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JNC 8:
Applying the New Guidelines to the
Individual with Hypertension
Wendy L. Wright, MS, RN, APRN, FNP, FAANPAdult/Family Nurse Practitioner
Owner – Wright & Associates Family Healthcare @ Amherst, NH
Owner – Wright & Associates Family Healthcare @ Concord, NH
Partner – Partners in Healthcare Education, LLC
Disclosures
• Speaker Bureau: Novartis, GSK, Sanofi-Pasteur, Merck, Takeda, Vivus, Arbor
• Consultant: Vivus, Sanofi-Pasteur, Takeda
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Objectives
• Upon completion of this lecture, the participant will be able to:
– Differentiate between stages of hypertension (Pre-hypertension through Stage 2) given blood pressure
– Identify potential target organ damage secondary to hypertension
– Discuss impact of selected classes of hypertensive medications relative to attenuation of target organ damage; including the importance of combination therapy
– Implement and monitor impact of selected agents on blood pressure and target organ damage
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CVD Is the Most Common Health Problem in the United States
More than 60 million Americans
(>20%) have some form of
cardiovascular disease
Adapted from American Heart Association. Heart Disease and Stroke Statistics – 2003 Update. Dallas, Tex; 2002.
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Evolution in Understanding Cardiovascular Disease: Total Risk Perspective
Cardiovascular Disease Is an Interplay of Risk Factors
Age Gender
SmokingDyslipidemia Hypertension
Diabetes
Mellitus
Kannel WB. Am J Hypertens. 2000;13:3S-10S; Poulter N. Am J Hypertens. 1999;12:92S-95S.
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Impact of Hypertension
• Hypertension is the most common condition seen in primary care
• 50 million individuals in the United States have hypertension1
• 277,000 deaths annually in US due to hypertension2
1American Association of Clinical Endocrinologists Medical Guidelines For Clinical Practice for the Diagnosis and Treatment of Hypertension. Endocrine Practice, Vol 12 No. 2 March/April 20062National Center for Health Statistics. Health, United States, 2005, with Chartbook on the Health of Americans. Hyattsville, Maryland: 2004. Available at: http://www.cdc.gov/nchs/hus.htm
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Hypertension Remains One of the Most Important Multipliers of CV Risk
BP >140/90 mm Hg is associated with:
• 277,000 deaths in 2003
BP, blood pressure; CHF, congestive heart failure; MI, myocardial infarction.
Rosamond W et al. Circulation. 2007;115:1-103.7Wright, 2014
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It is currently estimated that…
• 90% of normotensive 55 year olds will develop hypertension at some point in his/her lifetime
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Hypertension and Management:Old School
Hypertension = Systemic disease
Hemodynamics altered
Treat the blood pressure
Therapeutic options
BetaBlockers
ACE ARB Diuretics CCB Others
Adapted from Vascular Biology Working Group, University of FloridaCollege of Medicine, Carl Pepine, MD, DirectorWright, 2014
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Hypertension and Management: New School
Hypertension = Disease of the blood vessels
Vascular biology altered
Treat the vasculature
Therapeutic options
BetaBlockers
ACE ARB Diuretics CCB Others
Adapted from Vascular Biology Working Group, University of FloridaCollege of Medicine, Carl Pepine, MD, DirectorWright, 2014
Case Study: MS
• 62 year old white female presents today for a complete PE
– Feeling well without complaints
• Last visit in clinic 3 months ago
– VS: 97.9, 84 bpm, 16 respirations/min, BP 152/94
– BMI: 32
– Eye: retinal examination normal
– AAO, smiling, conversant
– Carotids: 2+ bilaterally, no bruits
– Heart: S1S2, RRR, no S3, S4, murmurs
– PV: DPPT – 2+ bilaterally without edemaWright, 2014 11
Today:
• Diagnosis 3 months ago:
–Obesity
–Elevated blood pressure without diagnosis of hypertension (796.2)
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Patient: MS
• 62 year old white female presents today for a complete PE
– Feeling well without complaints
• Todays visit
– VS: Pulse: 88 bpm, BP 160/96 mm/Hg
– BMI: 32
– Eye: retinal examination normal
– AAO, smiling, conversant
– Carotids: 2+ bilaterally, no bruits
– Heart: S1S2, RRR, no S3, S4, murmurs
– PV: DPPT – 2+ bilaterally without edemaWright, 2014 13
Do We Have a Diagnosis of Hypertension?
