Diabetes Mellitus, Metabolism Journal Club

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Diabetes Mellitus, MetabolismJournal Club
Rosuvastatin to Prevent Vascular Events in Men
and Women with Elevated C-Reactive Protein, The
primary objective of the Justification for the
Use of Statins in Prevention an Intervention
Trial Evaluating Rosuvastatin (JUPITER) NEJM Nov
20, 2008 vol. 359 no. 21 Low-Dose Aspirin for
Primary Prevention of Atherosclerotic Events in
Patients With Type 2 Diabetes, A Randomized
Controlled Trial The Japanese Primary Prevention
of Atherosclerosis With Aspirin for Diabetes
(JPAD) trial JAMA, November 12, 2008 Vol 300, No.
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• November 27, 2008
• Rei Suganaga, MD
• Diabetes and Endocrine Department,
• Kameda Medical Center

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Rosuvastatin to Prevent Vascular Events in Men
and Womenwith Elevated C-Reactive Protein

• The primary objective of the Justification for
  the Use of
• Statins in Prevention an Intervention Trial
  Evaluating
• Rosuvastatin (JUPITER)
• NEJM Nov 20, 2008 vol. 359 no. 21

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Background

• ?????????????????
• MI?stroke?death from CV cause ????statin?????????
  
• ??????MI?Stroke??????LDL??????????
• ???CRP????future vascular events??????????
• LDL?????????????????
• ???statin????CRP?????????????
• ???LDL?????CRP?????
• ????statin???????????????????
• JUPITER??
• rosuvastatin20mg/day????CV events ?????????

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Methods

• A randomized, double-blind, placebo-controlled,
• multicenter trial conducted at 1315 sites in
  26 countries
• intention-to-treat basis
• Inclusion Criteria
• did not have a Hx of cardiovascular disease
• LDL?130 mg/dl and high-sensitivity CRP? 2.0 mg/l
• a willingness to participate for the duration of
  the trial
• TG ? 500 mg/dl

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Methods

• Exclusion criteria
• previous or current use of lipid-lowering
  therapy,
• current use of postmenopausal HRT
• hepatic dysfunction , CK ?, Cr gt2,0mg/dl
• sBPgt190 or dBP gt100
• cancer within 5 years before
• uncontrolled hypothyroidism
• a recent Hx of alcohol or drug abuse or another
  medical

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Methods

• Trial Protocol
• randomly assigned in a 11 ratio to receive
  either
• Rosuvastatin 20 mg daily,
• Placebo
• Follow-up visits occur at 13weeks and then
• 6, 12, 18, 24, 30, 36, 42, 48, 54,60 months
  after randomize

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End points

• Primary outcome
• occurrence of a first major cardiovascular event,
  
• defined as nonfatal MI, nonfatal stroke,
• hospitalization for unstable angina,
• an arterial revascularization procedure,
• or confirmed death from cardiovascular
  causes.
• Secondary end points
• the components of the primary end point
• considered individually and death from any
  cause.

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Results

• Baseline Characteristics
• Feb 4, 2003 Dec 15, 2006
• 89,800 enrollment
• ?72,088 ineligible (80.2) (LDLgt130(52.2), CRP
  lt2.0(36.1))
• ?17,802 assigned
• Rosuvastatin 8,901
• Placebo 8,901

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Results

• Effect of Rosuvastatin
• Compliance 75

-37
-50
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-17
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Results

• End points
• median follow-up 1.9 years (max 5.0 years)
• first major CV event 142 Rosuvastatin vs 251
  placebo

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NNT
NNT
95 31 ??25
(2years) (4years) (5years)

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Results

• Subgroup analyses

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Results

• Adverse events

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Conclusions

• ?Among apparently healthy men women
• who didnt have HL but have elevated level of
  CRP,
• Rosuvastatin significantly reduced the incidence
  of major CV events, and death from any cause.
• Consistent effects were observed in all
  sub-groups
• no significant increase about adverse events

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Limitations

• Not include people with low level of CRP
• Short follow-up time
• ?longer-term therapy should be considered.

