The|DT problem|NN Three|CD published|VBN [|NN 1|CD 2|CD 3|CD ]|NN and|CC one|CD recently|RB presented|VBN [|NN 4|CD ]|NN randomized|JJ placebo-controlled|JJ clinical|JJ trial|NN have|VBP unequivocally|RB demonstrated|VBN that|IN 3|CD -|: Hydroxy-|NNP 3|CD -|: methylgluatryl|NN coenzyme|NN A|DT (|( HMG|NNP CoA|NNP )|) reductase|NN inhibitors|NNS (|( statins|NNS )|) reduce|VB the|DT morbidity|NN and|CC mortality|NN associated|VBN with|IN coronary|JJ disease|NN .|. 
These|DT trials|NNS found|VBD that|IN when|WRB compared|VBN with|IN placebo|NN ,|, statins|NNS significantly|RB reduced|VBD the|DT incidence|NN of|IN death|NN ,|, myocardial|NN infarction|NN ,|, unstable|JJ angina|NN ,|, percutaneous|JJ and|CC surgical|JJ coronary|JJ revascularization|NN ,|, and|CC stroke|NN in|IN persons|NNS with|IN stable|JJ coronary|JJ disease|NN .|. 
Because|IN patients|NNS who|WP had|VBD experienced|VBN an|DT acute|JJ coronary|JJ syndrome|NN within|IN three|CD to|TO six|CD months|NNS of|IN enrollment|NN were|VBD excluded|VBN ,|, these|DT trials|NNS did|VBD not|RB assess|VB the|DT effect|NN of|IN lipid-lowering|JJ therapy|NN on|IN adverse|JJ cardiovascular|JJ events|NNS in|IN those|DT with|IN recently|RB unstable|JJ coronary|JJ disease|NN .|. 
Whether|IN lipid-lowering|JJ therapy|NN would|MD provide|VB incremental|JJ benefit|NN if|IN initiated|VBN immediately|RB following|VBG an|DT acute|JJ coronary|JJ syndrome|NN is|VBZ an|DT important|JJ issue|NN as|IN the|DT risk|NN of|IN a|DT recurrent|JJ adverse|JJ cardiac|JJ events|NNS is|VBZ much|RB greater|JJR in|IN patients|NNS with|IN unstable|JJ coronary|JJ disease|NN than|IN in|IN the|DT stable|JJ setting|NN .|. 
The|DT Myocardial|NNP Ischemia|NNP Reduction|NNP with|IN Aggressive|NNP Cholesterol|NNP Lowering|NNP (|( MIRACL|NNP )|) trial|NN set|VBN out|IN to|TO answer|VB this|DT question|NN .|. 

The|DT answer|NN ?|. MIRACL|NNP enrolled|VBD 3,086|CD patients|NNS within|IN 24|CD -|: 96|CD hours|NNS (|( mean|VB 63|CD hours|NNS )|) of|IN admission|NN for|IN unstable|JJ angina|NN or|CC a|DT non-|NN Q-|NNP wave|NN myocardial|NN infarction|NN and|CC randomized|JJ them|PRP to|TO 16|CD weeks|NNS of|IN atorvastatin|NN 80|CD mg|NN or|CC placebo|NN once|RB daily|JJ [|NN 5|CD ]|NN .|. 
The|DT major|JJ exclusion|NN criteria|NNS were|VBD :|: total|JJ cholesterol|NN level|NN greater|JJR than|IN 270|CD mg|NN /|NN dL|NN ;|: Q-|NNP wave|NN myocardial|NN infarction|NN on|IN admission|NN or|CC during|IN the|DT previous|JJ month|NN ;|: and|CC ,|, coronary|JJ revascularization|NN in|IN the|DT months|NNS before|IN admission|NN ,|, during|IN the|DT index|NN hospitalization|NN or|CC anticipated|VBN following|VBG hospital|NN discharge|NN .|. 
The|DT primary|JJ efficacy|NN endpoint|NN was|VBD a|DT composite|NN of|IN death|NN ,|, non-fatal|JJ myocardial|NN infarction|NN ,|, resuscitated|JJ sudden|JJ cardiac|JJ death|NN or|CC emergent|NN rehospitalization|NN for|IN worsening|VBG symptomatic|JJ myocardial|NN ischemia|NN .|. 
Secondary|JJ endpoints|NNS included|VBD stroke|NN ,|, worsening|VBG heart|NN failure|NN ,|, need|NN for|IN coronary|JJ revascularization|NN and|CC change|NN in|IN lipid|NN levels|NNS throughout|IN the|DT study|NN .|. 
