《ACC2005公布的临床试验的启课件.ppt》由会员分享，可在线阅读，更多相关《ACC2005公布的临床试验的启课件.ppt（51页珍藏版）》请在三一文库上搜索。
1、ACC2005公布的临床试验的启,1,ACC 2005: Message from the trials,Valentin Fuster MD Director, Cardiovascular Institute Mount Sinai Medical Center New York, NY Christopher Cannon MD Staff cardiologist Brigham and Womens Hospital Boston, MA James Ferguson MD Associate Director, Cardiology St Lukes Episcopal Hospi
2、tal and Texas Heart Institute Houston, TX,ACC2005公布的临床试验的启,2,Womens Health StudyUse of aspirin for primary prevention COMMIT and CLARITYUse of clopidogrel in acute-MI patients TNTHigh-dose atorvastatin in stable CHD patients ASCOT-BPLA Calcium channel blocker plus ACE inhibitor reduced all-cause mor
3、tality and other cardiovascular end points,Topics,ACC2005公布的临床试验的启,3,Womens Health Study Use of aspirin for primary prevention,ACC2005公布的临床试验的启,4,Womens Health Study: Design,Use of aspirin for primary prevention in women (N Engl J Med 2005: published March 7th) 39 876 initially healthy women 45 year
4、s of age or older Randomized to 100 mg of aspirin on alternate days or placebo Monitored for first major CV event (nonfatal MI, nonfatal stroke, or death from CV causes) 10-year follow-up,ACC2005公布的临床试验的启,5,WHS: Cardiovascular end points,ACC2005公布的临床试验的启,6,WHS: Stroke end points,ACC2005公布的临床试验的启,7,W
5、HS: Ambitious trial,Glass half-full vs half-empty Reduces stroke in a primary- prevention population But does not reduce mortality, which may have been an ambitious end point, in retrospect,Ferguson,ACC2005公布的临床试验的启,8,WHS: Surprising results,Benefit in stroke and myocardial infarction reduction in w
6、omen older than 65 years You do have to be at risk to get benefit from aspirin.,Cannon,ACC2005公布的临床试验的启,9,Gender differences,Significant differences in stroke reduction in the Womens Health Study and the Physicians Health Study Does stroke occur earlier in women than it does in men?,ACC2005公布的临床试验的启
7、,10,Gender differences,Mean ages roughly the same, but different follow-up Physicians Health Study: 5-year follow-up Womens Health Study: 10-year follow-up These are not apples and apples were comparing. - Ferguson,ACC2005公布的临床试验的启,11,WHS: Aspirin dose,We dont know what the right dose of aspirin is
8、right now. - Ferguson Physicians Health Study used 325-mg dose Antithrombotic Trialist Collaboration suggests doses less than 75 mg/day not as effective,ACC2005公布的临床试验的启,12,WHS: The guidelines,Changing guidelines? No need . . . Aspirin used in primary prevention only when patients risk-factor pro in
9、termediate based on Framingham risk score But may need to revisit the stroke reduction benefit,Fuster,ACC2005公布的临床试验的启,13,WHS: Who gets aspirin?,How low down the risk spectrum do we go? No benefit in younger patients Need to categorize women at high risk for stroke to direct aspirin therapy to them,
10、Cannon,ACC2005公布的临床试验的启,14,WHS: Not change practice,Its telling us what we sort of knew already. Not everybody needs to be taking aspirin. Benefits tied to the degree of risk Stroke-prevention data need to be teased out further,Ferguson,ACC2005公布的临床试验的启,15,COMMITClopidogrel and Metoprolol in Myocard
11、ial Infarction Trial CLARITYClopidogrel as Adjunctive Reperfusion Therapy - Thrombolysis in Myocardial Infarction (TIMI) 28,ACC2005公布的临床试验的启,16,New data about clopidogrel,CLARITY (N Engl J Med 2005: published March 9, 2005) 3500 patients Clopidogrel improved infarct-related artery patency in MI pati
12、ents receiving thrombolysis -Reduced occluded arteries by 36% -Reduced death, MI, or recurrent ischemia requiring revascularization at 30 days by 20%,ACC2005公布的临床试验的启,17,New data about clopidogrel,COMMIT 46 000 patients Addition of clopidogrel in patients with ST-segment-elevation MI with or without
