20120628OSCAR - 埼玉医科大学総合医療センター 内分泌

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Ogawa H, Kim-Mitsuyama S, Matsui K, Jinnouchi T, Jinnouchi H,
Arakawa K; OlmeSartan and Calcium Antagonists Randomized
(OSCAR) Study Group.
Angiotensin II Receptor Blocker-based Therapy in Japanese Elderly,
High-risk, Hypertensive Patients.
Am J Med. 2012 Apr 14. [Epub ahead of print]
2012年6月28日 8:30-8:55
8階 医局
埼玉医科大学 総合医療センター 内分泌・糖尿病内科
Department of Endocrinology and Diabetes,
Saitama Medical Center, Saitama Medical University
松田 昌文
Matsuda, Masafumi
doi:10.1016/j.amjmed.2011.12.010
http://www.oscar-study.jp/
BACKGROUND: It is unknown whether
high-dose angiotensin II receptor
blocker therapy or angiotensin II
receptor blocker + calcium channel
blocker combination therapy is better in
elderly hypertensive patients with high
cardiovascular risk. The objective of the
study was to compare the efficacy of
these treatments in elderly, high-risk
Japanese hypertensive patients.
METHODS: The OlmeSartan and Calcium
Antagonists Randomized (OSCAR) study was a
multicenter, prospective, randomized, open-label,
blinded-end point study of 1164 hypertensive
patients aged 65 to 84 years with type 2 diabetes or
cardiovascular disease. Patients with uncontrolled
hypertension during treatment with olmesartan 20
mg/d were randomly assigned to receive 40 mg/d
olmesartan (high-dose angiotensin II receptor
blocker) or a calcium channel blocker+20 mg/d
olmesartan (angiotensin II receptor blocker +
calcium channel blocker). The primary end point was
a composite of cardiovascular events and
noncardiovascular death.
ARB = angiotensin II
receptor blocker; CCB =
calcium channel blocker;
BMI = body mass index;
BP = blood pressure;
eGFR = estimated
glomerular filtration rate
(men: 194 × Cr-1.094 ×
age-0.287; women: 194 ×
Cr-1.094 × age-0.287 ×
0.739); HDL = high-density
lipoprotein.
Data are mean ± standard
deviation for continuous
variables and number (%)
for categoric variables.
P values were calculated
using t tests for continuous
variables and chi-square
tests for categoric variables.
Figure 2 Time course of systolic and diastolic blood pressure in the 2 groups (A) and difference in blood pressure
between the 2 groups (B) during follow-up. Blue values show mean systolic and diastolic blood pressure of highdose ARB group, while red values show those of ARB plus CCB group. BP = blood pressure; ARB = angiotensin
II receptor blocker; CCB = calcium channel blocker. * P < .05, †P < .01 statistically significant difference
between the 2 treatment groups at each time point.
Figure 3 Kaplan-Meier curves for primary composite endpoint during the follow-up period in overall patients (A), patients with
cardiovascular disease at baseline (B), and patients without cardiovascular disease at baseline (with only type 2 diabetes) (C). In (A),
there were 58 patients with events (10.03%) in the high-dose ARB group, compared with 48 patients with events (8.19%) in the ARB
+ CCB group. The number of patients with cardiovascular disease in (B) was 405 and 407 in high-dose ARB and ARB + CCB
combination groups, respectively, and the number of patients without cardiovascular disease in (C) was 173 and 179 in high-dose
ARB and ARB + CCB combination groups, respectively. ARB = angiotensin II receptor blocker; CCB = calcium channel blocker;
HR = hazard ratio; CI = confidence interval.
Adverse Events
The number of serious adverse events, one of
the secondary end points in this study, was 47
(8.1%) in the high-dose angiotensin II receptor
blocker group and 51 (8.7%) in the angiotensin II
receptor blocker + calcium channel blocker
group, with no significant difference between the
2 groups (P = .75). New cancer diagnosis was
not significantly different between the treatment
groups (10 [1.7%] in the highdose angiotensin II
receptor blocker group vs 21 [3.6%] in the
angiotensin II receptor blocker + calcium
channel blocker combination group; P = .07).
Study Limitations
The OSCAR study has several limitations.
The first limitation is the use of the Prospective Randomized Open
Blinded End-point (PROBE) method. The PROBE method has the
potential drawback of investigator bias. However, we believe that
aggressive treatment for blood pressure control was similarly performed
in both groups, as shown by the high percentage of patients who
achieved target blood pressure control and good compliance in both
groups. Therefore, the use of PROBE design appeared not significantly
to affect the main outcomes in this study.
