Putting the 2014 Evidence Based Guidelines for the Management of High Blood Pressure in Adults Into Practice

Moderator James A. Underberg, MD

Clinical Assistant Professor of Medicine New York University School of Medicine Director, Bellevue Hospital Lipid Clinic New York University Center for Prevention of Cardiovascular Disease New York City

Panelists Louis Kuritzky, MD

Clinical Assistant Professor University of Florida Gainesville, Florida

Raymond R. Townsend, MD

Professor of Medicine Perelman School of Medicine Philadelphia, Pennsylvania

2014 Evidence-Based Guideline for the Management of High Blood Pressure in Adults Report From the Panel Members Appointed to the JNC 8

Paul A. James, MD; Suzanne Oparil, MD; Barry L. Carter, PharmD; William C. Cushman, MD; Cheryl Dennison-Himmelfarb, RN, ANP, PhD; Joel Handler, MD; Daniel T. Lackland, DrPH; Michael L. LeFevre, MD, MSPH; Thomas D. MacKenzie, MD, MSPH; Olugbenga Ogedegbe, MD, MPH; Sidney C. Smith Jr, MD; Laura P. Svetkey, MD, MHS; Sandra J. Taler, MD; Raymond R. Townsend, MD; Jackson T. Wright Jr, MD, PhD; Andrew S. Narva, MD; Eduardo Ortiz, MD, MPH James PA, et al.

JAMA.

2014;311:507-520.

[1]

Questions to the JNC 8 Panel

•

At what level should you treat BP?

•

To what level should it be treated?

•

How do you do that?

Target Audience for JNC 8

“Statements and recommendations for [BP] treatment based on a systematic review of the literature to meet user needs, especially the needs of the primary care clinician.” James PA, et al.

JAMA.

2014;311:507-520.

[1]

Focus of the Recommendations

•

Age

•

Diabetic

•

Black/nonblack

•

Chronic kidney disease (CKD)

Age Recommendations, JNC 2014

• 18 years old and younger: Not considered • 30 years old and younger: We have little to no data • 30 to 59 years old: In the general population younger than 60 years, initiate pharmacologic treatment to lower BP at a DBP of 90 mm Hg and treat to a goal DBP lower than 90 mm Hg.

Strong Recommendation: Grade A

• 60 years old: In the general population aged 60 years or older, initiate pharmacologic treatment to lower BP at an SBP of 150 mm Hg or higher or a DBP of 90 mm Hg or higher and treat to a goal SBP lower than 150 mm Hg and goal DBP lower than 90 mm Hg.

Strong Recommendation: Grade A

• 80 years old: Based on HYVET James PA, et al.

JAMA.

2014;311:507-520.

[1]

JNC Panel Recommendation for Patients With Diabetes and Hypertension

• In the population aged 18 years and older with diabetes, initiate pharmacologic treatment to lower BP at an SBP of 140 mm Hg or a DBP of 90 mm Hg and treat to a goal of SBP lower than 140 mm Hg and goal DBP lower than 90 mm Hg.

Expert Opinion: Grade E

James PA, et al.

JAMA.

2014;311:507-520.

[1]

ACCORD

Mean Number of Medications Prescribed

Time, y 1 2 3 4 5 6 7 8

Intensive therapy group 3.2

3.4

3.4

3.5

3.5

3.5

3.4

3.4

Standard therapy group 1.9

2.1

2.1

2.2

2.2

2.3

2.3

2.3

ACCORD Primary Outcome Intensive Therapy, % Standard Therapy, %

208 (1.87) 237 (2.09) ACCORD Study Group.

N Engl J Med.

2010;362:1575-1585.

[6]

JNC Panel Recommendation for Patients With CKD

• In the population aged 18 years with CKD, initiate pharmacologic treatment to lower BP at an SBP of 140 mm Hg or a DBP of 90 mm Hg and treat to goal of an SBP lower than 140 mm Hg and a goal DBP lower than 90 mm Hg.

Expert Opinion: Grade E

James PA, et al.

JAMA.

2014;311:507-520.

[1]

JNC Recommendation for Nonblack Patients

• In the general nonblack population, including those with diabetes, initial antihypertensive treatment should include – Thiazide-type diuretic – Calcium channel blocker (CCB) – Angiotensin-concerting enzyme (ACE) inhibitor – Angiotensin receptor blocker (ARB) –

Moderate Recommendation: Grade B

James PA, et al.

JAMA.

2014;311:507-520.