On|IN average|JJ ,|, patients|NNS were|VBD 65|CD years|NNS of|IN age|NN ,|, approximately|RB 65|CD %|NN were|VBD men|NNS ,|, 86|CD %|NN Caucasian|NNP and|CC the|DT mean|JJ baseline|NN low|JJ density|NN lipoprotein|NN (|( LDL|NNP )|) cholesterol|NN level|NN was|VBD 124|CD mg|NN /|NN dL|NN .|. 
Atorvastatin|NNP treatment|NN was|VBD associated|VBN with|IN a|DT 2.6|CD %|NN absolute|JJ reduction|NN in|IN the|DT risk|NN of|IN the|DT primary|JJ endpoint|NN (|( 14.8|CD %|NN vs.|NN 17.4|CD %|NN ;|: RR|NNP relative|JJ risk|NN [|NN RR|NNP ]|NN 0.84|CD ,|, 95|CD %|NN confidence|NN interval|NN [|NN CI|NNP ]|NN 0.70|CD -|: 1.00|CD ,|, p|NN =|SYM 0.048|CD )|) .|. 
This|DT reduction|NN was|VBD primarily|RB driven|VBN by|IN the|DT 2.2|CD %|NN absolute|JJ reduction|NN in|IN incidence|NN of|IN emergent|NN rehospitalization|NN for|IN symptomatic|JJ myocardial|NN ischemia|NN (|( 6.2|CD %|NN vs.|NN 8.4|CD %|NN ;|: RR|NNP 0.74|CD ,|, 95|CD %|NN CI|NNP 0.57|CD -|: 0.95|CD ,|, p|NN =|SYM 0.02|CD )|) .|. 
The|DT risk|NN of|IN death|NN ,|, nonfatal|NN myocardial|NN infarction|NN and|CC resuscitated|JJ sudden|JJ cardiac|JJ death|NN were|VBD each|DT no|DT different|JJ between|IN the|DT two|CD groups|NNS .|. 
While|IN there|EX were|VBD no|DT significant|JJ differences|NNS in|IN the|DT incidence|NN of|IN worsening|VBG heart|NN failure|NN or|CC need|NN for|IN coronary|JJ revascularization|NN ,|, atorvastatin|NN did|VBD reduce|VB the|DT incidence|NN of|IN fatal|JJ or|CC non-fatal|JJ stroke|NN by|IN 0.8|CD %|NN (|( 0.8|CD %|NN vs.|NN 1.6|CD %|NN ;|: RR|NNP 0.50|CD ,|, 95|CD %|NN CI|NNP 0.26|CD -|: 0.99|CD ,|, p|NN =|SYM 0.045|CD )|) .|. 
Atorvastatin|NNP also|RB significantly|RB reduced|VBN total|JJ and|CC LDL|NNP cholesterol|NN and|CC triglyceride|NN levels|NNS but|CC did|VBD not|RB significantly|RB change|VB high|JJ density|NN lipoprotein|NN (|( HDL|NNP )|) cholesterol|NN by|IN 16|CD weeks|NNS .|. 
By|IN 16|CD weeks|NNS ,|, the|DT adjusted|JJ mean|NN LDL|NNP cholesterol|NN decreased|VBD to|TO 72|CD mg|NN /|NN dL|NN in|IN atorvastatin-treated|JJ patients|NNS but|CC increased|VBN to|TO 135|CD mg|NN /|NN dL|NN among|IN placebo-treated|JJ patients|NNS .|. 
No|DT serious|JJ adverse|JJ events|NNS occurred|VBD as|IN the|DT result|NN of|IN treatment|NN with|IN atorvastatin|NN ,|, although|IN reversible|JJ liver|NN transaminase|NN elevation|NN more|JJR than|IN three|CD times|NNS the|DT upper|JJ limit|NN of|IN normal|RB occurred|VBD in|IN 2.5|CD %|NN of|IN atorvastatin-treated|JJ versus|CC 0.6|CD %|NN of|IN placebo-treated|JJ patients|NNS (|( p|NN <|NN 0.001|CD )|) .|. 

The|DT MIRACuLous|NNP The|DT efficacy|NN and|CC safety|NN findings|NNS from|IN MIRACL|NNP were|VBD unique|JJ for|IN a|DT number|NN of|IN reasons|NNS .|. 