The second limitation might be sample size. It is possible that the
absence of difference in the primary outcome in the OSCAR study may
be attributed to an underpowered sample size. However, the number of
primary end points in the OSCAR study was close to the expected
number of events. Therefore, the absence of difference in the primary
outcome between the groups seems to be explained by the
heterogeneity of treatment effects between 2 subgroups of patients,
those with cardiovascular disease and those without as discussed
above, although the possibility of insufficient sample size in the OSCAR
study cannot be completely excluded.
RESULTS: During a 3-year follow-up, blood pressure was
significantly lower in the angiotensin II receptor blocker +
calcium channel blocker group than in the high-dose
angiotensin II receptor blocker group. Mean blood pressure at
36 months was 135.0/74.3 mm Hg in the high-dose angiotensin
II receptor blocker group and 132.6/72.6 mm Hg in the
angiotensin II receptor blocker + calcium channel blocker
group. More primary end points occurred in the high-dose
angiotensin II receptor blocker group than in the angiotensin II
receptor blocker + calcium channel blocker group (58 vs 48
events, hazard ratio [HR], 1.31, 95% confidence interval, 0.891.92; P = .17). In patients with cardiovascular disease at
baseline, more primary events occurred in the high-dose
angiotensin II receptor blocker group (HR, 1.63, P = .03); in
contrast, fewer events were observed in the subgroup without
cardiovascular disease (HR, 0.52, P = .14). This treatment-bysubgroup interaction was significant (P = .02).
CONCLUSION: The angiotensin II receptor
blocker and calcium channel blocker
combination lowered blood pressure more
than the high-dose angiotensin II receptor
blocker and reduced the incidence of
primary end points more than the high-dose
angiotensin II receptor blocker in patients
with cardiovascular disease. The addition of
a second antihypertensive agent is more
effective at lowering blood pressure than
simply doubling the dose of an existing
agent.
Message
高齢のハイリスク日本人高血圧患者を対象に、高用量のARB投与とARBとCa拮抗
薬併用のどちらが、心血管系疾患発症抑制において有用か検討する目的で実施
された初めての大規模臨床研究。試験はPROBE法で行われた。登録期間は、
2005年6月~07年5月までで、日本国内の134施設から登録された。
対象は、少なくとも心血管系疾患発症リスク(脳血管疾患、心疾患、血管疾患、
腎疾患、2型糖尿病)を1つ以上もつ65~84歳の外来高血圧患者で、オルメサ
ルタン20mg/日を単独投与されている1164例。
①オルメサルタン高用量(40mg/日)群578例
②オルメサルタン20mg/日+Ca拮抗薬(アゼルニジピンまたはアムロジピン)投
与群586例
――の2群に分け、治療効果を比較した。主要評価項目は、致死性または非致
死的心血管系イベントの複合(脳血管疾患、心血管系疾患、心不全、そのほか
アテローム血栓症、糖尿病性微小血管障害、腎疾患)+総死亡。
ITT解析を行ったところ、主要評価項目は、ARB高用量群で58例、ARB+Ca拮抗薬
併用群では48例に発生し、ハザード比は1.31で両群間に有意差はみられなかっ
た(95%CI:0.89~1.92、P値=0.1717)。なお、血圧値はARBとCa拮抗薬併
用群で、ARB高用量群に比べ、有意に低かった(P値<0.05)。
Message
◎心血管系疾患の有無で最適な治療異なる可能性も
サブグループ解析の結果、心血管系疾患の既往例では、主要評価項目の発生が
ARB高用量群(405例)では51例、ARB+Ca拮抗薬併用群(407例)では34例で、
ARB高用量群で有意に高い結果となった(P値=0.0261)。
一方で、心血管系疾患の既往がなく、糖尿病だけを合併する患者では、主要評
価項目が、ARB高用量群(173例)の7例に対し、ARB+Ca拮抗薬群(179例)
では14例発生し、ARB高用量群で低い結果となった(P値=0.1445)。
高齢者のハイリスク高血圧患者における治療戦略として「ARB高用量群とARBと
Ca拮抗薬併用群で有意な差はみられなかった」と結論付けた。その上で、心血
管系疾患の既往があるかないか(2型糖尿病のみを合併)により、「2つの治
療の効果が相対的に異なる」可能性を示唆した。
http://www.mixonline.jp/Article/tabid/55/artid/40615/Default.aspx

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