aspectos relevantes de la nueva guía esh/esc de hipertensión 2013
DESCRIPTION
Bloque: NUEVOS RETOS EN PREVENCIÓN Y TRATAMIENTO DE LA ENFERMEDAD CARDIOVASCULAR Ponente: Dr. Giuseppe Mancia Curso Medicina Cardiovascular que tuvo lugar el 8 y 9 octubre 2012 en Barcelona. Enlace: www.riesgocardiovascular.comTRANSCRIPT
How to Diagnose HT
17264 M
! Still to based on clinic BP?
! Needs to be based on / confirmed by ambulatory / home BP?
Shoud diagnosis be based on ABP/Home BP?
17266 M
! If properly measured Clinic BP is a good predictor
! “BP “ epidemiology still largely based on clinic BP
! Trial evidence on protective effect of BP reduction exclusively based on clinic BP(no outcome trials with ABP-Home BP)
! Large scale adoption of out-of office BP measurements is very complex/expensive
Predictive Ability of Clinic SBP Alone or in Combination with Home, 24h or Both
16612 M
All-cause deaths
0 0.1 0.2 0.3 0.4 0.5 0.6 0.7 0.8 0.9 1.0
0 0.1 0.2 0.3 0.4 0.5 0.6 0.7 0.8 0.9 1.0
Sens
itivi
ty
1-Specificity
CV events
0 0.1 0.2 0.3 0.4 0.5 0.6 0.7 0.8 0.9 1.0
0 0.1 0.2 0.3 0.4 0.5 0.6 0.7 0.8 0.9 1.0 Se
nsiti
vity
1-Specificity * Sigificantly superior to Clinic alone
Clinic Clinic + 24h Clinic + Home + 24h * Ref Clinic + Home *
Clinic Clinic + 24h Clinic + Home + 24h * Ref Clinic + Home *
Zanchetti, Mancia, J Hypertens 2012; 30: 660
17274 M
Should white coat hypertension be regarded as normotension?
CV and All Cause Mortality in WCH Diagnosed by 24h or Home Normality
17883 M Mancia et al., submitted
Cumulative incidence 0.16
0.14
0.12
0.10
0.08
0.06
0.04
0.02
0.00
Cumulative incidence 0.40
0.35
0.30
0.25
0.20
0.15
0.10
0.05
0.00 0 2 4 6 8 10 12 14 16 18 20
Years 0 2 4 6 8 10 12 14 16 18 20
Years
CV mortality All cause mortality
FU 16 years P < 0.0001
FU 16 years P < 0.0001
HT
WCH
NT
HT
WCH
NT
Events: 48 (12.9%)
21 (5.4%)
8 (1.0%)
Events: 112 (30.0%)
77 (19.7%)
53 (6.4%)
04/02/13 10:40 pm 7
PAMELA Study: SBP Values and LVH Prevalence
1770 M
80 90 100 110 120 130 140 150 160 170 180 190 200 210 220 230 Clinic
80 90
100 110 120 130 140 150 160 170 180 24 h mean
Prevalence: 9% LVH: 14%
Prevalence: 67% LVH: 4%
Prevalence: 12% LVH: 26%
Prevalence: 12% LVH: 15%
Sega R. et al., Circulation 2001; 104: 1385
Metabolic Risk Factors in Subjects with Combined or Selective Elevation in Office and Out-of-office BP
22
24
26
28
30
200
210
220
230
240
250
40
80
120
160
50
52
54
56
58
60
N WCH H
80
85
90
95
100
0
10
20
30
40
0
2
4
6
8
10
0
4
8
12
16
12885a M
Office vs 24h
Office vs Home
Office vs 24h
Office vs Home
Office vs 24h
Office vs Home
Office vs 24h
Office vs Home
Office vs 24h
Office vs Home
Office vs 24h
Office vs Home
Office vs 24h
Office vs Home
Office vs 24h
Office vs Home
BMI (kg/m2) Total chol. (mg/dl) Triglycerides (mg/dl) HDL-chol. (mg/dl)
Glucose (mg/dl) MS (%) DM (%) IFG (%)
* p < 0.05
* * * *
*
* * * *
* *
* *
* *
* *
* * * *
* * *
* *
*
* *
* * *
* * * *
Mancia, Facchetti, Bombelli, Grassi, Sega, Hypertension 2006; 47: 846-853 16967 M
Office and Out-of-office BP in NT and WCHT
