Transcript Targeting cardiometabolic risk in patients with intra

Thank you for joining us.
Managing Hypertension in the
African American Population
The webinar will begin promptly at 11:30 a.m. (CST) / 12:30 p.m. (ET)
Please standby
This presentation is brought to you by
Managing Hypertension in
the African American
Population
Quality Insights Quality Innovation Network
January 15, 2015
Keith C. Ferdinand, MD, FACC, FAHA, FNLA, FASH
Professor of Clinical Medicine,
Tulane University School of Medicine
Keith C. Ferdinand, MD
Has disclosed the following affiliations. Any real or
apparent COIs related to the presentation have
been resolved.
Speaker’s Bureau
-None
Grant/Research Support
-Boerhinger Ingelheim, Lilly
Consultant
-Astra Zeneca, Amgen, Sanofi, Boerhinger
Ingelheim
Learning Objectives
• Describe the impact of hypertension (HTN)
in African American (AAs)
• Review treatment of HTN, including
therapeutic lifestyle and unique
pharmacotherapy, especially resistant HTN
in AAs
• Describe best practices, new guidelines and
reports for current goals for blood pressure
control
Introduction
• Health, life expectancy, and care
improved dramatically for Americans
over last century
• Distribution of benefits not occurred
equitably
–Current mortality gap between black &
white persists since 19601
• Large portion of disparity due to CVD2
1. Smedley et al [eds]. Unequal treatment: Confronting racial and ethnic disparities in
health care. National Academies Press, 2002
2. Wong et al. NEJM 2002;347(20)1585-92
Development of Hypertension
Guidelines: the JNCs and Drug and
ASH/ISH
Device Therapy
ESC
JNC I
Earliest
Guidelines
1972
NHBPEP
STARTS
JNC III
JNC II
JNC 7
JNC V
JNC IV
1973 1976 1980 1984
ACC/AHA/CDC
“JNC 8”
JNC VI
1988 1993
1997
2003
34 drugs
Diuretics
28 drugs
DBP 105
Diuretics
84 drugs
50 drugs
7 options
ACEI, CAs
added
43 drugs
68 drugs
> 125 drugs
Low-dose
Diuretics
Diuretics/
diuretics,
b-blockers
b-blockers
Added
2014-15
JNC = Joint National Committee
RD=renal denervation
BAT and
RD
Devices?
BAT=Baroreflex Activation Therapy
Costs & Consequences of Unmanaged HTN:
Organ Damage
Hypertension
TIAs, stroke,
dementia
LVH, CHD,
HF, angina
Peripheral arterial
disease
Chronic kidney
disease
CHD=coronary heart disease; HF=heart failure; LVH=left ventricular hypertrophy
Chobanian AV, et al. Hypertension. 2003;42:1206-1252.
Long-term Anti-HTN Therapy
Significantly↓ CV Events
Stroke
0
Average
reduction
in events
(%)
Myocardial
infarction
Heart failure
-10
-20
20%25%
-30
-40
-50
-60
35%-40%
N= 201,566
Blood Pressure Lowering Treatment
Trialists’ Collaboration. Lancet. 2000;355:1955-1964.
>50%
CVD Deaths U.S. 1900-2008
National Center for Health Statistics
●
Age-adjusted prevalence trends for HBP in adults ≥20
years of age by race/ethnicity, sex
Heart Disease and Stroke Statistics—2015 Update Circulation. 2015;131
Age-adjusted prevalence trends for HBP in adults ≥20
years of age by race/ethnicity, sex
Heart Disease and Stroke Statistics—2015 Update Circulation. 2015;131
Extent of awareness, treatment, and control of HBP
by race/ethnicity (NHANES: 2007–2012).
●
●
●
Heart Disease and Stroke Statistics—2015 Update Circulation. 2015;131
Hypertension: a common and manageable chronic
condition – recent national data from 2011–2012
• HTN treatment (75.7%) exceeded Healthy People
(HP) 2020 target goal of 69.5%
• 51.9% BP controlled <140/90 mm Hg
• However, control of HTN neither met goal of the HP
2020 (61.2% by 2020)
• Nor the Million Hearts Initiative (65% by 2017)
• “These results provide evidence for continued
efforts to improve the management of hypertension
in order to attain these goals”
Nwankwo T, Yoon SS, Burt V, Gu Q. Hypertension among adults in the US: National Health and Nutrition
Examination Survey, 2011–2012. NCHS data brief, no 133. Hyattsville, MD: National Center for Health
Statistics. 2013
Heart Disease & Stroke Mortality Disparities
• Black men & women much more likely to die
of heart disease & stroke than whites
• CHD & stroke not only leading cause of
death in the U.S., but also account for
largest proportion of inequality in life
expectancy between whites & blacks
• Despite existence of low-cost, highly
effective preventive treatment
MMWR. January 14, 2011. Vol. 60. No. 1 pp 1.
