HYPERTENSION: HOW LOW DO WE GO?

MICHAEL LEFEVRE, MD, MSPHPROFESSOR AND VICE CHAIR

DEPARTMENT OF FAMILY AND COMMUNITY MEDICINEUNIVERSITY OF MISSOURI

DISCLOSURE: MEMBER OF THE JNC 8 PANEL4/6/18

SET THE STAGE• Background: JNC 8• How to diagnose BP?• SPRINT• AHA Guideline• ACP/AAFP Guideline• Now what?

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)

MARCH 2008 NHLBI CONVENED

PANELS

• “The JNC 8 will review and synthesize

the latest available scientific evidence...”

QUESTIONS• When to initiate drug treatment?• How low should you go?• How do you get there?

IN THE GENERAL POPULATION AGE<60 YEARS

• Diastolic threshold/goal of < 90 mm Hg

• For age 30-59 years Strong (Grade A) recommendation

• For age 18-29 years expert opinion

• Systolic threshold/goal of <140 mm Hg

• Expert opinion

RECOMMENDATION• In the general population age > 60 years • Threshold and goal 150/90

(Strong Recommendation – Grade A)

LOWER SYSTOLIC GOAL?ACCORD BP

WHAT?• Intensive treatment• Target systolic BP < 120• Standard treatment• Target a systolic BP of 135 to 139 mm Hg • The dose was reduced if systolic blood

pressure was less than 130 mm Hg on a single visit or less than 135 mm Hg on two consecutive visits

BP OUTCOME

Systolic BP 14.2 mm Hg lower in intensive group

HEALTH OUTCOMES

• Primary outcome was a composite of

CVD events

• 1.87% per year in intensive

• 2.09% per year in control

• Hazard ratio 0.88 (0.73-1.06), p=0.20

SECONDARY OUTCOMES• Stroke • Intensive 0.32 % per year• Standard care 0.53 % per year• Hazard ratio 0.59 (0.39–0.89)• NNT over duration of study 91

JNC 8 RECOMMENDATION• In the diabetic population aged > 60

years • Threshold and goal 140/90• Expert opinion

JNC 8

JNC Ain’t

DIAGNOSING HYPERTENSION

ABPM IS THE BEST METHOD FOR DIAGNOSING HYPERTENSION.

2015 USPSTF recommendation

12 HOUR OR 24 HOUR HOME BP AN ALTERNATIVE

FAST FORWARD FOUR YEARS:A TALE OF TWO GUIDELINES

ACP/AAFP VS ACC/AHA

ONE NEW STUDY DRIVES THE CURRENT HYPERTENSION

DIALOGUE

ORIGINAL ARTICLEA Randomized Trial of Intensive versus Standard Blood-Pressure ControlThe SPRINT Research GroupN Engl J Med 2015; 373:2103-2116November 26, 2015

WHO?• Age > 50 years• Average 67.9• Systolic blood pressure of 130 to 180

mm Hg

WHO?• Increased cardiovascular risk• Clinical or subclinical cardiovascular

disease other than stroke; • Chronic kidney disease, (eGFR) of 20 to

less than 60 ml per minute per 1.73 m2 • 10-year risk of cardiovascular disease of

15% or greater on the basis of the Framingham risk score;

• Or…age of 75 years or older

WHO?• Patients with diabetes mellitus or prior

stroke were excluded

WHAT?• Intensive treatment• Target systolic BP < 120• Standard treatment• Target a systolic BP of 135 to 139 mm Hg • The dose was reduced if systolic blood

pressure was less than 130 mm Hg on a single visit or less than 135 mm Hg on two consecutive visits

WHAT?• 87% of patients in control group had

medication reduced

HOW?• The protocol encouraged, but did not

mandate: • Thiazide-type diuretics (encouraged as the

first-line agent), loop diuretics (for participants with advanced chronic kidney disease), • Chlorthalidone was encouraged as the primary

thiazide-type diuretic• Beta-adrenergic blockers (for those with

coronary artery disease).• Amlodipine as the preferred calcium-channel

blocker

Systolic Blood Pressure in the Two Treatment Groups over the Course of the Trial.

