2/9/2017. Financial Disclosures/Unapproved Use. Achieving Harmony in Blood Pressure Guidelines Around the Globe. Roger S. Blumenthal, MD.

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1 Achieving Harmony in Blood Pressure Guidelines Around the Globe Roger S. Blumenthal, MD The Kenneth Jay Pollin Professor of Cardiology Director, The Johns Hopkins Ciccarone Center for the Prevention Of Heart Disease Disclosures: None Financial Disclosures/Unapproved Use I have no financial relationships with a commercial entity that is relevant to the content of this presentation. I will/will not reference unlabeled or unapproved uses of drugs or other products. Objectives 1. Review our understanding of normal blood pressure and our definition of hypertension 2. Discuss major trials that have shaped our approach to hypertension Rx, with a focus on recent data (SPRINT, HOPE-3, ACCORD) 3. Introduce the concept of using CVD risk to personalize the treatment of hypertension 4. Summarize novel research in the field 3 1

2 65 year-old man with HTN, obesity (BMI 31), OSA, prediabeteswho is self-referred for CV evaluation. His mean BP in the office on HCTZ 25mg daily is 155/76. What is the optimal SBP goal in this patient? <150 <140 <130 <120 The Changing of Hypertension JNC (JAMA 2003;289(19): Guidelines JAMA. 2014;311(5):

3 Major Points from JNC 8: General population, age 60 years Treat if SBP 150 mmhg for goal SBP <150 mmhg (strong recommendation, grade A) DM, age 18 years Treat if SBP is 140 for goal <140/90 (expert opinion, grade E) The latest on BP guidelines: 2017 Ann Intern Med. [Epub ahead of print 17 January 2017] doi: /M ACP/AAFP Guideline Recommendations 1. Initiate treatment in adults 60 years: if SBP >150 to achieve a target SBP<150 (Grade: strong recommendation, high-quality evidence) 2. In adults 60 years with prior history of TIA or CVA: Target SBP<140 (Grade: Weak recommendation, moderate-quality evidence) 3. In adults 60 years with high cardiovascular risk Target SBP<140 (Grade: weak, low-quality evidence) 3

4 More Recent BP Trials Have Stirred Debate Yusuf and Lonn: doi: /jamacardio But isn t a lower target even better? The SPRINT Research Group. A randomized trial of intensive versus standard blood-pressure control. N EnglJ Med 2015 Nov 9; SPRINT: Is more intensive BP control better? (NEJM 2015 Nov 9) N: 9361 Multicenter RCT: SBP<120 vssbp<140 Inclusion Criteria: SBP (treated or untreated) Age >50 years Increased risk of CVD: Clinical or subclinical CVD (excluding stroke) CKD (egfr 20 to less than 60) Framingham Global CVD Risk 10- year score of 15% Age 75 years Exclusion Criteria: Diabetes Prior stroke 4

5 Baseline Characteristics (NEJM 2015 Nov 9) Intensive Rx vs Standard Rx in SPRINT (NEJM Nov ) mmhg mmhg SPRINT: Primary & Secondary Outcomes (NEJM Nov 9, 2015) Primary Outcomes: MI, non-mi ACS, stroke, heart failure, death from cardiovascular cause 5

6 SPRINT: Adverse Events (NEJM Nov 9, 2015) SPRINT- Cost Effectiveness Intensive BP management cost $23,777 per QALY gained Serious AEs would need to occur at 3 times the rate observed in SPRINT to prefer standard Mx JAMA Cardiol. Published online September 14, doi: /jamacardio Recent Landmark Trials: Risk (re) takes Center Stage What explains the difference in treatment effect between SPRINT and HOPE-3? The most plausible possibility is that they asked fundamentally different questions. SPRINT examined an intensive treatment strategy in a population with elevated BP and at high risk for CVD. The HOPE-3 BP trial examined the value of a fixed-dose BP lowering combination pill, without a specific BP treatment target, in a population where risk for CVD was much lower. PK Whelton et al. Published Online: September 7, doi: /jamacardio