Mortality from HTN Higher in Blacks
Overall Mortality Rates from Causes Related to
HTN, 2010
Mortality Rate, %
60
50
50.2
37.1
40
30
15.0
17.2
20
10
0
Male
Female
Male
Black
Heart Disease and Stroke Statistics – 2014 Update. Circulation. 2014;129:e28-e292.
Female
White
Salient Aspects of HBP in Blacks
• Increased incidence of target organ
damage, including stroke, MI mortality,
LVH, HF, retinopathy and CKD/end-stage
renal disease, especially premature
• HTN prevalence in U.S. blacks among the
highest in the world
• Compared with whites, blacks develop
HTN at an earlier age and average BPs
much higher
Flack JM et al for the International Society on Hypertension in Blacks.
Hypertension. 2010;56:780-800.
Ferdinand KC, Ferdinand DP. Expert Rev Cardiovasc Ther. 2008;10:1357-1366.
Projected HF: Race/Ethnicity 2012-2030
Heidenreich, Albert, NM et al Circ Heart Fail. 2013;6:00-00
Complications: Kidney Disease
• ESRD incidence has risen significantly among AAs
www.usrds.org http://www.usrds.org/2012/pdf/v2_ch1_12.pdf
Life Expectancy at Birth
CDC/NCHS, Health, United States, 2012, Figure 1. National Vital Statistics System.
Hypertension in
African Americans:
Unique Aspects?
Potential Physiologic and Hemodynamic
Determinants of HTN in Blacks
• Obesity-Non-Hispanic blacks highest age-adjusted
rates (47.8%) followed by Hispanics (42.5%), nonHispanic whites (32.6%)
• Higher salt sensitivity2
• Low levels of plasma renin2
• Vascular function (sympathetic overactivity)2
• Attenuated nocturnal fall in blood pressure3
• Greater comorbidity (especially diabetes)2
• Inactivity1
• Family history1
1. Heart Disease and Stroke Statistics – 2014 Update. Circulation. 2014;129:e28-e292
http://www.cdc.gov/obesity/data/adult.html/
2. Gadegbeku CA et al. Med Clin North Am. 2005;89:921-933
3. Profant J et al. Hypertension.1999;33:1099-1104
Individual
-biology
-genotype
DISEASE
Environment
-diet, lifestyle
-SES,
exposures
“Race”
is a crude
proxy.
Social Determinants of Health
• The circumstances in which people
are born, grow up, live, work, and
age, as well as the systems put in
place to deal with illness
• These circumstances in turn shaped
by a wider set of forces: economics,
social policies, and politics
www.cdc.gov/socialdeterminants
Addressing Cultural Contexts in Health
Care
HEALTH
CARE
SYSTEM
FAMILY
PATIENT
COMMUNITY
HEALTH
CARE
PROVIDER
T.D. Goode. The National Center for Cultural Competence. 2005
According to the IOM, what five risk factors
constitute the bulk of the HTN problem?
•
•
•
•
•
Overweight
Unhealthy diet
Lack of physical activity
High sodium intake
Low potassium intake
Institute of Medicine. A Population-Based Policy and Systems Change
Approach to Prevent and Control Hypertension. Washington, DC: The
National Academies Press, 2010.
Three Therapeutic Approaches
• Therapeutic Lifestyle Changes
(Non-pharmacological)
• Pharmacotherapy
• Future Interventions - Devices
Lifestyle Modification:
Indicated All Patients w/ HTN
Modification
~SBP Reduction
Weight reduction
5-20 mm Hg
(in overweight patients)
(10-kg weight loss)
Adopt DASH eating plan
8-14 mm Hg●
Dietary sodium reduction
2-8 mm Hg●
Increase physical activity
4-9 mm Hg
Moderation of alcohol
intake
2-4 mm Hg
Chobanian AV, et al. JAMA. 2003;289(19):2560-2572.
