1. A Case of Hypertension: Overcoming Resistance Requires Change COPYRIGHT © 2015, ALL RIGHTS RESERVED From the Publishers of

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3. Guys: I am in our outpatient office and I need your help. It’s a case that you will not be able to resist. My patient is 55 years old and has a long history of hypertension. During the past year an elevation of his blood pressure has prompted that I increase his antihypertensive regimen and it now consists of three antihypertensive agents: hydrochlorothiazide +enalapril+ amlodipine. Despite titration to near maximum doses, his blood pressure taken at home and in the office has been 155/90. His blood pressure control has been resistant to three agents. What do I do now ? Guys: I am in our outpatient office and I need your help. It’s a case that you will not be able to resist. My patient is 55 years old and has a long history of hypertension. During the past year an elevation of his blood pressure has prompted that I increase his antihypertensive regimen and it now consists of three antihypertensive agents: hydrochlorothiazide +enalapril+ amlodipine. Despite titration to near maximum doses, his blood pressure taken at home and in the office has been 155/90. His blood pressure control has been resistant to three agents. What do I do now ? Copyright © 2015

4. Resistant Hypertension Consider secondary hypertension Results of the evaluation: Renal function normal Renal artery ultrasound- 70% left renal artery stenosis Plasma aldosterone / renin activity ratio is normal- no primary aldosteronism Hypertension is not episodic – no pheo No Cushings features Copyright © 2015

5. Exam: BMI 32 Afebrile BP: 155/90 right and left arm (large cuff) HR: 70 bpm Lungs clear. Cardiac rhythm regular. Heart sounds normal. No murmur. Abdominal exam: no mass or bruit. Extremity exam is normal. No pulse delay Labs Electrolytes: Na 135, K 4.0 Cr 0.8 Plasma aldosterone / renin is normal Renal artery doppler: 70% left renal artery stenosis Copyright © 2015 Resistant Hypertension

6. 55 year-old man BP 155/90 and confirmed at home BMI 32 Diuretic (hctz) + ACE-I (enalapril) + long acting dihydropyrdine calcium channel blocker (amlodipine) and compliant Left renal artery stenosis (70%)  Renal artery stenosis in up to 20% of patients  OSA in up to 70% of patients  Primary aldosteronism in up to 20% of patients Copyright © 2015

7. Resistant Hypertension Copyright © 2015 BP that remains above goal despite three antihypertensive agents (one of which is a diuretic) 20% of patients with hypertension So, what is the goal? It depends who you ask…..

8. *Calhoun DA et al. Resistant Hypertension: Diagnosis, Evaluation, and Treatment. Hypertension. 2008 Jun;51(6):1403-19. doi: 10.1161/HYPERTENSIONAHA.108.189141. Epub 2008 Apr 7.

9. *James PA, Oparil S, Carter BL, et al. 2014 Evidence-Based Guideline for the Management of High Blood Pressure in Adults: Report From the Panel Members Appointed to the Eighth Joint National Committee (JNC 8). JAMA. 2014;311(5):507-520. doi:10.1001/jama.2013.284427. Age 60 or above: < 150/90 Below age 60: < 140/90

10. *Go AS, Bauman MA, Coleman King SM, Fonarow GC, Lawrence W, Williams KA, Sanchez E. An effective approach to high blood pressure control: a science advisory from the American Heart Association, the American College of Cardiology, and the Centers for Disease Control and Prevention. Hypertension. 2014;63:878–885. December 2014 < 140/90

11. *Weber MA, et al. Clinical Practice Guidelines for the Management of Hypertension in the Community. The Journal of Clinical Hypertension, 16: 14–26. doi: 10.1111/jch.12237 December 2014 < 140/90 Age 80 or older : < 150/90 ( if diabetic or CKD < 140/90)

12. *Rosendorff C, et al. and on behalf of the American Heart Association, American College of Cardiology, and American Society of Hypertension. Treatment of hypertension in patients with coronary artery disease: a scientific statement from the American Heart Association, American College of Cardiology, and American Society of Hypertension. Hypertension. 2015. May 2015 Stable patient <140/90 Prior MI, stroke, TIA <130/80

13. BP < 140/80

14. *The Sprint Group. N Engl J Med. 2015 Nov 9. [Epub ahead of print]

15. Our Patient Age 55 No CAD Non-diabetic Left renal artery stenosis Copyright © 2015 Target < 140 / 90 Target < 140 / 90

16. Non-pharmacologic Diet Salt restriction  Moderate reduction: 4mmHg lowering systolic BP Exercise  40 minutes, three times weekly: systolic BP reduction 5 mmHg OSA?  Treatment would only lower systolic BP approximately 3mm Hg Copyright © 2015

17. *Cooper CJ et al. Stenting and medical therapy for atherosclerotic renal-artery stenosis N Engl J Med 2014 Jan 2;370(1):13-22. doi: 10.1056/NEJMoa1310753. Epub 2013 Nov 18.

18. Coral Trial 947 patients with RAS > 60% AND resistant hypertension or > stage 3 CKD Medical therapy with or without stenting mean stenosis 73% 43 month follow up No difference in death, MI, stroke, hospitalization for heart failure, renal insufficiency, need for permanent dialysis Systolic BP 2.3 mm Hg lower in the stent group *Cooper CJ et al. Stenting and medical therapy for atherosclerotic renal-artery stenosis N Engl J Med 2014 Jan 2;370(1):13-22. doi: 10.1056/NEJMoa1310753. Epub 2013 Nov 18

19. Medications Diuretic key to the regimen  Persistent volume expansion common  Even in the absence of edema HCTZ  Consider replacing with chlorthalidone  Twice as potent as HCTZ in lowering blood pressure  Within recommended doses probably a more potent antihypertensive effect over 24 hours If GFR < 30 mL/min thiazide less effective  Consider loop diuretic  Furosemide short acting so twice daily  Torsemide once daily Copyright © 2015

20. Medications In addition to diuretic:  Angiotensin converting enzyme inhibitor  Calcium channel blocker Copyright © 2015 Add a fourth medication?

21. Spironolactone

22. Pearls Copyright © 2015 Know the target BP and confirm resistance with home BP Rule out confounding causes, life style causes and noncompliance Optimize the ACEI and calcium channel blocker Switch from HCTZ to chlorthalidone If remains resistant on three agents investigate for secondary hypertension as clinically indicated No evidence that renal artery revascularization improves BP Don’t forget primary aldosteronism Fourth agent: Add mineralocorticoid receptor antagonist (spironolactone, eplerenone) Follow potassium

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