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Hypertension 2012: What Will The JNC 8Guideline Look Like?
Annual Primary Care Kiawah ConferenceKiawah Island, South Carolina
July 3, 2012
Jan Basi le, MDSeinsheimer Cardiovascular Health ProgramProfessor of Medicine
Medical University of South CarolinaRalph H. Johnson VA Medical CenterCharleston, South Carolina
DISCLOSURE OF FINANCIAL RELATIONSHIPS
Jan N. Basile, MD
Grant/Research support: NHLBI (SPRINT)
Consultant: Daiichi-Sankyo, Forest, Takeda
Speakers Bureau: Daiichi-Sankyo , Forest, Takeda,Boehringer Ingelheim, Lilly
Major stock shareholder: None
Other: None
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Why Are We Still Talking About HTN?
Its prevalent
Over 74 milli on in U.S. have HTN
Abou t 70 mi ll ion in U.S. have prehypertens ion
Increasing p revalence with aging of popu lation and
epidemic of overweight/obesity
Control of BP leads to a reduction in events
Approx imately 50% reduction in heart fai lu re
Approx imately 40% reduction in stroke
Approx imately 20%25% reduction in MI
Ong KL et al. Hypertension. 2007;49:69.Hebert PR et al.Arch Inten Med. 1993;153:578.Kannel WB. JAMA. 1996;275:1571.Moser M, Hebert P. J Am Coll Cardiol. 1996;27:1214.
HTN, hypertension; BP, blood pressure
j22
20-Year Trends in Hypertensionin the U.S.: 19882008
Hajjar I et al. JAMA. 2003;290:199.Egan BM et al. JAMA. 2010;303:2043.
0
10
20
30
40
50
60
70
80
90
Prevalence Awareness Treatment Control(With RX)
Control (AllHypertension)
%
19881991 19911994 19992000 20072008
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Slide 6
22 NOTE: Our reference format includes only first page number of article (not full page range). Also, nocomma before "et al" and refs flush right. Abbreviations and footnotes should not appear in the sametext box as refs.simmons, 7/31/2010
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It's tough to make predictions,especially about the future.
Y. Berra (1925- )
Trying to Predict JNC 8
Is it the Antihypertensive Class or theBP Achieved That Best Improves
Outcome in Those with Hypertensionand No Compelling Indication?
Question 1
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0.5 1.0 2.0
BP-Lowering Treatment TrialistsComparisons of different active treatments
Lancet 2003; 360:1903
Relative Risk RR (95% CI)
BP Difference
(mm Hg)
FavorsFirst Listed
FavorsSecond Listed
Major CV Events
CV Mortalit y
Total Mor tality
1.02 (0.98, 1.07)2/0ACE vs. D/BB
1.03 (0.95, 1.11)2/0ACE vs. D/BB
1.00 (0.95, 1.05)2/0ACE vs. D/BB
1.04 (0.99, 1.08)1/0CA vs. D/BB
1.05 (0.97, 1.13)1/0CA vs. D/BB
0.99 (0.95, 1.04)1/0CA vs. D/BB
0.97 (0.95, 1.03)1/1ACE vs. CA
1.03 (0.94, 1.13)1/1ACE vs. CA
1.04 (0.98, 1.10)1/1ACE vs. CA
FavorsFirst Listed
FavorsSecond Listed
0.5 1.0 2.0
BP-Lowering Treatment TrialistsComparisons of different active treatments
Lancet 2003; 360:1903
Relative Risk RR (95% CI)BP Difference
(mm Hg)
CA vs. D/BB 1.33 (1.21, 1.47)1/0
0.93 (0.86, 1.01)CA vs. D/BB 1/0
1.01 (0.94, 1.08)CA vs. D/BB 1/0
ACE vs. CA 0.82 (0.73, 0.92)1/1
1.12 (1.01, 1.25)ACE vs. CA 1/1
0.96 (0.88, 1.05)ACE vs. CA 1/1
Stroke
Coronary Heart Disease
Heart Failure
1.09 (1.00, 1.18)ACE vs. D/BB 2/0
0.98 (0.91, 1.05)ACE vs. D/BB 2/0
1.07 (0.96, 1.19)ACE vs. D/BB 2/0
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Question 2
What Is The Optimal BP For OutcomeImprovement in Special Populations?