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Diagnosis
• 2 readings; separated apart
• Patient should not ingest caffeine or smoke for 30 minutes before readings
• Patient should sit for 5 minutes with arm at heart level before blood pressure is checked
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With Today’s Diagnosis
• CBC
• CMP
• TSH
• Lipid profile
• Urine dip
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JNC VIII
• Made numerous recommendations regarding treatment
• The following slides will present these recommendations:
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Recommendation 1
• In the general population aged > 60 years, initiate pharmacologic treatment to lower BP at systolic blood pressure (SBP) of 150 mmHg or higher or diastolic blood pressure (DBP) of 90mmHg or higher and treat to a goal SBP lower than 150mmHg and goal DBP lower than 90mmHg
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Case Study: MS
• > 60 years of age
• 2 readings confirm diagnosis
• Benign Essential Hypertension
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Recommendation 2
• In the general population < 60 years, initiate pharmacologic treatment to lower BP at DBP of 90 mm Hg or higher and treat to a goal DBP of lower than 90mmHg
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Recommendation 3
• In the general population < 60 years, initiate pharmacologic treatment to lower BP at SBP of 140 mm Hg or higher and treat to a goal SBP of lower than 140mmHg.
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Recommendation 4
• In the population > 18 years or older with CKD, initiate pharmacologic treatment to lower BP at SBPof 140mmHg or higher or DBP of 90mmHg or higher and treat to goal SBP of lower than 140mm Hg and goal DBP lower than 90mmHg
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Recommendation 5
• In the population > 18 years or older with diabetes, initiate pharmacologic treatment to lower BP at SBP of 140mmHg or higher or DBP of 90 mm Hg or higher and treat to a goal SBP of lower than 140mmHg and goal DBP lower than 90mmHg.
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Treatment of Hypertension
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Benefits of Lowering Blood Pressure
Average Percent Reduction
Stroke:35% - 40%
MI: 20% - 25%
CHF: 50%
The Seventh Report of the Joint National Committee on Prevention, Detection, Evaluation,And Treatment of High Blood Pressure. http://jama.ama-assn.org/cgi/content/full/289.19.2560v1. Assessed 5-1-08
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Case Study: MS
• What to do with her?
• Lifestyle recommendations were provided 3 months ago
• No significant changes were made
• BP remains elevated
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No comment in JNC VIII
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Lifestyle Modifications to Manage Hypertension
Modification Recommendation Systolic Diastolic ChgsWeight Reduction BMI 18.5-24.9 5-20mm/10 kg wt loss
Adopt DASH eating Diet rich in fruits 8-14 mm Hg
vegetables and low
fat with reduced
saturated and total fat
Dietary Sodium 2.4g Na 2-8 mm Hg
Physical Inactivity Brisk exercise 30” day 4-9 mm Hg
most days of week
Moderation of
Alcohol intake 2 drinks day max 2-4 mm Hg
24 oz beer; 10 oz wine
2 oz 100 proof whiskeyJAMA. 2003:289:2560-2577.
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Pharmacologic Treatments
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)
Wright, 2014 30JAMA. 2013;():. doi:10.1001/jama.2013.284427
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Treatment Recommendation
• In the general nonblack population, including those with diabetes, initial antihypertensive treatment should include a thiazide-type diuretic, calcium channel blocker (CCB), angiotensin-converting enzyme inhibitor (ACEI), or angiotensin receptor blocker (ARB).
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Case Study: MS
• Treatment recommendation for her:
–CCB, Thiazide, ACE or ARB
–Clinician choice of medication/class of agent
• Suggestion:
–Look at other risk factors and attempt to optimize treatment
• Lisinopril 10 mg once daily was my choice
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Treatment Recommendation
• In the general black population, including those with diabetes, initial antihypertensive treatment should include a thiazide-type diuretic or CCB
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Treatment Recommendation
• In the population aged 18 years or older with CKD and hypertension, initial (or add-on) antihypertensive treatment should include an ACEI or ARB to improve kidney outcomes.
• This applies to all CKD patients with hypertension regardless of race or diabetes status.