NT WCH
100
110
120
130
140
150 SB
P (m
mH
g)
Office 24h Home
140
125
132
118
144
113 117
113
128
16969 M
10-Year Incidence and Adjusted Risk (HR) of Developing Established HT, Diabetes and LVH in NT and WCHT Based on Office and Ambulatory BP Data
0
10
20
30
40
50
NT WCHT
18.2
42.6
32.2
13.4 2.0
6.5
Diabetes LVH Established
HT
758 225 152 597 738 217 n
Incidence
HR
NT WCHT NT WCHT NT WCHT
Established HT
%
0.1 0.2 0.5 1 2 5 10
2.51 (1.79-3.74)
P < 0.0001
LVH
Diabetes
1.98 (1.27-3.06)
2.89 (1.34-6.22)
P = 0.002
P = 0.007
How to Assess CV Risk
17265 M
! Many new CV risk factors available • Measures of organ damage • Inflammatory markers • Others
! How much do they add to the prediction provided by algorithms based on classical risk factors?
12
Receiver-Operating–Characteristic Curves for Death and Major Cardiovascular Events
Wang TJ et al. N Engl J Med. 2006;355:2631-2639.
Biomarkers for death Conventional: Age, BMI, Smoking, Diabetes, BP, TC, HDL-C, Cr Newer Biomarkers: B-type natriuretic peptide, CRPn, th Age, BMI, Smoking, Diabetes, BP, TC, HDL-C, Cr e urinary albumin-to-creatinine ratio, homocysteine, and renin. Biomarkers for major cardiovascular events: B-type natriuretic peptide and the urinary albumin-to-creatinine ratio.
0 0.1 0.2 0.3 0.4 0.5 0.6 0.7 0.8 0.9 1.0 0
1.0
0.8
0.6
0.4
0.2
1–specificity
Sensitivity
Death
0 0.1 0.2 0.3 0.4 0.5 0.6 0.7 0.8 0.9 1.0 0
1.0
0.8
0.6
0.4
0.2
1–specificity
Sensitivity
Major Cardiovascular Events
With new biomarkers
Without biomarkers
With new biomarkers
Without biomarkers
The Cumulative Probability (%) and Hazard Ratios of CV Death in Subgroups, according to SCORE and Presence of Subclinical Organ Damage
15751 M Sehestedt T et al., Eur Heart J 2010; 31: 883-891
15
10
5
0 0 2 4 6 8 10 12 14
Years
Cum
ulat
ive
prob
abili
ty o
f CV
dea
th (%
)
Trend: P < 0.001
SCORE ≥ 5% - SOD present HR: 17.1 (8.4-34.6)
SCORE ≥ 5% - No SOD HR: 5.9 (2.0-7.7)
SCORE < 5% - SOD present HR: 4.0 (1.7-9.2)
SCORE < 5% - No SOD Reference
Stratification of CV Risk in Four Categories
11657 M
Very high added risk
Very high added risk
Very high added risk
High added risk
Very high added risk
Very high added risk
High added risk
High added risk
Moderate added risk
Moderate added risk
Moderate added risk
Low added risk
Blood Pressure (mmHg)
Other Risk Factors, OD or Disease
Grade 1 HT SBP 140-159 or DBP 90-99
Grade 2 HT SBP 160-179
or DBP 100-109
Grade 3 HT
SBP ≥ 180 or DBP ≥ 110
3 or more Risk Factors, MS, OD or Diabetes
Very high added risk
Very high added risk
High added risk
Moderate added risk
Average risk
Low added risk
Low added risk
Average risk
Normal
SBP 120-129 or DBP 80-84
High Normal SBP 130-139 or DBP 85-89
SBP: systolic blood pressure; DBP: diastolic blood pressure; CV: cardiovascular; HT: hypertension. Low, moderate, high, very high risa refer to 10year risk of a CV fatal or non-fatal event. The term “added” indicates that in all categories risk is greater than average. OD: subclinical organ damage; MS: metabolic syndrome.
