1. Hypertension: what is new…and old GREG FOTIEO, MD

2. Objectives  Background  Review JNC 8 Recommendations through clinical cases  Discuss concerns about JNC 8  Figure out how to apply JNC 8 to your practice (hopefully)

3. Prevalence  1/3 of adults  About 60 million hypertensives in the US  Most common chronic condition seen in primary care  Most common risk factor for heart attack and stroke  Prevalence increases with increasing age

4. Why worry?  There is a strong relationship between blood pressure and the risk of CV events, strokes and kidney disease  The risk is lowest at 115/75 and for each increase of 20 mm in SBP or 10 mm in DBP the risk of major CV event or stoke doubles  Treatment of hypertension has been shown to reduce risk of adverse CV outcomes by 20-25% and stroke by 30- 40%

5. How are we doing?  Not so good  2005-8 NHANES survey found only 46-51% of persons with HTN had their blood pressure controlled <140/90.

6. JNC HISTORY  JNC 1: published 1976  JNC 2: published 1980  JNC 3: published 1984  JNC 4: published 1988  JNC 5: published 1992  JNC 6: published 1997  JNC 7: published 2003  JNC LATE

8. Questions Addressed by the JNC 8 Panel 1. In adults with hypertension, does initiating antihypertensive pharmacologic therapy at specific BP thresholds improve health outcomes? Thresholds 2. In adults with hypertension, does treatment with antihypertensive pharmacologic therapy to a specified BP goal lead to improvement in health outcomes? Targets 3. In adults with hypertension, do various antihypertensive drugs or drug classes differ in comparative benefits and harms on specific health outcomes? Impact of drugs

9. The 9 Recommendations  Recommendations 1-5 address thresholds and goals for BP treatment.  Recommendations 6-8 address selection of antihypertensive drugs.  Recommendation 9 is a summary of strategies based on expert opinion for starting and adding antihypertensive drugs.

10. Case #1  A 72 yo Caucasian man with HTN, COPD, BPH and a history of prostate cancer s/p radical prostatectomy presents for routine f/u. He feels well except for SOB with heavy exertion that responds to his albuterol inhaler. His BP is 118/78. He is currently on albuterol MDI prn, Lisinopril 10 mg qday, and HCTZ 12.5 mg qday. His labs are unremarkable. What should you do with his hypertensive regimen?

11. RECOMMENDATION 1  In the general population aged ≥60 years, initiate pharmacological treatment to lower BP at SBP of ≥150 mm Hg or DBP of ≥ 90mm Hg and treat to a goal SBP < 150 mm Hg and DBP <90 mmHg.  Strong recommendation – Grade A.

12. Basis  Treating to goal SBP of 150 decreases stroke, heart failure, and CV events  Decreasing goal SBP to 140 provides no additional benefit  Trials used  HYVET  Syst-Eur (The Systolic Hypertension in Europe Trial)  SHEP (Systolic Hypertension in the Elderly Program)  JATOS (Japanese Trial to assess Optimal Systolic blood pressure in elderly hypertensive patients)  VALISH (VALsartan in elderly Isolated Systolic Hypertension Study)  CARDIO-SIS

13. Corollary Recommendation  In the general population aged ≥ 60 years, if pharmacological treatment for high BP results in lower achieved SBP (for example <140 mm Hg) and treatment is not associated with adverse effects on health or quality of life, treatment does not need to be adjusted.  Expert opinion – Grade E.

14. Case #2  A 44 yo Asian man with asthma, obesity, and OSA presents for new patient visit. He has no complaints but is concerned about his blood pressure. His last doctor told him that he did not need any medications but needed to exercise and lose weight. He brings in a log of home BP readings for the last 6 months in the range of 120-140/ 86-104. He has a BMI of 32. His BP is 132/98 and 138/100 on repeat. He is currently on fluticasone MDI, albuterol MDI prn, and uses his CPAP nightly. His labs are unremarkable. How would you approach his BP?

