Clinica Results临床的的结果

1、ce-1a-heftresults and conclusionsclyde yancy, mdprofessor of medicineuniversity of texas southwesternmedical center at dallasce-2a-heft efficacyce-3primary endpoint composite score scoredeath (at any time during the trial) 3 alive at end of trial 0first hf hospitalization (adjudicated) 1no hf hospit

2、alization 0change in qol at 6 mo(or last measurement, if earlier than 6 mo)improvement 10 units +2improvement 5 and 10 units +1change 5 units 0worsening 5 and 10 units 1worsening 10 units 2possible score = 6 to +2dv a hefft csr pg 66-67 taylor_acc-5ce-4primary endpointcomposite scorep = 0.016dv a-he

3、ft csr t 24 composite score range, 6 to +2.0.160.47mean semce-5components of primary composite endpointa-heftdeathfirst hospitalization for hfchange in qol at 6 mo relative to baselinemarked improvementmarked worseningpatients, n (%)bidil(n = 518)32 (6.2)85 (16.4)180 (38.1)80 (16.9)placebo(n = 532)5

4、4 (10.2)130 (24.4)166 (33.4)117 (23.5)37dv a-heft csr t26ce-6all cause mortalityevent rate6.210.2051015percentbidilplacebolog-rank p = 0.012n = 54n = 32dv a-heft csr pg 114 and pg 149ce-7bidil 518463407360314253placebo53246640134028523343% decrease in relative risk of mortalitybidilplacebohr = 0.57

5、(0.37, 0.89)p = 0.012dv a-heft csr pg 18patients at risk, ntime since baseline visit date, days8590951000100200300400500survival, %ce-8cause-specific mortalitya-heftdeathstotalcardiac due to lv dysfunctionsudden cardiacpump failuremi-relatednon-cardiaccerebrovascular accidentvascular-relatednon-card

6、iovascularnon-cardiovascular causeunknown causepatients, n (%)bidiln = 51832 (6.2)21 (4.1)17 (3.3)4 (0.8)0 (0.0)5 (1.0)4 (0.8)1 (0.2)6 (1.2)3 (0.6)3 (0.6)placebon = 53254 (10.2)42 (7.9)24 (4.5)16 (3.0)2 (0.4)3 (0.6)3 (0.6)0 (0.0)9 (1.7)5 (0.9)4 (0.8)fishers exact p value0.0120.0090.3430.0120.5010.60

7、5dv a-heft csr t3116 log-rank p value.ce-9first hospitalization for hfevent rate16.424.40102030percentbidilplacebolog-rankp 0.001n = 85n = 130dv a-heft csr t26, t34ce-10bidil decreases relative risk of first hf hospitalization by 39%dv a-heft csr f 5 and table 32607080901000100200300400500placebobid

8、ilhr = 0.61 (0.46, 0.80)p 0.001bidil 5184303573052531976placebo53240732926420316012patients at risk, nwithout hospitalization, %time since baseline visit date, daysce-11first hf hospitalization event rates and total days in hospital for hfevent rate for first hf hospitalizationdays in hospital for h

9、f per patient with hf hospitalization nmean sdmedianrangebidiln = 51885 (16.4)8513.7 (16.6)92 - 122placebon = 532130 (24.4)13015.3 (20.2)92 - 164hr (95% ci)0.61 (0.46, 0.80)p value 0.0010.539 log-rank test. two-sample t test.a-heft csr t32hf hospitalizations25dv nitromed bb t26total number of hf hos

10、pitalizationsmean number of hf hospitalizations per patienthospitalizations by frequency0123 4total number of hospital days for hfmean number of days in the hospital for hf per patientmean (sd) days per hospitalizationpercent days hospitalized for hfbidiln = 5181730.34334420101111672.36.7 (9.8)0.6pl

11、acebon = 5322510.5402693871619953.87.9 (9.0)1.1p value0.0020.0080.0010.001 wilcoxon rank-sum test.ce-12ce-13time since baseline visit date, daysbidil decreases relative risk of mortality or first hf hospitalization by 37%dv a-heft fig 6 pg 119bidil 51843336331226120313placebo53241133727020816415pati