No other risk factors
1-2 risk factors
Established CV or renal disease
04/02/13 10:40 pm 15
The Cumulative Probability (%) and Hazard Ratios of CV Death Adjusted for (mean or ratio) Age and Gender or SCORE (< / ≥ 5%)
according to the Total Number of Different Types of Subclinical Organ Damage *
15750 M Sehestedt T et al., Eur Heart J 2010; 31: 883-891
20
15
10
5
0 0 2 4 6 8 10 12 14
Years
Cum
ulat
ive
prob
abili
ty o
f CV
dea
th (%
)
0 2 4 6 8 10 12 14 Years
20
15
10
5
0
25
N° of SOD HR (95% CI)
4 11.9 (3.8-37.2)
3 7.0 (3.2-15.3)
2 3.6 (1.8-7.2)
1 1.9 (1.0-3.6)
0 Reference
Adjustment for age / gender
Adjustment for SCORE
N° of SOD HR (95% CI)
4 18.3 (5.9-57.1)
3 11.4 (5.2-25.0)
2 5.7 (2.9-11.4)
1 2.6 (1.3-5.1)
0 Reference
* LVH, Atherosclerotic plaques / PWV >12 m/s / UACR ≥ 90th percentile
Trend: P < 0.001 Trend: P < 0.001
14865 M
Combined Effects of Albuminuria and eGFR Levels at Baseline on the Risk for Adverse Outcomes in ADVANCE
Ninomaya, Mancia, Chalmers,et al J Am Soc Nephrol 2009; 20: 1813
Cardiovascular events Cardiovascular death Renal events
0
1
2
3
4
Macro- albuminuria
Micro- albuminuria
Normo- albuminuria
eGFR ≥ 90
eGFR 60-89
eGFR < 60
Baseline eGFR
Baseline UACR
Hazard Ratio
0
1
2
3
4
5
Macro- albuminuria
Micro- albuminuria
Normo- albuminuria
eGFR ≥ 90
eGFR 60-89
eGFR < 60
Baseline eGFR
Baseline UACR
Hazard Ratio
0
5
10
15
20
25
Macro- albuminuria
Micro- albuminuria
Normo- albuminuria
eGFR ≥ 90
eGFR 60-89
eGFR < 60
Baseline eGFR
Baseline UACR
Hazard Ratio
Can we improve estimates of CV Protection by Treatment?
17266 M
! Clinic BP reduction still the most important factor?
! Effect on alternative BPs (ambulatory / home / central)?
! Reduction of 24h BP / visit-to-visit BP variability?
! Are changes in markers of organ damage (proteinuria / LVH etc) predictive of event-based benefits?
Prognostic Value of T-induced Changes in Organ Damage
17158 M
Time to change
Slow
Very slow (years)
Fast (weeks)
Middle (months)
Slow (months)
Fast (weeks)
EKG eGFR UAE Echo LV Car. Wall Thickness PWV
Prognostic value of T-induced change
Yes
Yes
Yes
Yes
Uncertain ?