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Thiazide Diuretics
• Dosing:–Start @ 12.5 mg of HCTZ
– Increase to 25 mg at 6 weeks
• Benefits–55% reduction in CHF
–37% reduction in CVA
–27% reduction in cardiac events
• If not adequately controlled, add additional agents
Chlorthalidone
• Making a come back into thiazide arena
• Dosage: 25 mg once daily
• May increase dosage to 100 mg once daily
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Decreased Efficacy
• When GFR decreases below 30 mL/min, thiazide diuretics are likely ineffective
• Consider changing to loop diuretic at that time
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Diuretic Precautions
• Electrolyte imbalances
• Syncope/presyncope when combined with ACE/ARB
• Hemoconcentration
• Decrease in urate excretion
• Worsening of insulin resistance at higher doses
• Fatigue
Product inserts accessed 04-20-2008Wright, 2014
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Angiotensin Converting Enzyme (ACE) Inhibitors
•Increased nitrous oxide at vessel for vasodilatation•Improved glucose disposal•Reduction in LV geometry changes•Reduction in inflammation•Stabilization of fibrous cap of lipid lesion•Decreased proteinuria •Improves endothelial function•Reduced mortality in patients with CHF•Decreases post-MI mortality
Sato Atsuhisa, Pleiotropic effects of angiotensin-converting enzyme inhibitors; differentiationAmong ace inhibitors may lead to further organ protection. Abstr 21st Sci Meet Int Soc Hypertens2006. 423(2006)
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ACE Inhibitor Trials
1985 1986 1987 1988 1989 1990 1991 1992 1993 1994 2000 2001
CONSENSUS I
ValHeFT II
SOLVD treatment
SAVE
AIRE
TRACE
SMILE
CATS
CONSENSUS II
GISSI-3
ISIS-4
PEACE
HOPE
Latini, et al. Curr Perspect. 1995;92:3132-7
CCS-1
CHF
Anterior
AMI
AMI
CAD
LVD
Post-AMI
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ACE Inhibitors PrecautionsACE Inhibitors Precautions
• Hyperkalemia
• Increase in creatinine
• May improve insulin sensitivity
• Decrease in serum Na+ may result in syncope and dizziness when used with diuretics
Product inserts accessed 04-20-2009
• Angioedema
• Cough
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Effects on Hypoglycemia
• Several studies have shown the ability of ACE inhibition to improve glycemic control – even decrease the risk of hypoglycemia in patients using sulfonylureas.
Thamer M, Ray NF, Taylor T. Association between antihypertensive drug use and
hypoglycemia: A case-control study of diabetic users of insulin or sylfonylureas. Clin Therapeutics 1999; 21:1387
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But…
ACE InhibitorsAre Highly Effective..
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* * * ** * * *
* = p<0.001 versus placebo
Plasma ACE(mmol/ml/min)
Plasma ANG II(pg/ml)
*
Placebo 4h 24h 1 2 3 4 5 6
Hospital MonthsModified from Journ Cardiovasc Pharm 1982; 966-72
Long Term Effect of Enalapril (20mg)
on Plasma ACE and Angiotensin II
Vascular Biology Working Group, University of Florida
College of Medicine, Carl Pepine, MD, Director
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If you block the receptor
site, you don’t have to worry
about the angiotension levels…
AT1
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Angiotensin ReceptorBlockers
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Angiotension Receptor Blockers (ARB’s)
• Utilized since April 1995
• Blocks uptake at receptor site
• Angiotension II produced in locations other than in the lungs
• BP decreased by reducing vascular tone and enhancing NA+ and water clearance
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Metabolic Effects of ARB’sMetabolic Effects of ARB’s
• Angiotensin II Receptor Blockers
• Metabolically neutral
• No impact on lipids
• No impact on insulin
• No impact on K+
• Lowers uric acid levels
• Minimal side effect profile
Product Inserts accessed 04-20-2009Wright, 2014
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ARB Trials
1995 1996 1997 1998 1999 2000 2001 2002 2003 2004 2005 2006
ValHeFTELITE I
ELITE II
IDNT
RENAAL
IRMA II
OPTIMAAL
LIFE
VALIANT
VALUE
CHARM
MARVAL
ON TARGET
CHF
CV
MI
Renal/CV
Renal
IPreserve
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ACE vs ARBONTARGET Trial
Goal: 1. Assess the effects of ACE VS ARB in terms of efficacy
2. Assess if the combination ACE & ARB was superior
Results: Telmisartan was found to be “noninferior” to ramipril in patients with vascular disease or high risk diabetes
Combination of these two agents was associated with more adverse events without an increase in benefit.
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Yusuf, S, Teo KK, Pogue, J et al for the ONTARGET investigators. Telmisartan, ramipril, or both in patients At high risk for vascular events N Engl J Med 2008;358:1547-1559.
