. Atenolol 50 mg QD 4. KCL 20meq BID 5. Clonidine 0.2 mg BID plus 0.1 mg PRN BP >180/110 How to address: a) medication regimen? b) hyponatremia? c) secondary HTN?
BP reduction 1.25 mg indapamide =25 mg chlorthalidone = 60 mg HCTZ Similar metabolic side-effects
Incidence per 100,00 person-years Women 60 y/o Men
Hyponatremia-Associated Symptoms
Monotherapy dose escalation BP Reduction Side- Effects Dose
Combining drugs from different classes is 5 times more effective lowering BP than doubling the dose of one drug.
Three 1 st Line Drug Classes for Hypertension in 2016 Thiazide diuretics Calcium channel blockers (CCBs) Renin angiotensin system blockers ACEI or ARB
Discontinuation rates at 1 year: Worst with thiazides: 75% Intermediate with CCBs, ACEIs: 48% Best with ARBs: 35%
Resistant (Difficult) HTN Office BP > 140/90 x 3 drugs Pseudo-Resistant White coat HTN Medication regimen Patient non-compliance Interfering meds (NSAIDs) Truly Resistant Secondary HTN adrenal (aldo, pheo) renal, renovascular Difficult primary HTN Aldosterone antagonist
Subclinical 1972
Initial Rx 1. HCTZ 2. KCl 3. Losartan 4. Lisinopril 4. Atenolol 5. Clonidine (+PRN dosing) Na, K ARB plus ACEI increases risk of AKI No stroke protection Rebound BP surges
New Rx 1. Amlodipine 5 mg (CCB) 2. Telmisartan 80 mg (ARB) 3. Coreg CR 40 mg (vasodilating BB)- add on 1 st line Office SBP much better but Normal spells 143 at CBC 4.2 home with 69 SBP Normal >200. Plasma 102 lipids 29 metanephrines normal. 16 0.8
Spells with Palpitations New Regimen Averages Day: 131/79 Night: 114/67
EPS: Atrial tachycardia
Final Rx Hypertension Amlodipine 5 mg Telmisartan 80 mg Atrial Tachycardia Metoprolol 100 mg Diltiazem 360 mg
Daytime BP >135/85 Sleep BP > 125/75 MY APPROACH Initiate or intensify drug therapy if: Less intensive therapy for frail elderly More intensive therapy for high risk patients First-line combination drug therapy CCB plus ARB Add-on therapy Thiazide Aldosterone antagonist Vasodilating β-blocker Hypertension Center