Sensitivity for change
Low
Very low
Middle
High
Very low
High
Adjusted Risk of CV Events, Renal Events and Mortality in Relation to Treatment-induced Difference in Albuminuria (n = 23480; FU 32 months )*
15343 M Schmieder, Mann, Schumacher, Gao, Mancia, Weber, McQueen, Koon, Yusuf, J Am Soc Nephrol 2011; 22: 1353-1364
* Minor change of albuminuria was taken as reference group (HR = 1.0)
0 1 2 decrease > 50%
increase > 100%
Decrease > 50% vs minor change minor change
Increase > 100% minor change
Decrease > 50% vs minor change minor change
Increase > 100% minor change
Decrease > 50% vs minor change minor change
Increase > 100% minor change
Decrease > 50% vs minor change minor change
Increase > 100% minor change
0.0253
< 0.0001
< 0.0001
0.1715
0.0466
< 0.0001
0.2742
0.0003
All-cause mortality
CV mortality
Composite CV endpoint
Combined renal endpoint
Searching for OD
17909 M
! Better quantification of total CV risk ! Better identification of high CV risk patients (multifold
therapeutic implications) ! Better estimate of CV risk changes by treatment
! May help trials to explore not only high risk but also low-moderate risk conditions (younger patients, earlier treatment phases etc)
Helps appropriate treatment modifications
Meets questions / requirements by patients
Which 1st Step Drug(s)?
17269 M
! Disagreements between / within guidelines
! Disagreements even on which diuretic to consider
! Wide or restricted choice?
! Age-related choice?
! Do we still need 1st / 2nd/ 3rd …. choice classification?
Average BP ↓ over 24 Hours (Peak and Trough) from 357 Randomized Trials (n = 40000 Treated and 16000 Placebo Patients)
12437 M Law MR et al., Brit Med J 2003; 326: 1427
Half standard Standard Twice standard
-12
-9
-6
-3
Thiazides Beta-blockers ACEI ARB CA
Half standard Standard Twice standard
-9
-6
-3
0
Δ S
BP
(mm
Hg)
Δ D
BP
(mm
Hg)
BP-Lowering Regimens Based on Different Drug Classes and Total Major CV Events in Younger and Older Patients
13000a M
ACEI vs D or BB Age < 65 Age ≥ 65 CA vs D or BB Age < 65 Age ≥ 65 ACEI vs CA Age < 65 Age ≥ 65 ARB vs others Age < 65 Age ≥ 65
2nd listed
1066/12012 2525/14429
1430/23236 3363/24981
568/ 4919 1608/ 8140
204/ 722 487/ 3171
P for homogeneity
0.44
0.38
0.37
0.78
0.5 1.0 2.0 Favours 2nd listed
Difference in SBP/DBP (mmHg)
1.3/0.1 2.0/0.5
1.1/-0.2 0.5/-0.4
0.9/0.6 1.0/1.0
-1.7/-0.3 -2.0/-1.2
Favours 1st listed
BPLTTC, BMJ 2008; 336: 1121
Risk ratio (95%CI)
1.05 (0.96-1.14) 1.01 (0.95-1.06)
1.06 (0.98-1.14) 1.02 (0.97-1.06)
0.91 (0.78-1.06) 0.98 (0.92-1.05)
0.89 (0.75-1.05) 0.91 (0.81-1.02)
Risk ratio (95%CI)
1st listed
819/ 9448 1795/10783
1165/20358 2653/21204
548/ 5130 1583/ 8170
183/ 742 438/ 3167
No. of events/patients
14688 M ESH Task Force, J Hypertens 2009
Is ranking antihypertensive agents in order of choice useful
or deceiving in clinical practice?
