1. Making Sense of the New Guidelines: Hypertension The More We Learn, the Less We Know Zeb K. Henson, M.D. Assistant Professor, Department of Medicine & Department of Pediatrics University of Mississippi Medical Center

2. Financial Disclosures Nothing to disclose

3. Objectives “Don’t run back inside, Darling, you know just what I’m here for…” Briefly review 2014 JAMA HTN Guidelines Use clinical scenarios to discuss and provide justification for some of these recommendations Discuss clinical barriers to implementation of these guidelines

4. JNC 7 Review Issues addressed in JNC-7 Prevalence and Burden Measurement Definition Lifestyle and Pharmacologic Treatment Secondary Hypertension Resistant Hypertension JNC-7 Classifications of HTN:

5. Lifestyle Modifications Not at goal BP <140/90, or <130/80 for diabetes, CKD or CAD, or <120/80 for LV dysfunction Initial Drug Choices Compelling Indications No Compelling Indications Stage 1 HTN 1. Thiazides for most 2. Consider ACEI, ARB, BB, CCB or combo Stage 2 HTN Two-drug combo for most; usually thiazide and ACEI, ARB, BB, or CCB Drugs for compelling indications; others as needed

6. “Compelling Indications”

7. 2003 2014 JNC-7JNC-8 2005 2007 2009 2011 REIN-2 ESH/ESC AHA ACCOMPLISH ONTARGET HYVET ACCORD-BP NICE ACCF/AHA ESH/ESC ASH/ISH CAMELOT ALTITUDE Growing Up

8. The story of the committee…

9. End Result

10. It’s not JNC 7; nor was it ever meant to be. It’s “the facts” of what we have learned from RCTs.

11. 2014 JAMA HTN Guidelines Clinical Questions 1.“In adults with hypertension, does initiating antihypertensive pharmacologic therapy at specific BP thresholds improve health outcomes?” 2.“In adults with hypertension, does treatment with antihypertensive pharmacologic therapy to a specified BP goal lead to improvements in health outcomes?” 3.“In adults with hypertension, do various antihypertensive drugs or drug classes differ in comparative benefits and harms on specific health outcomes?”

12. RecommendationLevel of Evidence 1. General population > 60 y/o, initiate medications and treat to BP goal of 150/90 mmHg. A 2. General population < 60 y/o, initiate medications and treat to DBP goal of 90 mmHg. A/E 3. General population < 60 y/o, initiate medications and treat to SBP goal of 140 mmHg. E 4. In population > 18 y/o with CKD, initiate medications and treat to BP goal of 140/90 mmHg. E 5. In population > 18 y/o with DM, initiate medication and treat to BP goal of 140/90 mmHg. E 2014 JAMA Hypertension Guideline Recommendations

13. RecommendationLevel of Evidence 6. In nonblack population (including DM), initial anti-hypertensive therapy should consist of thiazide diuretic, CCB, ACE-I or ARB. B 7. In general black population (including DM), initial anti-hypertensive therapy should include thiazide diuretic or CCB. C 8. In population with CKD, initial (or add-on) anti-hypertensive therapy should include ACE-I or ARB. B 9. Main objective of therapy is to attain and maintain a BP goal and can be accomplished in one of two ways if not accomplished with initial therapy: 1. Increase dose of initial agent. 2. Add a second or, eventually, third agent from above list. ACE-I and ARB should not be used in combination. Other agents may be necessary if goal BP cannot be attained or maintained from above list. E 2014 JAMA Hypertension Guideline Recommendations

14. Date of download: 6/17/2014 Copyright © 2014 American Medical Association. All rights reserved. From: 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 Guideline Comparisons of Goal BP and Initial Drug Therapy for Adults With Hypertension Figure Legend :

15. A 67 year old male presents to your primary care clinic having recently moved to town. He has no complaints. His PMHx includes high cholesterol (with an unknown LDL) for which he takes Simvastatin 10mg. He had one prior hospitalization for chest pain, but was told “nothing was wrong” with his heart after a 1 night hospital stay. He has a 15 pck-yr history of tobacco use and quit 17 years ago. He swims regularly and abides by a strict Mediterranean diet. On exam, his BP = 146/86 (repeated to verify) and other vital signs are normal. His cardiovascular and eye exam are unremarkable. Lab studies reveal a normal CBC, normal serum creatinine, and no proteinuria. His EKG exhibits voltage criteria for LVH. How would you manage his BP (assume his reading is verified by home monitoring)? A.Encourage more exercise and a better diet B.Order 24 hr ambulatory monitoring and decide therapy based on those results C.Begin therapy with a thiazide-type diuretic D.Inform him that based on new guidelines, no anti-hypertension therapy is needed E.Let him decide if he wants to take medicines