Sacks FM, et al; DASH-Sodium Collaborative Research Group. N Engl J Med. 2001;344(1):3-10.
Kotchen TA et al.
N Engl J Med
2013;368:12291237
Risk Factor: Sodium and Potassium Levels
• Middle-aged and older individuals, African
Americans, and individuals consuming
>1500 mg of sodium/day tend to battle HTN
• One of the most prevalent and modifiable
HTN risk factors is inadequate consumption
of K+
• Only 2% of U.S. adults meet current
guideline for dietary potassium (at least 4.7
grams/day)
Institute of Medicine. A Population-Based Policy and Systems Change Approach to Prevent and Control Hypertension.
Washington, DC: The National Academies Press, 2010.
DASH Diet
• BP can be significantly reduced with diet
abundant in fruits, vegetables, complex
carbohydrates, and low-fat dairy
• The DASH diet includes these daily
servings:
DASH = Dietary Approaches to Stop Hypertension
http://www.nhlbi.nih.gov/health/public/heart/hbp/dash/new_dash.pdf
Mean SBP Changes in DASH-Sodium Trial
Appel L J et al. Hypertension 2006;47:296-308
Treatment Advances: Medications
• For all patients, including blacks, thiazide-type diuretics
and CCBs effective as initial therapy and well-tolerated
• First-line therapy: diuretics to reduce BP, stroke, heart
failure (HF) and overall CVD, and CCBs similarly,
except for new onset HF
• When additional agents needed, thiazides and CCBs
increase the efficacy of agents such as BBs, ACEIs,
and ARBs
• If BP not at goal, optimize doses or add additional
drugs until goal BP is reached
Chobanian AV, et al. Hypertension. 2003;42:1206-1252.
Ferdinand KC, Ferdinand DP. Expert Rev Cardiovasc Ther. 2008;10:1357-1366.
Uncontrolled Blood
Pressure
Pseudoresistance
• Poor BP
technique
• Poor adherence
• Whitecoat effect
Resistant
Hypertension
Medications that Can Interfere with BP Control
• NSAIDs, including COX-2 inhibitors
• Sympathomimetic agents (decongestants,
diet pills, cocaine)
• Stimulants (amphetamines)
• Alcohol
• Cyclosporine
• Erythropoietin
• Natural licorice
• Herbal compounds (ephedra or ma huang)
Calhoun DA et al. Circulation. 2008;117:E510.
Ferdinand,K. and Nasser,S. Curr Cardiovasc Risk Rep
DOI 10.1007/s12170-012-0252-2
Drug Classes Used to Treat Hypertension
•
•
•
•
•
•
•
•
•
•
Thiazide and Loop Diuretics
Calcium Channel Blockers
Angiotensin-converting Enzyme Inhibitors
Angiotensin Receptor Blockers
Renin Inhibitors
Aldosterone Blockers and Potassium Sparing
Diuretics
Ɓeta-adrenergic Blockers
Alpha 1 Adrenoreceptor Antagonists
Direct-acting Vasodilators
Central Sympatholytic Drugs
ALLHAT Baseline Characteristics
JAMA. 2002;288:2981-2997
Chlorthalidone
Amlodipine
Lisinopril
15,255
9,048
9,054
146 / 84
146 / 84
146 / 84
Mean age, y
67
67
67
Black, %
35
36
36
Women, %
47
47
46
Hx of CHD, %
26
24
25
Type 2 DM, %
36
37
36
Mean SBP/DBP
Pooled Estimates of Decrement in BP
with Antihypertensive Treatments
Mean BP Reduction*
Drug
Category
Whites
11.5/9.1
Diuretics
15.3/12.6
CCBs
β-Blockers 11.7/11.3
12.8/11.4
ACE-Is
Blacks
WhiteBlack
Difference
15.0/10.7
16.9/13.3
5.9/9.5
8.5/8.0
–3.5/–1.5
–2.4/–0.6
6.0/2.9
4.6/3.0
White-black response difference: negative values indicating greater
response in blacks and positive indicating greater response in whites.