Although|IN lipid-lowering|JJ therapy|NN was|VBD associated|VBN with|IN a|DT significantly|RB lower|JJR mortality|NN when|WRB initiated|VBN early|RB after|IN an|DT acute|JJ coronary|JJ syndrome|NN in|IN two|CD large|JJ observational|NN studies|NNS [|NN 6|CD 7|CD ]|NN ,|, MIRACL|NNP was|VBD the|DT first|JJ randomized|JJ trial|NN to|TO suggest|VB that|IN statins|NNS confer|VBP clinical|JJ benefits|NNS in|IN this|DT setting|VBG .|. 
It|PRP was|VBD also|RB the|DT first|JJ trial|NN to|TO identify|VB a|DT short-term|JJ (|( ie|NN ,|, within|IN 16|CD weeks|NNS )|) clinical|JJ benefit|NN from|IN statin|NN therapy|NN ;|: in|IN previous|JJ secondary|JJ prevention|NN trials|NNS ,|, the|DT benefit|NN of|IN statin|NN therapy|NN was|VBD not|RB evident|JJ for|IN one|CD to|TO two|CD years|NNS .|. 
And|CC ,|, while|IN clinical|JJ trial|NN safety|NN endpoints|NNS may|MD be|VB considered|VBN less|RBR glamorous|JJ ,|, MIRACL|NNP 's|POS most|RBS important|JJ contribution|NN may|MD have|VB been|VBN that|IN high-dose|JJ statin|NN therapy|NN was|VBD not|RB associated|VBN with|IN serious|JJ harm|NN ,|, despite|IN its|PRP$ use|NN in|IN the|DT unstable|JJ setting|NN .|. 
Earlier|RBR secondary|JJ prevention|NN statin|NN trials|NNS had|VBD excluded|VBN patients|NNS with|IN unstable|JJ coronary|JJ syndromes|NNS largely|RB out|IN of|IN theoretical|JJ concern|NN that|IN statin-mediated|JJ reductions|NNS in|IN vascular|NN smooth|JJ muscle|NN cell|NN proliferation|NN might|MD destabilize|VB healing|VBG plaque|NN .|. 
That|DT no|DT harm|NN resulted|VBD from|IN this|DT aggressive|JJ treatment|NN strategy|NN should|MD allay|VB theoretical|JJ fears|NNS and|CC by|IN doing|VBG so|RB remove|VB a|DT major|JJ obstacle|NN to|TO the|DT inpatient|NN initiation|NN of|IN lipid-lowing|JJ therapy|NN after|IN coronary|JJ events|NNS .|. 

The|DT not|RB so|RB MIRACuLous|NNP Despite|IN these|DT unique|JJ and|CC important|JJ findings|NNS ,|, there|EX were|VBD a|DT number|NN of|IN inherent|JJ study|NN limitations|NNS worth|JJ noting|VBG .|. 
First|LS and|CC foremost|RB ,|, the|DT possibility|NN of|IN a|DT null|NN treatment|NN effect|NN can|MD not|RB be|VB ignored|VBN given|VBN the|DT wide|JJ confidence|NN intervals|NNS (|( and|CC hence|RB marginally|RB significant|JJ p|NN value|NN of|IN 0.048|CD )|) for|IN the|DT effect|NN of|IN atorvastatin|NN on|IN the|DT primary|JJ efficacy|NN endpoint|NN .|. 
Furthermore|RB ,|, while|IN the|DT number|NN of|IN patients|NNS lost|VBD to|TO follow|VB up|RP was|VBD small|JJ ,|, if|IN adverse|JJ events|NNS had|VBD occurred|VBN in|IN those|DT treated|VBN with|IN atorvastatin|NN (|( n|NN =|SYM 3|CD )|) but|CC not|RB placebo|NN (|( n|NN =|SYM 8|CD )|) ,|, the|DT overall|JJ trial|NN results|NNS may|MD have|VB been|VBN neutral|JJ rather|RB than|IN positive|NN .|. 

The|DT types|NNS of|IN events|NNS prevented|VBN in|IN MIRACL|NNP are|VBP also|RB worth|JJ noting|VBG .|. 
While|IN rehospitalization|NN for|IN recurrent|JJ myocardial|NN ischemia|NN is|VBZ an|DT important|JJ determinant|NN of|IN quality|NN of|IN life|NN and|CC health|NN care|NN costs|NNS ,|, other|JJ important|JJ endpoints|NNS were|VBD not|RB significantly|RB affected|VBN (|( eg|NN ,|, death|NN ,|, myocardial|NN infarction|NN ,|, resuscitated|JJ sudden|JJ cardiac|JJ death|NN ,|, worsening|VBG heart|NN failure|NN ,|, need|NN for|IN coronary|JJ revascularization|NN ,|, etc|FW )|) .|. 
