Status Report on the NHLBI-Sponsored CVD Prevention Guidelines

Evidence-Based Clinical Practice Guidelines for CVD Prevention


HIGH BLOOD PRESSURE

Status Report on the

NHLBI-Sponsored

CVD Prevention Guidelines

Paul A. James, M.D.

Roy J. and Lucille A. Carver College of Medicine

The University of Iowa

Iowa City IA


Joint National Committee on

Prevention, Detection,

Evaluation, & Treatment of

High Blood Pressure (JNC)

JNC 7: 2003

JNC 6: 1997

JNC 5: 1992

JNC 4: 1988

JNC 3: 1984

JNC 2: 1980

JNC 1: 1976

Detection, Evaluation,

&Treatment of High Blood

Cholesterol

in Adults (ATP, Adult

Treatment Panel)

ATP III Update: 2004

ATP III: 2002

ATP II: 1993

ATP I: 1988

Clinical Guidelines on the

Identification, Evaluation, &

Treatment of Overweight

and Obesity in Adults

Obesity: 1998

NHLBI Adult CVD Prevention Guidelines

NHLBI-SPONSORED

ADULT CVD PREVENTION GUIDELINES

80

85

90

95

100

105

110

115

120

125

130

JNC I JNC II JNC III JNC IV JNC V JNC VI

Consider therapy

Hyper- tensive

Mild Mild Mild

Stage 1 Stage 1

Moderate Moderate Moderate

Stage 2

Severe Severe Severe Stage 3 Stage 3

Stage 2

Stage 4

High- normal

High- normal

High- normal

High- normal

Normal Normal Normal Normal

Optimal

DBP

(mm Hg)

Optimal

JNC 7

Stage 1

Stage 2

Prehyper- tension

Normal

JNC IV. Arch Intern Med. 1988;148:1023-1038.

JNC V. Arch Intern Med. 1993;153:154-183.

JNC VI. Arch Intern Med. 1997;157:2413-2446.

Chobanian AV et al. JAMA. 2003;289:2560-2572.

JNC I. JAMA. 1977;237:255-261.

JNC II. Arch Intern Med. 1980;140:1280-1285.

JNC III. Arch Intern Med. 1984;144:1045-1057.

Hypertension: A Moving Target JNC Classifications: Diastolic Blood Pressure

JNC V

Optimal 110

120

130

140

150

160

170

180

190

200

210

220

JNC IV. Arch Intern Med. 1988;148:1023-1038.

JNC V. Arch Intern Med. 1993;153:154-183.


Chobanian AV et al. JAMA. 2003;289:2560-2572.

JNC I JNC II JNC III JNC IV JNC VI

Border- line

ISH

Stage 1 Stage 1

Stage 2

Stage 3

High- normal

High- normal

Normal Normal

Optimal

SBP

(mm Hg)

Normal

Border- line

ISH

Stage 4

No recommendations

for SBP in JNC I

or JNC II

JNC 7

Stage 1

Prehyper- tension

Normal

Stage 3

Stage 2

JNC I. JAMA. 1977;237:255-261.

JNC II. Arch Intern Med. 1980;140:1280-1285.

JNC III. Arch Intern Med. 1984;144:1045-1057.

Hypertension: A Moving Target JNC Classifications: Systolic Blood Pressure

Stage 2


OPTIMAL < 120 and < 80

NORMAL < 130 and < 85

STAGE 1 140-159 or 90-99

STAGE 2 160-179 or 100-109

STAGE 3 ≥ 180 or ≥ 110

NORMAL < 120 and < 80

PREHYPERTENSION 120-139 or 80-89

STAGE 1 140-159 or 90-99

STAGE 2 ≥ 160 or ≥ 100

JNC 7 (2003) JNC VI (1997)

JNC 7 Emphasized Importance of

Lower Blood Pressure

HIGH NORMAL 130-139 or 85-89

JNC 7. JAMA. 2003;289(19):2560-2572.



Institute of Medicine Report:

Quality Chasm “In its current form, habits, and environment, American health

care is incapable of providing the public with the quality health

care it expects and deserves.”

Current: Decision making is based on training and experience.

New: Decision making is based on evidence.

Patients should receive care based on the best available

scientific knowledge. Care should not vary illogically from

clinician to clinician or from place to place.

