Resistant Hypertension Topic Discussion Brian Skinner, PharmD PGY-1 Pharmacy Resident St. Vincent Indianapolis Hospital

Objectives Define the term “resistant hypertension” Describe possible underlying resistance mechanisms Identify nonpharmacological interventions for resistant hypertension Identify pharmacological interventions for resistant hypertension

Hypertension by the Numbers 70 million people with high blood pressure 33.6 million people with uncontrolled high blood pressure Up to 28% of patients have uncontrolled blood pressure despite the use of 3 different medications Circulation. 2011;124(9):

Definition Blood pressure that remains above goal despite the use of three or more antihypertensive agents, with one agent being a diuretic OR Blood pressure that is controlled with the use of four or more antihypertensive agents Circulation. 2008;117:e510-e526

Treatment Algorithm Identification of Possible Causes Non- Pharmacological Intervention Pharmacological Intervention Circulation. 2008;117:e510-e526

IDENTIFICATION OF POSSIBLE CAUSES

Pseudoresistance Improper blood pressure technique ◦ Utilization of wrong cuff size ◦ Not allowing patient to sit quietly prior to BP reading White coat hypertension ◦ Increased blood pressure at the doctor’s office but normal blood pressures at home Circulation. 2008;117:e510-e526

Ambulatory Blood Pressure Monitoring

Non-adherence How can we assess adherence? ◦ Self-reporting by the patient ◦ Pill counting ◦ Prescription refill rates ◦ Electronic monitoring Circulation. 2008;117:e510-e526

Secondary Hypertension Obstructive sleep apnea Renal Artery Stenosis Hyperthyroidism Pheochromocytoma Cushing’s Disease Primary Hyperaldosteronism Circulation. 2008;117:e510-e526 J Am Board Fam Med. 2012;25: JAMA. 2014;311(21):

Medication Induced Hypertension Corticosteroids Erythropoietin NSAIDs, COX-2 inhibitors, ASA Amphetamines Decongestants SNRI’s Circulation. 2008;117:e510-e526 J Am Board Fam Med. 2012;25:

NON-PHARMACOLOGICAL INTERVENTIONS

Reversible Lifestyle Factors Obesity Physical inactivity Excessive alcohol ingestion High salt, low fiber diet Circulation. 2008;117:e510-e526 JAMA. 2014;311(21):

PHARMACOLOGICAL INTERVENTIONS

First Line Agents for BP Angiotensin Converting Enzyme Inhibitor Angiotensin Receptor Blocker Thiazide Dihydropyridine Calcium Channel Blocker JAMA. 2014;311(5):

Optimization of Current Regimen Increase agents to maximum tolerated dose Maximize diuretic therapy ◦ Switch to chlorthalidone If CrCl <30ml/min ◦ Switch to loop diuretic Circulation. 2008;117:e510-e526 JAMA. 2014;311(21):

Additional Agents Mineralocorticoid Receptor Blockers ◦ Spironolactone ◦ Eplerenone Side effects: ◦ Hyperkalemia ◦ Gynecomastia (spironolactone) ◦ GI upset JAMA. 2014;311(21):

Additional Agents Beta Blockers ◦ Carvedilol ◦ Labetalol ◦ Nebivolol Side effects ◦ Bradycardia ◦ Orthostatic hypotension ◦ Mask signs and symptoms of hypoglycemia JAMA. 2014;311(21):

Additional Agents Alpha Blockers ◦ Doxazosin ◦ Terazosin ◦ Prazosin Side effects ◦ Orthostatic hypotension ◦ Headache ◦ Edema JAMA. 2014;311(21):

Additional Agents Non-DHP Calcium Channel Blockers ◦ Verapamil ◦ Diltiazem Side Effects ◦ Bradycardia ◦ Gingival hyperplasia ◦ Constipation JAMA. 2014;311(21):

Additional Agents Centrally Acting Alpha Agonists ◦ Clonidine ◦ Guanfacine Side effects ◦ Orthostatic hypotension ◦ Drowsiness ◦ Depression JAMA. 2014;311(21):

Additional Agents Direct Vasodilators ◦ Hydroxyzine ◦ Minoxidil Side Effects ◦ Reflex tachycardia ◦ Lower extremity edema ◦ Hirsutism (minoxidil) ◦ Drug-induced lupus (hydroxyzine) JAMA. 2014;311(21):

Which agent should we use? Heart Failure Post Myocardial Infarction Heart rate < 60bpm Heart rate > 80bpm

Resistant Hypertension Topic Discussion Brian Skinner, PharmD PGY-1 Pharmacy Resident St. Vincent Indianapolis Hospital