基于临床试验高血压治疗策略

1、会计学1基于临床试验高血压治疗策略基于临床试验高血压治疗策略第1页/共46页第1页/共45页第2页/共46页TrialsYear Contributions VA Trial The VA Cooperative Study on Antihypertension Drugs1967 Severe HT should be treatedHDFPThe HT Detection and Follow-up Program(Australia)1976 Large-scale CT could be conducted well & successfully in communityANBPSA

2、ustralian National BP Study1979 A 4-month observation period is advisable before instituting drug treatmentMRC trialThe MRC Trial of Treatment in Mild HT(British)1977 Absolute benefits were small in mild HT, treat 850 pts save 1 stroke Mild HT, a weak claim for status as an entity第2页/共45页第3页/共46页Tri

3、alsYear Contributions BHAT- blocker Heart Attack Trial 1981 CHD could be reduced in POST-MI pts. by -blocker EWPHEThe European working Party on High BP in the Elderly 1984Elderly HT pts. would benefit from anti HT treatmentMRC ELDERLY TRIALMedical Research Council Trial of Treatment of HT in Older A

4、dults1987demonstrated a significant reduction in stroke, cardiac and all CVD events STOP-HTThe Swedish Trial in Old Pats. with HT1991Drug treatment in HT pts. 70-84 reduce CVD morbidity & mortality & total mortality第3页/共45页第4页/共46页TrialsYear Contributions SHEPSystolic HT in the Elderly Reduced Total

5、 Stroke and all CHD 1991Systolic HT in the elderly, ISH should be treated in older pts. VA study on Monotherapy 1990HCHZ greatly enhanced the efficacy of non-diuretic drugs, HCTZ 12.5mgCDN Captopril in Type 1 Diabetic Nephropathy 1992 Captopril can reduce progression of renal disease improved surviv

6、al Doubling of Serum Cr. EndpointSyst.-ChinaChnese Systolic HT in the Elderly Trial 1992Total mortality, CVD mortality & Stroke mortality reduced by CCB based treatment第4页/共45页第5页/共46页TrialsYear ContributionsTOMHS StudyThe Treatment of Mild HT Study1993Combined lifestyle/drug intervention in stage I

7、 HT is beneficialPATs Post Stroke Anti HT Treatment Study 1993 BP reduction in post stroke pts. is beneficial, even in normotensive Syst.-Eur. Syst.-Eur. Multicentre Trial1997 New antihypertensive drugs Prognosis of ISH, DM & dementia ABP is a significant predictor of outcomeHOT HT Optimal Treatment

8、 Trial1997 BP to goal is possible Comb. therapy was necessary in 70% pts. Goal tolerability of anti HT therapy No risk in “normalizing” BP Intensive BP lowering in DM HT pts. (130/80) Benefits of antiplatelet agents第5页/共45页第6页/共46页TrialsYear ContributionsSTOP-HT-2Swedish Trial in Old Pts. With HT199

9、8Older & newer agents are effective in treating elderly HT pts.PROGRESSPerindopril Protection Against Recurrent Stroke Study2000BP reduction in post stroke pts. treated by Perindopril based treatment reduced stroke recurrence, even in normotensive CONVINCE Controlled Onset Verapamil Investigation fo

10、r CVD Endpoints 2001 Large simple trials of treatment of a chronic disease Clinical practice Technological progress第6页/共45页第7页/共46页TrialsYear ContributionsLIFELosartan Intervention for endpoint Reduction in HT2001Losartan vs Atendol, primary composite endpoints 25% first stroke 25% less new-onset DM

11、ALLHAT Antihypertensive therapy and lipid-lowering heart attack prevention trial2002Compare different antihypertensive drugs ANBP2Australian National BP Study 22002 comparison of ACEI & diuretics第7页/共45页第8页/共46页TrialsYear ContributionsVALUE Diovan Antihypertensive long-term Use Evaluation2004 Prompt

12、 BP control in high risk hypertensive pts. is important VAS can reduce new onset DMASCOT2005CCB + ACEI B-blocker + DiureticsFEVERChinese Felodipine Event Reduction Trial2005 More or less antihypertensive treatment on stroke Reach target is important 第8页/共45页第9页/共46页Is antihypertensive treatment bene

13、ficial? Trials of active treatment vs. placebo (or more vs. less)When should drug treatment start?(BP level? Mild hypertension? Risk stratifications?)Whom should be treated? (Severe, mild, ISH)To what extent?Is BP lowering by different antihypertensive agents equally beneficial?Necessity of Conducti

14、ng Large-scale Clinical Studies using Asian Subjects第9页/共45页第10页/共46页Isolated systolic hypertension(%)0102030405001020304050(%)Systolic-diastolic hypertensionEvent Reduction in Patients on Active Antihypertensive Treatment versus Placebo or No TreatmentESH-ESC Hypertension Guidelines. J Hypertens. 2

15、003.第10页/共45页第11页/共46页BPLT Trialists Collaboration. Lancet. 2003;362:152735.Results of ProspectivelyDesigned Overviewsof Randomized TrialTrialsPatientsCV EventsAll-together29162,34117,348ACEI or CA vs Placebo925,7113548More or less intensive521,9821191ARB vs Control416,7912478ACEI, CA vs D, BB16101,