DiabeticCKD
Elderly
One Million Adults, 61 Prospective Studies
Ischemic Heart Disease Mortality Stroke Mortality
Lewington S, et al. Lancet. 2002;360:1903-1913.
Increasing Systolic Blood Pressure and Age
Elevates Risk of Ischemic Heart Disease (IHD) andStroke Mortality
Usual Systolic BP (mm Hg)
256
128
64
32
16
8
4
2
1
120 140 160 180
IHDMortality
(AbsoluteRiskand95%
CI)
Age at Risk (y)
80-89
70-79
60-69
50-59
40-49
Usual Systolic BP (mm Hg)
256
128
64
32
16
8
4
2
1
120 140 160 180
StrokeMortality
(AbsoluteRiskand95%
CI)
Age at Risk (y)
80-89
70-79
60-69
50-59
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Chobanian AV et al. JAMA. 2003;289:2560.Arauz-Pacheco C et al. Diabetes Care. 2003;26:S80.
Flack JM et al. Hypertension 2010;56:780.Bakris GL et al.Am J Kidney Dis. 2000;36:646.
Condition mm Hg
Essential HTN
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What Is The Optimal BP For OutcomeImprovement in Special Populations?
DiabeticCKD
Elderly
HOT Trial Events byTarget DBP Groups*
0
30
60
90
120
150
180
210
240
270
Majorcardiovascular
events
AllmyocardialInfarction
All stroke CardiovascularMortality
TotalMortality
Hansson L, et al. Lancet. 1998;351:17551762.
*The outcomes for different BP groups were not statistically significant
90 85 80
Numberofevents
N =18,790
DBP Target:
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Hansson L et al. Lancet . 1998;351:17551762.
HOT: Results in High-Risk Subgroup(Diabetic Patients)
p=0.005 for
trend
MajorCVEvents
Per1,0
00PatientYears
Target DBP, mmHg
(n=501) (n=501) (n=499)
RR=1.32
RR=1.56
RR=2.06
05
1015202530
808590
Major CV Event Reduction by Target Blood Pressure
UKPDS:
Effect of Tight Glucose Control vsTight BP Control on CV Events
* P
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Trial N
Mean SBP
less intense
Mean SBP
more intense
CVD Risk
Reduction
SHEP 583 155 143 22-56%
Syst-EUR 492 162 153 62-69%
HOT 1,501 148 142 30-67%
UKPDS 1,148 154 144 32-44%
ABCD 470 138 132 No CVD
ADVANCE 11,140 140 135 14% mortality
Cushman, et al. Am J Cardiol 2007;99[suppl]:44i55i;
Patel, et al. Lancet. 2007;370:829840
ACCORD: Achieved SBP
Mean no. of medications prescribed:Intensive 3.2 3.4 3.4 3.5 3.5 3.5 3.4 3.4Standard 1.9 2.1 2.1 2.2 2.2 2.3 2.3 2.3
No. of patients:Intensive 2,174 2,071 1,973 1,792 1,150 445 156 156Standard 2,208 2,136 2,077 1,860 1,241 504 203 201
Years Since Randomization876543210
SBP(mmHg)
Standard
Intensive
140
130
120
110
0
Average : 133.5 standard vs. 119.3 int ensiv e, Delta = 14.2 at year 1
The ACCORD Study Group. New Engl J Med. 2010;362:1575.
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ACCORD Blood Pressure Trial:Primary Outcome and Total Stroke
Primary OutcomeNonfatal MI, Nonfatal Stroke, or CVD Death
Total Stroke
HR = 0.8895% CI (0.731.06)P=0.20
HR = 0.5995% CI (0.390.89)P=0.01
The ACCORD Study Group. New Engl J Med. 2010;362:1575.
