Transcript PowerPoint プレゼンテーション - 埼玉医科大学総合医療センター 内分泌

Journal Club
Indian Polycap Study (TIPS), Yusuf S, Pais P, Afzal R, Xavier D, Teo K, Eikelboom J,
Sigamani A, Mohan V, Gupta R, Thomas N.
Effects of a polypill (Polycap) on risk factors in middle-aged individuals without
cardiovascular disease (TIPS): a phase II, double-blind, randomised trial.
Lancet. 2009 Apr 18;373(9672):1341-51.
Haritoglou C, Gerss J, Sauerland C, Kampik A, Ulbig MW; CALDIRET study group.
Effect of calcium dobesilate on occurrence of diabetic macular oedema (CALDIRET study):
randomised, double-blind, placebo-controlled, multicentre trial.
Lancet. 2009 Apr 18;373(9672):1364-71.
2009年4月23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
Salim Yusuf, Population Health Research Institute,
Hamilton Health Sciences and McMaster University
Lancet 2009; 373: 1341–51
Background
The combination of three blood-pressurelowering drugs at low doses, with a statin,
aspirin, and folic acid (the polypill), could
reduce cardiovascular events by more than
80% in healthy individuals. We examined
the effect of the Polycap on blood pressure,
lipids, heart rate, and urinary thromboxane
B2, and assessed its tolerability.
Methods
In a double-blind trial in 50 centres in India, 2053 individuals
without cardiovascular disease, aged 45–80 years, and with
one risk factor were randomly assigned, by a central secure
website, to the Polycap (n=412) consisting of low doses of
thiazide (12・5 mg), atenolol (50 mg), ramipril (5 mg),
simvastatin (20 mg), and aspirin (100 mg) per day, or to eight
other groups, each with about 200 individuals, of aspirin alone,
simvastatin alone, hydrochlorthiazide alone, three
combinations of the two blood-pressure-lowering drugs, three
blood-pressure-lowering drugs alone, or three blood-pressurelowering drugs plus aspirin. The primary outcomes were LDL
for the effect of lipids, blood pressure for antihypertensive
drugs, heart rate for the effects of atenolol, urinary 11dehydrothromboxane B2 for the antiplatelet effects of aspirin,
and rates of discontinuation of drugs for safety. Analysis was
by intention to treat. This study is registered with
ClinicalTrials.gov, number NCT00443794.
LDL cholesterol was measured with a direct enzymatic photocolourimetric
assay (Roche Hitachi 912 analyser with LDL cholesterol second generation
kits; Roche Diagnostics, Mannheim, Germany)
Total-C
LDL-C
HDL-C
TG
4.7 mM = 181mg/dl
3.0 mM = 116mg/dl
1.1 mM = 42mg/dl
1.9 mM = 168 mg/dl
=-31mg/dl
The strategy was to simultaneously reduce four
cardiovascular risk factors (low density lipoprotein
cholesterol, blood pressure, serum homocysteine, and
platelet function) regardless of pretreatment levels.
Design We quantified the efficacy and adverse effects of
the proposed formulation from published meta-analyses
of randomised trials and cohort studies and a metaanalysis of 15 trials of low dose (50-125 mg/day) aspirin.
BMJ VOLUME 326 28 JUNE 2003 bmj.com 1419
Findings
Compared with groups not receiving blood-pressure-lowering drugs,
the Polycap reduced systolic blood pressure by 7・4 mm Hg (95% CI 6・
1–8・1) and diastolic blood pressure by 5・6 mm Hg (4・7–6・4), which was
similar when three blood-pressure-lowering drugs were used, with or
without aspirin. Reductions in blood pressure increased with the
number of drugs used (2・2/1・3 mm Hg with one drug, 4・7/3・6 mm Hg
with two drugs, and 6・3/4・5 mm Hg with three drugs). Polycap reduced
LDL cholesterol by 0・70 mmol/L (95% CI 0・62–0・78), which was less
than that with simvastatin alone (0・83 mmol/L, 0・72–0・93; p=0・04); both
reductions were greater than for groups without simvastatin (p<0・0001).
