2. The Jury is Deliberating (JNC 8): Select Cases Pamela L. Stamm, PharmD, CDE, BCPS Associate Professor Auburn University Harrison School of Pharmacy December 8, 2011

3. Disclosures This presenter has nothing to disclose. 3

4. Which best describes the frequency in which you select, monitor, or modify therapy in hypertensive patients? 4 Daily or most days A couple of times a week A couple of times a month Almost never or never

5. Objectives  Determine when it is appropriate to combine vs. titrate antihypertensive therapy  Recognize select secondary causes of hypertension  Understand the potential role of spironolactone in resistant hypertension  Establish treatment goals in the very elderly 5

6. Marty Graw, 50 yo overweight male, likely hypertensive. C/O fatigue, dry skin, “recent” 10 lb weight gain, and snoring  Exercise:  NA  Diet:  Mostly canned vegetables  Lunch meats for lunch  Fresh meats for supper, occasional “Brat”  Vitals  174/106, 78 bpm, today  168/104, 76 bpm,1 week ago  Pain scale: 2 (1-10)  Current Medications:  Simvastatin 20mg QPM  Loratidine 10mg daily  Multivitamin for men daily  Labs:  Chemistry wnl  Lipids controlled 6

7. Think – Pair - Share  Take 5 minutes to develop an assessment and plan for this patient  What is your assessment?  Stage the HTN  Etiology of this patient’s HTN  Plan  What lifestyle modifications do you recommend?  What labs do you want?  What referrals or tests are needed?  Time permitting – share you’re Assessment and Plan with your neighbor 7

8. What is his current BP Stage? 174/106 today 168/104 1 week ago Stage 1 Stage 2 8 StageBP Value Normal<120 / 80 Pre-hypertensive121 –139 / 81 – 89 Stage 1140 – 159 / 90 – 99 Stage 2160 – 179 / 100– 109

9. Which of the following should be addressed today? 9 R/O Obstructive Sleep Apnea R/O Thyroid diseaseDiet Exercise

10. Assessment Approach in HTN  Rule out secondary causes  OSA  Thyroid disease  Drug use  Vitals  BP, HR, Wt, Pain  Urine protein  Chem 7 + eGFR  SCr, BUN, Glucose  Lipid panel  12 lead EKG  Possibly TSH 10

11. 11 Secondary causesSBP Change (mmHg) DBP Change (mmHg) Obstructive Sleep Apnea3.4-9.53.3-10.5 Hypothyroid13-37.58-21 Hyperthyroid5 Diet8-14 Physical Inactivity4-9 Weight (-10lb)5-20 Becker et al. Circulation 2003; 107:68-73. Pepperell et al. The Lancet. 2002;359:204-209. Demellis et al. Am Heart J. 2002; 143:718-24. Iglesias P et al. Clin Endocrinol 2005; 63:66-72. JNC 7. www.nhlbi.nih.govwww.nhlbi.nih.gov

12. Combining Sodium Reduction and DASH 12 Sacks F, et al. N Eng J Med 2001; 344: 3-10

13. Which medication(s) should be started? 13 Chlorthalidone Beta blocker Dihydropyridine CCB + ACEI HCTZ + ACEI

14. Why not maximize a single agent first?  Blood pressure reduction is greater (additive) when drugs are combined compared to titrating the dose  Most classes exhibit a poor dose response relationship  Gain 1/5 of initial response  Blood pressure goals achieved faster  Lower risk of ADRs compared to dose titration of a single agent 14 Wald DS, et al. Am J Med. 2009; 122:290-300 Law MR, et al. BMJ 2003; 326:1427-34. Gradman AH, et al. JASH 2010; 4:42-50.

