ueda2011 hypertensive diabetic patient-d.adel
TRANSCRIPT
Amlodipine Valsartan: The Rational Combination In Diabetic Hypertensive
Patients
By
Adel A El-Sayed MD
Page 2
Hypertension affecting 20–60% of patients with diabetes.
In type 2 diabetes, hypertension is often present as
part of the metabolic syndrome while in type 1 diabetes, hypertension may reflect the onset of diabetic nephropathy.
Hypertension substantially increases the risk of both macrovascular and microvascular complications.
Hypertension & Diabetes
Adapted from UKPDS BMJ 1998;317:703–713.
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0
50
100
150
200
250
300
≥200180–199160–179140–159120–139<120
Systolic blood pressure (mmHg)
CV
D d
eath
rate
(p
er 1
0,00
0 pe
rson
-yea
rs)
Without diabetesWith diabetes
Adapted from Stamler J et al Diabetes Care 1993;16(2):435–444.
*This analysis by Stamler et al included a cohort of more than 342,000 men aged 35 to 57 years who did not have diabetes, and a cohort of 5163 men who did have diabetes at baseline. The health status of study participants was followed through an average of 12 years .
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aMulticenter, randomized, controlled trialbMean blood pressures: 144/82 mmHg (tight control) and 154/87 mmHg (less-tight control)cp<0.05 vs. less-tight control dp<0.01 vs. less-tight controlAdapted from UKPDS BMJ 1998;317:703–713.
%R
isk
redu
ctio
n w
ith
tight
vs.
less
-tigh
t con
trol
Study 1Tight blood pressure controlb
–50
0
–10
–20
–30
–40
20
10
Aggregate EndpointsStroke
Microvascular disease Any diabetes-related endpoint
Death related to diabetes
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aMulticenter, randomized, controlled trialbGoal fasting blood glucose: <6.0 mmol/L (intensive control) and <15.0 mmol/L (conventional treatment)
cp<0.05 vs. less-tight controldp<0.01 vs. less-tight control
Adapted from UKPDS Lancet 1998;352:837–853.
%R
isk
redu
ctio
n w
ith
tight
vs.
less
-tigh
t con
trol
Study 2Intensive blood glucose controlb
–50
0
–10
–20
–30
–40
20
10
Aggregate EndpointsStroke
Microvascular disease Any diabetes-related endpoint
Death related to diabetes
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–80
–60
–40
–20
0
Stroke p<0.13
Total mortality
p<0.04
Cardiovascular mortality p<0.02
Cardiovascular events p<0.01
With diabetes
–55%
–76%–69%
–73%
Adapted from Tuomilehto J et al. N Engl J Med 1999;340:677–84
–38%
–6%–13%
–26%
Without diabetes
Red
uctio
n in
inci
denc
e)%
(
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Unmet Need in the Treatment of Hypertension
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Approximately 70-80 % of hypertensive diabetic Patients* in Europe Do Not Reach BP Goal
Wolf-Maier et al. Hypertension 2004;43:10–17
*Treated for hypertensionBP goal is <140/90 mmHg
60 79 70 81 72
0
20
40
60
80
100BP goal achieved BP goal not achievedPatients (%)
England Sweden Germany Spain Italy
Back to section content
Multiple Antihypertensive Agents are Needed to Reach BP Goal
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Average no. of antihypertensive medications
1 2 3 4
Trial (SBP achieved)
Bakris et al. Am J Med 2004;116(5A):30S–8 Dahlöf et al. Lancet 2005;366:895–906; Jamerson et al. Blood Press 2007;16:80–6
ASCOT-BPLA (136.9 mmHg)
ALLHAT (138 mmHg)
IDNT (138 mmHg)
RENAAL (141 mmHg)
UKPDS (144 mmHg)
ABCD (132 mmHg)
MDRD (132 mmHg)
HOT (138 mmHg)
AASK (128 mmHg)
ACCOMPLISH* (132 mmHg)Initial 2-drug combination therapy*Interim 6-month data
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Rationale for Multiple-mechanism Therapy in Hypertension diabetic
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Recommendations for Multiple-mechanism Therapy: What the Treatment Guidelines Say: ESH–ESC
More than one agent is necessary to achieve target BP in the majority of patients
Treatment can be initiated with monotherapy or a combination of two drugs at low doses• Drug dose or number of drugs may be increased if necessary
A combination of two drugs at low doses preferred 1st step when• Initial BP in grade 2–3 range
• Total CV risk high/very high
Fixed combinations of two drugs simplify treatment/favor compliance
Task Force of ESH/ESC. J Hypertens 2007;25:1105–87
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Enhanced antihypertensive efficacy
Potential for attenuation of certain class-specific adverse events
May improve patient compliance (multiple-mechanism agent in a single pill versus free combination therapy)
Potentially cost effective
Recommended by treatment guidelines
Advantages of Multiple-mechanism Therapy
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Rationale for Dual-mechanism Therapy with Amlodipine/Valsartan:
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Amlodipine: Wealth of CV Outcomes Data
1Pitt et al. Circulation 2000;102:1503–10; 2Nissen et al. JAMA 2004;292:2217–26; 3Dahlof et al. Lancet 2005;366:895–906 4Williams et al. Circulation 2006;113:1213–25; 5Leenen et al. Hypertension 2006;48:374–84
PREVENT1
825 CAD patients (≥30%): Multicenter, randomized, placebo controlled
Primary outcome: No difference in mean 3 yr coronary angiographic changes vs. placebo
35% hospitalization for heart failure + angina33% revascularization procedures
CAMELOT2
1,991 CAD patients (>20%): Double-blind, randomized study vs. placebo and enalapril 20 mg
Primary outcome: 31% in CV events vs. placebo
41% hospitalization for angina27% coronary revascularization
ASCOT-BPLA/CAFE3,4
19,257 HTN patients: Multicenter, randomized, prospective study vs. atenolol
Primary outcome: 10% in non-fatal MI & fatal CHD
16% total CV events and procedures30% new-onset diabetes27% stroke11% all-cause mortality
central aortic pressure by 4.3 mmHg
ALLHAT5
18,102 HTN patients: Randomized, prospective study vs. lisinopril
Primary outcome: No difference in composite of fatal CHD + non-fatal MI vs. lisinopril6% combined CVD23% stroke
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Valsartan: Wealth of CV Outcomes Data
1Julius et al. Lancet 2004;363:2022–31; 2Pfeffer et al. N Engl J Med 2003;349:1893–906; 3Maggioni et al. Am Heart J 2005;149:548–57; 4Wong et al. J Am Coll Cardiol 2002;40:970–5; 5Cohn et al. N Engl J Med 2001;345:1667–7;6Mochizuki et al. Lancet 2007;369:1431–9
VALUE1
15,245 high-risk HTN patients; Double-blind, randomized study vs. amlodipine
No difference in composite of cardiac mortality and morbidity (primary)
23% new-onset diabetes
VALIANT2
14,703 post-myocardial infarction patients; Double- blind, randomized study vs. captopril and vs. captopril + valsartan
No difference vs. captopril in all-cause mortality (primary)
(valsartan is as effective as standard of care)
Val-HeFT3–5
5,010 heart failure II–IV patients; Double-blind, randomized study vs. placebo
13% morbidity and mortality (primary) left ventricular remodeling37% atrial fibrillation occurrence heart failure signs/symptoms28% heart failure hospitalization
JIKEI HEART6
3,081 Japanese patients on conventional treatment for hypertension, coronary heart disease, heart failure or combination of these; Multicenter, randomized, controlled trial comparing addition of valsartan vs. non-ARB to conventional treatment
39% composite CV mortality and morbidity40% Stroke/transient ischemic attack47% Hospitalization for heart failure65% Hospitalization for angina
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Amlodipine/Valsartan: BP Reductions Across All Grades of Hypertension - (Exzellent Trial1)
DBP ↓ (mmHg) –17 –18 –29
n = n = 18001800
n = n = 22932293
n = n = 890890
1Schrader J et al. PS38 Late Breaking Abstracts Session. ESH/ISH Congress, 14 June 2008.
-19
-32
-49
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Amlodipine/Valsartan FDC: BP Reductions for Patients with Diabetes– (Exzellent Trial1)
n = n = 639639
n = n = 795795 n = n =
295295
1Schrader J et al. PS38 Late Breaking Abstracts Session. ESH/ISH Congress, 14 June 2008.
-19
-32
-48
DBP ↓ (mmHg) –11 –15 –18
syst
.BP
redu
ctio
n (m
mH
g)
Amlodipine/Valsartan: Up to 9 Out of 10 Patients Reach BP Goal <140/90 mmHg
77.184.4
78.485.2
69.780
0
20
40
60
80
100All patients Non-diabetic patients Diabetic patients
Amlodipine/Valsartan 5/160 mg Amlodipine/Valsartan 10/160 mg
Diabetic patients with BP <130/80 mmHg at Week 8 were 47.0% and 49.2% for 5/160 mg and 10/160 mg doses, respectively
Patie
nts
(%)
Data shown are at Week 8No hydrochlorothiazide add-on was permitted until after Week 8Randomized, double-blind, multinational, parallel-group, 16-week study
n=440 n=369 n=71 n=449 n=375 n=74
80.0
Adapted fromAllemann et al. J Clin Hypertens 2008;10:185–94
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Tolerability
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Tolerability and Risk Factor Modification: CCB-induced Peripheral Edema Minimized by the ARB
Single mode of action of the CCB
Dual mode of action of the CCB/ARB
Illustration modified from www.lotrel.com
ARB dilates arteries and veins
ReducesCCB-induced
peripheral edema
Capillary overload
forces fluid into
surrounding tissue
CCB dilates arteries
Veins remain constricted
Messerli et al. Am J Hypertens 2001;14:978–9
ConclusionsCoexistence of diabetes and hypertension
is common and serious condition.
Aggressive treatment of hypertension in diabetic patients is important to avoid serious and potentially fatal complications.
Amlodipine Valsartan combination is a rational, safe and effective therapy for this serious health problem.