15. RECOMMENDATION 2  In the general population < 60 years, initiate pharmacological treatment to lower BP at DBP of ≥90 mmHg and treat to a goal DBP of lower than 90 mmHg.  For ages 30-59 years, Strong recommendation - Grade A.  For ages 18-29 years. Expert opinion –grade E.

16. Basis  Treating to goal DBP of 90 decreases stroke, heart failure, and overall mortality  Setting goal DBP <90 provides no additional benefit  Trials used  HDFP (Hypertension Detection and Follow uP)  Hypertension – Stroke Cooperative  MRC  ANBP  VA Cooperative  HOT

17. What if he had a BP of 154/80?

18. RECOMMENDATION 3  In the general population younger than 60 years, initiate pharmacological treatment to lower BP at SBP of ≥140 mm Hg and treat to a goal SBP of < 140 mm Hg.  Expert opinion – Grade E

19. Basis  In the absence of any RCTs that compared the current SBP standard of 140 mm Hg with another higher or lower standard in this age group, there was no compelling reason to change current recommendations.  In the DBP trials, many of the study participants who achieved target DBP were also likely to have achieved SBP <140 mmHg with Rx. It was not possible to determine the outcome benefits were due to lowering of DBP, SBP or both.

20. RECOMMENDATION 6  In the general nonblack population, including those with diabetes, initial antihypertensive treatment should include a thiazide-type diuretic, calcium channel blocker (CCB), angiotensin- converting enzyme inhibitor (ACEI),or angiotensin receptor blocker(ARB).  Moderate recommendation –Grade B.

21. Basis  Only used RCT comparing one class of antihypertensives to another  Each of the 4 drug classes yielded comparable effects on overall mortality and CV, cerebrovascular and kidney outcomes.  Do not recommend β blockers because of increased risk of CVA in one study.

22. Case #3  A 22 yo Hispanic man with a history of HTN and CKD presents for routine f/u. He feels well and has been adherent to his regimen of furosemide 20 mg and amlodipine 10 mg. His BP is 148/78. His labs are significant for a K+ 4.6, creatinine 1.74 and GFR of 39. What should you do with his hypertensive regimen?

23. RECOMMENDATION 4  In the population aged 18 years or older with CKD, initiate pharmacological treatment to lower BP at SBP of ≥ 140 mm Hg or DBP of ≥ 90 mmHg and treat to goal SBP of < 140 mm Hg and DBP < 90 mm Hg.  Expert opinion – grade E. (Younger <70 yrs. with eGFR or measured GFR <60 ml/min/1.73m2 People of any age with albuminuria >30mgalb/g of creatinine)

24. Basis  In patients with CKD, no trials showed benefit in CV or cerebrovascular outcomes, mortality, or progression of renal disease by lowering BP below 140/90  There is no evidence to make a recommendation about BP goal in patients over 70 with GFR <60.

25. RECOMMENDATION 8  In the population aged 18 years or older with CKD and hypertension, initial (or add-on) antihypertensive treatment should include ACEI or ARB to improve kidney outcomes. This applies to all CKD patients with hypertension regardless of race or diabetes status.  Moderate Recommendation – Grade B.

26. Basis  This recommendation is based mainly on kidney outcomes because there is less evidence for CV outcomes in patients with CKD.  AASK study showed the benefit of an ACEI on kidney outcomes in black patients with CKD and provides additional evidence that supports ACEI use in that population.

27. Case #4  A 52 yo Hispanic man with a history of DM schedules an appointment with you because his friends told him that he should be on a BP medication since he has DM. His current meds are metformin, ASA, atorvastatin, and glargine. BP reading is 138/88. Labs show GFR 78, no microalbumin, and HgA1c 6.8%. Do his friends know what they are talking about?

28. RECOMMENDATION 5  In the population aged 18 years or older with diabetes, initiate pharmacological treatment to lower BP at SBP of ≥ 140 mm Hg or DBP of ≥90 mm Hg and treat to a goal SBP < 140 mm Hg goal DBP < 90 mm Hg  Expert opinion Grade E.