13、 thrombolysis -Death/MI/stroke reduced by 9% -Death reduced by 7%,ACC2005公布的临床试验的启,18,CLARITY and COMMIT,This adds the final piece of the puzzle that clopidogrel is beneficial in ST-segment-elevation MI - Cannon,ACC2005公布的临床试验的启,19,CLARITY and COMMIT,Substantial clinical benefit in keeping vessels o
14、pen COMMIT counterintuitive: most of the benefit in patients presenting within first 12 hours Trend toward benefit in patients also treated with fibrinolytics,Ferguson,ACC2005公布的临床试验的启,20,Mechanisms,Same mechanism as aspirin? After 180 minutes, the arteries open more and stay open because of the com
15、bination Prevention of reocclusion is likely the operative mechanism Two agents are better than one.,Cannon,ACC2005公布的临床试验的启,21,CLARITY and COMMIT,If you have risk, more antiplatelet therapy provides incremental benefit Opportunity to significantly improve aspirin,Ferguson,ACC2005公布的临床试验的启,22,TNT Tr
16、eating to New Targets High-dose atorvastatin in stable CHD patients,ACC2005公布的临床试验的启,23,TNT: Design,Lowering LDL cholesterol levels in stable CHD patients substantially below current guidelines (N Engl J Med 2005: published March 8, 2005) Parallel-group study randomizing 10 001 patients to atorvasta
17、tin 10 mg or 80 mg Patients included were men and women aged 35 years to 75 years with clinically evident CHD Primary end point was first major CV event (death from CHD, nonfatal MI, nonfatal and fatal stroke, or resuscitation after cardiac arrest) 5-year follow-up,ACC2005公布的临床试验的启,24,TNT: LDL chole
18、sterol levels,ACC2005公布的临床试验的启,25,TNT: Primary efficacy outcomes,ACC2005公布的临床试验的启,26,TNT: What does it add?,PROVE-IT showed that lower is better in ACS patients, but did it apply to stable CHD patients? Yes! Confirms and supports that lower LDL cholesterol is better, but also expands the principle t
19、o more than 30 million US patients,Cannon,ACC2005公布的临床试验的启,27,TNT: What does it add?,Baseline LDL cholesterol levels low in TNT No longer good enough to simply put a statin in the drinking water Level of LDL cholesterol matters need to get it down even further than we thought we did,ACC2005公布的临床试验的启
20、,28,Is it all about the LDL?,Looking down the road to tease out benefit What happens when patients are stratified by LDL cholesterol levels coming into the study? Is it all LDL? What happens above and beyond LDL lowering?,Ferguson,ACC2005公布的临床试验的启,29,Beyond the guidelines,Patient with angina and pri
21、or MI Goal to bring LDL cholesterol level to 70 mg/dL Do I start treatment at the maximum 80-mg dose of atorvastatin?,Fuster,ACC2005公布的临床试验的启,30,ACS vs stable CHD,In ACS patients, start with a high-dose statin, as PROVE-IT showed benefit emerged after 10 days In stable CHD patients, slower titration
22、 is an option, but getting control of LDL and CRP is key,Cannon,ACC2005公布的临床试验的启,31,TNT: Safety issues,1.2% of patients treated with atorvastatin 80 mg had a persistent elevation in alanine aminotransferase, aspartate aminotransferase, or both, compared with 0.2% of patients receiving atorvastatin 1
23、0 mg (p0.001),ACC2005公布的临床试验的启,32,TNT: Safety issues,99% of the patients didnt need any dose adjustment with atorvastatin 80 mg It seems to me that in the future we will start looking at LDL cholesterol levels after the patient is treated, rather than before. - Fuster,ACC2005公布的临床试验的启,33,Evolution o
24、f therapy,Changing patient populations for aspirin, clopidogrel, and statin therapy If a drug works, it works. - Cannon,ACC2005公布的临床试验的启,34,Evolution of therapy,The chronic treatment arena is a whole different scenario . . . Side effects, drug interactions, tolerance, and compliance become issues Ti