PatientsWithEvents(%)
0
5
10
15
20
Years Postrandomization
0 1 2 3 4 5 6 7 8
PatientsWithEvents(%)
0
5
10
15
20
Years Postrandomization
0 1 2 3 4 5 6 7 8
ACCORD Blood PressureTrial: Conclusions
Intensive antihypertensive therapy did notreduce the primary composite outcome(nonfatal stroke, nonfatal MI, and CV death) vsstandard therapy in patients with type 2 DM athigh risk of CV events
Intensive antihypertensive therapy did reduceboth total strokes (P=0.01) and nonfatal stroke
(P=0.03) vs standard therapy, which weresecondary end points, and there were moreadverse events in the intensive group
The ACCORD Study Group. New Engl J Med. 2010;362:1575.
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SBP
UKPDSADV
UK Prospective Diabetes Study, BMJ Volume 321, August 12, 2000.
ACCORD
Standards of Medical Care inDiabetes, 2012: HTN/BP Control
Diabetes Care. 2012;Vol 35: Suppl 1,S6.
A systol ic BP goal
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What Is The Optimal BP For OutcomeImprovement in Special Populations?
DiabeticCKD
Elderly
BP Targets in Chronic Kidney Disease:Proteinuria as an Effect Modifier
3 RCTs (8 reports) with a total of 2272 participants
MDRD (Modif ication o f Diet in Renal Disease) Study
AASK (African American Study of Kidney Disease and
Hypertension) Trial
REIN-2 (Ramipril Efficacy in Nephropathy 2) trial
Mostly no diabetes
2- to 4-year trial follow-up
[Renal outcomes (not CVD) ]
MDRD Study and AASK Trial also posttrial observational
follow-up
All tr ials with subgroup analyses by baseline proteinuria levels
Upadhyay A, et al. Annals Intern Med 3/2011
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Standard control 300 mg/dayStandard control 176 165 134 113 81 66 45 32 26 22 13
Intensive control 181 172 151 128 109 87 67 56 47 40 25
300 mg/dayStandard control 376 373 362 353 332 302 267 234 214 196 128Intensive control 357 350 335 321 306 282 254 228 206 189 128
Adap ted wi th permi ssi on fro m Appel LJ et al fo r the AA SK Coll abor ativ e Research Group . N Engl J Med. 2010;363:918929.
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Systematic Review: BP Target in CKDProteinuria as an Effect Modifier
Evidence does not conclusively show that the currentlyrecommended BP target of < 130/80 mm Hg improvesclinical outcomes more than a conventional target of 300 to 1000 mg/d.
We suggest that practitioners use discretion inpatients with CKD and proteinuria and base the
BP target on individualized risk-benefit assessment.Treatment to a lower target may require greatervigilance to monitor for and avoid possib le symptomsand adverse events from hypotension.
Upadhyay, A et al.Ann In tern Med 2011;154:541-548.
CKD is a major risk factor for CVD; however, patients withCKD have been under represented in most CV trials that testinterventional strategies, such as BP lowering.
Reducing SBP to levels 4,000 participants with eGFR
20-59 and comparing < 120 mm Hg to < 140 mm Hg.
CKD in SPRINT
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What Is The Optimal BP For OutcomeImprovement in Special Populations?
DiabeticCKD
Elderly
BP Targets and Achieved BP in HTNIntervention Studies in Elderly
1. SHEP Cooperative Researc h Group. JAMA. 1991;265(24):3255-3264. 2. Staessen JA, et al. Lancet. 1997;
350(9080):757-764. 3. Beckett NS, et al; for HYVET Study Group. N Engl J Med. 2008;358(18):1887-1898.
SHEP1 Syst-Eur2 HYVET3
Subjects, n 4736 4695 3845
Inclusion BP
Criteria, mm Hg160-219/
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Systolic BP values
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Question 3
What Antihypertensive MedicationsShould Be Recommended as Init ial
Therapy?