12、ents at risk, n607080901000100200300400500survival, %bidilplacebohr = 0.63 (0.49, 0.81)p 125 mm hgdiabetes mellituschronic renal insufficiencyfemalemale 125 mm hgdiabetes mellituschronic renal insufficiencyfemalemale 125 mm hgdiabetes mellituschronic renal insufficiencyfemalemale 65 65yesnoyesnoyesn

13、oyesnoyesnoyesno1050420630742308242808406644940110537513429621181869dv a-heft csr fig 4 ptt f7ce-21subgroup analyses of hr for first hf hospitalization (2)ace inhibitorsarbsace inhibitors or arbs-blockersaldosterone agonistsdigitalis glycosidesdiuretics: non-aldosteroneantagonistsccbsyesnoyesnoyesno

14、yesnoyesnoyesnoyesnoyesno7862642368149737787117940964162842296783213837nfavors bidilfavors placeborelative risk (95% ci)00.511.526dv taylor_ a- a-heft ptt f7ce-22change in blood pressure from baselinedv data from client; a-heft ptt 20systolic bpchange from baseline, mm hgmean sem*diastolic bp* p 0.0

15、5-8-6-4-20240369121518bidilplacebo*ce-23effect of bp lowering on bidil treatment effectsvariablesunadjustedadjusted for baseline variables and average systolic bpmortalityriskratio0.570.4995% ci0.37 0.890.29 0.83p value0.0120.008first hf hospitalizationriskratio0.610.5995% ci0.46 0.800.45 0.79p valu

16、e0.00040.000323dvce-24summary of bidil efficacy bidil is efficacious in the treatment of symptomatic heart failure in black patients: decreases the risk of mortalitydecreases hospitalization for hf risk for first hospitalization number of hospitalization days in the hospitalimproves quality of lifed

17、vce-25a-heftclinical safetydvce-26adverse eventsheadache (all)severedizzinessdyspneaexacerbation of hfhypotensionincreased coughperipheral edemasinusitisventricular tachycardiapalpitationssevere exacerbation of hftachycardiapatients, %bidil49.55.231.912.69.57.95.24.84.34.13.91.52.1placebo21.10.913.7

18、17.515.24.47.87.01.72.72.72.51.1p value 0.0001 0.001 0.00010.0300.006 0.05nsns 0.05nsnsns favors bidil.a-heft csr t 43, 46; 5-11-05 bd p 85ce-27aes of special interestheadachedizzinesshypotensionpatients, %bidiln = 517ae49.531.97.9discontinued7.43.71.4placebon = 527ae21.113.74.4discontinued0.80.80.6

19、dv pg 143 csr table 54/ptt 21.5 by severity discontinued study medication due to aes.ce-28most frequent 1% serious aessafety populationat least 1 serious aechest painheart failure (exacerbation)ventricular tachycardiapneumoniasyncopedyspneaarrhythmiahypotensioncerebrovascular accidentheart arrestdiz

20、zinessdiabetes mellituscellulitispatients, %bidiln = 51735.06.43.1 2.72.32.11.91.71.51.41.41.41.21.2placebon = 52734.75.57.8 1.51.51.52.31.30.62.51.70.00.90.4dv a-heft csr t49 p 0.00116ce-29patients in the analysis populationsdv a-heft csr t13, p 88itt populationsafety populationper-protocol populat

21、ionexcluded from per-protocol population, totalpermanent premature discontinuation of study drugpermanent study drug discontinuationdue to aesup to 30 days before eventpatients, %bidiln = 518100.099.841.758.338.821.0 (109)5.6 (29)placebon = 532100.099.140.459.633.111.8 (63)8.8 (47)16of the 301 events in the itt populations (first hf hospitalization or death) only 40 events remained in the per-protocol population(1 death, 39 hospitalizations)ce-30conclusionce-31summary of bidil efficacy and safety a-heft confirms the hypothesis generated from v-heft i and v-heft ii bidil is efficacious in th