Future Antihypertensive Treatment
12687 M
Approach based on 1st / 2nd / n choice drugs to be abandoned in favour of recommendations on
which drugs to use in which patients under which circumstances
11817 M
2007 ESH/ESC Guidelines Conditions favouring Use of Some Antihypertensive Drugs versus Others
Thiazide diuretics • Isolated systolic hypertension (elderly)
• Heart failure • Hypertension in blacks ACE inhibitors • Heart failure • LV dysfunction • Post-MI • Diabetic nephropathy • Non-diabetic nephropathy • LV hypertrophy • Carotid atherosclerosis • Proteinuria / Microalbuminuria
• Atrial fibrillation • Metabolic syndrome
Beta-blockers • Angina pectoris • Post-MI • Heart failure • Tachyarrhythmias • Glaucoma • Pregnancy
Angiotensin receptor antagonists
• Heart failure • Post-MI • Diabetic nephropathy • Proteinuria / Microalbuminuria
• LV hypertrophy • Atrial fibrillation • Metabolic syndrome • ACEI-induced cough
Calcium antagonists (verapamil/diltiazem) • Angina pectoris • Carotid atherosclerosis • Supraventricular tachycardia
Loop diuretics • End stage renal disease • Heart failure
Calcium antagonists (dihydropyridines)
• Isolated systolic hypertension (elderly)
• Angina pectoris • LV hypertrophy • Carotid/Coronary Atherosclerosis
• Pregnancy • Hypertension in blacks
Diuretics (antialdosterone) • Heart failure • Post-MI
04/02/13 10:40 pm 27 11821 M
2007 ESH/ESC Guidelines
Choice of Antihypertensive Drugs
! Previous patient’s experience with drug class ! Effect of drugs on CV risk factors ! Presence / absence of OD / CVD / KD / DM ! Other disorders limiting particular drug use ! Cost of drugs ! 24h BP coverage ! Once-a-day administration ! Continuing attention to side effects
Cumulative Incidence of Modification of Initial Antihypertensive Monotherapy over 5 Years in Newly Treated Hypertensives (Lombardia Data-base, n = 445.356))
13154 M Corrao, Zambon, Parodi, Poluzzi, Baldi, Merlino, Cesana, Mancia, J Hypertens 2008; 26: 819-824
Cum
ulat
ive
inci
denc
e
0 12 24 36 48 600
0.1
0.2
0.3
0.4
0.5
0.6
Months since starting antihypertensive treatment
Discontinuation
Combining
Switching
0
-10
-20
-30
-40
-50 Cerebrovascular events Coronary events
0
-10
-20
-30
-40
-50
16248 M
Effects of Persistence or Adherence with Antihypertensive Drug Therapy on the Reduction in Hazard Ratio† of Coronary (n = 6665) and
Cerebrovascular (n = 5351) Outcomes in 242.594 Patients
† Estimates are adjusted for gender, age, initial antihypertensive regimen, number of different classes of antihypertensive medications dispensed during FU, use of other drugs during FU, and categories of Charlson comorbidity index score. * At least 1 episode of no prescription coverage for > 90 days
Haz
ard
ratio
red
uctio
n (%
)
Adherence level Very low
(reference) Low Intermediate High Continuing use Discontinuing use*
(reference)
-37% -36%
-16% -21%
-24% -23%
Persistence category
Corrao, Parodi, Nicotra, Zambon, Merlino, Cesana, Mancia, J Hypert 2011; 29: 610-618
04/02/13 10:40 pm 30 12026 M
Cumulative Incidence of Discontinuation of Initial Antihypertensive Monotherapy over 1 Year in Newly Treated Hypertensives (Lombardia Data-base; n = 445356)
0.5 1.0 2.0
Diuretics Beta-blockers Alpha-blockers Calcium channel blockers ACE-inhibitors Angiotensin-receptor blockers
1.83 (1.81-1.85) 1.64 (1.62-1.67) 1.23 (1.20-1.27) 1.08 (1.06-1.09) 0.92 (0.90-0.94)
- +
Corrao, Zambon, Parodi, Poluzzi, Baldi, Merlino, Cesana, Mancia, J Hypert 2008; 26: 819-824
17240 M
Monotherapy or combination therapy ?
