Luis Ruilope, Unidad de Hipertension Madrid, Spain Cardio-renal - - PowerPoint PPT Presentation

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Luis Ruilope, Unidad de Hipertension Madrid, Spain Cardio-renal - - PowerPoint PPT Presentation

Mar 18, 2024 278 likes •468 views

Asian Chapter Asian Chapter Achieving Blood Pressure targets: Current & future options in blocking the Renin Angiotensin System Luis Ruilope, Unidad de Hipertension Madrid, Spain Cardio-renal continuum REGRESS Target organ damage

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SLIDE 1

Asian Chapter

Achieving Blood Pressure targets: Current & future options in blocking the Renin Angiotensin System

Luis Ruilope,

Unidad de Hipertension Madrid, Spain

Asian Chapter

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SLIDE 2

Cardio-renal continuum

Risk factors Atherosclerosis

REGRESS

Target organ damage Asymptomatic Target organ damage Symptomatic Death CKD ESRD New risk factors

CKD=chronic kidney disease; ESRD=end-stage renal disease

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SLIDE 3
  • ARTERIAL HYPERTENSION
  • HEART FAILURE
  • POST-MI
  • DIABETIC NEPHROPATHY WITH PROTEINURIA
  • HIGH CV RISK (HOPE, EUROPA & PEACE)
  • PATIENTS WITH 3 OR MORE ASSOCIATED CVRF
  • PATIENTS WITH METABOLIC SYNDROME
  • PATIENTS WITH TOD
  • PATIENTS WITH DIABETES
  • Actually 30-50% of hypertensives in Europe receive

either an ACEi or an ARB since stage 1

USE OF RAAS SUPPRESSION

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SLIDE 4

25 50 100 mg Losartan 80 160 320 mg Valsartan 75 150 300 mg Irbesartan

Reduction in diastolic BP (mmHg) Losartan Valsartan Irbesartan

  • 10
  • 8
  • 6
  • 4
  • 2

Elmfeldt et al 2002

Meta-Analysis based on US New Drug Application Evaluation Reports

Candesartan

4 8 16 mg Candesartan

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SLIDE 5

ESH 2010 Oral Presentation

Run-in Period Screening (Day -28 to -21)

OLM-M 20 → 40 mg (N=290)* VAL 160 → 320 mg (N=282)* AZL-M 40 → 80 mg (N=285)* AZL-M 20 → 40 mg (N=280)* Placebo (N=154)*

Baseline ABPM & Randomization Week 2 Forced Titration Week 4 Week 6 Final ABPM

*Number of patients randomized.

Schematic of Study Design

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SLIDE 6

ESH 2010 Oral Presentation

24-Hour Mean Systolic BP by ABPM

Change from Baseline to Week 6

(LS mean ± SE, mm Hg)

a

P<0.001 vs placebo. b P≤0.001 vs VAL. c P=0.009 vs OLM-M.

*Superiority of AZL-M 40 mg vs VAL 320 mg was not examined because the stepwise analysis was halted at a previous step.

  • 13.4a,b*
  • 14.5a,b,c
  • 10.2a
  • 12.0a
  • 0.3
  • 18
  • 14
  • 10
  • 6
  • 2

VAL 320 mg Placebo AZL-M 40 mg AZL-M 80 mg OLM-M 40 mg

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SLIDE 7

ESH 2010 Oral Presentation

24-Hour Mean Diastolic BP by ABPM

Change from Baseline to Week 6

(LS mean ± SE, mm Hg)

  • 8.7a,b
  • 9.4a,c,d
  • 7.1a
  • 7.7a
  • 0.1
  • 10
  • 6
  • 2

a

P<0.001 vs placebo. b P=0.02 vs VAL.

c

P<0.001 vs VAL. d P=0.011 vs OLM-M.

VAL 320 mg Placebo AZL-M 40 mg AZL-M 80 mg OLM-M 40 mg

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SLIDE 8

ESH 2010 Oral Presentation

24-Hour Systolic BP Profile by ABPM

6 12 18 24 120 125 130 135 140 145 150 155 Placebo AZL-M 40 mg AZL-M 80 mg OLM-M 40 mg VAL 320 mg

Hour After Dosing SBP (mm Hg)

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SLIDE 9

ESH 2010 Oral Presentation

Safety & Tolerability

Data are n (%) of subjects. DC = discontinuation. Placebo N=155 AZL-M 40 mg N=280 AZL-M 80 mg N=284 VAL 320 mg N=277 OLM-M 40 mg N=290 Adverse event Leading to DC Serious Death

74 (47.7)

3 (1.9) 2 (1.3)

134 (47.9)

7 (2.5) 2 (0.7)

145 (51.1)

8 (2.8) 3 (1.1)

131 (47.3)

7 (2.5) 3 (1.1)

151 (52.1)

6 (2.1) 4 (1.4) In ≥3% of all subjects Headache Dizziness 14 (9.0) 4 (2.6) 18 (6.4) 10 (3.6) 12 (4.2) 10 (3.5) 21 (7.6) 5 (1.8) 23 (7.9) 9 (3.1)

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SLIDE 10

Study udy Desi sign

ASH 2010 Late-Breaking Clinical Trials

Phase 3, multicenter, double-blind randomized study

2-Week Placebo Run-In Week 2 Week 6 ABPM Week 10 Final ABPM AZL-M 40 mg AZL-M–CLD 40 mg + 12.5 mg AZL-M–CLD 40 mg + 25 mg AZL-M + HCTZ 40 mg + 12.5 mg AZL-M + HCTZ 40 mg + 25 mg Follow-up Week 12 Day 1 Randomization, baseline ABPM AZL-M 40 mg

Monotherapy Forced addition

  • f CLD or HCTZ

Target BP titration

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SLIDE 11

Primary ary Ef Efficacy y En Endp dpoi

  • int

nt

Change in Trough Sitting Clinic SBP (mm Hg)

ASH 2010 Late-Breaking Clinical Trials

Data are least-squares mean ± SE.