The SPRINT Research Group. N Engl J Med 2015;373:2103-2116

OUTCOMES• Primary outcome was composite• MI or other acute coronary syndromes• Stroke• Heart failure• CV death

PRIMARY OUTCOMEAVE F/U 3.26 YEARS

Goal < 120 Goal < 140 H.R. (95% c.i.)Overall 5.2% 6.8% .75 (.64-.89)

Age < 75 4.2% 5.2% .80 (.64-1.0)Age > 75 7.7% 10.9% .67 (.51-.86)

SPRINT: SERIOUS ADVERSE EVENTSIntensive Rx Standard Rx

Overall 38.3% 37.1%Hypotension 2.4% 1,4%Syncope 2.3% 1.7%

Electrolyte abnormality 3.1% 2.3%AKI 4.1% 2.5%

ACC/AHA GUIDELINE

283 PAGES, 99 RECOMMENDATIONS

SYSTEMATIC REVIEW QUESTIONS ON HIGH BP IN ADULTS CATEGORIES OF BP IN ADULTS

BP category BPNormal <120/<80Elevated 120-129/<80Stage I hypertension 130-139/80-89Stage II hypertension >140/>90

BP indicates blood pressure (based on an average of ≥2 careful readings obtained on ≥2 occasions

PREVALENCE OF HYPERTENSION WITH NEW CRITERIA REDEFINING A CUTOFF POINT

ABOVE WHICH THE VALUE OF A PHYSIOLOGIC

MEASUREMENT REFLECTS A DISEASE HAS HUGE

IMPLICATIONS.

ACC/AHA SHINES LIGHT ON MEASUREMENT

• For diagnosis and management of high BP, proper methods are recommended for accurate measurement and documentation of BP

OFFICE BP• Instruct the patient to avoid caffeine,

exercise, and smoking for at least 30 minutes before the visit

• Have the patient relax, sitting in a chair (feet on floor with back supported) for at least five minutes

• Ensure that the patient has emptied his/her bladder

• Refrain from talking during the rest period and measurement

OFFICE BP• Remove all clothing covering the area where

the cuff will be placed• Use the correct cuff size • Support the patient’s arm• Position the middle of the cuff on the patient’s

upper arm at the level of the right atrium (the midpoint of the sternum)

• Separate repeated measurements by one to two minutes

• Take the average of at least two measurements

THIS WOULD BE A HUGE SHIFT IN PROTOCOL FOR BP

MEASUREMENT IN OUR CLINICS

ACC/AHA SHINES LIGHT ON MEASUREMENT

• Out-of-office BP measurements are recommended to confirm the diagnosis of hypertension and for titration of BP-lowering medication, in conjunction with telehealth counseling or clinical interventions

OBJECTIONS TO OUT OF OFFICE BP MEASUREMENT

• Cost• Compliance

AUTOMATED OFFICE BP MONITORING

BOTH ACCORD-BP AND SPRINT USED AUTOMATED OFFICE BP • 5-8 mm Hg lower than routine manual

office BP measurement• Much better correlation with ambulatory

blood pressure measurement

BP MEASUREMENT• Our current approach to routine office BP

measurement should not be used to implement the targets recommended in this guideline

WHAT NEW EVIDENCE SUPPORTS THESE LOWER TARGETS?

ACC/AHA META-ANALYSIS• American College of Cardiology, American

Heart Association. Systematic review for the 2017 ACC/AHA/AAPA/ABC/ACPM/AGS/APhA/ASH/ASPC/NMA/PCNA guideline for the prevention, detection, evaluation, and management of high blood pressure in adults: supplemental tables and figures. http://hyper.ahajournals.org/content/hypertensionaha/suppl/2017/11/13/HYP.0000000000000067.DC2/Data_Supplement. pdf. Accessed December 20, 2017.

ACC/AHA META-ANALYSIS• Nine trials incorporated

• All trials selectively enrolled persons at high risk of cardiovascular disease (CVD)

• Follow-up ranging from 2.0 to 5.7 years. • The two largest trials followed patients for

an average of 3.3 and 4.7 yrs• SPRINT & ACCORD

ACC/AHA META-ANALYSIS• No statistically significant benefit• all-cause mortality• CVD mortality• heart failure• renal events • Difference for fatal or nonfatal

myocardial infarction was borderline nonsignificant.