16、22810,131第11页/共45页第12页/共46页BPLT Trialists Collaboration. Lancet. 2003;362:152735.第12页/共45页第13页/共46页BPLT Trialists Collaboration. Lancet. 2003;362:152735.第13页/共45页第14页/共46页BPLT Trialists Collaboration. Lancet. 2003;362:152735.第14页/共45页第15页/共46页BPLT Trialists Collaboration. Lancet. 2003;362:152735.第15

17、页/共45页第16页/共46页BPLT Trialists Collaboration. Lancet. 2003;362:152735.第16页/共45页第17页/共46页Zanchetti, Ruilope. J Hypertens. 2002;20:2099110.第17页/共45页第18页/共46页Zanchetti 2004第18页/共45页第19页/共46页Zanchetti 2004第19页/共45页第20页/共46页Confirmation of previous WHO-ISH guidelines: the main benefits of antihypertensive

18、 therapy are due to lowering BP per seESH-ESC Hypertension guidelines J Hypertens 2003第20页/共45页第21页/共46页第21页/共45页第22页/共46页第22页/共45页第23页/共46页第23页/共45页第24页/共46页Mortality in China, Japan, UK, USAWHO statisticsOtherOtherOtherOtherStrokeStrokeCHDCHDCVDMortality 1/100000 Male 35-740 0500500100010001500150

19、0China UrbanChina UrbanChina RuralChina RuralUSAUSAUKUKJapanJapan第24页/共45页第25页/共46页 0 0200200400400600600800800China UrbanChina UrbanChina RuralChina RuralJapanJapanUKUKUSAUSACHDCHDStrokeStrokeOther CVDOther CVDOtherOtherMortality 1/100000 Female 35-74WHO statisticsMortality in China, Japan, UK, USA

20、第25页/共45页第26页/共46页Sample sizeFUyrs.BP End PointSyst.-China2,39439/4 Total/CVD/Stroke MortalitySTONE1,6323Events 59% PATs5,66525/3 Stroke recurrence 29% PROGRESS1,520+8154.59/4 Prevent 1% stroke/year Asian benefited more 2%/yr. ICH benefit more2.5%/yr.第26页/共45页第27页/共46页第27页/共45页第28页/共46页Note: 10,400

21、pts, av FU 3 yrs, av SBP 9 mmHg, DBP 4 mmHg. Trials: PATS, Syst-China, STONE and CNIT. T = Treatment, C = Control737313613610310320120136361616353515151391391741741711712762761391391711711181181331330 0100100200200300300400400500500StrokeStrokeCHDCHDCardiovasCardiovasVascularVascularOthersOthersFata

22、l eventsFatal eventsNon-fatal eventsNon-fatal events 36% 3% 34% 22% 15% (p0.001) (p=0.89) (p0.001) (p=0.03) (p=0.19)第28页/共45页第29页/共46页第29页/共45页第30页/共46页第30页/共45页第31页/共46页VALUE: Main ResultsGood BP control was achieved with both treatment regimens, but BP decrease in the amlodipine group was more pro

23、nounced, particularly early in the trialDespite BP differences, the primary composite cardiac endpoint in both groups was not differentJulius S et al. Lancet. June 2004;363.第31页/共45页第32页/共46页VALUE: Other Results Incidence of stroke was lower, but not significantly, in the amlodipine group Incidence

24、of non-fatal MI was significantly lower in the amlodipine group There was a positive trend in favour of valsartan for less heart failure but this did not reach significance There was a highly significant lower rate of new-onset diabetes in the valsartan groupJulius S et al. Lancet. June 2004;363.第32

25、页/共45页第33页/共46页 The observed difference in stroke rates appears to be strongly related to differences in achieved BPs The benefits of valsartan in heart failure prevention emerged later in the study when BP differences were smaller, indicating that there is a potential beneficial effect of valsartan

26、 beyond BP controlVALUE: InterpretationsJulius S et al. Lancet. June 2004;363.第33页/共45页第34页/共46页VALUE: Interpretations VALUE is the first trial to show a lower rate of new-onset diabetes when an ARB (valsartan) was compared to a CCB (amlodipine) Long-term implications and mechanisms of this importan

27、t finding deserve further investigationJulius S et al. Lancet. June 2004;363.第34页/共45页第35页/共46页 Our results provide an important lesson about the design, conduct, and analysis of future trials in hypertension VALUE shows the importance of analysisof data at time-specific intervals over the course of

28、 a trialVALUE: ImplicationsJulius S et al. Lancet. June 2004;363.第35页/共45页第36页/共46页 Prompt blood pressure control in hypertensive patients at high cardiovascular risk is very important The between-group differences in heart failure and diabetes suggest that valsartan may offer benefits beyond BP con

29、trolVALUE: ConclusionsJulius S et al. Lancet. June 2004;363.第36页/共45页第37页/共46页important end point to be examined in future clinical trials第37页/共45页第38页/共46页第38页/共45页第39页/共46页第39页/共45页第40页/共46页TrialsYear Contributions VA Trial The VA Cooperative Study on Antihypertension Drugs1967 Severe HT should be treatedHDFPT