SBP/DBP
Brewster LM, et al Ann Intern Med 2004; 141:614-627
Number of Antihypertensive Agents
Required to Achieve BP Goal
UKPDS (<85 mm Hg, diastolic)
MDRD (92 mm Hg, MAP)
HOT (<80 mm Hg, diastolic)
AASK (<92 mm Hg, MAP)
RENAAL (<140/90 mm Hg)
IDNT (135/85 mm Hg)
1
MAP = mean arterial pressure
2
3
4
Number of BP Medications
Bakris et al. Am J Kidney Dis. 2000;36:646-661; Brenner et al. N Engl J Med. 2001;345:861-869;
Lewis et al. N Engl J Med. 2001;345:851-860.
Angioedema
Bramante RM, Rand M. N Engl J Med 2011;365:e4.
ALLHAT
Black vs. Non-Black
Lisinopril/Chlorthalidone
RR and 95% Cls
Non-Black
Black
Nonfatal MI + CHD
Death
1.10 (0.94 - 1.28)
0.94 (0.85 - 1.05)
All-Cause Mortality
1.06 (0.95 - 1.18)
0.97 (0.89 - 1.06)
Combined CHD
1.15 (1.02 - 1.30)
1.01 (0.93 - 1.09)
Combined CVD
1.19 (1.09 - 1.30)
1.06 (1.00 - 1.13)
1.40 (1.17 - 1.68)
1.00 (0.85 - 1.17)
1.29 (0.94 - 1.75)
0.93 (0.67 - 1.30)
1.30 (1.10 - 1.54)
1.13 (1.00 - 1.28)
Stroke
End Stage Renal
Disease
Heart Failure
Wright JT, et al., JAMA
2005:293:1595-1608
0.50
Favors
Lisinopril
1
2
Favors
Chlorthalidone
0.50
Favors
Lisinopril
1
2
Favors
Chlorthalidone
Additional BP Reduction w/ Spironolactone
Resistant HTN
Pimenta, Calhoun, Oparil. Arq Bras Cardiol 2007; 88(6) : 604-613
Spironolactone Practical Considerations
• Dosing 12.5–50 mg daily
Generally well tolerated up to 25
mg
Eplerenone 50-100 mg/d (less
potent but favorable side-effects)
• Breast tenderness/gynecomastia
dose dependent
Spironolactone Practical Considerations
• Hyperkalemia uncommon if
good renal function and
K+<4.5 meq/L
• CKD, ACEI/ARB, renin
inhibitor, NSAIDs increase
risk
Treatment of Resistant Hypertension
•Withdrawal or down titration interfering
substances
•Use adequate long-acting thiazide,
preferably chlorthalidone
• Combine different mechanisms of action
• Recommended triple regimen:
- ACE inhibitor or ARB
- Calcium channel blocker
- Thiazide diuretic
Calhoun, D. A. et al. Circulation. 2008;117:e510-e526.
Resistant HTN: Optimal Use of Diuretics
• For thiazides, less effective eGFR
falls <50 ml/min/1.73 m2
• Chlorthalidone still effective to
eGFR 40 ml/min/1.73 m2 if
hypoalbuminemia or hyperkalemia
not present
Pantelis A. et al: JACCl, 11-25-08; 52: 1749 - 1757
Loop Diuretics
When eGFR <30-40 mL/min
(serum creatinine ~>2.5
mg/dL), use a loop diuretic
Izzo JL, Sica DA, Black HR, eds, Hypertension Primer. 4th ed.2008:439-445
Emerging Interventions for
Resistant HTN
1.Baroreflex Activation
Therapy (BAT)
2. Renal Denervation
The
Renal/central
SNS
Bertog, S. C.
et al. J Am
Coll Cardiol
Intv
2012;5:249258
Baroreflex Activation Therapy (BAT)
Continuously Modulates Autonomic Nervous System
Carotid Baroreceptor Stimulation
Brain
Autonomic Nervous System
Inhibited Sympathetic Activity
Enhanced Parasympathetic Activity
De Leeuw. ESC. 2011.
