HYPERTENSION ALGORITHM

UPDATE
Jennifer L. Simon, Pharm.D., CPP
PGY2 Ambulatory Care Pharmacy Resident
UNC Health Care
jlsimon@unch.unc.edu
Current IM Hypertension Algorithms
• Algorithms
• http://www.med.unc.edu/im/staff/clinic
• Hypertension without Diabetes
Clinic Tools HTN Protocol

• Hypertension with Diabetes

Clinic Tools DM Protocols

• Do not apply to patients with renal disease,

recent MI, or decompensated CHF
• Based on JNC7 Guidelines (2003)
Hypertension Algorithm Summary
• Blood pressure goals
• General population: < 140/90 mmHg
• Hypertension with diabetes: < 130/80 mmHg
• Preferred agents for General Population
• First-line
• Thiazide Diuretic : HCTZ
• ALLHAT Trial
• Second-line
• ACE inhibitor: Enalapril
• Third-line
• Beta-blocker (BB): Atenolol
• Calcium Channel Blocker (CCB): Amlodipine
Hypertension Algorithm Summary:
Preferred Agents for Diabetes
• First-line
• ACE inhibitor: Enalapril
• Second-line
• History of Coronary Artery Disease (CAD)
• Beta-blocker: Atenolol
• Without CAD
• Thiazide diuretic: HCTZ

• Third-line
• Thiazide diuretic: HCTZ
• Beta-blocker: Atenolol
New Guidelines for Hypertension
• National Institute for Health and Clinical Excellence (NICE),
2011
• Kidney Disease: Improving Global Outcome (KDIGO), 2012
• European Society of Hypertension/European Society of
Cardiology, (ESH/ESC), 2013
• American Diabetes Association (ADA), 2014
• American Society of Hypertension and the International Society
of Hypertension (ASH/ISH), 2014
• Eighth Joint National Committee (JNC8), 2013
Comparison of JNC Guidelines
JNC7
• Nonsystematic literature
review and expert opinion
• Range of study designs
• No grading system for
recommendations
• Recommendations:
• Lifestyle modifications
• Initial therapy for HTN
• Compelling indications
• Addressed secondary HTN and
resistant HTN
JNC8
• Systematic review
• Randomized, controlled
trials (RCT) only
• Graded recommendations
• Recommendations:
• No specific lifestyle
recommendations
• Initial therapy for HTN
• Racial, CKD, and diabetic
subgroups addressed
• Addressed three key questions
JNC8: Key Questions
• In adults with HTN, does initiating antihypertensive
pharmacologic therapy at specific BP thresholds improve
health outcomes?

• In adults with HTN, does treatment with antihypertensive

pharmacologic therapy to a specified BP goal lead to
improvements in health outcomes?