Week 6 Week 10

  • 35.1a
  • 29.5
  • 37.8a
  • 32.8
  • 40
  • 30
  • 20
  • 10

AZL-M–CLD AZL-M + HCTZ

a P<0.001

Baseline 164.7± 0.55 Baseline 164.4± 0.56 Baseline 164.7± 0.55 Baseline 164.4± 0.56

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SLIDE 12

Change nge by y Stud udy y Week

ASH 2010 Late-Breaking Clinical Trials

Study Week

  • 40
  • 30
  • 20
  • 10

2 4 6 8 10 AZL-M–CLD AZL-M + HCTZ

Target BP titration Forced addition

  • f CLD or HCTZ

Monotherapy

Change in Trough Sitting Clinic SBP (mm Hg)

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SLIDE 13

Change nge in SBP by AB y ABPM

Change in Mean 24-Hour SBP (mm Hg) by ABPM

ASH 2010 Late-Breaking Clinical Trials

  • 25.7a
  • 19.9
  • 26.6a
  • 22.4
  • 30
  • 20
  • 10

Week 6 Week 10 AZL-M–CLD AZL-M + HCTZ

a P<0.001

Baseline 146.5± 0.89 Baseline 145.4± 0.88 Baseline 146.5± 0.89 Baseline 145.4± 0.88

Data are least-squares mean ± SE.

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SLIDE 14

Safety Results

CLD vs. HCTZ on background of AZL-M

AZL-M–CLD N=302 AZL-M + HCTZ N=303 Any adverse event 158 (52.3) 144 (47.5) Event leading to Discontinuation 28 (9.3) 22 (7.3) Serious adverse event 6 (2.0) 5 (1.7) Death a 1 (0.3) 1 (0.3)

Data are n (%) of subjects.

a Two sudden deaths were considered not related (n=1, AZL-M–CLD group) or possibly related

(n=1, AZL-M + HCTZ group) to the study drug by the investigators.

Creatinine elevations were more frequent with AZL-M_CLD than with AZL-M+HCTZ; most were transient

Bakris et al. Results of a double-blind randomized study comparing CLD and HCTZ combined with the new ARB Azilsartan Medoxomil in primary HTN. Late breaking Clinical Trial session presented at:: American Society of Hypertension Annual Scientific Meeting and Exposition; 2010 May 1-4; NYC,NY

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SLIDE 15

Study Design

Azilsartan Medoxomil in Combination with Amlodipine

Day -14 Week 4 ABPM Day 1 Week 7 Follow-up Day -21 (or -28)

AZL-M 40 mg QD AML 5 mg QD N=190* AZL-M 80 mg QD AML 5 mg QD N=188* Placebo + AML 5 mg QD N=189*

Screening and Single-Blind Placebo Run-in

Day -7 ABPM Week 6 Week 2

Weber et al. Antihypertensive Efficacy of the New Angiotensin Receptor Blocker Azilsartan Medoxomil in Combination with Amlodipine. Poster session presented at: American Society of Hypertension Annual Scientific Meeting and Exposition; 2010 May 1-4; NYC,NY ABPM = ambulatory blood pressure monitoring; QD = once daily *number of patients randomized; includes 1 subject given AZL-M 40 mg + AML 5 mg who was treated but not randomized

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SLIDE 16

aP<0.001 vs placebo +

AML 5 mg

  • 24.8a
  • 24.5a
  • 13.6
  • 28
  • 24
  • 20
  • 16
  • 12
  • 8
  • 4

Placebo + AML 5 mg AZL-M 40 mg + AML 5 mg AZL-M 80 mg + AML 5 mg

Weber et al. Antihypertensive Efficacy of the New Angiotensin Receptor Blocker Azilsartan Medoxomil in Combination with Amlodipine. Poster session presented at: American Society of Hypertension Annual Scientific Meeting and Exposition; 2010 May 1-4; NYC,NY

Primary Endpoint: Change from Baseline to Week 6 in 24-Hour Mean SBP by ABPM

Azilsartan Medoxomil in Combination with Amlodipine

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SLIDE 17
  • 15.3a
  • 15.4a
  • 7.8
  • 18
  • 14
  • 10
  • 6
  • 2

aP<0.001 vs placebo +

AML 5 mg Placebo + AML 5 mg AZL-M 40 mg + AML 5 mg AZL-M 80 mg + AML 5 mg

Weber et al. Antihypertensive Efficacy of the New Angiotensin Receptor Blocker Azilsartan Medoxomil in Combination with Amlodipine. Poster session presented at: American Society of Hypertension Annual Scientific Meeting and Exposition; 2010 May 1-4; NYC,NY

Change from Baseline to Week 6 in 24-Hour Mean DBP by ABPM

Azilsartan Medoxomil in Combination with Amlodipine

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SLIDE 18

PHARMACOLOGICAL NEEDINGS IN HYPERTENSION

- One drug 20% - Two drugs 50% - Three or more 30% *

 * Includes resistant hypertension (12%)

 CAN AZILSARTAN CONTRIBUTE TO DIMINISH THE

PHARMACOLOGICAL NEDINGS AND IMPROVE BP CONTROL IN THE HYPERTENSIVE POPULATION?