7 Recent Landmark Trials: BP reduction put into Context HOPE 3 SPRINT Alberto ZanchettiCircRes. 2015;116: Jan StaessenLancet 2001; 358: ACCORD: SBP<120 vs SBP<140 in DM2 patients The New England Journal of Medicine (17) N: 4773 ACCORD: Is more intensive BP control in DM2 patients better? Multicenter RCT: SBP<120 vssbp<140 Inclusion Criteria: Type 2 DM -Hemoglobin A1C 7.5% Age 40 yrswith CVD Age 55 yrswith any of the following: Atherosclerosis Albuminuria LVH 2 CV risk factors (dyslipidemia, hypertension, smoking, or obesity) Exclusion Criteria: BMI >45 kg/m2 Creatinine >1.5mg/dL(132.6 umol/l) Other serious illness 7

8 Baseline Characteristics in ACCORD (NEJM 2010) Intensive Rx vs Standard Rx in ACCORD (NEJM 2010) mmhg 119 mmhg ACCORD: Primary and Secondary Outcomes Primary Outcome: Composite of non fatal MI, non fatal CV, CVD death 8

9 ACCORD vssprint ACCORD was Underpowered: Almost ½ of expected event rate Sample size almost ½ of SPRINT Young patient population (62 yrs vs. 68 yrs)?lower Risk with dyslipidemia arm Excluded patients with creatinine >1.5 However Trend towards reduction in primary outcome Making sense of ACP/AAFP Recommendations Rec 1: Initiate treatment in adults 60 years: if SBP >150 to achieve a target SBP<150 (Grade: strong recommendation, high-quality evidence) Weiss J, Freeman M, Low A, Fu R, Kerfoot A, PaynterR, et al. Benefits and Harms of Intensive Blood Pressure Treatment in Adults Aged 60 Years or Older: A Systematic Review and Meta-analysis. Ann Intern Med.[Epub ahead of print 17 January 2017] doi: /M Making sense of ACP/AAFP Recommendations REC 2. Target SBP<140 with prior history of TIA or CVA (Grade: Weak recommendation, moderate-quality evidence) 9

10 Making sense of ACP/AAFP Recommendations REC 3. Target SBP<140 if there is high CV risk (Grade: weak, lowquality evidence) Study (Year) BP Goal N F/u ACCORD (2010) <120 vs < yrs Cardio-Sis (2009) <130 vs < yrs JATOS (2008) <140 vs < yrs SPRINT (2015) <120 vs < yrs VALISH (2010) <140 vs < yrs Weiss J, Freeman M, Low A, Fu R, Kerfoot A, PaynterR, et al. Benefits and Harms of Intensive Blood Pressure Treatment in Adults Aged 60 Years or Older: A Systematic Review and Meta-analysis. Ann Intern Med.[Epub ahead of print 17 January 2017] doi: /M Making sense of ACP/AAFP Recommendations REC 3. Target SBP<140 if there is high cardiovascular risk (Grade: weak, low-quality evidence) Meta-analysis of 6 trials: N: All-cause mortality: RR 0.86, (95% CI ) Reduction in cardiac events RR 0.82 (95% CI ) evidence for mortality & cardiac events should be considered lowstrength because the results have important inconsistencies &because the CIs are relatively wide, encompassing possibility of both marked benefit & no effect. Weiss J, Freeman M, Low A, Fu R, KerfootA, PaynterR, et al. Benefits and Harms of Intensive Blood Pressure Treatment in Adults Aged 60 Years or Older: A Systematic Review and Meta-analysis. Ann Intern Med.[Epubahead of print 17 January 2017] doi: /M Canadian BP Guidelines: 2016 Canadian Journal of Cardiology32.5 (2016):