15. Initial Combinations  Preferred combinations  ACE inhibitor / diuretic ▪ ACEI inhibitor / CCB  ARB / diuretic ▪ ARB / CCB  Start with ½ of standard dose  Continue home BP monitoring  Reassess every 2-4 weeks  Telecare or pt visit 15 Wald DS, et al. Am J Med. 2009; 122:290-300 Law MR, et al. BMJ 2003; 326:1427-34. Gradman AH, et al. JASH 2010; 4:42-50.

16. Kay Jin, 66 yoa female with HTN, COPD, and OA  Exercise:  Walks 35 min. daily  Diet:  Low sodium, high in fruits and vegetables, lean meats  SH:  Denies tobacco X 10 yrs  5 oz wine daily  Current Cardiac Medications:  Felodipine 10 mg daily  Lisinopril 40mg daily  HCTZ 25mg daily  ASA 81mg daily  Vitals  150/86 today  148/88 last week  142-154/82-88 at home  HR 64-72  Wt 140 lbs, BMI 25

17. Think – Pair - Share  Take 5 minutes to develop an assessment and plan for this patient  What is your assessment?  Stage the HTN  What is your tentative plan?  What lifestyle modifications do you recommend?  What labs do you want?  What referrals or tests are needed?  What therapy would you consider?  Time permitting – share you’re Assessment and Plan with your neighbor 17

18. Which defines “Resistant HTN”? 18 Uncontrolled BP despite 2 or more medications Uncontrolled BP despite 3 or more medications Controlled BP on > 4 medications Uncontrolled BP despite 2 or more medications Uncontrolled BP despite 3 or more medications Controlled BP on > 4 medications Calhoun D, et al. Hypertension 2008; 51:1403-1419.

19. Causes of Resistant Hypertension  Nonadherence  Diet  Medications / dietary supplements  Obstructive Sleep Apnea  Thyroid disease  Chronic Kidney Disease (Stage > 4)  Primary Aldosteronism  Cushings  Renal Artery Stenosis  Coarctation of the Aorta  Pheochromocytoma 19

20. How should one manage Resistant HTN? (150/86 today; 148/88 last week; 142-154/82-88 at home) 20 Send patient for labs, renal US, etc Switch HCTZ to chlorthalidone Give trial of spironolactone Add a 4 th antihypertensive of any kind 1 2 2

21. HCTZ vs Chlorthalidone Chlorthalidone 25mg (mmHg) n=14 HCTZ 50mg (mmHg) n=16 Office readings Wk 2*-15.7 ± 2.2-6.1 ± 1.9-4.5 ± 2.1-2.9 ± 1.7 Wk 6-19.6± 3.4-10.8 ± 3.5 Wk 8-17.1 ± 3.7-10.8 ± 3.5 21 Hypertension 2006; 47: 352-8. *p<.05

22. Which of the following statements accurately describe HCTZ? Majority of BP lowering effect is seen w/ 12.5mg HCTZ exhibits a flat dose response curve BP lowering increases significantly up to 50mg HCTZ may not provide full 24 hour coverage 22

23. How should one manage Resistant HTN? (150/86 today; 148/88 last week; 142-154/82-88 at home) 23 Send patient for labs, renal US, etc Switch HCTZ to chlorthalidone Give trial of spironolactone 1 2 2

24. Adding Spironolactone Baseline BP (mmHg) Median dose mg (range) Office Mean (95% confidence interval) 24 hr Ambulatory Monitoring Mean (95% confidence interval) De Souza et al 2010 n=175 169 ± 2750 (25-100) -14 (9-18) -7 (4-9) -16 (13-18) -9 (4-9) ASCOT-BPLA n=1411 156.9/85.3 41 ± 25-21.9 (20.8-23) -9.5 (9-10.1) 24 De Souza F, et al. Hypertension 2010; 55: 147-52. Chapman N, et al. Hypertension 2007; 49: 839-45.

