ThePROVEITStudy

1、The PROVE IT StudyCraig M. Hileman, M.D.Journal ClubMay14th, 2004The Article“Comparison of Intensive and Moderate Lipid Lowering with Statins after Acute Coronary Syndromes”, NEJM April 8, 2004PROVE IT-TIMI 22 (Pravastatin or Atorvastatin Evaluation and Infection Therapy-Thrombolysis in Myocardial I

2、nfarction 22)The GoalsTo determine whether lowering lipid levels below recommended values would increase the clinical benefit of statinsshhhalso to prove nonsuperiority of Atorvastatin over Pravastatin (sponsored by Bristol-Myers Squibb)VSThe Methods4162 pts from 349 hospitals in 8 countriesInclusio

3、n criteria18 years oldHospitalized for ACS (AMI or unstable angina) in the last 10 daysTotal cholesterol 240 if not on lipid medsTotal cholesterol 3xs normal (not related to MI)Creatinine 2ProtocolDouble Blinded, Double Dummy40mg of Pravastatin (Pravachol) or 80mg of Atorvastatin (Lipitor)Followed u

4、p 30days, and 4, 8, 12, 16, up to 36 monthsIn Addition:If 2 visits had LDL 125, increase pravastatin to 80mgHalve the dose of either drug if abnl LFTs, myalgias or inc CKTrial pre-planned to stop when 925 events reported (adequate power)No prespecified rules to stop if superiority determinedOutcomes

5、Primary OutcomeTime from enrollment to occurrence of:Death (from any cause)MCVEMIUnstable angina needing hospitalizationCath 30 days after enrollmentCABG 30 days after enrollmentStrokeOutcomesSecondary outcomesRisk of death from:CADNon-fatal MIRevascularizationValidityThese results are validPatients

6、 were randomized and all patients were accounted forStudy personnel were double blinded, the groups were similar and were treated equallyRelevanceThese results are relevantThe outcomes were patient oriented, they were similar to our patients, and had a significant measurable differenceResultsPatient

7、 ComparisonWell matched except for more PAD in pravastatin groupAveragesAge-58Sex-78% maleRace-90% whiteSee TableTable 1Table 1 (cont.)ResultsLipid Lowering EffectPravastatinchanged LDL from 106 to 95 (11%)If statin nave- dec by 22% in 1st 30 daysIf prior statin-no changeAtorvastatinChanged LDL from

8、 106 to 62 (42%)If statin- nave dec by 51% in 1st 30 daysIf prior statin-dec by 32%Figure 1ResultsPrimary OutcomesPravastatin-26.3% event rateAtorvastatin-22.4% event rate16% reduction in the hazard ratio (relative risk/time) favoring atorvastatinNNT is 50The benefit was noted as early as 30 daysRes

9、ultsSecondary OutcomesPravastatin-22.3% event rateAtorvastatin-19.7% event rateThe risk of death, MI, or urgent revascularization was reduced by 25% in the atorvastatin groupNNT is 100Figure 2Figure 3Figure 4Figure 5SubgroupsThe subgroup with a baseline LDL125 had a greater benefit that the subgroup

10、 with a baseline LDL125. Hmmm?ConclusionsAfter ACS, high dose atorvastatin resulted in a lower mean LDL than moderate dose pravastatinAuthors feel that this correlates well to the results from the Heart Protection Study in Lancet in 2002Effects were seen as soon as 30 daysMaybe after ACS we should h

11、ave lower LDL goalsButButCould not exclude that the difference in outcomes could be more related to the pleiotropic effects of the statins than their lipid lowering abilityThe continued long term benefit may be due to lower LDL or the fact that these patients unstable plaques were now stabilizedThe

12、REVERSAL trial from Nissen et al (JAMA 2004)Positives/NegativesPositivesGood validity and relevancePatient population mostly similar to oursNegativesShort duration of follow upPer exclusion criteria, a lot of our pts would not qualifyShould this change my practice?Probably not too muchOnly about a 1/3 of people who need a statin are on oneCost40mg Pravastatin$120.0080mg Atorvastatin?Statins account for the largest portion of prescription drug expenditureMore side effects with Atorvastatin Future studies pendingSummaryHigh dose Atorvastatin lowers LDL more that mod dose Pravasta