ChinaCoronarySecondary

PreventionStudy

(CCSPS)

Shui-PingZhaoCentralSouthUniversityChangsha,ChinaBackground

since1994,large-scaleclinicaltrialssuchas4S,CAREandLIPIDhaveshownthatlipid-loweringtherapyforpatientswithcoronaryheartdiseaseDecreasescardiovasculareventsimprovesqualityoflifereducesmedicalexpenses

Background

Allthesetrialsusedstatins

AllconductedinWesterncountriesNostudyconductedinChineseSignificanceofCCSPS(1)Orientalpopulation(CCSPS)Westenpopulations(4S、CARE、LIPID)DifferenceSerumlipidsMorbidity

&Mortality

ofCHDDietGenetic

LifestyleQuestionstoAnswerbyCCSPSXuezhikangtherapyCanreducetheincidenceofthere-occurrenceofAMIandmortalityfromCHD?Canlowertheincidenceandmortalityfromcerebrovasculardiseases?Canlowertotalmortality?Candecreasecoronaryevents?EfficiencyandsafetyoflongtermuseofXuezhikang

ResearchDesignDoubleBlind,RandomizedandPlacebo-controlledTrialNumberofsubjects:4,870Subjects:18~75yearsoldChinesemenandwomen whosurvivedfromMISerumTCLevel:4.40~6.47mmol/L(170-250mg/dl)SerumTGLevel:≤4.52mmol/L(400mg/dl)Drugusing:Xuezhikngorplacebo0.6BidFollow-upperiod:average4yearsPrimaryEndPoint

Non-fatalAMIFatalMICHDsuddendeathSomeotherCHDdeaths

SecondaryEndPoints

OthercardiocerebrovasculareventsNon-cardiovascularevents(cancer,incidentaldeath,suicide,etc)NeedforPCIorCABGTotaldeath

TreatmentScheduleXuezhikangorplacebo0.6gtwiceadayFollowupin6to8weeksandevery6monthsthereafterserumlipidlevelandsafetyindexcomplianceandeventsDemographicDataSubjectsControlgroupn=2429Treatmentgroupn=2441Psex（n）Malefemale1996(82%)433(18%)1990（82%）451(18%)

NSage（yr）Malefemale58.19.9(1993)62.96.7(432)58.09.7(1989)62.67.4(451)BMI24.82.9(2412)24.72.8(2430)BP(mmHg)Systolic

diastolic129.017.4(2427)

80.110.4(2427)128.617.6(2441)79.910.1(2441)

HR（bpm）74.59.3(2427)74.39.0(2438)MedicalHistoryandMedicationsControlgroup(%)n=2429Treatmentgroup(%)n=2441PMedicalhistorysmoking824(33.92%)865(35.44%)

NSdrinking344(14.16%)356(14.58%)2-typeDM285(11.68%)306(12.60%)HT1341(54.94%)1363(56.11%)Medications

Aspirin2307(94.51%)2301(94.73%)β-blokers1348(55.22%)1377(56.69%)ACEI1211(49.61%)1182(48.66%)Nitrateesters2241(91.81%)2211(91.03%)CCB905(37.07%)886(36.48%)SerumlipidsControlgroupn=2441Treatmentgroupn=2429PTCTGLDL-CHDL-C207.625.4164.273.9129.128.646.014.9207.226.2164.276.6128.928.445.914.5NSNSNSNS(mg/dl)Studytime:November,1996toDecember31,2003Subjects: 4870followup: average4years maximum7yearsDropout

controlgroupn＝2441

treatmentgroupn＝2429

Pn

n471.93%461.89%p=0.9357Serumlipids

ControlgroupTreatmentgroupPDifference％Differ-ence％TC

-6-2.9-27.3-13.2<0.0001TG-8.8-5.3-24.7-15.0<0.0001LDL-C-4.5-3.5-26-20.2<0.0001HDL-C

+0.3+0.7+2.2+4.90.006Testedafter3.5yrClinicalEvents

ComparisonofCHDEventsFollowingtime(year)CHDeventsriskloweredby45.1%P<0.0001TreatmentgroupControlgroupCHDeventsinclude:non-fatalAMIfatalAMIsuddendeathotherCHDdeathsCumul-ativesurvivalratewithoutCHDeventsFollow-uptime(year)Riskloweredby31%

P=0.0048

treatmentgroup

controlgroupCHDdeathincludes:fatalAMIsuddendeathotherCHDdeathsCumulative

survivalrateCardiacDeathAMIeventsFollow-uptime(year)Riskloweredby56.0%P<0.0001treatmentgroupControlgroupAMIeventsincludes:fatalAMInon-fatalAMICumulate

survivalratewithoutAMIeventsTotalDeathFollowingtime(year)Riskloweredby33.0%P=0.0003controlgroupTreatmentgroupCumulativesurvivalrateSecondaryeventsSecondaryeventsinclude:strokecancerPCI/CABG