11 Canadian Guidelines: Recommended Treatment Targets Adapted from CHEP Taskforce European Society of Hypertension Guidelines: 2013 European Society of Hypertension Guidelines 11

12 WHO/International Society of Hypertension Guidelines : Target BP HTN at low &medium risk: Target SBP <140 HTN at high risk: Reasonable to target SBP<130 World Health Organization, International Society of Hypertension Writing Group World Health Organization (WHO)/International Society of Hypertension (ISH) statement on management of hypertension. J Hypertens. 2003;21: Using CV Risk to guide BP (and other preventive meds) is not a new idea. That which has been done is that which will be done. So there is nothing new under the sun. Ecclesiastes 1:9 35 Because the goal of antihypertensive therapy is to prevent CVD events,& the likelihood of such events is determined by absolute risk assessment, risk, rather than level of BP, should determine the need for therapy

13 37 Our Research Specifically within the context of a risk-based BP Rx paradigm 1. Can non-contrast CT imaging for CAC provide additional risk information to guide BP Rx decision making? 2. Can blood-based biomarkers be used to monitor impact of blood pressure on individual risk for clinical outcomes? 38 Research Focus No. 1- CAC The King of the Risk Jungle <1 msv 13

14 CAC- MESA + Heinz-Nixdorf N Engl J Med 2008; 358: J Am Coll Cardiol 2010;56: CAC informs NNT for statins Blaha et al. Lancet 2011; 378: Nasir et al. J Am Coll Cardiol 2015;66:

15 Can CAC inform NNT for BP Rx intensity? JW McEvoy et al. Circ 2017 Jan 10; 135: Poor BP Control is associated with hs-ctnt elevation and temporal change in hs-ctnt JW McEvoy et al. Int J Cardiol. 2015;187: JW McEvoy et al. JAMA Cardiol. 2016;1(5):

16 Hs-Troponin may identify adults with abnormal BP who will develop a Dxof HTN Fully adjusted Cox* Visit 2 hs-ctnt Categorical HR (95% CI) p-value JW McEvoy et al. Circulation. 2015;132: <5 ng/l 1.00 (ref.) 5-8 ng/l 1.16 ( ) < ng/l 1.29 ( ) < ng/l 1.31 ( ) Continuous Log(hs-cTnT) 1.14 ( ) < JW McEvoy et al. Circulation. 2015;132: Troponin to gauge on-treatment risk? SPRINT suggests that SBP targets should be between mmhg, particularly when CV risk is higher What are the implications for dropping Diastolic BP too low? Observational DBP J Curve CLARIFY registry- 22,672 CAD pts Vidal-Petiot et al. Lancet

17 Restricted cubic spline for the association of Diastolic BP with hs-ctnt 14 ng/l JW McEvoy et al. J Am Coll Cardiol Oct 18;68(16): Take Home Messages 1. We have come along way in Rx of elevated BP 2. Now pushing the boundaries of how low we can go 3. Estimated CV risk becomes important additional parameter to consider, over & above actual BP level 4. Shared decision making and risk discussion increasingly important (Martin SS, J Am Coll Cardiol Apr 7;65(13):1361-8) 5. Subclinical imaging and biomarkers have the potential to help personalize risk based decision making for BP Rx 50 Conclusion: Limitations of meta-analysis data led to surprising new ACP/AAFP guidelines Discordance in treatment target in different guidelines but lifestyle improvements are always welcome to lower BP Stay Tuned: ACC/AHA guidelines in late

18 65 year-old man with HTN, obesity(bmi 31), OSA, prediabetesself-referred for CV evaluation. His mean BP in the office on HCTZ 25mg daily is 153/76. What is the optimal SBP goal in this patient? <150 <140 <130 <120 The ABCDE Approach A B C D E Assessment Aspirin Blood pressure Cholesterol Diabetes Prevention Diet Exercise Proposal for an ABCDE Approach 18

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