The|DT question|NN of|IN whether|IN statins|NNS can|MD prevent|VB these|DT and|CC other|JJ adverse|JJ events|NNS when|WRB initiated|VBN soon|RB after|IN an|DT acute|JJ coronary|JJ syndrome|NN will|MD require|VB further|JJ study|NN .|. 

The|DT short|JJ duration|NN of|IN follow-up|JJ is|VBZ also|RB particularly|RB troubling|JJ .|. 
While|IN it|PRP is|VBZ impressive|JJ that|IN a|DT clinical|JJ benefit|NN was|VBD realized|VBN after|IN only|RB 16|CD weeks|NNS of|IN statin|NN therapy|NN ,|, the|DT increased|JJ risk|NN of|IN adverse|JJ clinical|JJ events|NNS persists|VBZ throughout|IN the|DT year|NN following|VBG an|DT acute|JJ coronary|JJ syndrome|NN .|. 
Without|IN longer|RBR clinical|JJ follow|VB up|RB ,|, it|PRP is|VBZ not|RB possible|JJ to|TO assess|VB the|DT intermediate-term|JJ effect|NN (|( if|IN any|DT )|) of|IN atorvastatin|NN on|IN hard|JJ endpoints|NNS such|JJ as|IN death|NN or|CC myocardial|NN infarction|NN .|. 
To|TO do|VB so|RB would|MD be|VB critical|JJ in|IN light|NN of|IN the|DT lack|NN of|IN effect|NN on|IN these|DT important|JJ endpoints|NNS at|IN 16|CD weeks|NNS .|. 
Unfortunately|RB ,|, no|DT late|JJ clinical|JJ follow|VB up|RB is|VBZ planned|VBN .|. 

There|EX were|VBD also|RB a|DT number|NN of|IN limitations|NNS that|WDT may|MD have|VB hampered|VBN the|DT study|NN 's|POS generalizability|NN .|. 
First|LS ,|, patients|NNS who|WP underwent|VBD recent|JJ revascularization|NN or|CC in|IN whom|WP it|PRP was|VBD planned|VBN were|VBD excluded|VBN .|. 
Specifically|RB ,|, patients|NNS who|WP underwent|VBD percutaneous|JJ transluminal|NN coronary|JJ angioplasty|NN (|( PTCA|NNP )|) or|CC coronary|JJ artery|NN bypass|NN graft|NN (|( CABG|NNP )|) surgery|NN within|IN the|DT previous|JJ three|CD or|CC six|CD months|NNS respectively|RB were|VBD not|RB eligible|JJ for|IN inclusion|NN .|. 
The|DT investigators|NNS reasoned|VBD that|IN recurrent|JJ ischemic|JJ events|NNS in|IN this|DT population|NN were|VBD likely|JJ to|TO result|VB from|IN restenosis|NNS or|CC bypass|VB graft|NN closure|NN and|CC that|IN statins|NNS would|MD be|VB less|RBR likely|JJ to|TO affect|VB these|DT processes|VBZ [|NN 8|CD ]|NN .|. 
Nevertheless|RB ,|, a|DT number|NN of|IN trials|NNS have|VBP established|VBN the|DT benefits|NNS of|IN statin|NN therapy|NN early|RB after|IN coronary|JJ revascularization|NN [|NN 9|CD 10|CD 11|CD ]|NN .|. 
Furthermore|RB ,|, a|DT number|NN of|IN recent|JJ trials|NNS have|VBP suggested|VBN that|IN higher|JJR risk|NN patients|NNS with|IN non-|NN ST|NNP elevation|NN acute|JJ coronary|JJ syndromes|NNS fair|JJ better|JJR when|WRB an|DT early|JJ invasive|JJ strategy|NN is|VBZ applied|VBN [|NN 12|CD 13|CD 14|CD ]|NN and|CC it|PRP is|VBZ not|RB uncommon|JJ for|IN patients|NNS to|TO be|VB treated|VBN in|IN this|DT fashion|NN .|. 