Compelling Indications for
Individual Drug Classes
Diuretic
-blocker ACEI ARB CCB
Aldo
Antag. Clin ical Trial Basis
HF
ACC/AHA HF guideline;
MERIT-HF; COPERNICUS,CIBIS, SOLVD; AIRE, TRACE,Val-HeFT; RALES
Post-MI ACC/AHA post-MI guideline;BHAT; SAVE, CAPRICORN,EPHESUS/VALIANT
High CAD
Risk
ALLHAT; HOPE, ANBP2; LIFE;CONVINCE, ONTARGET
Diabetes NKF-ADA guideline; UKPDS;
ALLHAT
CKD NKF guideline; CAPPP;RENAAL; IDNT, REIN, AASK
Stroke PROGRESS, LIFE
Chobanian AV et al. JAMA. 2003;289:2560-2572.
MI=myocardial infarction
CKD=chronic kidney disease
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Stage 1 Hypertension
(SBP 140159 or DBP 9099 mmHg)
Thiazide-type diuretics for m ost
May cons ider ACEI, ARB,-blocker, CCB, or c ombination
In Patients With Hypertension
INITIAL DRUG CHOICES
LIFESTYLE MODIFICATIONS
Not at Goal Blood Pressure (100 mmHg)
2-drug combination for most
(usually thiazide-type diuretic and
ACEI or ARB or-blocker or CCB)
Management of Blood Pressure
Adapted f rom Cho banian AV et al. Hypertension. 2003;42:12061252.
Years to CHD Event
0 1 2 3 4 5 6 7
C
umulativeCHDEventRate
0
0.04
0.08
0.12
0.16
0.20RR (95% CI) p value
A/C 0.98 (0.901.07) 0.65
L/C 0.99 (0.911.08) 0.81
ChlorthalidoneAmlodipine
Lisinopril
Cumulative Event Rates for the Primary Outcome
(Fatal CHD or Non-fatal MI) by ALLHAT Treatment Group
Adapted with per mission from ALLHAT Of fic ers and Coo rdi nator s for the ALLHAT Collaborat iv e
Research Group. JAMA. 2002;288:29812997.
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ALLHAT Secondary Endpoints: Heart Failure*Rate Lower in Diuretic vs. ACEI or CCB
*Heart failure is a component of combined cardiovascular disease.
Adapted f rom ALLHAT Co llaborativ e Research Grou p. JAMA. 2002;288:29812997.
1.38 (1.251.52)
RR (95% CI)
Favors Am lodipineFavors Li sinopril
Heart failure (fatal, non-fatal,
hosp italized or treated)
1.19 (1.071.31)
Amlod ip ine
Lisinopril
Hospitalized/fatal heart failure
1.35 (1.211.50)
1.10 (0.981.23)Amlod ip ine
Lisinopril
FavorsChlorthalidone
0.5 2.01
JNC-8: What Might Be Expected?
Either a thiazide-type diuretic, CCB,ACEI/ARB will be recommended as ini tialdrug therapy for most patients. Direct renininhibitors wil l be recommended as anadditive but not first l ine agent
Chlorthalidone or indapamide should be
highl ighted as the evidence-based thiazide-type diuretic of choice
Moser M, Basile J, Kaplan M, and Victor R. Med Roundtable Cardiovasc Ed. 2010 pg 267-275.
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Dose-Response Curve With HCTZ: HaveWe Gone Too Far With Low-Dose HCTZ?
Compared w ith HCTZ 25 mg ABP: P = NS vs 12.5 mg (both systolic and diastolic), P=0.0001 vs50 mg systolic, and P = NS vs 50 mg diastolic. N indicates number of patients.
24-HrBPChange
(mmHg)
0
-6
-12
-14
-4
-8
-10
-2
5 Studies(N=123)
50 mg
9 Studies(N=503)
25 mg
4 Studies(N=129)
12.5 mg
-3.3
-5.7
Systolic ambulatory BP (ABP)
Diastolic ABP
-5.4
-7.6
-5.4
-12
Messerli FH et al. J Am Coll Cardiol. 2011:57:590.
