Objectives. Describe results and implications of recent landmark hypertension trials

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1 Hypertension Update Daniel Schwartz, MD Assistant Professor of Medicine Associate Medical Director of Heart Transplantation Temple University School of Medicine

2 Disclosures I currently have no relationships of any kind with any company whose products or services in any way relate to the practice of medicine, medical education or research.

3 Objectives Following this presentation, participants should be able to: Describe evidence-based guideline recommendations for screening and treatment of high blood pressure Describe results and implications of recent landmark hypertension trials Apply an evidence-based approach to the management of hypertension With attention to specific risk factors or populations

4 Background US Adults Prevalence > 20yo 33% 80 million > 60yo 65% Of those with High Blood Pressure 83% are aware of diagnosis 77% are treated 54% are controlled Risk factor for CV morbidity and mortality #1 cause of death in women, #2 for men (versus other dietary, lifestyle and metabolic risks smoking #1 for men) Mozaffarian D et al, Circulation 2015

5 Guidelines - Screening USPSTF 2015 adopted by AAFP Risk factors: High-normal BP Overweight or obese African American Confirm out of office Interval: >40 y and risk: annually 18-39y, no risk factors: q3-5 years Siu AL et al, Annals Int Med 2015

6 Screening Ambulatory BP Monitoring Predicts end organ dysfunction and CV events better in than in office Used to confirm a diagnosis of HTN Can clarify white coat HTN (lower at home) masked HTN (higher at home) non-dippers (higher at night) Consider for: Episodic HTN Treatment response Resistant HTN Hypotensive symptoms Autonomic dysfunction

7 Guidelines JNC7 Shrout T et al, Current Opinion Pharmacology 2017

8 Guidelines JNC8 In adults with HTN 1. Does initiating therapy at specific BP threshold improve outcome? 2. Does treatment to specified BP goal improve outcome? 3. Do various drugs/classes differ in outcomes? James PA et al, JAMA 2014

9 Guidelines JNC y initiate and treat to <150/90 2. <60y initiate and treat to <140/90 Regardless of comorbidities 3. Initial therapy with: ACE-I, ARB, CCB, TD. BB no longer 1 st line. 4. In black population: CCB or TD James PA et al, JAMA 2014 Shrout T et al, Current Opinion Pharmacology 2017

10

11 Guidelines JNC8 Simpler but controversial Raising BP goal for elderly What is the evidence? Leaves out many (~6million treatment eligible) No racial or gender considerations in the age change worse effect on these populations? All Beta blockers created equal?

12 Trial Evidence Focus on Special Populations Elderly Diabetes Black Intermediate Risk

13 HTN in the Elderly JNC8 Recommendation 1 In the general population aged 60 years, initiate pharmacologic treatment to lower blood pressure at systolic blood pressure 150 mm Hg or diastolic blood pressure 90 mm Hg and treat to a goal SBP <150 mm Hg and goal DBP <90 mm Hg Corollary Recommendation In the general population aged 60 years, if pharmacologic treatment for high BP results in lower achieved SBP (eg, <140 mm Hg) and treatment is well tolerated and without adverse effects on health or quality of life, treatment does not need to be adjusted. (Expert Opinion Grade E)

14 HTN in the Elderly Cochrane Review from 2009: Treating patients to lower than standard BP targets, / mmhg, does not reduce mortality or morbidity But HYVET trial SHEP trial SPRINT trial Recent meta-analysis

15 January, 2014

16 HYVET trial Aged >80y, SBP > 160 Indapamide +/- perindopril vs. placebo At 2 years, reductions in stroke (not statistically significant), HF and all cause death Beckett NS et al, NEJM 2008

17 SHEP trial Aged >60y, SBP >160 (isolated systolic) Stepped treatment, starting with Chlorthalidone (then BB) At 5 years, 36% reduced stroke rate and 32% reduction in CV disease SHEP Trial group, JAMA 1991