Second|JJ ,|, patients|NNS with|IN Q-|NNP wave|NN myocardial|NN infarction|NN were|VBD not|RB eligible|JJ for|IN enrollment|NN because|IN it|PRP was|VBD felt|VBN that|IN statins|NNS would|MD not|RB influence|VB the|DT development|NN of|IN important|JJ prognostic|JJ determinants|NNS such|JJ as|IN left|VBN ventricular|NN systolic|JJ dysfunction|NN ,|, ventricular|NN arrhythmias|NNS or|CC mechanical|JJ complications|NNS [|NN 5|CD ]|NN .|. 
Nevertheless|RB ,|, patients|NNS who|WP develop|VBP electrocardiographic|JJ Q-|NNP waves|NNS represent|VBP a|DT substantial|JJ proportion|NN of|IN all|DT patients|NNS with|IN myocardial|NN infarction|NN .|. 
While|IN their|PRP$ short-term|JJ risk|NN following|VBG hospital|NN discharge|NN is|VBZ lower|JJR relative|JJ to|TO those|DT with|IN a|DT non-|NN Q-|NNP wave|NN myocardial|NN infarction|NN ,|, it|PRP is|VBZ still|RB much|RB greater|JJR than|IN in|IN patients|NNS with|IN stable|JJ coronary|JJ disease|NN ,|, and|CC the|DT need|NN for|IN secondary|JJ prevention|NN in|IN this|DT population|NN is|VBZ equally|RB important|JJ .|. 
Third|NNP ,|, despite|IN the|DT high|JJ risk|NN nature|NN of|IN enrolled|VBD patients|NNS (|( ie|NN ,|, electrocardiogram|NN [|NN ECG|NNP ]|NN changes|NNS and|CC /|NN or|CC other|JJ objective|NN evidence|NN of|IN ischemia|NN )|) ,|, the|DT rate|NN of|IN platelet|NN glycoprotein|NN IIb|NNP /|NN IIIa|NNP inhibitor|NN utilization|NN was|VBD quite|RB low|JJ (|( 1.1|CD %|NN )|) .|. 
Such|JJ therapy|NN appears|VBZ to|TO be|VB cost|VBN effective|JJ [|NN 15|CD 16|CD ]|NN ,|, especially|RB among|IN high|JJ risk|NN patients|NNS and|CC is|VBZ recommended|VBN under|IN current|JJ American|NNP College|NNP of|IN Cardiology|NNP /|NN American|NNP Heart|NNP Association|NNP guidelines|NNS [|NN 17|CD ]|NN .|. 
Fourth|JJ ,|, it|PRP may|MD not|RB be|VB possible|JJ to|TO ascertain|VB whether|IN these|DT findings|NNS apply|VBP to|TO all|DT patients|NNS with|IN recent|JJ acute|JJ coronary|JJ syndromes|NNS regardless|RB of|IN baseline|NN lipid|NN levels|NNS .|. 
The|DT small|JJ difference|NN in|IN number|NN of|IN primary|JJ endpoint|NN events|NNS between|IN atorvastatin|NN and|CC placebo|NN groups|NNS make|VBP it|PRP difficult|JJ to|TO dissect|NN the|DT relationship|NN between|IN baseline|NN lipid|NN levels|NNS and|CC treatment|NN effect|NN further|RB .|. 
Consequently|RB ,|, it|PRP remains|VBZ uncertain|JJ whether|IN one|PRP can|MD extrapolate|NN the|DT MIRACL|NNP trial|NN results|NNS to|TO those|DT who|WP undergo|VBP coronary|JJ revascularization|NN shortly|RB before|IN or|CC after|IN a|DT coronary|JJ event|NN ,|, who|WP present|JJ with|IN a|DT Q-|NNP wave|NN myocardial|NN infarction|NN ,|, who|WP are|VBP treated|VBN with|IN platelet|NN glycoprotein|NN IIb|NNP /|NN IIIa|NNP inhibitors|NNS ,|, or|CC who|WP have|VBP relatively|RB low|JJ admission|NN LDL|NNP cholesterol|NN levels|NNS .|. 

Time|NNP to|TO change|VB current|JJ practice|NN Although|IN MIRACL|NNP and|CC the|DT two|CD aforementioned|JJ cohort|NN studies|NNS suggest|VBP that|IN lipid-lowering|JJ agents|NNS exert|VB short-term|JJ clinical|JJ benefits|NNS when|WRB initiated|VBN soon|RB after|IN an|DT acute|JJ coronary|JJ syndrome|NN ,|, this|DT remains|VBZ an|DT open|JJ question|NN .|. 