NS, not significant
Evidence for Chlorthalidone
MRFIT C or HCTZ vs usual care
TOMHS C vs enalapril, amlodipine (A)doxazosin (D), acebutolol, andplacebo
SHEP C vs placebo
ALLHAT C vs lisinopril, A, and D
1.MRFIT Grimm RH J r et al.Arch Intern Med . 1985;145:1191.2.MRFIT Ci rc ulation1990;82:1616.3.MRFIT Hypert ension 2011;57;689.4.TOMHS Neaton JD et al. JAMA. 1993;270:713.5.SHEP Cooperativ e Res Group. J AMA 1991; 265:3255.6.ALLHAT Col laborativ e Research Group. J AMA 2002; 288: 2981.
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12.411.4
13.5
7.48.1
6.4
-16
-14
-12
-10
-8
-6
-4
-2
0
CLD 25 mg HCTZ 50 mg
Chlorthalidone Has Greater BP-LoweringEfficacy vs HCTZ, Especially at night
CLD=chlorthalidon e; HCTZ=hydrochlorothiazide.
ReductioninMeanSBP
BaselinetoWeek8,mmHg
24-hour Mean SBP Dayt ime Mean SBP Night-time Mean BP
Daytime was 6:00 AM to 10:00 PM; nigh t-t ime, 10:00 PM to 6:00 AM.
P=0.009
P=0.054 P=0.230
Ernst ME, et al. Hypertension. 2006;47:352-358.
Chlorthalidone Has a Longer Half-lifeand Duration of Action vs. HCTZ
Half-life, hours Duration of Action, hours
Single doseLong-term
dosingSingle dose
Long-term
dosing
HCTZ 6-9 8-15 12 16-24
CLD 40 45-60 24-48 48-72
Carter BL, et al. Hypertension. 2004;43:4-9
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Al iskerin
FDA Approved at 150 or 300 mg as initial or additional therapy
ALiskerin Trial In Type 2 Diabetes Using CV
and Renal Disease Endpoints (ALTITUDE)
- Aliskerin vs placebo on top of ACEI or ARB
in type 2 diabetes with renal impairment
- stopped early when DMSB noted more
nonfatal strokes, renal complications,
hyperkalemia, and hypotension over 18-24months follow-up
- still awaiting final publication
No outcomes available as initial antihypertensive
Future Evidence for Aliskerin
ASTRONAUT AliSkerin TRial ON Acute HeartFailure oUTcomes
ATMOSPHEREAliskerin Trial to Minimize
OutcomeS in Patients with
HEart failuRE
APOLLOAliskerin in the Prevention OfLater
Life Outcomes
Gheorghiade M, et al. Eur J Heart Fail. 2011; 13: 100-106.Krum H, et al. Eur J Heart Fail. 2011; 13: 107-14.
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Lifestyle ModificationEspecially Diet and Exercise
Algori thm for BP Contro l in Non-Compell ing Situation(May Start with 2-Drug Combination)
Not at Goal
All Patients
(ACEI or ARB) orThiazideDiuretic
(Use alternative not used above)
(Mineralocortico id Receptor Blocker)
(Vasodilatory BB)
Not at Goal
or Amlod ip ine orNon-Atenolol
BB
Primary Prevention MRC Older AdultsCoronary Events
Cumulative% of events
Follow-up (y)
Atenolol
Placebo
Hctz +Amiloride
MRC Working Party, Br Med J. 1992;304:405-12.