18 SPRINT trial Age >50y, SBP Intensive goal (<120) vs. standard (<140) Any drugs Primary outcome: First occurrence of MI, ACS, stroke, HF, or CV mortality Participants Age >75y only 28% Mean SBP % on some HTN med at start Results: Intensive BP lowering in high risk patients reduced CV events and all cause death Beckett NS et al, NEJM 2008

19 SPRINT trial Beckett NS et al, NEJM 2008

20 SPRINT trial No differences across subgroups Beckett NS et al, NEJM 2008

21 SPRINT trial Caveats BP measuring technique Unattended, automated Not applicable to real-world? Diabetics excluded No stroke reduction More adverse events with intensive HF reduction Uptitration of diuretics masking HF? Why 120mmHg? Beckett NS et al, NEJM 2008

22 Meta -Analysis 4 major trials included JATOS, VALISH, Wei et al, and SPRINT- SENIOR (SPRINT subjects >75y) Age >65y Intensive vs. standard Reductions in MACE, CV mortality and HF were shown Possible risks, however Also remember: many trials exclude those with DM, CKD, prior stroke. SPRINT also did not include Nursing Home residents. Bavishi C et al, JACC 2017

23 HTN in Diabetes ACCORD Trial SBP 120 vs. 140mmHg in Diabetes Inclusion: Diabetics with A1c 7.5% SBP Age 40 yrs with CVD or 55 yrs with CV features or risk factors Exclusion: BMI >45, creatinine > 1.5 The ACCORD Study Group, NEJM 2010

24 ACCORD trial - results Good BP lowering No reduction in MI, stroke or CV death Reduction in stroke minimal (<1%/year) The ACCORD Study Group, NEJM 2010

25 ACCORD trial - results Increased adverse events The ACCORD Study Group, NEJM 2010

26 HTN in black population JNC8 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)

27 HTN in black population HTN rates higher, presents earlier, more severe compared to whites Incidence and prevalence of CV and renal disease higher than other ethnicity/races

28 ALLHAT Trial Double blind, RCT comparing CV outcomes with Lisinopril Amlodipine Chlorthalidone (Doxasozin) Age >55, BP >140/90 Results: No difference for MI/CHD death, but TD better than CCB for HF TD better than ACE-I for CVD, stroke, HF ALLHAT Research Group, JAMA 2002

29 ALLHAT race subgroup follow-up Blacks had higher stroke, ESRD and mortality BP was lowered in Blacks by all meds (less by ACE-I) No difference across meds for outcome except HF with CCB No difference across meds by race Wright JT, JAMA 2005

30 HTN in Intermediate Risk Sub study of HOPE-3 trial Intermediate Risk: Annual risk of major cardiovascular events of approximately 1% Systolic blood pressure < 160 Could be on anti-htn meds already Candesartan + HCTZ Lonn EM, NEJM 2016

31 HTN in Intermediate Risk No difference in CVD outcomes Lonn EM, NEJM 2016

32 HTN in Intermediate Risk Except if SBP >143.5mmHg had improved outcomes Lonn EM, NEJM 2016

33 Take Home Points From SPRINT: Higher risk (non-diabetic) patients (including > aged 60) 120mmHg From ACCORD: Diabetics below 140 mm Hg, not intensive From Intermediate Risk NEJM Study: 120 not necessary But remember, trials aren t perfect and guidelines try to take all data into account

34 Guidelines JNC y initiate and treat to <150/90 2. <60y initiate and treat to <140/90 Regardless of comorbidities 3. Initial therapy with: ACE-I, ARB, CCB, TD. BB no longer 1 st line. 4. In black population: CCB or TD James PA et al, JAMA 2014 Shrout T et al, Current Opinion Pharmacology 2017

35 Take Home Points From SPRINT: Higher risk (non-diabetic) patients (including > aged 60) 120mmHg From ACCORD: Diabetics below 140 mm Hg, not intensive From Intermediate Risk NEJM Study: 120 not necessary So Understand the trials, including caveats Use Guidelines to guide Recognize special populations Use good clinical judgment

36 Thank You

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