16. Closer Look What do we do with HTN in the elderly? (Better yet, who is elderly?) RecommendationLevel of Evidence 1. General population > 60 y/o, initiate medications and treat to BP goal of 150/90 mmHg. A

17. HTN in the Elderly Comparison: – 2014 JAMA: > 60 y/o = < 150/90 – ESH/ESC: >80 y/o or elderly < 80 y/o = < 150/90 – CHEP: >80 y/o = < 150/90 – NICE: > 80 y/o = < 150/90 – ASH/ISH: > 80 y/o = < 150/90

18. Closer Look **No convincing evidence that 140/90 is too low** Corollary RecommendationLevel of Evidence 1. General population > 60 y/o, if treatment results in BP < 140/90 mmHg and is well-tolerated, treatment does not need to be adjusted E

19. HTN in the Elderly Advantages Decreased medication burden Evidence-”proven” Disadvantages Individual consequences Population consequences

20. Medical Education & Information – for all Media, all Disciplines, from all over the World Powered by 2013 ESH/ESC Guidelines for the management of arterial hypertension The Task Force for the management of arterial hypertension of the European Society of Hypertension (ESH) and of the European Society of Cardiology (ESC) - J Hypertension 2013;31:1281-1357 Clinical scenarioRecommendations Elderly patients with SBP ≥160 mmHgReduce SBP to 140-150 mmHg Fit elderly patients aged <80 years with initial SBP ≥140 mmHg Consider antihypertensive treatment Target SBP: <140 mmHg Elderly >80 years with initial SBP ≥160 mmHgReduce SBP to 140-150 mmHg providing in good physical and mental condition Frail elderlyHypertension treatment decision at discretion of treating clinician, based on monitoring of treatment clinical effects Continuation of well- tolerated hypertension treatment Consider when patients become octogenarians All hypertension treatment agents are recommended and may be used in elderly Diuretics, CCBs, preferred for isolated systolic hypertension Hypertension treatment in the elderly SBP, systolic blood pressure; CCB, calcium channel blockers.

21. What would I do? A.Encourage more exercise and a better diet B.Order 24 hr ambulatory monitoring and decide therapy based on those results C.Begin therapy with a thiazide-type diuretic D.Inform him that based on new guidelines, no anti-hypertension therapy is needed E.Let him decide if he wants to take medicines

22. A 43 y/o woman with HTN returns for a follow up visit of her BP. She is without complaints but admits that she has gained about 15 pounds over the last year due to stress, poor diet, and inactivity. At her last visit 6 months ago, her BP was 132/78 mmHg on Lisinopril HCTZ 20/12.5mg. On exam today, her BP is 138/88 (and verified on repeat). Her exam is unchanged. Her serum creatinine is 1.3 mg/dL, and her RUA reveals > 500 mg/dL of proteinuria. What would be your next step in managing her blood pressure and proteinuria? A.Encourage improved lifestyle adherence and weight reduction but make no medication changes B.Increase her thiazide diuretic C.Increase her ACE-inhibitor D.Increase both her ACE-I and her TZD

23. Closer Look Comparison: – ESH/ESC: no proteinuria = < 140/90 with proteinuria = < 130/90 -- CHEP: < 140/90 for all -- KDIGO: no proteinuria = < 140/90 with proteinuria = < 130/80 RecommendationLevel of Evidence 4. In population > 18 y/o with CKD, initiate medications and treat to BP goal of 140/90 mmHg. E

24. Why the confusion? RCTs Modification of Diet in Renal Disease (MDRD) African-American Study of Kidney Disease and Hypertension (AASK) Ramipril Efficacy in Nephropathy (REIN-2) Meta-analyses Annals of Internal Medicine (2011) Canadian Medical Association Journal (2013) VS.

25. What would I do? A.Encourage improved lifestyle adherence and weight reduction but make no medication changes B.Increase her thiazide diuretic C.Increase her ACE-inhibitor D.Increase both her ACE-I and her TZD Nothing beyond “expert opinion” to govern specific medication titration.

