2/9/2017

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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

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What is the optimal SBP goal in this patient?

� <150

� <140

� <130

� <120

65 year-old man with HTN, obesity (BMI 31), OSA, prediabetes who is self-referred for CV evaluation. His mean BP in the office on HCTZ 25mg daily is 155/76.

The Changing of Hypertension

JNC-7 2003 (JAMA 2003;289(19):2560

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2014 Guidelines

JAMA. 2014;311(5):507-20

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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: 10.7326/M16-1785

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)

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More Recent BP Trials Have Stirred Debate

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Yusuf and Lonn: doi:10.1001/jamacardio.2016.2169

But isn’t a lower target even better?

The SPRINT Research Group. A randomized trial of intensive versus standard blood-pressure control. N Engl J Med 2015

Nov 9;

SPRINT: Is more intensive BP control better? (NEJM 2015

Nov 9)

� N: 9361

� Multicenter RCT:

� SBP<120 vs SBP<140

� Inclusion Criteria:

� SBP 130-180 (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

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Baseline Characteristics (NEJM 2015 Nov 9)

Intensive Rx vs Standard Rx in SPRINT (NEJM Nov 9 2015)

121.5 mmHg

136.2 mmHg

SPRINT: Primary & Secondary Outcomes (NEJM Nov 9, 2015)

� Primary Outcomes: MI, non-MI ACS, stroke, heart failure, death from

cardiovascular cause

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SPRINT: Adverse Events (NEJM Nov 9, 2015)

SPRINT- Cost Effectiveness

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• 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, 2016. doi:10.1001/jamacardio.2016.3517

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.”

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PK Whelton et al. Published Online: September 7, 2016. doi:10.1001/jamacardio.2016.2051.

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Recent Landmark Trials:

BP reduction put into Context

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Jan Staessen Lancet 2001; 358: 1305–15

Alberto Zanchetti Circ Res. 2015;116:1058-1073

HOPE 3

SPRINT

ACCORD: SBP<120 vs SBP<140 in DM2 patients

The New England Journal of Medicine. 2010. 362(17) 1575-1585.

ACCORD:

Is more intensive BP control in DM2 patients better?

� N: 4773

� Multicenter RCT:

� SBP<120 vs SBP<140

� Inclusion Criteria:� Type 2 DM - Hemoglobin A1C ≥7.5%

� Age ≥40 yrs with CVD

� Age ≥55 yrs with 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

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Baseline Characteristics in ACCORD (NEJM 2010)

Intensive Rx vs Standard Rx in ACCORD (NEJM 2010)

133.5 mmHg

119 mmHg

ACCORD: Primary and Secondary Outcomes

� Primary Outcome: Composite of non fatal MI, non fatal CV, CVD death

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ACCORD vs SPRINT

� 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

Weiss J, Freeman M, Low A, Fu R, Kerfoot A, Paynter R, 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: 10.7326/M16-1754

Rec 1: Initiate treatment in adults ≥60 years:

if SBP >150 to achieve a target SBP<150

(Grade: strong recommendation, high-quality evidence)

Making sense of ACP/AAFP Recommendations

�REC 2. Target SBP<140 with prior history

of TIA or CVA (Grade: Weak

recommendation, moderate-quality evidence)

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Making sense of ACP/AAFP Recommendations

� REC 3. Target SBP<140 if there is high CV risk (Grade: weak, low-

quality evidence)

Study (Year) BP Goal N F/u

ACCORD (2010) <120 vs <140 4733 4.7 yrs

Cardio-Sis (2009) <130 vs <140 1110 2.0 yrs

JATOS (2008) <140 vs <160 4418 2.0 yrs

SPRINT (2015) <120 vs <140 9361 3.3 yrs

VALISH (2010) <140 vs <150 3079 3.0 yrs

Weiss J, Freeman M, Low A, Fu R, Kerfoot A, Paynter R, 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: 10.7326/M16-1754

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: 41491

� All-cause mortality: RR 0.86, (95% CI 0.69-1.06)

� Reduction in cardiac events RR 0.82 (95% CI 0.64 -1.00)

“evidence for mortality & cardiac events should be considered low-strength 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, Kerfoot A, Paynter R, 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: 10.7326/M16-1754

Canadian BP Guidelines: 2016

Canadian Journal of Cardiology 32.5 (2016): 569-588.

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Canadian Guidelines: Recommended Treatment

Targets

Adapted from CHEP Taskforce

European Society of Hypertension Guidelines: 2013

European Society of Hypertension Guidelines

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WHO/International Society of Hypertension Guidelines :

Target BP

World Health Organization, International Society of Hypertension Writing Group. 2003 World Health Organization (WHO)/International Society of Hypertension (ISH) statement on management of hypertension. J Hypertens. 2003;21:1983-1992.

• HTN at low & medium risk: Target SBP <140� HTN at high risk: “Reasonable” to target SBP<130

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

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• “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.”

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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?

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<1 mSv

Research Focus No. 1- CAC

The King of the “Risk” Jungle

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CAC- MESA + Heinz-Nixdorf

N Engl J Med 2008; 358:1336-1345

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J Am Coll Cardiol 2010;56:1397–406

CAC informs NNT for statins

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Blaha et al. Lancet 2011; 378: 684–92 Nasir et al. J Am Coll Cardiol 2015;66:1657–68

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Can CAC inform NNT for BP Rx intensity?

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JW McEvoy et al. Circ 2017 Jan 10; 135:153-65

Poor BP Control is associated with hs-cTnT

elevation and temporal change in hs-cTnT

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JW McEvoy et al.

Int J Cardiol. 2015;187:651-7.

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JW McEvoy et al. JAMA Cardiol. 2016;1(5):519-528.

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Hs-Troponin may identify adults with

abnormal BP who will develop a Dx of HTN

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Fully adjusted Cox*

Visit 2hs-cTnT HR

(95% CI) p-valueCategorical

<5 ng/L 1.00 (ref.)

5-8 ng/L

1.16 (1.08-1.25) <0.001

9-13 ng/L

1.29 (1.14-1.47) <0.001

≥14 ng/L

1.31 (1.07-1.61) 0.010

Continuous

Log(hs-cTnT)

1.14 (1.09-1.19) <0.001

JW McEvoy et al.

Circulation. 2015;132:825-833

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JW McEvoy et al.

Circulation. 2015;132:825-833

Troponin to gauge on-treatment risk?

• SPRINT suggests that SBP targets should be between 120-130 mmHg, particularly when CV risk is higher

• What are the implications for dropping Diastolic BP too low?

• Observational DBP “J Curve”

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CLARIFY registry- 22,672 CAD ptsVidal-Petiot et al. Lancet 2016

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Restricted cubic spline for the association of Diastolic BP with

hs-cTnT ≥14 ng/L

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JW McEvoy et al. J Am Coll Cardiol. 2016 Oct 18;68(16):1713-1722

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. 2015 Apr 7;65(13):1361-8)

5. Subclinical imaging and biomarkers have the potential to help personalize risk based decision making for BP Rx

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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 2017

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What is the optimal SBP goal in this patient?

� <150

� <140

� <130

� <120

65 year-old man with HTN, obesity(BMI 31), OSA, prediabetes self-referred for CV evaluation. His mean BP in the office on HCTZ 25mg daily is 153/76.

The ABCDE Approach

A

B

D

C

E

AssessmentAspirin

Blood pressure

Cholesterol

Diabetes PreventionDiet

Exercise

Proposal for an ABCDE Approach