VALUE: BP in the Censored and ITT Population
Julius S et al., Hypertension 2006; 48: 385-391 13241 M
Mean SBP Mean DBP
0 6 12 18 24 30 36 42 48 54 60 66130
135
140
145
150
155
0 6 12 18 24 30 36 42 48 54 60 6675
80
85
90
Valsartan Amlodipine
0 6 12 18 24 30 36 42 48 54 60 66130
135
140
145
150
155
0 6 12 18 24 30 36 42 48 54 60 6675
80
85
90
mm
Hg
mm
Hg
Patients censored at discontinuation of monotherapy Patients censored at discontinuation of monotherapy
Patients on monotherapy at 6 months ITT population
Patients on monotherapy at 6 months ITT population
Time (months) Time (months)
Ratio of observed to expected incremental blood pressure-lowering effects* of adding a drug or doubling the dose according to the class of drug (n = 11000, 42 studies)
13974 M Wald DS et al., Am J Med 2009; 122: 290
Incr
emen
tal S
BP
redu
ctio
n ra
tio
of o
bser
ved
to e
xpec
ted
addi
tive
effe
cts
* The expected incremental effect is the incremental blood pressure reduction of the added (or doubled drug), assuming an additive effect and allowing for the smaller reduction from 1 drug (or dose of 1 drug) given the lower pretreatment blood pressure because of the other
1.5
1.0
0.5
0.0
Adding a drug from another class (on average standard doses) Doubling dose of same drug (from standard dose to twice standard)
1.04 (0.88-1.20)
1.00 (0.76-1.24)
1.16 (0.93-1.39)
0.89 (0.69-1.09)
1.01 (0.90-1.12)
0.19 (0.08-0.30)
0.23 (0.12-0.34) 0.20
(0.14-0.26)
0.37 (0.29-0.45)
0.22 (0.19-0.25)
Thiazide Beta- blocker
ACE- inhibitor
Calcium channel blocker
All classes
17241 M
Which combinations ?
ESH/ESC Guidelines
17117 M Mancia et al., 2003; Mancia et al., J Hypert 2007;
2003 2007
Thiazide diuretics
ACE inhibitors
Calcium antagonists
ß-blockers AT1-receptor antagonists
α-blockers
Thiazide diuretics
ACE inhibitors
Calcium antagonists
ß-blockers AT1-receptor antagonists
α-blockers
Combination Treatment in the 2009 ESH Reappraisal
17084 M Mancia et al., J Hypert 2009; 27: 2121
PROGRESS ADVANCE HYVET
Syst-Eur Syst-China INVEST ASCOT STAR ACCOMPLISH
FEVER ELSA VALUE HOT
ACEI / D ARB / D ACEI / CA CA / D ARB / CA
LIFE SCOPE RENAAL TRANSCEND
RENAAL (?)
RAS blocker +
Diuretic
Diuretics
ACE inhibitors
Angiotensin receptor antagonist Calcium antagonists
Calcium antagonist
CA / BB
HOT (2nd used)
ACCOMPLISH
13018 M
SBP over time Kaplan-Meier for primary endpoint
mmHg
Month 5731 5387 5206 4999 4804 4285 2520 1045 5709 5377 5154 4980 4831 4286 2594 1075
Pts.
*Mean values are taken at 30 months F/U visit
129.3 mmHg
130 mmHg
Difference of 0.7 mmHg p<0.05*
DBP: 71.1 DBP: 72.8
ACEI / HCTZ N=5733 CCB / ACEI N=5713
Cumulative event rate
HR (95% CI): 0.80 (0.72, 0.90)
20% Risk Reduction
Time to 1st CV morbidity/mortality (days)
p = 0.0002
ACEI / HCTZ
CCB / ACEI 650
526
17088 M
Replication of ACCOMPLISH data by a second “independent” trial
desirable
Selecting Patients Suitbale for RAS Blockade with CCB or Diuretic
16601 M
RAS blocker
CCB Thiazide diuretic
! Metabolic syndrome ! Impaired fasting glucose
! Family history of diabetes
! Lipid profile alterations ! Need to avoid hypokalemia
! No metabolic problems ! Low risk of developing diabetes
! Hypervolemia
! Advanced nephropathy
Advantages of Fixed vs Free Drug Combinations
17081 M Bangalore S et al., Am J Med 2007; 120: 713 - Gupta et al. Hypertension 2010, 55, 399
Study Dezii CM et al, 2000 Dezii CM et al, 2000 NDC Dataset, 2003 Taylor AA et al, 2003 Overall
Compliance to treatment
Risk ratio (95% CI)
0.74 (0.65-0.84)
0.71 (0.62-0.80)
0.81 (0.77-0.86)
0.74 (0.67-0.81)
0.76 (0.71-0.81)
Favors free drug combinations
Favors fixed dose combinations
0.1 1 10
Risk ratio
SBP reduction
-22.8 Favours FDC Favours
free combination
Non-randomised Forrest et al. 1980 Bengtsson et al. 1979 Ebbutt et al. 1979 Schweizer et al. 2007 Subtotal Randomised Nissinen et al. 1980 Asplund et al., 1984 Solomon et al. 1980 Olvera et al. 1991 Mancia et al. 2004 Subtotal Overall
22.8 0
Mean SBP diff.