P=0.0009
10
8
6
4
2
0
0 1 2 3 4 5 6 7
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ASCOT-BPLA
ELSA
INVEST
LIFE
MRC Old
UKPDS
Total events
0.5 0.7 1 1.5 2
Atenolol Other drug RR RR(n/N) (n/N) (95% Cl) (95% Cl)
422/9618
14/1157
201/11309
309/4588
56/1102
17/358
1019/28132
327/9639
9/1177
176/11267
232/4605
45/1081
21/400
810/28169
1.29 (1.121.49)
1.58 (0.693.64)
1.14 (0.931.39)
1.34 (1.131.58)
1.22 (0.831.79)
0.90 (0.481.69)
1.26 (1.151.38)
Favorsatenolol Favorsother drug
-Blocker Meta-analysisStroke: Atenolol vs Other Antihypertensive Agents
ASCOT-BPLA, Anglo-Scandinavian Cardiac Outcomes TrialBlood Pressure Lowering Arm; CI,confidence interval; ELS A, European Lacidipine Study on Atherosclerosis; INVEST, InternationalVerapamil-Trandolapril Study; L IFE, Losartan Intervention For Endpoint reduction; MRC, MedicalResearch Council; RR, relative risk; UKPDS, United Kingdom Prospective Diabetes Study.
Lindholm LH et al. Lancet. 2005;366(9496):1545-1553.
NICE Treatment of HypertensionUpdate 2011New Cost-Effectiveness Review
of Drug Therapy for Hypertension
NICE. Clinical gui delines (CG127). August 2011. Availabl e at:http://www.nice.org.uk /nicemedia/liv e/13561/56007/56007.pdf. Access ed May 8, 2012.
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Cost Effectiveness ofAntihypertensive Treatment 2011
No intervention Thiazide-type diuretics Calcium-channel blockers
B et a-bl oc ker s ACE i nh ibi to rs /ang iot ens on -II rec ep to r an tag on is ts
4,800
4,600
4,400
4,200
4,000
3,800
9.40 9.60 9.80 10.00 10.20 10.40
Mean Effect (QALYsPer Person, Discounted)
MeanCost(2009UK
PerPerson,Discounted)
1,960
5,400
5,200
4,800
4,600
4,400
4,200
9.80 10.00 10.20 10.40 10.60 10.80
Mean Effect (QALYs
Per Person, Discounted)
1,520
5,000
Men Women
Treating high blood pressure is cheaper than doing nothing
Beta-blockers are the least cost-effective treatment.
apart from no treatment at all Bryan Williams 2011
Base case results (65-year-old, 2% cardiovascular risk, 1.1% diabetes risk, 1% HF risk)
NICE. Clinical gui delines (CG127). August 2011. Availabl e at:http://www.nice.org.uk /nicemedia/liv e/13561/56007/56007.pdf. Access ed May 8, 2012.
Antihypertensive Drug Treatment AlgorithmNICE 2011
Age
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National Institute for Health and Clinical Excellence (NICE)
Places -Blockers as Fifth-Line Treatment for
Uncomplicated Hypertension
NICE Clinical Guideline 127, August 2011.
Beta-blockers are not a preferred initial therapy for uncomplicatedhypertension.
If treatment with three drugs is required, the combination of ACEinhibitor or ARB, calcium-channel blocker and thiazide-like diuretic should beused.
Beta-blockers may be considered in younger people, particularly:-those with an intolerance or contraindication to ACE inhibitors and ARBs-women of child-bearing potential
-people with evidence of increased sympathetic drive.
If therapy is initiated with a beta-blocker and a second drug isrequired, add a calcium-channel blocker rather than a thiazide-likediuretic to reduce the persons risk of developing diabetes.
Question 4
When should 2 or more antihypertensive agents be
recommended as initial therapy, either as a fixed-dose
combination (FDC) or as 2 individual agents?
Which 2 drug combinations have the greatest BP-
lowering effect?
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0.19
In
crementalSBPreductionratio
ofobservedtoexpectedadditiveeffects
Thiazide
Wald DS et al.Am J Med. 2009;122:290-300.