Risk↓31.1%p<0.0004

SecondaryEvents

Safety

nameControlgroupn＝2441

Treatmentgroupn＝2429

Pntime/1000perpon

ntime/1000perpon

Gastrointestinalsymptom145.7208.20.3469Neurologicalandpsychiatricsymptoms62.520.80.1586Allergicreaction83.3114.50.4840Myalgiaandmuscleweakness41.652.10.7332Sexdysfunction52.000.00.0253Arthralgia00.020.80.1537Dysuria10.400.00.3174Subcutaneoushaematoma00.020.80.3174Others10.410.40.9972Total3916.04317.70.6842CasesstoppedforADR281.15%

371.52%

0.2527

AdverseReactionsLaboratoryDatanamecontrolgroupn＝2441

treatmentgroupn＝2429difference％Pn％

n％ALT(>ULN×3)220.90150.62-31

0.25

CK(>ULN×5)20.0800.00-1000.49

(>ULN×10)10.0400.00-1001.00

Cr(>ULN)893.651044.28

170.26

BUN(>ULN)1315.37

1245.10-50.68

CCSPSHypertensionSubgroupNumberofsubjects:2740hypertensivesin4870CHDpopulationDrugusing:ACEI,calcium-channelblocker(CCB),β-blockerChangeofbloodpressurelevel

Comparedwiththelevelbeforetreat:#p<0.01,calculatethecontrolratewiththestandardofSBP<140mmHg&DBP<90mmHg.Itemcontrolgroup(n=1341)Treatgroup(n=1363)SBP(before)137.7±16.8137.7±16.5DBP84.4±10.184.7±10.3Controlamount(%)444(33.1)425(31.2)SBP(after)132.9±14.5#132.2±14.3#DBP80.7±9.5#80.4±8.7#Controlamount(%)717(53.5)#759(55.7)#Comparisonofeventrisksbetweenhypertensivesandnon-hypertensivesRate(%)

Non-hypertensives

hypertensivesP=0.0005P=0.0020P<0.0001P=0.0004?41.5％?49.2％?51.9％?179.6％Comparisonofeventsreducedbetweenhypertensivesandnon-hypertensiveshypertensivesNon-hypertensives44.047.431.031.935.828.632.03.23Riskreduced(%)CCSPSDiabetesSubgroupThereare591diabetescasesinthe4870subjects.controlGroup:285TreatGroup:306Average3.7years,maximum7yearsComparisonofdiabetesgroupandnondiabetesgroupRate(%)NondiabetesDiabetes13.717.299.483.9712.185.68****P<0.0001ComparisonofriskdeceasedRiskdecrease(%)NondiabetesDiabetes43.950.860.363.827.244.130.244.1

Long-termXuezhiKangtherapylowersriskofcardiovascularmobidityandmortalityeventsintheChineseCHDpatients.XuezhiKangdoesnothaveobviouslyadverseeffects.XuezhikangcontainsstatinsandotheractivecompoundsthatmaycontributetoitsoverallbeneficialeffectsDiscussionDiscussion

TherisksofCHDandstrokeeventsinCHDwithhypertensionhadobviouslyincreased.Thetotaldeathwasalsoobviouslyincreasing.CHDwithhypertensionbelongstoveryhighriskgroup,needmoreaggressivetreatmentonloweringbloodpressureandlipids.AftertreatmentwithXuezhikang,CHDwithhypertensiongainedgreaterbenefitsindecreasingstrokeandtotaldeathevents.Discussion

AmongCHDwithdiabetes,theriskofCHDeventsareobviouslyhigherthanthesubjectswithoutdiabetes.

Xuezhikangissuitabletotreatdiabetes.Itcaneffectivelydecreasethecomplicationofthecardiovascular,lowerCHDeventsby50.8%andCHDdeathby44.1%.Naturalstatins※6mgUnsaturatedfattyacids24mg18typesofaminophenol

25.7mgErgosterin0.3%alkaloid0.41%Flavonoids0.045%Traceelements

2.25%

Palmiticacid18.61%Linoleicacid

48.13%Oleicacid

28.78%Stearicacid

4.49%EffectivecomponentofXuezhikangEachcapsule(0.3g)contains:

※Naturalstatins:12typesofstatins,oneofthemis:Lovastatin2.5mgXuezhikangAnextractofCholestinapprovedbytheFoodandDrugAdministrationasaChinesered-yeastricefordietarysupplement.(Heber