[1]

ALLHAT

Outcomes in Hypertensive Black Patients Treated With Chlorthalidone, Amlodipine, and Lisinopril

6-Year Rate per 100 Persons Outcome

Total randomized CHD (nonfatal MI + fatal CHD) All-cause mortality Cardiovascular mortality Combined CHD Combined CVD Stroke End-stage renal disease Cancer Hospitalized for gastrointestinal bleeding

Chlorthalidone No.

5369

Rate (SE)

400 821 362 655 1211 257 93 417 282 9.6 (0.5) 17.9 (0.6) 8.1 (0.5) 15.2 (0.6) 26.8 (0.7) 6.0 (0.4) 2.3 (0.3) 9.4 (0.5) 8.9 (0.5)

Amlodipine No.

3213

Rate (SE)

243 481 215 407 767 145 65 245 169 9.5 (0.6) 17.0 (0.8) 8.4 (0.6) 15.8 (0.8) 28.4 (1.0) 5.7 (0.5) 2.7 (0.4) 9.8 (0.7) 8.6 (0.7)

No.

3210

Lisinopril Rate (SE)

260 520 224 444 836 212 71 254 209 10.3 (0.7) 18.0 (0.8) 8.4 (0.6) 17.3 (0.8) 31.1 (1.0) 8.0 (0.6) 3.1 (0.4) 9.9 (0.7) 11.1 (0.8) Wright JT, et al.

JAMA

. 2005;293(13):1595-1608.

[17]

JNC Recommendation for Black Patients

• In the general black population, including those with diabetes, initial antihypertensive treatment should include – Thiazide-type diuretic – CCB • For the general black population: –

Moderate Recommendation: Grade B

• For black patients with diabetes: –

Weak Recommendation: Grade C

James PA, et al.

JAMA.

2014;311:507-520.

[1]

Recommendations for Hypertension Management

Recommendation 1

: In the general population aged 60 years, initiate pharmacologic treatment to lower BP at systolic BP (SBP)150 mm Hg or diastolic BP (DBP) 90 mm Hg and treat to a goal SBP lower than 150 mm Hg and goal DBP lower than 90 mm Hg. (Strong Recommendation : Grade A)

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)

Recommendation 2

: In the general population younger than 60 years, initiate pharmacologic treatment to lower BP at DBP 90 mm Hg and treat to a goal DBP lower than 90 mm Hg. (For ages 30 to 59 years, Strong Recommendation : Grade A; for ages 18 to 29 years, Expert Opinion: Grade E)

Recommendation 3

: In the general population younger than 60 years, initiate pharmacologic treatment to lower BP at SBP to 140 mm Hg and treat to a goal SBP lower than 140 mm Hg. (Expert Opinion : Grade E)

Recommendation 4

: In the population aged 18 years with CKD, initiate pharmacologic treatment to lower BP at SBP 140 mm Hg or DBP 90 mm Hg and treat to goal SBP lower than 140 mm Hg and goal DBP lower than 90 mm Hg. (Expert Opinion: Grade E)

Recommendation 5

: In the population aged 18 years with diabetes, initiate pharmacologic treatment to lower BP at SBP 140 mm Hg or DBP 90 mm Hg and treat to a goal SBP lower than 140 mm Hg and goal DBP lower than 90 mm Hg. (Expert Opinion: Grade E) James PA, et al.

JAMA.

2014;311:507-520.

[1]

Recommendations for Hypertension Management (cont)

Recommendation 6

: In the general nonblack population, including those with diabetes, initial antihypertensive treatment should include a thiazide-type diuretic, CCB, angiotensin-converting enzyme inhibitor (ACEI), or angiotensin receptor blocker (ARB). (Moderate Recommendation: Grade B)

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)

Recommendation 8

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

Recommendation 9

:The main objective of hypertension treatment is to attain and maintain goal BP. 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, or ARB). The clinician should continue to assess BP and adjust the treatment regimen until goal BP is reached. 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 an ARB together in the same patient. If goal BP cannot be reached using only the drugs in recommendation 6 because of a contraindication or the need to use more than 3 drugs to reach goal BP, antihypertensive drugs from other classes can be used. Referral to a hypertension specialist may be indicated for patients in whom goal BP cannot be attained using the above strategy or for the management of complicated patients for who additional clinical consultation is needed. (Expert Opinion : Grade E) James PA, et al.

JAMA.

2014;311:507-520.

