Effect of High-dose Angiotensin II Receptor Blocker (ARB) Monotherapy versus ARB plus Calcium Channel Blocker Combination on Cardiovascular Events in Japanese Elderly High-risk Hypertensive Patients (OSCAR): a Randomized Trial - PowerPoint PPT Presentation

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Effect of High-dose Angiotensin II Receptor Blocker (ARB) Monotherapy versus ARB plus Calcium Channel Blocker Combination on Cardiovascular Events in Japanese Elderly High-risk Hypertensive Patients (OSCAR): a Randomized Trial

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Title: Effect of High-dose Angiotensin II Receptor Blocker (ARB) Monotherapy versus ARB plus Calcium Channel Blocker Combination on Cardiovascular Events in Japanese Elderly High-risk Hypertensive Patients (OSCAR): a Randomized Trial


1
Effect of High-dose Angiotensin II Receptor
Blocker (ARB) Monotherapy versus ARB plus Calcium
Channel Blocker Combination on Cardiovascular
Events in Japanese Elderly High-risk Hypertensive
Patients (OSCAR) a Randomized Trial
  • Hisao Ogawa1, Shokei Kim-Mitsuyama2, Tomio
    Jinnouchi3, Hideaki Jinnouchi3, Kunihiko Matsui4
    and Kikuo Arakawa5, for the OSCAR Study Group

1 Department of Cardiovascular Medicine, Kumamoto
University Graduate School of Medical Sciences,
Kumamoto, Japan 2 Department of Pharmacology and
Molecular Therapeutics, Kumamoto University
Graduate School of Medical Sciences, Kumamoto,
Japan 3 Jinnouchi Clinic, Diabetes Care Center,
Kumamoto, Japan 4 Department of General
Medicine, Yamaguchi University Hospital, Ube,
Japan 5 Second Department of Internal Medicine,
School of Medicine, Fukuoka University, Fukuoka,
Japan
2
Disclosure Information
  • Hisao Ogawa, MD, PhD
  • Effect of High-dose Angiotensin II Receptor
    Blocker (ARB) Monotherapy versus ARB plus Calcium
    Channel Blocker Combination on Cardiovascular
    Events in Japanese Elderly High-risk Hypertensive
    Patients
  • Financial Disclosures
  • Grant support for OSCAR from Japan Heart
    Foundation (Japan)
  • Grant support from Astellas, AstraZeneca, Bayer,
    Boehringer Ingelheim, Daiichi-Sankyo, Eisai,
    Kowa, Kyowa Hakko Kirin, MSD, Novartis, Pfizer,
    Sanofi-Aventis, Schering-Plough, and Takeda, for
    the past 5 years. No other potential conflict of
    interest relevant to this study was reported.

3
Study Background
  • ARBs are effective for the treatment of not only
    hypertension but also stroke, MI, HF, diabetic
    nephropathy, etc
  • High-dose ARB is more effective than low-dose ARB
    in the prevention of CVD in patients with
    diabetic nephropathy or HF.
  • However, it remains to be determined which
    therapeutic strategy is more effective, high-dose
    ARB or ARB plus CCB.

Ogawa H, et al. Hypertens Res. 2009 32 575-580
4
OSCAR Study
  • OSCAR Study compared high-dose ARB vs. ARB plus
    CCB in the prevention of cardiovascular events in
    high-risk Japanese elderly hypertensive patients
  • Multicenter, active-controlled, two-arm, parallel
    group comparison using PROBE method
  • Enrolment from June 2005 to May 2007 with 3yrs.
    follow-up
  • Conducted at 134 institutions in Japan

Ogawa H, et al. Hypertens Res. 2009 32 575-580
5
Study Design
High-dose ARB group
Other drugs
Registration/ randomization
Olmesartan (40 mg)
Screening
Step 1
Olmesartan (20 mg)
3 years
Step 2
Run-in treatment
Olmesartan (20 mg)
Calcium channel blocker
Other drugs
ARB plus CCB group
Azelnidipine or Amlodipine. Other than ARBs,
ACEIs, and CCBs.
Ogawa H, et al. Hypertens Res. 2009 32 575-580
6
Inclusion Criteria
  • Outpatients aged 65-84 years
  • Olmesartan 20 mg/day monotherapy with SBP 140
    mmHg and/or DBP 90 mmHg
  • At least one of the following CV risk factors
  • Cerebrovascular disease
  • Cardiac disease
  • Vascular disease
  • Renal dysfuntion
  • Type 2 DM

Ogawa H, et al. Hypertens Res. 2009 32 575-580
7
Primary Endpoints
  • Composite of
  • Fatal and nonfatal CV events
  • Cerebrovascular disease
  • Coronary artery disease
  • HF
  • Other arteriosclerotic diseases
  • Diabetic microvascular diseases
  • Renal dysfunction
  • Non-CV death

Ogawa H, et al. Hypertens Res. 2009 32 575-580
8
Secondary Endpoints
  • Incidence of each CV event
  • Blood pressure (SBP, DBP) change
  • Serious AEs other than primary endpoints

Ogawa H, et al. Hypertens Res. 2009 32 575-580
9
Statistical analysis
  • ITT principle
  • Primary endpoint Log-rank test stratified by
    gender, age, and risk factors (baseline CV
    disease and type2 DM)
  • HR and 95CI were calculated by stratified Cox
    proportional hazards model.
  • Subgroup analysis (predefined)Interaction-P
    between Treatment and Pts with CV disease
    (Cerebrovascular disease, Cardiac disease,
    Vascular disease, Renal dysfunction) and Pts
    without CV disease (only type2 DM) was estimated.