ACC/AHA META-ANALYSIS:STATISTICALLY SIGNIFICANT

RESULTS

• Composite major CVD events

• 6.2% vs. 7.3%; relative risk = 0.84; number needed to treat = 91

• Combination of fatal and nonfatal stroke

• 2.4% vs. 2.9%; relative risk = 0.82; number needed to treat = 200

RECOMMENDATIONS FOR PHARMACOLOGIC RX

• BP > 130 systolic or > 80 diastolic and• an estimated 10-year ASCVD risk of 10%

or higher • or age > 60 years• All adults >140/90

REDEFINING A CUTOFF POINT ABOVE WHICH THE VALUE OF A

PHYSIOLOGICMEASUREMENT REFLECTS A

DISEASE HAS HUGE IMPLICATIONS.

ACP/AAFP GUIDELINE

AGE > 60

4/6/18

EVIDENCE SUMMARY – LOWER TARGET

• Inconsistent trial results, with imprecise estimates of benefit

• The results for mortality were non-significant

• Evidence was most consistent for a reduction in stroke, with an absolute risk reduction of 0.49% and a number needed to treat (NNT) of 204.

• For cardiac events borderline non-significant, with an NNT of 106

THE AAFP HAS DECLINED TO ENDORSE THE ACC/AHA GUIDELINE AND CONTINUESTO ENDORSE THE 2014 EVIDENCE-BASEDGUIDELINE FOR THE MANAGEMENT OF HIGH BLOOD PRESSURE IN ADULTS

MY CONCLUSIONS• In treating hypertension, we are treating a risk

factor in asymptomatic patients to prevent disease, not treating a disease to relieve suffering.

• Most persons who receive preventive medication will not benefit, and many will be harmed.

• Choosing a threshold and target for treatment should be based on the science supporting CVD risk eduction, while considering the benefits and harms in individual patient circumstances and respecting patient choice.

QUESTIONS?

Original Article

Blood-Pressure Lowering in Intermediate-Risk Persons without Cardiovascular Disease

N Engl J MedVolume 374(21):2009-2020

May 26, 2016

WHO?• Men age 55 years and older; women age 65

years and older• At least one:• Elevated waist-hip ratio• Low HDL• Current/recent smoking• Dysglycemia• Family hx premature CAD• Mild renal dysfunction

WHO?• Average age 65.7 +/- 6.4• Average baseline SBP 138.2 +/- 14.7• Average baseline DBP 82.0 +/- 9.4

WHAT?• RCT 2x2 factorial design• Intervention• 16 mg candesartan• 12.5 mg HCTZ• Office BP, average of 2 readings after 5

minutes rest

Systolic Blood Pressure over the Course of the Trial, According to Trial Group.

Lonn EM et al. N Engl J Med 2016;374:2009-2020

OUTCOMES• Primary outcome was composite• MI or other acute coronary syndromes• Stroke• CV death• Secondary outcome also included• Heart failure• Revascularization

Cumulative Incidence of Major Cardiovascular Events, According to Trial Group.

Lonn EM et al. N Engl J Med 2016;374:2009-2020

Original Investigation | June 28, 2016

Intensive vs Standard Blood Pressure Control and Cardiovascular Disease Outcomes in Adults Aged ≥75 YearsA Randomized Clinical Trial

JAMA. 2016;315(24):2673-2682.

AGE > 75 EXCLUSIONS• Dementia• Predicted survival of < 3 years• Unintentional weight loss past 6 months• SBP < 110 mm Hg after 1 min standing• Nursing home• Too many BP meds

BASELINE MEDICATIONS AND ELIGIBILITY (SBP MM HG)

0-1 meds

2 meds

3 meds

4 meds

130 150 160 170 180

eligible not eligible

OUTCOMES IN AGE > 75 YRS• Primary outcome (composite)• Intensive Rx 102/1317 7.7%• Standard Rx 148/1319 11.2%• Hazard ratio 0.66 (0.51-0.85)• Risk difference 3.5%