[1]

JNC Management Guideline Algorithm

Adult aged 18 years and older who have hypertension Implement lifestyle interventions (continue throughout management) Set BP goal and initiate BP-lowering medication on the basis of age, diabetes status, and CKD

Age General population (no diabetes or CKD) ≥ 60 years Age < 60 years

BP goal SBP < 150 mm Hg DBP < 90 mm Hg

Nonblack

Initiate thiazide-type diuretic or ACEI or ARB or CCB, alone or in combination BP goal SBP < 140 mm Hg DBP < 90 mm Hg

Black

Initiate thiazide-type diuretic or CCB, alone or in combination

Diabetes or CKD present All ages/with CKD/ with or All ages/with diabetes/no CKD

BP goal SBP < 140 mm Hg DBP < 90 mm Hg

All races without diabetes

BP goal SBP < 140 mm Hg DBP < 90 mm Hg Initiate thiazide-type diuretic or CCB, alone or in combination

Select a drug treatment titration strategy

A. Maximize first medication before adding second or B. Add second medication before reaching maximum dose of first medication or C. Start with 2 medication classes separately or as fixed-done combination

No At goal BP?

Reinforce medication and lifestyle adherence For strategies A and B, add and titrate thiazide-type diuretic or ACEI or ARB or CCB (use medication class not previously selected and avoid combined use of ACEI and ARB).

For strategy C, titrate doses of initial medications to maximum.

No

Reinforce medication and lifestyle adherence Add and titrate thiazide-type diuretic or ACEI or ARB or CCB (use medication class not previously selected and avoid combined use of ACEI and ARB).

Reinforce medication and lifestyle adherence Add additional medication class (eg, beta-blocker, aldosterone antagonist, or others) and/or refer to physician with expertise in hypertension management.

No At goal BP?

At goal BP?

At goal BP?

James PA, et al.

JAMA.

2014;311:507-520.

[1]

Continue current treatment and monitoring

ASCOT

Summary of All End Points

Primary

Nonfatal MI (including silent) + fatal CHD

Secondary

Nonfatal MI (excluding silent) + fatal CHD Total coronary end point Total cardiovascular event and procedures All-cause mortality Cardiovascular mortality Fatal and nonfatal stroke Fatal and nonfatal heart failure

Tertiary

Silent MI Unstable angina Chronic stable angina Peripheral arterial disease Life-threatening arrhythmias New-onset diabetes mellitus New-onset renal impairment

Unadjusted hazard ratio (95% CI)

0.90 (0.79-1.02) 0.87 (0.76-1.00) 0.87 (0.79-0.96) 0.84 (0.78-0.90) 0.89 (0.81-0.99) 0.76 (0.65-0.90) 0.77 (0.66-0.89) 0.84 (0.66-1.05) 1.27 (0.80-2.00) 0.68 (0.51-0.92) 0.98 (0.81-1.19) 0.65 (0.52-0.81) 1.07 (0.62-1.85) 070 (0.63-0.78) 0.85 (0.75-0.97)

Post hoc

Primary end point + coronary revascularization procedures 0.86 (0.77-0.96) 0.84 (0.76-0.92) CV death + MI + stroke 0.50

Amlodipine

 0.70

1.00

perindopril better

1.45

Atenolol

 2.00

thiazide better

Dahlöf B.

Lancet

. 2005;366:895-906.

[18]

Strategies for Reaching BP Goal

Start 1 drug, titrate to maximum dose, and then add a second drug Start 1 drug and then add a second drug before achieving maximum dose of the initial drug Begin with 2 drugs at the same time either as 2 separate pills or as a single pill combination

James PA, et al.

JAMA.

2014;311:507-520.

[1]

Abbreviations

ACCORD = Action to Control Cardiovascular Risk in Diabetes ACE = angiotensin-converting enzyme ALLHAT = Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial ARB = angiotensin receptor blockers ASCOT = Anglo-Scandinavian Cardiac Outcomes Trial BP = blood pressure CCB = calcium channel blocker CHADS = congestive heart failure, hypertension, age, diabetes mellitus, and stroke CHD = coronary heart disease CI = confidence interval CKD = chronic kidney disease DBP = diastolic blood pressure HYVET = Hypertension in the Very Elderly Trial JNC 8 = Eighth Joint National Committee MI = myocardial infarction SBP = systolic blood pressure

References

1. James PA, Oparil S, Carter BL, et al. 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).

JAMA

. 2014;311:507-520.

2. Chobanian AV, Bakris GL, Black HR, et al; National Heart, Lung, and Blood Institute Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure; National High Blood Pressure Education Program Coordinating Committee. The Seventh Report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure: the JNC 7 report.