Betablocker
Calciumchannelblocker
Adding a drug from another class (on average standard doses)Doubling dose of same drug (from standard dose to twice standard)
1.04
1.00
1.16
0.89
1.01
0.20.23
0.37
ACEinhibitor
Allclasses
0.22
Combining Drugs from Different Classes is
Approximately 5 Times More Effective in Lowering
BP than Doubling the Dose of 1 Drug
1.00
0.60
0.40
0.20
0
1.40
0.80
1.20
Guideline Recommendations Regarding
Initial Use of Combination Therapy
JNC 7 >20/10 mm Hg
ISHIB >15/10 mm Hg
ESH >20/10 mm Hg OR high cardiovascular risk
AHASBP 160 mm Hg or DBP 100 mm Hgirrespective of the BP goals
NKF K/DOQISBP >20 mm Hg above goal according to
the stage of CKD and CVD risk
J NC 7, Seventh Report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure.ISHIB, International Society on Hypertension in Blacks.ESH, European Society of Hypertension.
AHA, American Heart Association.NKF K/DOQI , National Kidney Foundation Kidney Disease Outcomes Quality Initiative.
1. Chobanian AV, et al. Hypertension. 2003;42:1206-1252. 2. Douglas J G, et al.Arch Intern Med. 2003;163: 525-541.3. K/DOQI.Am J Kidney Dis. 2004;43 (suppl 1):S65-S230. 4. Mancia G, et al.J Hypertens. 2007;25:1105-1187.
5. Rosendorff C, et al. Circulation. 2007;115;2761-2788.
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Hypertension 20
20thAnnual Primary Care Conference
45 practices (2048 patients) in southern Ontario randomized to:
Guideline-based stepped care
Based on Canadian Health System Guidelines(similar to J NC 6)
STITCH care algorithm
Start tab single-pill fixed-dose combination of ACEI-diureticor ARB-diuretic
Increase dose of combination tablet
Add calcium channel blocker
Add a peripheral alpha blocker, beta blocker or spironolactone
Primary Outcome = Proportion at BP target at 6 months
The Simpl ified Therapeutic Intervention To
Control Hypertension (STITCH) TrialMethods
Feldman RD, et al. Hypertension. 2009;53(4):646-653.
STITCH STUDY: Main Results
(Summary)Variable Usual Care STITCH P-Value
# of patients 1246 802
Baseline
SBP, mmHg 153.4 155.1 NS
DBP, mmHg 87.7 88.1 NS
Diabetic, % 15.9 15.1 NS
FDC, % 9.3 11.2 NS
BP control, % 0 0 NS
Final visi t
SBP, mmHg -17.5 -22.6
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Jan Basi le, M
Hypertension 20
20thAnnual Primary Care Conference
The Simpl ified Therapeutic Intervention To
Control Hypertension (STITCH) TrialResults
95% CI: 1.5% to 22.4%P=0.026
Feldman RD, et al. Hypertension. 2009;53(4):646-653.
52.764.7
0
10
20
30
40
50
60
70
Guideline-Based Care STITCH-Based Care
Contro l Rates (%)
6-Month Follow-up
Gradman AH, Basile JN, Carter BL, Bakris GL; American Society of Hypertension Writing Group. J Am Soc Hypertens. 2010;4:42.
Drug Combinations in HTN:Recommendations
Preferred
ACE inhibit or /diu ret ic*ARB/d iur etic *ACE inhibit or /CCB*ARB/CCB*
Acceptable
BB/diuretic* CCB (dihydropyridine)/BB CCB/diuretic Renin inhibitor/diuretic* Renin inhibitor/ARB*
Thiazide diuretics/K+ sparing diuretics*
Less effective
ACE inhibit or /ARBACE inhibit or /BBARB/BB CCB (nondihydropyridine)/BB Centrally acting agent/BB
*Single-pill comb inations available in the United States.
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Hypertension 20
20thAnnual Primary Care Conference
Hermida et al. Hypertension. 2009.
Bedtime Dosing of One BP Medication
in Resistant Hypertension
3 drugs onawakening
One of the drugsat bedtime
ChangeinSBP(mmHg)
-12
-15
-8
-6
-4
-2
0
2
Diurnal mean Nocturnal mean 24-hr mean
P
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Clinical Points
Most patients will require 2 or moreantihypertensive agents to get BP effectivelycontrol led which may be best approached withinitial combination therapy, either as a fixed-dose combination (FDC) or as 2 individual initialagents