29. Basis  Evidence that treating to a SBP <150 improves CV and cerebrovascular outcomes in patients with DM.  No RCT compared goal of 140 to 150 in patients with DM.  Recommend goal <140/90 to be consistent with BP goal in general population younger than 60.

30. What if he had a BP of 154/80?

31. RECOMMENDATION 6  In the general nonblack population, including those with diabetes, initial antihypertensive treatment should include a thiazide-type diuretic, calcium channel blocker (CCB), angiotensin- converting enzyme inhibitor (ACEI),or angiotensin receptor blocker(ARB).  Moderate recommendation –Grade B.

32. Case #5  A 62 yo African-American man with DM presents for routine f/u. His DM is poorly controlled on glipizide and metformin. His home BP readings have been in the 150-160/80-95 range. His BP is 170/92. His HgA1c is 9.2 and his GFR is 78. How will you deal with his BP?

33. RECOMMENDATION 7  In the general black population, including those with diabetes, initial antihypertensive treatment should include a thiazide – type diuretic or CCB.  For general black population: Moderate Recommendation –Grade B.  For black patients with diabetes: Weak recommendation – Grade C.

34. Basis  ALLHAT  A thiazide type diuretic was shown to be more effective in improving vascular outcomes compared to an ACEI in the black subpatient group(diabetic and non diabetics).  Thiazide type diuretics and CCB were found to have no difference in vascular outcomes.  51% higher rate of stroke in black patients on ACEI vs CCB.  ACEI are less effective than CCB in lowering BP

35. What if his GFR was 40?

36. RECOMMENDATION 8  In the population aged 18 years or older with CKD and hypertension, initial (or add-on) antihypertensive treatment should include ACEI or ARB to improve kidney outcomes. This applies to all CKD patients with hypertension regardless of race or diabetes status.  Moderate Recommendation – Grade B.

37. Case #5 continued  You start the patient on chlorthalidone 12.5 mg. When should you follow up with him?

38. RECOMMENDATION 9 If goal BP is not reached within a month of treatment, increase the dose of the initial drug or add a second drug from one of the classes in recommendation 6 (thiazide- type diuretic, CCB, ACEI, ARB). If goal BP cannot be reached with 2 drugs, add and titrate a third drug from the list provided. Do not use an ACEI and ARB together in the same patient. If goal BP cannot be reached using the drugs in recommendations, because of a contraindication or the need of > 3 drugs to reach goal BP, antihypertensive drugs from other classes can be used. Referral to a hypertension specialist if not controlled with this strategy.  Expert opinion –Grade E.

39. To Summarize….

40. Not everyone agrees

41. Dissention within JNC 8  5 members voiced exception to the recommendation to increase the target SBP from 140 to 150 mm Hg in patients over age 60  "The majority [of the JNC 8 panel] embraced the view that in the absence of definitive evidence, increasing the SBP goal was the optimum approach [in patients 60 or older]. We, the panel minority, believed that evidence was insufficient to increase the SBP goal from its current level of less than 140 mm Hg because of concern that increasing the goal may cause harm by increasing the risk for CVD and partially undoing the remarkable progress in reducing cardiovascular mortality in Americans older than 60 years.“

42. Other concerns  No cohort data, systematic reviews or meta-analysis included in review  Used trial data up to 2009 and a bridge search to 2013  Despite the goal to be evidence based  Only 2 recommendations were Grade A  4 recommendations were based on expert opinion  Recent European, Canadian, UK, ACC/AHA, and ASH/ISH guidelines favor SBP goal of 140 up to age 80  Mixed Messages  New cholesterol guidelines:  treat more people  abandon targets  New HTN guidelines:  treat less people  specify treatment targets

43. Cochrane Review: The other side of the coin

44. What do you think about JNC 8?