26. A 43 y/o AAM w/ Type 2 DM and HTN, presents for follow up. His is asymptomatic and adherent to his medication regimen: Metformin 500mg BID, Lis/HCT 20/25mg daily, Amlodipine 5mg, and ASA 81mg. On exam, his BP = 138/88 mmHg. His cardiovascular exam is normal. He has decreased pinprick sensation in his bilateral great toes. Peripheral pulses are normal. On lab review, his CBC, BMP, and RUA are normal. His A1c=8.3%. In addition to adjusting his Type 2 DM medication regimen, what additional changes would you make? A.None B.Increase Amlodipine to 10mg C.Increase Lisinopril to 40mg D.Add an additional BP agent, such as a beta-blocker

27. Closer Look Comparison: – ESH/ESC: < 140/85 – ASH/ISH: < 140/90 – CHEP: < 130/80 – ADA: < 140/80 RecommendationLevel of Evidence 5. In population > 18 y/o with DM, initiate medication and treat to BP goal of 140/90 mmHg. E

28. Why the confusion? Not enough patients Not enough uniformity in evidence Therefore, did not make recommendation different than “usual” BP control

29. What would I do? A.None B.Increase Amlodipine to 10mg C.Increase Lisinopril to 40mg D.Add an additional BP agent, such as a beta-blocker Nothing beyond “expert opinion” to govern specific medication titration.

30. The “other” recommendations…

31. Closer Look Too many comparisons to list RecommendationLevel of Evidence 6. In nonblack population (including DM), initial anti-hypertensive therapy should consist of thiazide diuretic, CCB, ACE-I or ARB. B 7. In general black population (including DM), initial anti-hypertensive therapy should include thiazide diuretic or CCB. C 8. In population with CKD, initial (or add-on) anti-hypertensive therapy should include ACE-I or ARB. B

32. What’s the controversy? “Demotion” of beta-blockers – Admittedly doesn’t include newer agents “Demotion” of ACE-I and ARBs in African- Americans – Unless CKD Absence of a specific recommendation for ACE-I and ARBs in Diabetics – In absence of albuminuria

33. RecommendationLevel of Evidence 1. General population > 60 y/o, initiate medications and treat to BP goal of 150/90 mmHg. A 2. General population < 60 y/o, initiate medications and treat to DBP goal of 90 mmHg. A/E 3. General population < 60 y/o, initiate medications and treat to SBP goal of 140 mmHg. E 4. In population > 18 y/o with CKD, initiate medications and treat to BP goal of 140/90 mmHg. E 5. In population > 18 y/o with DM, initiate medication and treat to BP goal of 140/90 mmHg. E 2014 JAMA Hypertension Guideline Recommendations

34. RecommendationLevel of Evidence 6. In nonblack population (including DM), initial anti-hypertensive therapy should consist of thiazide diuretic, CCB, ACE-I or ARB. B 7. In general black population (including DM), initial anti-hypertensive therapy should include thiazide diuretic or CCB. C 8. In population with CKD, initial (or add-on) anti-hypertensive therapy should include ACE-I or ARB. B 9. Main objective of therapy is to attain and maintain a BP goal and can be accomplished in one of two ways if not accomplished with initial therapy: 1. Increase dose of initial agent. 2. Add a second or, eventually, third agent from above list. ACE-I and ARB should not be used in combination. Other agents may be necessary if goal BP cannot be attained or maintained from above list. E 2014 JAMA Hypertension Guideline Recommendations

35. Concluding Remarks Five of 10 recommendations are “E” Only deals with one risk factor—BP No recommendation to decrease medicines in well-controlled elderly More recommendations to come – AHA/ACC Guidelines – SPRINT

36. Their own conclusions “The relationship between naturally occurring BP and risk is linear down to very low BP, but the benefit of treating to these lower levels with antihypertensive drugs is not established.” “These lifestyle treatments have the potential to improve BP control and even reduce medication needs…we support the recommendations of the 2013 Lifestyle Work Group.”

37. Their own conclusions “The recommendations from this evidence-based guideline from panel members appointed to the Eighth Joint National Committee (JNC 8) offer clinicians an analysis of what is known and not known about BP treatment thresholds, goals, and drug treatment strategies to achieve those goals based on evidence from RCTs. However, these recommendations are not a substitute for clinical judgment, and decisions about care must carefully consider and incorporate the clinical characteristics and circumstances of each individual patient.”