JAMA

. 2003;289:2560-2572.

3. Beckett NS, Peters R, Fletcher AE, et al; HYVET Study Group. Treatment of hypertension in patients 80 years of age or older.

N Engl J Med

. 2008;358:1887-1898.

4. Mancia G, Fagard R, Narkiewicz K, et al. 2013 ESH/ESC guidelines for the management of arterial hypertension: the Task Force for the Management of Arterial Hypertension of the European Society of Hypertension (ESH) and of the European Society of Cardiology (ESC).

Eur Heart J

. 2013;34:2159-2219.

5. Tight blood pressure control and risk of macrovascular and microvascular complications in type 2 diabetes: UKPDS 38. UK Prospective Diabetes Study Group.

BMJ

. 1998;317:703-713.

References (cont)

6. ACCORD Study Group, Cushman WC, Evans GW, Byington RP, et al. Effects of intensive blood-pressure control in type 2 diabetes mellitus.

N Engl J Med

. 2010;362:1575-1585.

7. Hebert LA, Kusek JW, Greene T, et al. Effects of blood pressure control on progressive renal disease in blacks and whites. Modification of Diet in Renal Disease Study Group.

Hypertension

. 1997;30(3 Pt 1):428-435.

8. Wright JT Jr, Bakris G, Greene T, et al; African American Study of Kidney Disease and Hypertension Study Group. Effect of blood pressure lowering and antihypertensive drug class on progression of hypertensive kidney disease: results from the AASK trial.

JAMA

. 2002;288:2421-2431.

9. Ruggenenti P, Perna A, Loriga G, et al; REIN-2 Study Group. Blood-pressure control for renoprotection in patients with non-diabetic chronic renal disease (REIN-2): multicentre, randomised controlled trial.

Lancet

. 2005;365:939-946.

10. ClinicalTrials.gov. Systolic Blood Pressure Intervention Trial (SPRINT). NCT01206062. http://clinicaltrials.gov/ct2/show/NCT01206062?term=SPRINT&rank=3 Accessed March 14, 2014.

References (cont)

11. Wright JT Jr, Harris-Haywood S, Pressel S, et al. Clinical outcomes by race in hypertensive patients with and without the metabolic syndrome: Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial (ALLHAT).

Arch Intern Med

. 2008;168:207-217.

12. Wright Jr JT, Fine LJ, Lackland DT, Ogedegbe G, Dennison Himmelfarb CR. Evidence Supporting a Systolic Blood Pressure Goal of Less Than 150 mm Hg in Patients Aged 60 Years or Older: The Minority View.

Ann Intern Med

. 2014. [Epub ahead of print] 13. Dahlöf B, Devereux RB, Kjeldsen SE, et al; LIFE Study Group. Cardiovascular morbidity and mortality in the Losartan Intervention For Endpoint reduction in hypertension study (LIFE): a randomised trial against atenolol.

Lancet

. 2002;359:995 1003.

14. Poulter NR, Wedel H, Dahlöf B, et al; ASCOT Investigators. Role of blood pressure and other variables in the differential cardiovascular event rates noted in the Anglo Scandinavian Cardiac Outcomes Trial-Blood Pressure Lowering Arm (ASCOT-BPLA).

Lancet

. 2005;366:907-913.

References (cont)

15. Law MR, Morris JK, Wald NJ. Use of blood pressure lowering drugs in the prevention of cardiovascular disease: meta-analysis of 147 randomised trials in the context of expectations from prospective epidemiological studies.

BMJ

. 2009;338:b1665.

16. Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial Collaborative Research Group. Diuretic versus alpha-blocker as first-step antihypertensive therapy: final results from the Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial (ALLHAT).

Hypertension

. 2003;42:239-246.

17. Wright JT Jr, Dunn JK, Cutler JA, et al; ALLHAT Collaborative Research Group. Outcomes in hypertensive black and nonblack patients treated with chlorthalidone, amlodipine, and lisinopril.

JAMA

. 2005;293:1595-1608.

18. Dahlöf B, Sever PS, Poulter NR, et al; ASCOT Investigators. Prevention of cardiovascular events with an antihypertensive regimen of amlodipine adding perindopril as required versus atenolol adding bendroflumethiazide as required, in the Anglo-Scandinavian Cardiac Outcomes Trial-Blood Pressure Lowering Arm (ASCOT BPLA): a multicentre randomised controlled trial.

Lancet

. 2005;366:895-906.