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Calcium Channel Blockers
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Calcium Channel Blockers
• Effectively treat systolic hypertension
• May be superior to other antihypertensives for stroke prevention
• Effective in patients with:
– Comorbid conditions (Raynauds, migraine)1
• Particularly effective in
– Elderly and African American’s2
1. Materson BJ, Reda DJ, eta l. Single drug therapy for hypertension in men. A comparison of sixAntihypertensive agents with placebo. N Engl J Med. 1993;328:914-921.
2. Tuomilehto J, Rastenyte D, et al. Effects of calcium channel blockade in older patients with Diabetes and hypertension. N Engl J med. 1999;340:677-684.
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The Calcium Blockers
Dihydropyridines
– Studies of DPH’s effects on
proteinuria have produced conflicting results
– NKF recommends that in
patients who have diabetes
and kidney disease, DPH’s should only be used in
combination with and ACE
or ARB
Nondihydropyridines
– Regression of proteinuria
– Combination of Verapamil +
ACE, reduction in proteinuria can be greater than
achievable with verapamil
alone.
– NKF now recommends adding a NDH to treat hypertension
with an ACE inhibitor or an
ARB to slow the progression of kidney disease.
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Thornley-Brown D, et al for the African American Study of Kidney Disease and Hypertension Study Group. Differing effects of antihypertensive drugs on the incidence
Of Diabetes mellitus among patients with hypertensive kidney disease. Arch Intern Med.2006;166(7):797-805.
National Kidney Foundation. K/DOQI clinical practice guidelines on hypertensionand antihypertensive agents in chronic kidney disease. Am J Kidney Dis. 2004;
43(suppl 1):S1-S290.Wright, 2014
Treatment Recommendation
• 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 following:
–Thiazide-type diuretic, CCB, ACEI, or ARB
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What About Other Antihypertensives?When Do You Use?
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: 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)
Downloaded From: http://jama.jamanetwork.com/ on 01/19/2014
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Beta Blockers
•Reduction in blood pressure•Decreased contractility
•Decreased heart rate•Decreased myocardial oxygen
demand
•Reduction in LVH•Reduced arrhythmias
The Seventh Report of the Joint National Committee on Prevention, Detection, Evaluation,And Treatment of High Blood Pressure. http://jama.ama-assn.org/cgi/content/full/289.19.2560v1. Assessed 5-1-08
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Alpha Blockers
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Alpha BlockersAlpha Blockers• End in azosin
• Block postsynaptic Alpha1 Receptors
• Results in vasodilatation
• Relatively inexpensive
• Fair tolerability; May cause postural effects
• Additive agent for older men to decrease BPH symptomatology
• Add-on agent only
• Should never be used as monotherapy due to increased risk of stroke and CHF
The Seventh Report of the Joint National Committee on Prevention, Detection, Evaluation,And Treatment of High Blood Pressure. http://jama.ama-assn.org/cgi/content/full/289.19.2560v1. Assessed 5-1-08
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Centrally Acting Blockers
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Centrally Acting AgentsCentrally Acting Agents• Stimulates central alpha2 receptors which results in:
– Inhibiting efferent sympathetic activity
• Additive agents
• Should be used 3rd or 4th line
– Examples: Clonidine (catapress, catapress TTS); methyldopa
• Caution: sedation, orthostatic hypotension
The Seventh Report of the Joint National Committee on Prevention, Detection, Evaluation,And Treatment of High Blood Pressure. http://jama.ama-assn.org/cgi/content/full/289.19.2560v1. Assessed 5-1-08
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Aldosterone Agonists
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• Spironolactone (Aldactone)
• HCTZ / spironolactone (Aldactazide)
• Eplerenone (Inspra)
Aldosterone Antagonists
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Aldosterone as a Therapeutic Target
• Aldosterone promotes:–Retention of sodium
–Loss of magnesium and potassium
–Sympathetic activation
–Parasympathetic inhibition
–Baroreceptor dysfunction
– Impaired arterial compliance
Mac Fadyen RJ, et al Aldosterone blockade reduces vascular collagen turnover, improves heart rate variability and reduces early morning rise in heart rate in heart failure patients. Cardiovasc Res 1997;35:30-34.
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• May be recommended in the following individuals:–Post MI
–NYHA Class III or IV
–Ejection fraction of < 35%
–Serum creatinine of < 2.5 mg/dl
–K+ < 5.0 mmol/LMardi Gomberg-Maitland, Baran DA, Fuster, V. Treatment of Congestive Heart FailureGuidelines for the Primary Care Physician and Heart Failure Specialist. Arch Intern
Med 2001;161:324-352et al. ACC/AHA 2005 Chronic Heart Failure Guideline Update. JACC.2005; 46:1116-43.