-12.0 - 2.0 -10.0 0.2 - 6.1
- 0.4 1.7 1.9 2.0 -14.7 - 2.4
- 4.1
2007 ESH/ESC Guidelines Monotherapy versus Combination Therapy Strategies
11659a M
Two-drug combination at low dose
Two-three drug combination at full doses
Previous agent at full dose
Switch to different agent at low dose
Previous combination at full dose
Add a third drug at low dose
Two-to-three drug combination at full dose
Full dose monotherapy
Choose between
If goal BP not achieved
If goal BP not achieved
Single agent at low dose
Mild BP elevation Low/moderate CV
risk Conventional BP
target
Marked BP elevation High/very CV high
risk Lower BP target
VALUE: Analysis of Results Based on Immediate Response*
Fatal/Non-fatal cardiac events
Fatal/Non-fatal stroke
All-cause death
Myocardial infarction
Heart failure hospitalisations
0.4 0.6 0.8 1.0 1.2 1.4 Immediate responders*
(n = 9336) Non-immediate responders
(n = 5663) Odds Ratio 95% CI
*Those not on previous tx: SBP ↓ ≥10 mmHg at one month; those on previous tx: SBP ≤ baseline at one month. **P < 0.05; †P < 0.01.
Pooled Treatment Groups
**
†
**
0.88 (0.79–0.97)
0.83 (0.71–0.98)
0.90 (0.81–0.99)
0.89 (0.76–1.04)
0.87 (0.75–1.01)
Odds Ratio
Weber MA et al. Lancet. 2004;363:2047–49.
Ambrosioni E, J Hypertens 2000; 18:1691-1699
Reasons for switching antihypertensive therapy
%
60
0
10
34.1
Inadequate���blood pressure���
control
40
20
Side ���effects
53.3
New ���antihypertensive���agent availability
8.2
Pharmacological���interactions
3.3
Other
1.1
50
30
Patient’s estimations of the Italian Pharmacoepidemiology Study ���on antihypertensive therapy
-62
Discontinuation Rate with Mono and Combination† Therapy vs Diuretic Monotherapy (9 months data, n = 433680)*
17116 M Corrao, Parodi, Zambon, Heiman, Filippi, Cricelli, Merlino, Mancia, J Hypertens 2010; 28: 1584-1590
* Adjusted for age / gender / use of non-hypertensive drugs; † Free combinations
-80
-60
-40
-20
0 Mono D Combo with D
% D
isco
ntin
uatio
n ra
te Δ
Use % 13.4 1.7 65.5 4.0 -73
-49
-80
-60
-40
-20
0 Mono Combo
Diuretic-based Non-diuretic-based
Effect of Initial and Subsequent BP Lowering Strategies on Coronary / Cerebrovascular Risk (n = 209650)
16328 M
Initial
Mono
Mono
Combo
Combo
1.00 (0.91-1.10)
0.96 (0.86-1.07)
0.74 (0.65-0.85)
OR*
0.5 1.0 2.0
FU
Mono
Combo
Mono
Combo
* Adjusted for age / gender / number of BP lowering drug classes during FU / concomitant use of drugs for CHF / CAD / diabetes etc
Corrao, Nicotra, Parodi, Zambon, Heiman, Merlino, Fortino, Cesana, Mancia, Hypertension 2011; 58: 566-572
Other “Therapeutic” Issues
17458 M
! Which evidence of long lasting protection? ! Fixed-dose combinations - To be extended to three-drugs? ! Polypill - Previous negative attitude to be retained? ! Treatment of resistant hypertension
- Which 4th / 5th / 6th drug? - Invasive procedures - Caution to be recommended?