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Low-Dose Aspirin for Primary Preventionof
Atherosclerotic Events in Patients With Type 2
Diabetes

• A Randomized Controlled Trial
• The Japanese Primary Prevention of
  Atherosclerosis
• With Aspirin for Diabetes (JPAD) trial
• JAMA, November 12, 2008
  Vol 300, No. 18

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Background

• ??????????????????????
• Framingham Heart Study Odds Ratios
• -Coronary heart disease(??)1.51.8
  -Stroke1.41.7
• aspirin????????????????????????
• ??????????????????????????????
• ?????????asprin???????????
• ADArecommend use of aspirin for DM a
• (a 40y.o.lt, Fx of coronary , HTN,
  smoke, HL, UAE)
• ??????????????????????????????
• /???????????????????
• ??????????????????aspirin??????
• ??????????

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Methods

• The Japanese Primary Prevention of
  Atherosclerosis With Aspirin for Diabetes (JPAD)
  trial
• A prospective, randomized, open-label,
  controlled trial with blinded end-point
  assessment.
• Patients were enrolled and followed up
• at 163 institutions throughout Japan.

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Methods

• Inclusion Criteria
• Dx of type 2 DM
• Age 30 85
• ability to provide informed consent.

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Methods

• Exclusion criteria
• ECG changes(ST??,Qwave)
• Hx of coronary heart disease(confirmed by
  angiography)
• Hx of cerebrovascular disease
• Hx of arteriosclerotic disease
• Af Pregnancy
• Use of antiplatelet or antithrombotic therapy
• Hx of severe gastric or duodenal ulcer
• Severe liver/renal dysfunction allergy to
  aspirin.

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Methods

• Trial Protocol
• randomly assigned
• 81 mg or 100 mg of aspirin once daily.
• Non aspirin group
• Follow-up visits
• every 2 weeks for patients seen in a
  clinic setting
• every 4 weeks for patients seen in a hospital
  setting
• Non aspirin group were allowed to use
  antiplatelet/thrombotic therapy,
• including aspirin, if needed and vice versa.

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End points

• Primary outcome
• any atherosclerotic event
• sudden death(coronary,cerebrovascular, and aortic
  causes)
• nonfatal AMI AP newly developed exertional
  angina
• nonfatal ischemic and hemorrhagic stroke TIA
• nonfatal aortic and peripheral vascular disease
  
• (ASO,dissection, mesenteric arterial
  thrombosis)
• Secondary end points
• each primary end point
• Combinations of primary end points
• death from any cause.

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Adverse events

• Adverse events
• gastrointestinal (GI) events
• any hemorrhagic events other than hemorrhagic
  stroke

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Results
study population
screened Dec 2002- May 2005 follow-up until
Apr 2008 median follow-up 4.37years
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Results

• Baseline Characteristics
• 2,567 screened ?2539 randomized
• ?aspirin 1262 vs nonaspirin1262
• ?193 lost to follow-up
• median follow-up 4.37years
• By the end of the study
• aspirin group123(10) patients had stopped
  taking Med
• nonaspirin group 6(0.5) aspirin,
• 3(0.2) other
  antiplatelet

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Results

• ?total 154 events occurred
• ?primary end point there is no significant
  difference
• secondary - fatal coronary and
  cerebrovascular events
• 
  gt significantly (P.0037)

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Results

• Subgroup Analyses
• 65 ? the events was significantly lower in
  aspirin group
• (HR 0.68 , 32 relative reduction)
• other subgroup show non-significant difference.

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Results

• Adverse events

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Results

• Adverse events
• serious bleeding that required transfusion
• asipirin 4 vs nonasipirin 0
• But no increase in hemorrhagic strokes
• in aspirin group

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Limitations

• Did not have advantages of a double-blind,
  randomized.
• (prospective, randomized, open-label,
  controlled trial
• with blinded end-point assessment)
• 2. Event rate was low and the study was
  underpowered
• ?larger trial is needed to determine the efficacy

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Conclusions

• ?JPAD trial is the first prospectively designed
  trial to evaluate the efficacy of low-dose
  aspirin for the primary prevention of
  atherosclerotic events in patients with type2 DM
• Low-dose aspirin as primary prevention didnt
  reduce the risk of cardiovascular events.
• -As for fatal coronary and cerebrovascular
  events,
• low-dose aspirin reduced the events
  significantly(P.0037 HR0.10)
• -65? 32 relative reduction in total
  atherosclerotic events
• no increase in hemorrhagic strokes
• but a small increase in serious GI hemorrhagic
  events

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