Aldosterone Antagonists
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Precautions• Must monitor electrolytes
• Must obtain baseline renal function
• Should discontinue the K+ supplement
• Should limit to use in severe heart failure and post MI patients
Clavell, Alfredo L. Common Mistakes made in the Treatment of Congestive Heart Failure. Success with
Failure: New Strategies for Evaluation and Treatment of CHF.
Whistler BC, Canada 8-2000.
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Direct Renin Inhibitor
Renin is the enzyme at thebeginning of the RAAS, oneof the key regulating centersfor blood pressure. Blockingthis enzyme can decrease the downstream impact of the RAAS system.
Suppression of the RAAShas been shown to treathypertension and reducetarget organ damage.
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Direct Renin Inhibition Inhibits the Entire Renin System1-4
Class
ACEI
ARB
Direct Renin Inhibitor (DRI)
PRA Ang I Ang II
Increased peptide levels have not been shown to overcome the blood pressure–lowering effect of these agents.ACEI, angiotensin-converting enzyme inhibitor; Ang, angiotensin; ARB, angiotensin receptor blocker;PRA, plasma renin activity.
1. Johnston CI. Blood Press Suppl. 2000;1:9(suppl 1):9-13.
2.Widdop RE et al. Hypertension. 2002;40:516-520.
3.Fabiani ME et al. Angiotensin II Receptor Antagonists. 2001:263-278.
4. Lin C et al. Am Heart J. 1996;131:1024-1034.68Wright, 2014
Warning re: Aliskiren
• Do not combine with ACE or ARB
• Avoid use of aliskiren and valdasartan (Valturna)
• Warning followed after early termination of the ALTITUDE trial
–Offered no benefit and was associated with an increased risk of CVA’s
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European Medicines Agency
• The EMA has announced plans to review all aliskiren products and, until the results of this review are available, it has recommended that:
– Aliskiren-containing medicines should not be prescribed to diabetic patients who are also taking an ACE inhibitor or an ARB
– Prescribers should review patients taking aliskiren at a routine (non-urgent) appointment and, if patients are diabetic and are also taking ACE inhibitors or ARBs, aliskiren should be stopped and alternative treatments considered
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http://www.pjonline.com/clinical-pharmacist/2012_jan/avoid_aliskiren_with_ACE_inhibitors_and_ARBs accessed 01-12-2012
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Combination Therapy
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AASK MAP <92
Target BP (mm Hg)
Multiple Antihypertensive Agents
Are Needed to Achieve Target BP
No. of antihypertensive agents
1
UKPDS DBP <85
ABCD DBP <75
MDRD MAP <92
HOT DBP <80
Trial 2 3 4
DBP, diastolic blood pressure; MAP, mean arterial pressure; SBP, systolic blood pressure.Bakris GL et al. Am J Kidney Dis. 2000;36:646-661.Lewis EJ et al. N Engl J Med. 2001;345:851-860.
IDNT SBP <135/DBP <85
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Treatment Recommendation: Combination Therapy
• Initiate therapy with 2 drugs simultaneously, either as 2 separate drugs or as a single pill combination
– For instance: start therapy with ≥2 drugs when SBP is >160 mm Hg and/or DBP is >100 mm Hg, or if SBP is >20 mm Hg above goal and/or DBP is >10 mm Hg above goal
• If goal BP is not achieved with 2 drugs, select a third drug from the list (thiazide-type diuretic, CCB, ACEI, or ARB)
• Avoid the combined use of ACEI and ARB
• Titrate the third drug up to the maximum recommended dose.
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Target Organ Damage
• Heart
– LVH, Angina, CHF, MI
• Brain
– Stroke or TIA
– Dementia
• Chronic Kidney Disease
• Peripheral Vascular Disease
• Retinopathy
JAMA. 2003:289:2560-2577.
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Consider Secondary Causes of Hypertension
• Pheochromocytoma
• Sleep apnea
• Renal artery stenosis
• Drug-induced
• Cushing’s syndrome
• Hyperthyroidism
• Polycystic kidney disease
• CKD
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Thank You For Your Time and Attention!
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Wendy L. Wright, ARNPAdult/Family Nurse Practitionerwww.4healtheducation.com