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

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

3. 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 http://www.cdc.gov/bloodpressure/facts.htm Circulation. 2011;124(9):1046-1058

4. 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

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

6. IDENTIFICATION OF POSSIBLE CAUSES

7. 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

8. Ambulatory Blood Pressure Monitoring https://www.lmhospital.org/services/cardiac-diagnostic-tests.aspx

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

10. 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;25:487-495 JAMA. 2014;311(21):2216-2224

11. 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;25:487-495

12. NON-PHARMACOLOGICAL INTERVENTIONS

13. Reversible Lifestyle Factors Obesity Physical inactivity Excessive alcohol ingestion High salt, low fiber diet Circulation. 2008;117:e510-e526 JAMA. 2014;311(21):2216-2224

14. PHARMACOLOGICAL INTERVENTIONS

15. First Line Agents for BP Angiotensin Converting Enzyme Inhibitor Angiotensin Receptor Blocker Thiazide Dihydropyridine Calcium Channel Blocker JAMA. 2014;311(5):507-520

16. 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):2216-2224

17. Additional Agents Mineralocorticoid Receptor Blockers ◦ Spironolactone ◦ Eplerenone Side effects: ◦ Hyperkalemia ◦ Gynecomastia (spironolactone) ◦ GI upset JAMA. 2014;311(21):2216-2224

18. Additional Agents Beta Blockers ◦ Carvedilol ◦ Labetalol ◦ Nebivolol Side effects ◦ Bradycardia ◦ Orthostatic hypotension ◦ Mask signs and symptoms of hypoglycemia JAMA. 2014;311(21):2216-2224

19. Additional Agents Alpha Blockers ◦ Doxazosin ◦ Terazosin ◦ Prazosin Side effects ◦ Orthostatic hypotension ◦ Headache ◦ Edema JAMA. 2014;311(21):2216-2224

20. Additional Agents Non-DHP Calcium Channel Blockers ◦ Verapamil ◦ Diltiazem Side Effects ◦ Bradycardia ◦ Gingival hyperplasia ◦ Constipation JAMA. 2014;311(21):2216-2224

21. Additional Agents Centrally Acting Alpha Agonists ◦ Clonidine ◦ Guanfacine Side effects ◦ Orthostatic hypotension ◦ Drowsiness ◦ Depression JAMA. 2014;311(21):2216-2224

22. Additional Agents Direct Vasodilators ◦ Hydroxyzine ◦ Minoxidil Side Effects ◦ Reflex tachycardia ◦ Lower extremity edema ◦ Hirsutism (minoxidil) ◦ Drug-induced lupus (hydroxyzine) JAMA. 2014;311(21):2216-2224

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

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