! Threshold-Target BP/J curve with treatment in different HT grades / ages / CV risk
! Cost-benefit calculations ! The earlier T the better, but when? ! Should post hoc data be considered / How to grade evidence?/class
or Drud related recommendations?
14676 M
BP Goals of Treatment
Mancia et al., ESH Task Force, J Hypertens 2009; 27: 2121
! On the basis of current data, it may be prudent to recommend lowering BP within the range of 130-139 / 80-85 mmHg in all HTs, and possibly close to lower values in this range
Achieved BP in the Elderly
16360 M
147
138
148 145
159
144
160
151
161
151
165
156
186
167 170
143
180
162
172
150
120
130
140
150
160
170
180
190
SBP
(mm
Hg)
EW
PL
Active
SHEP MRC S. China SCOPE CW STOP S. Eur HYVET JATOS
BP Δ Benefit No benefit
Zanchetti, Grassi, Mancia J Hypert 2009; 27: 923 - Mancia et al., J Hypert 2009; 27: 2121
145 140
FEVER
136 132
Cardiosys
15959 M
132129
130
124
136
130130
122
140
136
130
124
133
128
138
135
140
136
150150
141
132
149
143
100
110
120
130
140
150
160
136133133
119
144
141
145143144
140137
128
138
132
140
134
143
134
162
153
143
139
154
144
155
145
148
145
110
120
130
140
150
160
170
Achieved BP in Trials
Diabetes Previous CVD
BP Δ Benefit No benefit
Zanchetti, Grassi, Mancia J Hypert 2009; 27: 923 - Mancia et al., J Hypert 2009; 27: 2121
SBP (mmHg)
HOT SHEP
UKPDS S. Eur ADV ABCD REN HOPE PROG
HT
IDNT
AM NT IR
IDNT
PL
Active
SBP (mmHg)
PATS
PL
Active
PROG ACC
PROF HOPE
EU CAM-AM PREV
ACT CAM-EN
PEA TR
Stroke CHD
ACRD NAV
preDM
BP and CV Events in ACCORD
15721 M
SBP Primary outcome
The ACCORD Study Group, NEJM 2010; March 14
140
130
120
110
0 0 1 2 3 4 5 6 7 8
Years since randomization
(mmHg) Standard Mean 133.5 mmHg
Intensive Mean 119.3 mmHg
Mean no. of medications prescribed Intensive Standard No. of patients Intensive Standard
3.2 1.9
2174 2208
3.4 2.1
2071 2136
3.4 2.1
1973 2077
3.5 2.2
1792 1860
3.5 2.2
1150 1241
3.5 2.3
445 504
3.4 2.3
156 203
3.4 2.3
156 201
1.0
0.8
0.6
0.4
0.2
0.0 0 1 2 3 4 5 6 7 8
0 1 2 3 4 5 6 7 8 0.0
0.1
0.2 Standard
Intensive
Proportion with events
Years
P = 0.20
Serious Adverse Events Attributed to Antihypertensive Treatment
15333 M The ACCORD Study Group, NEJM 2010
0
1
2
3
4
5
Intensive Therapy
Standard Therapy
%
3.3 (n = 77)
1.3 (n = 30)
P < 0.001
Relationship between Target BP with Treatment and Events in Diabetic Patients of INVEST (n = 6400)
17752 M Cooper-DeHoff et al., JAMA 2010; 304: 61-68
40
30
20
10
0 0 0.5 1.0 1.5 2.0 2.5 3.0 3.5
Time to event, y
Cum
ulat
ive
even
t rat
e, %
SBP control Uncontrolled Tight Usual
Overall log-rank P < 0.001 Tight control vs usual control log-rank P = 0.19
Adj
uste
d H
azar
d R
atio
10
1.0
0.5 <110 110-<115 115-<120 120-<125 125-<130
SBP, mmHg
Kaplan-Meier curves (CV events)
Adjusted risk (all-cause mortality) with average on-T SBP < 130 mmHg