25、me will tell as we begin to get experience.,Ferguson,ACC2005公布的临床试验的启,35,Challenges,Changing definitions of chronic therapy The question in the chronic phase is going to be compliance and to be sure that side effects dont come along.,Fuster,ACC2005公布的临床试验的启,36,ASCOT-BPLA Anglo-Scandinavian Cardiac O
26、utcomes Trial Blood Pressure Lowering Arm,ACC2005公布的临床试验的启,37,ASCOT-BPLA: Stopped early,Primary outcome measure for the BP-lowering trial was nonfatal MI and fatal CHD Stopped by the ASCOT steering committee in November 2004 on the recommendation of the trials data and safety monitoring board,ACC200
27、5公布的临床试验的启,38,ASCOT-BPLA: Design,19 257 hypertensive patients with at least 3 other cardiovascular risk factors Patients had to have a baseline BP of,160 mm Hg systolic or 100 mm Hg diastolic untreated or 140 mm Hg systolic or 90 mm Hg diastolic despite being on treatment,ACC2005公布的临床试验的启,39,ASCOT-B
28、PLA: Design,Amlodipine (5/10 mg) with or without perindopril (4/8 mg) or Atenolol (50/100 mg) with or without the bendroflumethiazide (1.25-2.5 mg) as well as further treatment as required to reach a target BP 140/90 mm Hg,Randomized to,ACC2005公布的临床试验的启,40,Amlodipine/perindopril vs atenolol/bendrofl
29、umethiazide,ACC2005公布的临床试验的启,41,ASCOT-BPLA: Results,Amlodipine plus an ACE inhibitor vs atenolol plus a diuretic achieved similar blood-pressure control, and yet the results are quite different,Fuster,ACC2005公布的临床试验的启,42,ASCOT: Targeted therapy,My initial gut reaction was that the results were a lit
30、tle bit of a surprise. The mechanistically targeted therapy more effective than older strategies More going on than a simple reduction in blood pressure, but not sure if ACE inhibitor is driving the results,Ferguson,ACC2005公布的临床试验的启,43,ASCOT: Surprising results,My take-away is that calcium-channel b
31、lockers are back. Amlodipine plus an ACE inhibitor looks terrific in these patients Shifts the order we start choosing medicinesmoves calcium-channel blockers up,Cannon,ACC2005公布的临床试验的启,44,ASCOT: New onset diabetes with amlodipine/perindopril vs atenolol/ bendroflumethiazide,ACC2005公布的临床试验的启,45,ASCO
32、T: Diabetes data,Is the benefit providing a better milieu and a less likelihood for developing diabetes, or is the diabetes driving the negative results for atenolol? My guess is that the diabetes is not the driving force here - Ferguson,ACC2005公布的临床试验的启,46,ASCOT: Diabetes data,Time for diabetes to
33、translate into excess MI or mortality is longer than the duration of the study But the risk of developing diabetes should be a factor in deciding which therapy to select - Cannon,ACC2005公布的临床试验的启,47,Other drug effects,When you give a drug to move a parameter, such as blood pressure or LDL cholestero
34、l, these drugs often have other effects Other biologic effects may have more of an impact on the overall end point,Fuster,ACC2005公布的临床试验的启,48,Summary,WHS Aspirin continues to be a good drug and is effective in preventing stroke in women CLARITY and COMMIT Clopidogrel now shown to be effective in acu
35、te MI,ACC2005公布的临床试验的启,49,Summary,TNT Lower LDL cholesterol levels better in stable CHD patients ASCOT-BPLA Amlodipine/perindopril-based strategy significantly reduced all-cause mortality and other cardiovascular end points in hypertensive patients,ACC2005公布的临床试验的启,50,ACC 2005: Advances,I was deligh
36、ted to see an advance forward in ST-elevation MI. In the past, at least 12 other agents failed to improve STEMI outcomes,Cannon,ACC2005公布的临床试验的启,51,ACC 2005: Back to biology,Weve come back to the biology, but the biology as it impacts clinical care. Trials are also getting more complicated, looking at multiple end points Newer generation of clinical trials incorporates a broader understanding of the biology,Ferguson,