The reductions in heart rate with Polycap and other groups using
atenolol were similar (7・0 beats per min), and both were signifi cantly
greater than that in groups without atenolol (p<0・0001). The reductions
in 11-dehydrothromboxane B2 were similar with the Polycap (283・1
ng/mmol creatinine, 95% CI 229・1–337・0) compared with the three
blood-pressure-lowering drugs plus aspirin (350・0 ng/mmol creatinine,
294・6–404・0), and aspirin alone (348・8 ng/mmol creatinine, 277・6–419・
9) compared with groups without aspirin. Tolerability of the Polycap was
similar to that of other treatments, with no evidence of increasing
intolerability with increasing number of active components in one pill.
Interpretation
This Polycap formulation could be conveniently used
to reduce multiple risk factors and cardiovascular
risk.
Funding Cadila Pharmaceuticals, Ahmedabad, India.
TIPS does take a first and crucial step forward
and raises hope that, in conjunction with other
global efforts to improve diet and exercise, the
polypill could one day substantially reduce the
burden of cardiovascular disease in the world.
Department of Ophthalmology, Ludwig-Maximilians- University, Munich,
Germany (C Haritoglou MD, A Kampik MD, M W Ulbig MD); and
Department of Medical Informatics and Biomathematics, University of
Munster, Munster, Germany (J Gerss PhD, C Sauerland MSc)
Lancet 2009; 373: 1364–71
Calcium dobesilate, a venotonic drug, has
beneficial effects in vascular diseases such as
chronic venous insufficiency and
haemorrhoids and is prescribed in more than
60 countries. It seems to be safe, with
infrequent complications including fever,
gastrointestinal disorders, skin reactions,
arthralgia, and very rarely, agranulocytosis (0・
32 cases per million). In general,
pharmacological data for calcium dobesilate
indicate its ability to decrease capillary
permeability, platelet aggregation, and blood
viscosity.
Background
Medical treatment for diabetic
retinopathy could have an important
role in prevention of complications
such as visual loss. We aimed to
assess the effect of calcium
dobesilate on occurrence of diabetic
macular oedema.
Methods
We undertook a randomised, double-blind,
placebo-controlled, multicentre study in 40
centres in 11 countries. We enrolled outpatients
with adult-onset type 2 diabetes and mild-tomoderate non-proliferative diabetic retinopathy,
and randomly allocated them via sealed
envelopes either calcium dobesilate (1500 mg
per day) or placebo. The primary endpoint was
development of clinically significant macular
oedema (CSME) within a follow-up period of 5
years. Patients who dropped out of the study
early were censored. Analysis was by intention
to treat.
Figure 2: Estimated cumulative 5-year event probability
The log-rank test was used to calculate p values. (A) Total population
(intention-to-treat analysis). (B) Subpopulation with HbA1c concentrations 9%
or higher and systolic blood pressure of 140 mm Hg or more (post-hoc
analysis). (C) Women with HbA1c concentrations 9% or higher and systolic
blood pressure of 140 mm Hg or more (post-hoc analysis).
Findings
We enrolled 635 patients. 324 were randomly
allocated calcium dobesilate and 311 were
assigned placebo. In the calcium dobesilate group,
86 patients developed CSME compared with 69 in
the placebo group. Accounting for censored cases,
estimated cumulative 5-year CSME probability
was 35% and 28%, respectively (hazard ratio 1・32,
95% CI 0・96–1・81; p=0・0844). Adverse events did
not differ between treatment groups (78 [24%] on
calcium dobesilate and 90 [29%] with placebo).
No relevant drug-related complications were
noted. Nine patients (3%) died in the calcium
dobesilate group and eight (3%) deaths were
recorded on placebo.
Calcium dobesilate did not reduce
the risk of development of CSME.
Funding Sanofi ; OM Pharma; and Synthelabo.