Heart
Vessels
Kidneys
↓ HR
↑ Vasodilation
↓ Stiffness
↑ Natriuresis
↓ Renin
secretion
Catheter-based
Renal Denervation
(RD) Procedure
Renal Sympathetic Activation: Afferent Nerves
Kidney as Origin of Central Sympathetic Drive
Vasoconstriction
Atherosclerosis
Insulin
Resistance
Sleep
Disturbances
Renal
Afferent
Nerves
Hypertrophy
Arrhythmia
Oxygen Consumption
↑ Renin Release  RAAS
activation
↑ Sodium Retention
↓ Renal Blood Flow
N Engl J Med April 10, 2014
Primary Efficacy Endpoint
Δ = -2.39 (95% CI, -6.89 to 2.12)
Office SBP (mm Hg)
P=0.26*
Δ = -14.1±23.9
Δ = -11.7±25.9
P<0.001
P<0.001
180 mm Hg
180 mm Hg
168 mm Hg
166 mm Hg
(N=364)
(N=353)
*P value for superiority with a 5 mm Hg margin; bars denote standard deviations
(N=171)
(N=171)
Bhatt DL, Kandzari DE, O’Neill WW, et al. Bakris GL. N Engl J Med 2014
Best Practices:
Recent Guidelines
Effective for BP Control
2015 and Beyond
Major ISHIB Recommendations
• Goal or target BP levels viewed as
ceilings not floors
• Chlorthalidone is preferred thiazide-like
diuretic (eg, not HCTZ)
• Significant emphasis on HTN treatment in
special situations
– Limited financial resources
– Resistant HTN
• De-emphasize monotherapy; focus on
combination therapy
Flack JM, et al for the International Society on Hypertension in Blacks.
Hypertension. 2010;56:780-800.
BP Targets in Chronic Kidney Disease
(CKD)
● 3 RCTs (8 reports), total of 2272 participants:
MDRD (Modification of Diet in Renal Disease)
Study
AASK (African American Study of Kidney
Disease and Hypertension) Trial
REIN-2 (Ramipril Efficacy in Nephropathy 2)
trial
● No conclusive evidence favoring a BP target of
<125/75 to 130/80 mm Hg rather than <140/90
mm Hg.
Upadhyay A, et al (Tufts). Annals Intern Med 2011
Primary Outcome: Nonfatal MI,
Nonfatal Stroke or CVD Death
Patients with Events (%)
20
15
N Engl J Med
2010;362:15631574
10
HR = 0.88
95% CI (0.73-1.06)
5
0
0
1
2
3
4
5
6
7
Years Post-Randomization
8
BP Targets and Achieved BP: HTN in Elderly
SHEP1
Syst-Eur2
HYVET3
4736
4695
3845
Inclusion BP
Criteria (mm Hg)
160-219 / <90
160-219 / <95
160-190 / <110
Goal SBP (mm Hg)
<160 or
≥20
reduction
< 150 or ≥
20
reduction
<150
Mean Achieved BP
(mm Hg)
143/68
151/79
144/78
Follow-up (y)
4.5 (mean)
2.0 (median)
1.8 (mean)
Subjects (n)
1. SHEP Cooperative Research Group. JAMA. 1991
2. Staessen JA, et al. Lancet. 1997;350 3.Beckett NS, et al; for HYVET Study Group. N Engl J Med. 2008.
Risk of Adverse Outcomes
Elderly CAD Patients by Age & BP
Denardo et al. Am J
Med 123:719-726, 2010
BP nadirs indicate BPs with lowest hazard ratio at each age.
JAMA.
2014;311(5):507-520.
James,
Paul A. et al
doi:10.1001/jama.2013.284427
JAMA.
doi:10.1001/jama.2013.
284427
online December 18,
2013.
2014 US Guideline: Methodology
• Based on trials with >100 adults,
mortality/hard morbidity endpoints
– Mortality, CVD–, CKD–related mortality
– MI, heart failure, stroke,
revascularization
– ESRD, doubling of creatinine level,
halving of GFR
JAMA. 2014;311(5):507-520. doi:10.1001/jama.2013.284427.
Initial Medications for the
Management of Hypertension
Lifestyle Modification—Especially Diet and Exercise
Diuretics
b-blockers should be included in
Black population
the regimen if there is a compelling
indication for a b-blocker
ACE inhibitors
or
ARBs
JAMA 2014; 311(5): 507-520. Feb 5, 2014
Calcium
antagonists
James PA, et al. JAMA. 2014;311(5):507-520.
Five Guideline Authors Reject Change In
Blood Pressure Goal!
Original Research | 14 January 2014
Evidence Supporting a Systolic Blood Pressure Goal of Less Than 150
mm Hg in Patients Aged 60 Years or Older: The Minority View FREE
ONLINE FIRST
Jackson T. Wright Jr., MD, PhD; Lawrence J. Fine, MD, DrPH; Daniel T.