Ogawa H, et al. Hypertens Res. 2009 32 575-580
10
Overview of Disposition of Patients
1,217 pts. randomized
53 pts. excluded-17 withdrew consent before
trial phase-36 no data after randomization
1,164 pts. evaluableBP140/90 mmHg by olmesartan
20 mg
578 assigned high-dose ARB group (olmesartan 40
mg)
586 assigned ARB (olmesartan 20 mg) plus CCB
(azelnidipine or amlodipine) group
39 withdrew consent 31 lost to follow-up 11
refused follow-up from sites
31 withdrew consent 28 lost to follow-up 10
refused follow-up from sites
578 available for ITT analyses
586 available for ITT analyses
Late-breaking clinical trial ACC 60th Annual
Scientific session, April 5, 2011, in New
Orleans
11
Baseline Characteristics
High-dose ARB (n578) ARB plus CCB (n586) P value
Male, n () 254 (43.9) 261 (44.5) 0.8382
Age (years) 73.6?5.3 73.6?5.5 0.8627
BMI (kg/m2) 24.3?3.7 23.8?3.5 0.0216
Systolic BP (mmHg) 158.2?12.6 157.2?11.3 0.1512
Diastolic BP (mmHg) 85.2?10.1 84.6?9.8 0.3182
Heart rate (bpm) 73.9?9.7 72.9?9.4 0.0920
eGFR (mL/min/1.73 m2) 66.5?18.6 67.9?18.8 0.2323
Current smoker, n () 62 (10.8) 53 (9.0) 0.3313
Current alcohol, n () 178 (31.0) 193 (33.0) 0.4454
History of cardiovascular disease Stroke Myocardial infarction Heart failure 405 (70.1) 111 (19.2) 16 (2.8) 41 (7.1) 407 (69.5) 96 (16.4) 21 (3.6) 48 (8.2) 0.8192 0.2081 0.4278 0.4810
Type 2 diabetes 309 (53.5) 319 (54.4) 0.7382
Data are meanSD () t-tests or ?2-tests
Late-breaking clinical trial ACC 60th Annual
Scientific session, April 5, 2011, in New
Orleans
12
Time-course of SBP and DBP











Plt0.05 between groups (adjusted by Holms method)
Late-breaking clinical trial ACC 60th Annual
Scientific session, April 5, 2011, in New
Orleans
13
Primary Composite Endpoint
No. at risk
High-dose ARB
578
559
526
505
477
460
450
ARB plus CCB
586
579
553
533
507
494
478
Late-breaking clinical trial ACC 60th Annual
Scientific session, April 5, 2011, in New
Orleans
14
Primary and Secondary Endpoints
No. patients with event
High-dose ARB (n578)
ARB plus CCB (n586)
HR (95CI)
P value
Primary composite endpoint
58
48
1.31 (0.89-1.92)
0.1717
Fatal and nonfatal cardiovascular event
49
37
1.44 (0.94-2.21)
0.0910
Non-CV death
9
11
0.85 (0.35-2.06)
0.7203
Secondary endpoint
Cerebrovascular disease
24
15
1.75 (0.92-3.35)
0.0848
Coronary artery disease
6
7
0.92 (0.31-2.75)
0.8842
Heart failure
12
8
1.56 (0.64-3.83)
0.3251
Other arteriosclerotic disease
3
2
1.88 (0.31-11.25)
0.4842
Diabetic complications
2
4
0.54 (0.10-2.94)
0.4657
Renal dysfunction
2
1
2.39 (0.21-26.71)
0.4653
0
1
2
3
4
High-dose ARB better
ARB plus CCB better
Late-breaking clinical trial ACC 60th Annual
Scientific session, April 5, 2011, in New
Orleans
15
Primary Composite Endpoint in Patients with
Cardiovascular Disease
No. at risk
High-dose ARB
405
391
364
346
329
315
306
ARB plus CCB
407
404
387
369
352
344
331
Late-breaking clinical trial ACC 60th Annual
Scientific session, April 5, 2011, in New
Orleans
16
Primary Composite Endpoint in Subgroupof
Patients with CVD or only Type 2 DM
Cardiovascular Disease()
Cardiovascular Disease(-) (Only Type 2 Diabetes)
()
()
20
20
HR1.63 (95CI, 1.06-2.52) P0.0261
HR0.52 (95 CI 0.21-1.28) P0.1445
Patients with primary events
Patients with primary events
10
10
Interaction P 0.0241
0
0
0
6
12
18
24
30
36
0
6
12
18
24
30
36
(months)
(months)
Late-breaking clinical trial ACC 60th Annual
Scientific session, April 5, 2011, in New
Orleans
17
Summary
  • In the OSCAR study, BP was significantly lower in
    the ARB plus CCB group than in the high-dose ARB
    group.
  • There were no significant differences in primary
    endpoint rate between the high-dose ARB and the
    ARB plus CCB groups.
  • In subgroup of patients with CV disease, primary
    endpoint rate was significantly higher in the
    high-dose ARB group than ARB plus CCB group
    (P0.0261).
  • Conversely, in the subgroup of patients without
    CV disease (only with T2DM), the rate of
    composite primary endpoint tended to be lower in
    the high-dose ARB group than in the ARB plus CCB
    group (P0.1445).
  • There was a significant treatment-by-subgroup
    interaction for the primary endpoints for the
    subgroup between with and without CV disease
    (only T2DM) (P 0.0241).

18
Conclusion
  • The OSCAR study is the first large clinical trial
    to investigate the effect of high-dose ARB vs.
    ARB plus CCB in high-risk elderly hypertensive
    patients.
  • We did not observe any differences in reducing CV
    events/non CV death between the groups.
  • The OSCAR study suggest that the relative effect
    of the two therapies depends on the presence of
    CV disease or T2DM.
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