Evidence-based Clinical Practice Guidelines can help make

this vision a reality

Institute of Medicine, Crossing the Quality Chasm: New Health System for the Twenty-first Century. Washington: National Academy Press, 2001


AHA LEVEL OF "A“ EVIDENCE IN CURRENT GUIDELINES*

*in guidelines

with level of

evidence

11.7%

26.4%

15.3%

13.5%

12.0%

22.9%

6.4%

6.1%

23.6%

0.3%

9.7%

11.0%

19.0%

4.9%

4.8%

0% 10% 20% 30%

AF

Heart failure

PAD

STEMI

Perioperative

Secondary prevention

Stable angina

SV arrhythmias

UA/NSTEMI

Valvular disease

VA/SCD

PCI

CABG

Pacemaker

Radionuclide imaging

Scientific Evidence Underlying ACC/AHA Guidelines (JAMA. 2009; 301: 831 – 841)



Recent Evidence is changing practice

New Evidence is causing us to question aggressive

disease management strategies

Important health outcomes rather than markers of disease

are being examined.

Examples:

ACCORD (2010): Diabetics not improved with tighter control.

JATOS (2008) and Valish (2010): Hypertension: no

improvement in outcomes with Goal BP of <140 mm Hg in

elderly compared to 150 mm Hg.

Courage (2007): Stable angina: no benefit with PTCA over

medical management



ACCORD Trial: A study that will change

our practice.

High risk patients for CVD with Type 2 DM: Average age = 62.2

years old. 1/3 had previous CV event.

Studied intensive management of diabetes, blood pressure

and lipids. Baseline: A1c = 8.3%, BP = 139/76, T.Chol = 193

mg/dl

Documented the harms of intensive (overly exuberant?)

therapy to manage risk factors for CVD.



ACCORD Trial

Blood Pressure goal among high risk patients for CVD:

Lower is not always better. Systolic BP<140 just as good

as BP<120 for major CV events. Only stroke rate

improved but overall mortality did not.

Glycemic control with A1c of 6.5% compared to 7.5% did

not reduce major CV events but mortality increased with

more intensive treatment.

Lipid control with fenofibrate added to simvastatin did not

reduce major CV events, nonfatal MI or nonfatal stroke.



ACCORD Trial

If we do not see benefit in high risk persons, we must question

the goals of therapy in lower risk individuals.

We need better RCT’s and we should not rely on observational

data.

There are many incentives within our current health care

system to prescribe and over treat. We must further assess the

harms.



Adult CVD Guidelines:

NHLBI approach Advice to NHLBI from advisory groups:

Update risk factor guidelines (hypertension, cholesterol, obesity)

Develop an integrated guideline

Use an evidence-based approach including systematic reviews

The NHLBI guideline development process

Was established to assure rigor and to minimize bias

Methods being used meet many of the new IOM standards

Two recent IOM reports set new standards

“Finding What Works in Health Care” – standards for systematic

reviews

“Clinical Practice Guidelines We can Trust” – standards for developing

trustworthy CPGs



Expertise Represented

Hypertension, primary care, cardiology, nephrology,

clinical trials, research methodology, evidence-based

medicine, epidemiology, guideline development and

implementation, nutrition/lifestyle, nursing,

pharmacology, systems of care, and informatics

Panel also includes senior scientists from NHLBI and

NIDDK with expertise in hypertension, clinical trials,

translational research, nephrology, guideline

development, and evidence-based methodology



Disclosures

4 panel members had relationships with industry to

disclose

13 panel members had no relationships to disclose

Panel members disclose their relationships and recuse

themselves from voting on evidence statements and

recommendations relevant to their relationships

Guideline Executive Committee Policy on Disclosures: http://www.nhlbi.nih.gov/guidelines/cvd_adult/coi-rwi_policy.htm



How the Process Has Evolved

Strictly evidence-based

Focus only on randomized controlled trials assessing important

health outcomes (no use of intermediate/surrogate measures)

Every included study is rated for quality by two independent

reviewers using standardized tools

Evidence statements graded for quality using prespecified criteria

Separate grading for recommendations

Independent methodology team to ensure objectivity of the review

Initial set of recommendations focused on 3 key questions



How Were Questions Selected?

