aspectos relevantes de la nueva guía esh/esc de hipertensión 2013

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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.com

TRANSCRIPT

Page 1: Aspectos relevantes de la nueva guía ESH/ESC de hipertensión 2013
Page 2: Aspectos relevantes de la nueva guía ESH/ESC de hipertensión 2013

How to Diagnose HT

17264 M

! Still to based on clinic BP?

! Needs to be based on / confirmed by ambulatory / home BP?

Page 3: Aspectos relevantes de la nueva guía ESH/ESC de hipertensión 2013

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

Page 4: Aspectos relevantes de la nueva guía ESH/ESC de hipertensión 2013

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

Page 5: Aspectos relevantes de la nueva guía ESH/ESC de hipertensión 2013

17274 M

Should white coat hypertension be regarded as normotension?

Page 6: Aspectos relevantes de la nueva guía ESH/ESC de hipertensión 2013

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%)

Page 7: Aspectos relevantes de la nueva guía ESH/ESC de hipertensión 2013

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

Page 8: Aspectos relevantes de la nueva guía ESH/ESC de hipertensión 2013

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

* * * *

*

* * * *

* *

* *

* *

* *

* * * *

* * *

* *

*

* *

* * *

* * * *

Page 9: Aspectos relevantes de la nueva guía ESH/ESC de hipertensión 2013

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

Page 10: Aspectos relevantes de la nueva guía ESH/ESC de hipertensión 2013

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

Page 11: Aspectos relevantes de la nueva guía ESH/ESC de hipertensión 2013

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?

Page 12: Aspectos relevantes de la nueva guía ESH/ESC de hipertensión 2013

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

Page 13: Aspectos relevantes de la nueva guía ESH/ESC de hipertensión 2013

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

Page 14: Aspectos relevantes de la nueva guía ESH/ESC de hipertensión 2013

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

Page 15: Aspectos relevantes de la nueva guía ESH/ESC de hipertensión 2013

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

Page 16: Aspectos relevantes de la nueva guía ESH/ESC de hipertensión 2013

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

Page 17: Aspectos relevantes de la nueva guía ESH/ESC de hipertensión 2013

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?

Page 18: Aspectos relevantes de la nueva guía ESH/ESC de hipertensión 2013

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

Page 19: Aspectos relevantes de la nueva guía ESH/ESC de hipertensión 2013

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

Page 20: Aspectos relevantes de la nueva guía ESH/ESC de hipertensión 2013

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

Page 21: Aspectos relevantes de la nueva guía ESH/ESC de hipertensión 2013

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?

Page 22: Aspectos relevantes de la nueva guía ESH/ESC de hipertensión 2013

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)

Page 23: Aspectos relevantes de la nueva guía ESH/ESC de hipertensión 2013

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

Page 24: Aspectos relevantes de la nueva guía ESH/ESC de hipertensión 2013

14688 M ESH Task Force, J Hypertens 2009

Is ranking antihypertensive agents in order of choice useful

or deceiving in clinical practice?

Page 25: Aspectos relevantes de la nueva guía ESH/ESC de hipertensión 2013

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

Page 26: Aspectos relevantes de la nueva guía ESH/ESC de hipertensión 2013

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

Page 27: Aspectos relevantes de la nueva guía ESH/ESC de hipertensión 2013

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

Page 28: Aspectos relevantes de la nueva guía ESH/ESC de hipertensión 2013

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

Page 29: Aspectos relevantes de la nueva guía ESH/ESC de hipertensión 2013

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

Page 30: Aspectos relevantes de la nueva guía ESH/ESC de hipertensión 2013

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

Page 31: Aspectos relevantes de la nueva guía ESH/ESC de hipertensión 2013

17240 M

Monotherapy or combination therapy ?

Page 32: Aspectos relevantes de la nueva guía ESH/ESC de hipertensión 2013

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)

Page 33: Aspectos relevantes de la nueva guía ESH/ESC de hipertensión 2013

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

Page 34: Aspectos relevantes de la nueva guía ESH/ESC de hipertensión 2013

17241 M

Which combinations ?

Page 35: Aspectos relevantes de la nueva guía ESH/ESC de hipertensión 2013

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

Page 36: Aspectos relevantes de la nueva guía ESH/ESC de hipertensión 2013

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)

Page 37: Aspectos relevantes de la nueva guía ESH/ESC de hipertensión 2013

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

Page 38: Aspectos relevantes de la nueva guía ESH/ESC de hipertensión 2013

17088 M

Replication of ACCOMPLISH data by a second “independent” trial

desirable

Page 39: Aspectos relevantes de la nueva guía ESH/ESC de hipertensión 2013

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

Page 40: Aspectos relevantes de la nueva guía ESH/ESC de hipertensión 2013

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

Page 41: Aspectos relevantes de la nueva guía ESH/ESC de hipertensión 2013

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

Page 42: Aspectos relevantes de la nueva guía ESH/ESC de hipertensión 2013

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.

Page 43: Aspectos relevantes de la nueva guía ESH/ESC de hipertensión 2013

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

Page 44: Aspectos relevantes de la nueva guía ESH/ESC de hipertensión 2013

-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

Page 45: Aspectos relevantes de la nueva guía ESH/ESC de hipertensión 2013

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

Page 46: Aspectos relevantes de la nueva guía ESH/ESC de hipertensión 2013

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?

Page 47: Aspectos relevantes de la nueva guía ESH/ESC de hipertensión 2013

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

Page 48: Aspectos relevantes de la nueva guía ESH/ESC de hipertensión 2013

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

Page 49: Aspectos relevantes de la nueva guía ESH/ESC de hipertensión 2013

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

Page 50: Aspectos relevantes de la nueva guía ESH/ESC de hipertensión 2013

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

Page 51: Aspectos relevantes de la nueva guía ESH/ESC de hipertensión 2013

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

Page 52: Aspectos relevantes de la nueva guía ESH/ESC de hipertensión 2013

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