• In adults with HTN, do various antihypertensive drugs or drug

classes differ in comparative benefits and harms on specific
health outcomes?
JNC8: Methods
• Excluded sample size < 100 and f/up period < 1 year
• Only included randomized, controlled trials rated as
good or fair
• Only included studies reporting effects of
interventions on:
• MI
• Stroke
• ESRD, doubling of Scr, or halving of GFR
• Heart failure (HF) or hospitalization for HF
• Coronary revascularization or other revascularization
• Mortality (Overall mortality, CVD-related mortality, CKD-related
mortality)
JNC8: Strength of Recommendation
Grade Strength of Recommendation
A Strong: High certainty net benefit is substantial
Moderate
• Moderate certainty net benefit is moderate to
B
substantial, or
• High certainty that net benefit is moderate
C Weak: At least moderate certainty of small net benefit
Expert Opinion
• Insufficient evidence, or
E
• Evidence is unclear or conflicting
• Further research is recommended in this area
Recommendations for
General Population Age ≥ 60 Years
JNC 7 Evidence for JNC8
• BP Goal < 140/90 mmHg • HYVET Trial
(No age recommendations) • SHEP Trial
• JATOS Trial
JNC8 • VALISH Trial
• BP Goal < 150/90 mmHg
• Rated Grade A
Recommendations for
General Population Age < 60 Years
JNC 7
• BP Goal < 140/90 mmHg
JNC8
• SBP Goal < 140 mmHg
• Grade E
• DBP Goal < 90 mmHg
• Ages 30-59 years (Grade A)
• Ages 18-29 years (Grade E)
Evidence for JNC8
• HDFP Trial
• Hypertension-Stroke
Cooperative Trial
• MRC Trial
• ANBP Trial
• VA Cooperative Trial
Recommendations for
General Non-black Population (Including DM)
JNC 7 Evidence for JNC8
• First-line: Thiazide diuretics
• ALLHAT Trial
(no racial distinction made) • BP control more important
JNC8 than medication used
• Alpha blockers not
• First-line recommended first-line
• Thiazide diuretics • LIFE Study
• CCB • Beta-blockers not
• ACE inhibitor recommended first-line
• ARB • Insufficient evidence to
• Grade B recommend other classes
Recommendations for
General Black Population (Including DM)
JNC 7
• First-line: Thiazide diuretics
(no racial distinction made)
JNC8
• Initial treatment for black
population (Grade B) with
DM (Grade C)
• Thiazide diuretics
• CCB
ALLHAT Trial
• Pre-specified subgroup analysis
• Thiazide more effective in
improving CV outcomes
compared to ACEi in black
patient subgroup
• 51% higher rate of stroke (RR
1.51; 95% CI 1.22-1.86) with use
of ACEi as initial therapy in black
patients (compared to CCB)
• 46% of patients in subgroup
analysis had DM
Recommendations for
General Population Age ≥ 18 with CKD
JNC 7
• Goal BP: < 130/80 mmHg
• First-line agent: ACEi or ARB
JNC8
• Goal BP: < 140/90 mmHg
• Grade E
• Initial or add-on treatment:
ACEi or ARB
• Grade B
• Regardless of race or DM status
Evidence for JNC8
• AASK Trial
• MDRD Trial
• Potential benefit of goal
<130/80 for patients with
proteinuria (>3g/24 hours)
• REIN-2 Trial
• No trials showed goal
<130/80 mmHg significantly
lowered kidney or CV end
points compared to 140/90
Recommendations for
General Population Age ≥ 18 with DM
JNC 7 Evidence for JNC8
• Goal BP: < 130/80 mmHg • ACCORD-BP Trial
• No difference in outcomes with
SBP < 140 vs. SBP < 120
JNC8 • No good or fair quality trials
• Goal BP: < 140/90 mmHg to support DBP < 80
• Grade E
ADA Guidelines for 2014
• Goal BP for patients with DM
• Less than 140/80 mmHg
• ACCORD-BP trial
• HOT Trial
• Showed 51% reduction in major CV events in patients with DM
• Post-hoc analysis of small subgroup of the study (not pre-specified)
• Evidence graded as low quality by JNC8
• Preferred Agents
• ACEi or ARB
• HOPE Study
• Included non-hypertensive patients
• Decreased risk of stroke with ACEi
• Despite conflicting evidence, continue to recommend ACE/ARB
first-line
• Cite high CVD risk and high prevalence of undiagnosed CVD in patients
with DM
 Comparison of JNC8 and IM HTN Algorithm:
BP Goals
IM HTN Algorithm
• Age ≥ 60 years
• Not addressed
• General population: < 140/90
• No grade of evidence
• Hypertension & DM: < 130/80
• No grade of evidence
• ADA Guidelines: < 140/80
• Hypertension & CKD
• Not addressed
JNC8
• Age ≥ 60 years: < 150/90
• Grade A
• General population: < 140/90
• Grade E (Grade A: DBP, age 30-59)
• Hypertension & DM: < 140/90
• Grade E
• Hypertension & CKD: < 140/90
• Grade E
Comparison of JNC8 and IM HTN Algorithm:
Preferred Agents
IM HTN Algorithm JNC8
• General population • General population
• Thiazide Diuretic : HCTZ • Thiazide, CCB, ACEi, ARB (Grade B)
• Black population • Black population
• Not addressed • CCB or Thiazide (Grade B)
• DM • Grade C for black patients with DM

• ACEi or ARB • DM
• CKD • Thiazide, CCB, ACEi, ARB (Grade B)

• Excluded from algorithm • CKD

• ACEi or ARB (Grade B)
2014 IM HTN Algorithm Proposed Updates

Changes to Goal BP Changes to Preferred agents

• Patients age ≥ 60 years • General population
• Goal BP < 150/90 mmHg • Thiazide
• Patients with HTN and DM • CCB

• Goal BP < 140/80 mmHg • ACEi

• ARB
• Patients with HTN and CKD
• Goal BP < 140/90 mmHg • Black population
• Thiazide or CCB
Other Proposed Changes to IM Algorithm
Preferred Thiazide Preferred ACEi
• Chlorthalidone • Enalapril
• More potent • Twice daily
• 25mg= HCTZ 12.5
• Lisinopril
• Longer half-life
• Once-daily
• Used in ALLHAT and SHEP
• Used in ALLHAT trial
trials
• HCTZ
• Less expensive ($4 list)
JNC8: Treatment Strategies (Grade E)
• If goal BP not met after 1 month of treatment:
• Increase dose of initial drug, or
• Add a second drug (Thiazide, CCB, ACEi, or ARB)
• If goal BP not met with 2 medications:
• Add and titrate a third medication (Thiazide, CCB, ACEi, or
ARB)
• Do not use ACE and ARB together
• Other classes may be used in the following scenarios:
• Goal BP not met with 3 medications
• Contraindication to thiazide, ACE/ARB, or CCB
Strategies to Dose Antihypertensive Drugs
• Titrate to max dose, then add a second drug
• Add a second drug before achieving max dose
of the initial drug
• Start with 2 drugs at the same time
• If SBP ≥ 160mmHg and/or DBP ≥ 100 mmHg
• If SBP ≥ 20mmHg above goal and/or DBP ≥ 10mmHg
above goal
***Consider scheduling follow-up with the
Enhanced Care Clinic for titration of BP Meds
QUESTIONS?
Jennifer L. Simon, Pharm.D., CPP
PGY2 Ambulatory Care Pharmacy Resident
UNC Health Care
jlsimon@unch.unc.edu