Lackland, PhD; Gbenga Ogedegbe, MD, MPH, MS; and Cheryl R. Dennison
Himmelfarb, PhD, RN, ANP
JACC Vol.64,No.4,2014
JACC, Vol.64,No.4,2014
Potential Value of Single-Pill Combinations
• Greater convenience
– Less pill burden for patients vs. taking pills
separately
• Fewer titration steps
– In appropriate patients, beginning treatment
with SPCs may help reduce added steps of
titrations, add-ons, or switches that delay
achievement of BP goal
• Improved long term adherence
Chobanian AV, et al. Hypertension. 2003;42:1206-1252.
Algorithm AHA, ACC, and CDC
Go,AS
et al J
Am
Coll
Cardiol
. 2013;
Improved BP Control Associated with a Large-Scale
Hypertension Program
JAMA. 2013;310(7):699-705.
doi:10.1001/jama.2013.108769
Barriers & Strategies for
Achieving Goals
• Barriers to BP control exist at the:
- Patient level
- Provider level
- System level
Odedosu T, et al. Cleve Clin J Med. 2012;79(1):46-56.
Chowdhury EK, et al. J Hum Hypertens. 2013;27(9):545-551.
Barriers to HTN Control in AAs:
Patient-Related
• Lack of awareness
of disease and
consequences
• Lack of access to
patient education
• Delayed diagnosis ●
• Living in
disadvantaged
community ●
• Inadequate resources
to support healthful
lifestyle
• Poor diet ●
• Overweight, obesity ●
• Distrust of medical
professionals ●
• Adverse view of
medications ●
Douglas et al. Postgrad Med online. 2002;112.
Why Are We Not Achieving
BP Control?
Clinician Behavior:
Clinical inertia
Provider-Related Barriers to
Achieving Goal BP
• Failure to recommend treatment for patients with
HBP
• Nonadherence to evidence-based treatment
guidelines
• Failure to increase number and dose of treatments
• Failure to intensify the regimen if goals are not met
• Failure to emphasize therapeutic lifestyle changes
Odedosu T, et al. Cleve Clin J Med. 2012;79(1):46-56.
Chowdhury EK, et al. J Hum Hypertens. 2013;27(9):545-551.
Patient-Related Barriers to Achieving Goal BP
• Poor knowledge about HTN and its
consequences
• Poor adherence to medication
• False health beliefs
• Inability to change one’s lifestyle
• Side effects of antihypertensive drugs
• Unrealistic expectations of treatment (eg, cure)
• Demographic factors (eg, socioeconomic
status, education level, age, sex)
Odedosu T, et al. Cleve Clin J Med. 2012;79(1):46-56.
Chowdhury EK, et al. J Hum Hypertens. 2013;27(9):545-551.
Eight Dimensions of Patient-Centered Care
1. Respect for patients’ values, preferences and
expressed needs
2. Coordination and integration of care
3. Information and education
4. Physical comfort
5. Emotional support and alleviation of fear and anxiety
6. Access to care
7. Involvement of family and friends
8. Continuity and transition
National Research Corporation. 2014.
http://www.nationalresearch.com/products-and-solutions/patient-andfamily-experience/eight-dimensions-of-patient-centered-care/
What Can You Do?
• Six steps to improving patient understanding
1. Limit the amount of information provided at each visit
2. Slow down
3. Avoid medical jargon
4. Use pictures or models to explain important concepts
5. Assure understanding with the “show-me” technique
6. Encourage patients to ask questions
Weiss BD. Health Literacy and Patient Safety: Help Patients Understand. Manual
for Clinicians, 2nd edition. Chicago, IL: American Medical Association
Foundation, 2007
Take Home
Messages
Generalized Treatment Recommendations
• Lifestyle modifications (weight loss,
exercise, low-salt)
• Standard triple regimen: ACEI or
ARB, thiazide-like diuretic, and
long-acting CCB
• Preferential use of chlorthalidone
Generalized Treatment Recommendations
• Consider aldosterone antagonist
(spironolactone, eplerenone,
amiloride) as fourth drug
Generalized Treatment Recommendations
• Vasodilating beta-blocker as fifth drug
• Centrally-acting agent as fifth drug
(clonidine, guanfacine)
• Vasodilating agents (hydralazine,
minoxidil)
• Low dose reserpine last resort
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