Panel Chairs and NHLBI staff developed questions based on their

expertise, brief literature review, and speaking with colleagues

These questions were sent to panel members to review, revise,

and add or delete questions

Resulted in 23 questions, which were sent to all panel members

Panel members discussed these questions on conference calls, then

independently ranked the 3-5 questions felt to be of highest priority

The five highest ranked questions discussed further and

prioritized



Rationale for the Questions

Interest in assessing the evidence to support 140/90 mm Hg as a

treatment threshold or goal

Should the treatment threshold / goal be lower in populations with

diabetes, chronic kidney disease, coronary artery disease, stroke,

and other co-morbidities or characteristics?

Should the treatment threshold / goal be different in older adults?

Use of different treatment thresholds and goals is confusing

Is there evidence that treatment to lower BP with a particular drug

or drug class improves outcomes compared to another?



Question 1

Among adults with hypertension, does

initiating antihypertensive pharmacological

therapy at specific BP thresholds improve

health outcomes?

− When to initiate drug treatment?



Question 2

Among adults, does treatment with

antihypertensive pharmacological therapy

to a specified BP goal lead to

improvements in health outcomes?

− How low should you go?



Question 3

In adults with hypertension, do various

antihypertensive drugs or drug classes

differ in comparative benefits and harms on

specific health outcomes?

− How do you get there?



Inclusion/Exclusion Criteria

Randomized Controlled Trials

RCTs are subject to less bias and represent the gold

standard for determining efficacy and effectiveness1

Search dates: 1966 to present

Minimum one-year follow-up period

Studies with sample sizes less than 100 excluded

1 Institute of Medicine. 2011. Finding What Works In Health Care. Standards

For Systematic Reviews. Washington, DC: The National Academies Press.



Populations Included

Adults 18 years of age and

older

Prespecified subgroups

including:

Diabetes

Chronic kidney disease

Proteinuria

Coronary artery disease

Peripheral artery disease

Previous stroke

Heart Failure

Older Adults

Men and women

Racial and ethnic groups

Smoking



Outcomes

Overall mortality, CVD-related mortality, CKD-related mortality,

myocardial infarction, heart failure, hospitalization for heart

failure, stroke

Coronary revascularization (includes coronary artery bypass

surgery, coronary angioplasty and coronary stent placement),

peripheral revascularization (includes carotid, renal, and lower

extremity revascularization)

End stage renal disease (i.e., kidney failure resulting

in dialysis or transplant), doubling of creatinine, halving of

eGFR


Articles Screened = 1496

Good = 8

Included = 44

Total Abstracted = 26

Excluded = 1452 (Did not meet prespecified

inclusion criteria)

Poor = 18 Fair = 18

Question 1: Among adults with hypertension, does

initiating antihypertensive pharmacological therapy at

specific BP thresholds improve health outcomes?



Good = 17

Included = 92



inclusion criteria)

Poor = 36 Fair = 39

Question 2: Among adults, does treatment with

antihypertensive pharmacological therapy to a specified

BP goal lead to improvements in health outcomes?



Good = 15

Included = 101



inclusion criteria)

Poor = 35 Fair = 51

Question 3: In adults with hypertension, do various

antihypertensive drugs or drug classes differ in comparative

benefits and harms on specific health outcomes?



Data Abstraction and

Evidence Tables

Information from individual studies

Key data abstracted into a database

Evidence table for each study/paper: subjects, sample size, intervention, comparison, results

Evidence summaries by Critical Question

Tables and text of major elements relevant to the CQ

Graded evidence statements

Multiple ESs for each CQ

Graded recommendations based on the evidence

Multiple ESs could result in a single recommendation

27



NHLBI EVIDENCE QUALITY GRADING AND

RECOMMENDATION STRENGTH

Evidence Quality

High

Well-designed and conducted RCTs

Moderate

RCTs with minor limitations

Well-conducted observational studies

Low

RCTs with major limitations

Observational studies with major limitations

Recommendation Strength

A – Strong

B – Moderate

C – Weak

D – Against

E – Expert Opinion

N – No Recommendation

28



Adult CV Guideline

Report Content Methods description

Critical Questions

With study eligibility criteria and rationale

Summary of evidence for each CQ

Summary tables and text ( e.g. “24 studies, 10 RCTs…)

Graded evidence statements (ES)

Rationale for ES based on specific studies or previous systematic reviews

Graded High, Medium, Low

Graded recommendations

Rationale for the recommendation based on the evidence

Graded A, B, C, D, E, or N

Reference citations

29



Conclusion

The new NHLBI-sponsored adult CV guideline reports

Are strictly evidence based

Will not look like the previous guidelines

Will have more depth and rigor; will have less breadth

Will be released in 2012, one at a time as they are ready

Will subsequently be integrated

Will use evidence based strategies for Implementation

30



Next Steps

Evidence statements and recommendations (in progress)

Draft report (in progress)

Review of the draft report by:

Other federal agencies (CDC, CMS, AHRQ, HRSA, VA, etc.)