25. Summary  Rule out patient factors / common secondary causes  Consider switch to chlorthalidone  Consider trial of spironolactone vs. laboratory testing 25

26. Flor D. Lee, 82 yo female referred to you for HTN management. Started on amlodipine 2.5mg 2 weeks ago.  PMH: HTN, OA  Current medications:  ASA 81 mg daily  Chlorthalidone 12.5 mg daily  Amlodipine 2.5mg daily  Acetaminophen 650mg TID  Diet:  1500 kcal diabetic diet at local assisted living  Exercise:  Chair exercises at local assisted living  Vitals:  146/78 today  158/84 2 weeks ago  142-150/72-80 home 26

27. Think – Pair - Share  Take 2 minutes to develop an assessment and plan for this patient  What is your assessment?  Stage the HTN  Define your blood pressure goals  What is your tentative plan?  What lifestyle modifications do you recommend?  What therapy would you consider?  Time permitting – share you’re Assessment and Plan with your neighbor 27

28. Which best describes the BP goal for Flor D. Lee? 28 <130/80 mmHg <140/90 mmHg <150/80 mmHg <160/90 mmHg

29. Trials in the Elderly 29 TrialMean AgeISHMean BP SHEP72 (60 to > 80) Y144/68 Sys-Eur70 (> 60) Y151/79 VALISH76 (70-84) Y137/75 STOP76 (70-84) N157/87 MRCOA70 (65-74) N152/77 JAMA 1991;265:3255–64. Lancet 1997; 350(9080):757-64. Hypertension. 2010; 56: 196-202. Blood Press. 2004;13(3):137-41. BMJ. 1992 Feb 15;304(6824):405-12.

30. Hypertension in the Very Elderly (HYVET; n=3845) Rate per 1000 patient-years TreatmentPlaceboHR (95% CI) Stroke12.417.7.7 (.49-1.01) Stroke mortality6.510.7.61 (.38-.99) Any cardiovascular event 33.750.6.66(.53-.82) Total mortality47.259.6.79 (.65-.95) 30 Beckett NS, et al. NEJM 2008; 358:1887-98.

31. Hypertension in the Very Elderly (HYVET; 3845) Sitting Blood Pressure TreatmentPlacebo Baseline173 ± 8.4173 ± 8.6 At 2 years143.5 ± 15.4158.5 ± 13.5 Baseline90.8 ± 8.490.8 ± 8.5 At 2 years77.9 ± 9.584 ± 10.5 31 Beckett NS, et al. NEJM 2008; 358:1887-98.

32. Which best describes the BP goal for Flor D. Lee? 32 <140/90 mmHg <150/80 mmHg <160/90 mmHg

33. Which best describes the BP goal for Flor D. Lee? American Heart Association: Target SBP 130 mmHg 33 American Heart Association: Target SBP 130 Aronow WS, et al. J Am Coll Cardiol, 2011; 57:2037-2114.

34. J-Curve for Diastolic Blood Pressure  Risk increases with DBP < 60-65-70 mmHg  American Heart Association  Keep DBP > 65mmHg 34 Safar H, et al. HTN 2007; 50: 172-180. Fagard RH, et al. Arch Intern Med. 2007;167(17):1884-1891. Aronow WS, et al. J Am Coll Cardiol, 2011; 57:2037-2114.

35. Summary  In Stage 2 or higher, consider combination therapy using low doses  When titrating, consider combining therapies prior to maximizing dose  Rule out common secondary causes prior to treating hypertension  Consider spironolactone for resistant hypertension  Consider the evidence when establishing the BP target for the very elderly 35

36. JNC 8 update from AHA 1.Does initiating antihypertensive pharmacological therapy at specific BP thresholds improve health outcomes? When should you initiate treatment? 2. Does treatment with an antihypertensive pharmacological therapy to a specified BP goal lead to improvements in health outcomes? How low should you go? 3. Do various antihypertensive drugs or drug classes differ in comparative benefits and harms on specific health outcomes? How do you get there? Only using RCT evidence……. http://www.theheart.org/article/1310865.do 36