Invited organizations and individuals

Public

Revisions based on comments received

Final report



THANK YOU!

For more information on the NHLBI guidelines, go to:

http://www.nhlbi.nih.gov/guidelines/index.htm



Committee Members

Co-Chair: Suzanne Oparil, MD

Professor of Medicine and Physiology &

Biophysics, Director, Vascular Biology and

Hypertension Program, Division of

Cardiovascular Disease, Department of Medicine

University of Alabama at Birmingham School of

Medicine

Jackson T. Wright, Jr., MD, PhD

Director, Clinical Hypertension Program

Director, William T. Dahms Clinical Research

Unit, University Hospitals Case Medical Center

Professor of Medicine

Case Western Reserve University

Sandra J. Taler, MD

Associate Professor of Medicine

Division of Nephrology and Hypertension

Mayo Clinic College of Medicine

Co-Chair: Paul A. James, MD

Professor and Head, Department of Family

Medicine in the Carver College of Medicine,

Professor of Occupational and Environmental

Health in the College of Public Health, Donald J.

and Anna M. Ottilie Endowed Chair in Family

Medicine

University of Iowa

Laura Svetkey, MD, MHS

Director, Duke Hypertension Center

Director of Clinical Research at the Sarah W.

Stedman Nutrition and Metabolism Center


Duke University

Michael L. LeFevre, MD, MSPH

Professor, Department of Family and Community

Medicine, University of Missouri



Committee Members

Joel Handler, MD

Clinical Lead for Hypertension

Care Management Institute

Kaiser Permanente

Southern California Permanente Medical Group,

Department of Internal Medicine

Barry L. Carter, PharmD

Professor, Department of Pharmacy Practice and

Science, College of Pharmacy

Professor and Associate Head, Research

Department of Family Medicine

University of Iowa

Daniel T. Lackland, DrPH

Professor, Epidemiology and Medicine

Department of Biostatistics, Bioinformatics, and

Epidemiology

Medical University of South Carolina

Raymond R. Townsend, MD

Director, Hypertension Section


Department of Internal Medicine−Renal

University of Pennsylvania

William C. Cushman, MD

Chief, Preventive Medicine, Veterans Affairs

Medical Center

Lead Consultant in Hypertension to VA Medical

Service

Professor, Preventive Medicine and Medicine

University of Tennessee

Thomas D. MacKenzie, MD, MSPH

Chief Quality Officer, Denver Health and Hospital

Authority


University of Colorado School of Medicine



Committee Members

Sidney C. Smith, Jr., MD, FACC, FAHA, FESC

Director, Center for Cardiovascular Science and

Medicine, Professor of Medicine

University of North Carolina at Chapel Hill

Olugbenga Ogedegbe, MD, MPH, MS, FAHA


Division of General Internal Medicine

Department of Medicine

New York University School of Medicine

Cheryl Dennison Himmelfarb, RN, ANP, PhD,

FAAN

Associate Professor

Department of Health Systems and Outcomes

Johns Hopkins University School of Nursing

Division of Health Sciences Informatics

Johns Hopkins University School of Medicine

Andrew S. Narva, MD (Ex-Officio)

Director, National Kidney Disease Education

Program

Division of Kidney, Urologic and Hematologic

Diseases

National Institute of Diabetes and Digestive and

Kidney Diseases

Lawrence J. Fine, MD, DrPH (Ex-Officio)

Chief, Clinical Applications and Prevention Branch

Division of Prevention and Population Science

National Heart, Lung, and Blood Institute

Eduardo Ortiz, MD, MPH (NHLBI Lead,

Ex-Officio, Non-Voting Member)

Senior Medical Officer

Division for the Application of Research

Discoveries

National Heart, Lung, and Blood Institute

National Institutes of Health

Documents

Status Report on the NHLBI-Sponsored CVD Prevention Guidelines