Even|RB if|IN these|DT findings|NNS are|VBP not|RB confirmed|VBN after|IN further|JJ study|NN ,|, one|PRP could|MD still|RB make|VB a|DT compelling|JJ argument|NN that|IN lipid-lowering|JJ therapy|NN (|( barring|VBG contraindications|NNS )|) should|MD be|VB initiated|VBN early|JJ and|CC universally|RB in|IN patients|NNS who|WP present|JJ with|IN an|DT acute|JJ coronary|JJ syndrome|NN :|: First|CD ,|, the|DT long-term|JJ safety|NN and|CC effectiveness|NN of|IN statins|NNS for|IN the|DT secondary|JJ prevention|NN of|IN stable|JJ coronary|JJ disease|NN is|VBZ well-established|JJ [|NN 1|CD 2|CD 3|CD ]|NN ;|: Second|JJ ,|, as|IN evidenced|VBN by|IN MIRACL|NNP ,|, these|DT agents|NNS are|VBP safe|JJ when|WRB initiated|VBN at|IN the|DT time|NN of|IN hospitalization|NN for|IN an|DT acute|JJ coronary|JJ syndrome|NN ;|: Third|NNP ,|, the|DT in-hospital|JJ initiation|NN of|IN lipid-lowering|JJ therapy|NN appears|VBZ to|TO promote|VB greater|JJR long-term|JJ utilization|NN of|IN these|DT agents|NNS [|NN 18|CD 19|CD 20|CD 21|CD ]|NN .|. 
Finally|RB ,|, although|IN lipid|NN levels|NNS may|MD be|VB unreliable|JJ in|IN the|DT setting|NN of|IN an|DT acute|JJ coronary|JJ syndrome|NN (|( excepting|VBG total|JJ :|: HDL|NNP and|CC LDL|NNP :|: HDL|NNP cholesterol|NN ratios|NNS [|NN 22|CD ]|NN )|) the|DT overwhelming|JJ majority|NN of|IN patients|NNS with|IN coronary|JJ disease|NN will|MD ultimately|RB require|VB both|DT pharmacologic|JJ and|CC non-pharmacologic|JJ lipid-lowering|JJ interventions|NNS to|TO attain|VB recommended|VBD cholesterol|NN targets|NNS [|NN 23|CD 24|CD 25|CD ]|NN ;|: newer|JJR guidelines|NNS are|VBP even|RB more|RBR stringent|JJ [|NN 26|CD ]|NN .|. 
Furthermore|RB ,|, data|NNS from|IN the|DT recently|RB presented|VBN Heart|NNP Protection|NNP Study|NNP suggest|VBP that|IN clinical|JJ benefits|NNS may|MD accrue|VB independent|JJ of|IN baseline|NN cholesterol|NN level|NN [|NN 4|CD ]|NN .|. 
Thus|RB ,|, to|TO withhold|VB lipid-lowering|JJ therapy|NN from|IN patients|NNS who|WP present|JJ with|IN an|DT acute|JJ coronary|JJ syndrome|NN would|MD be|VB to|TO accept|VB the|DT status|NN quo|NN ,|, and|CC to|TO date|NN our|PRP$ efforts|NNS at|IN cholesterol|NN lowering|VBG in|IN the|DT secondary|JJ prevention|NN setting|VBG have|VBP been|VBN dismal|JJ [|NN 27|CD 28|CD ]|NN .|. 

More|JJR MIRACLes|NNP ahead|RB ?|. The|DT ascertainment|NN and|CC quantification|NN of|IN any|DT incremental|JJ benefit|NN conferred|VBD by|IN statin|NN therapy|NN initiated|VBD early|RB after|IN an|DT acute|JJ coronary|JJ syndrome|NN will|MD require|VB confirmation|NN .|. 
There|EX is|VBZ currently|RB only|RB one|CD ongoing|JJ randomized|JJ placebo-controlled|JJ trial|NN of|IN early|JJ versus|CC delayed|VBN statin|NN therapy|NN in|IN this|DT setting|NN ,|, A-|NNP 2|CD -|: Z|NNP (|( Aggrastat|NNP to|TO Zocor|NNP ,|, Merck|NNP )|) [|NN 29|CD ]|NN .|. 
The|DT A-|NNP 2|CD -|: Z|NNP study|NN is|VBZ evaluating|VBG the|DT efficacy|NN of|IN early|JJ treatment|NN with|IN simvastatin|NN in|IN 4,500|CD patients|NNS following|VBG an|DT episode|NN of|IN unstable|JJ angina|NN or|CC a|DT non-|NN Q|NNP wave|NN myocardial|NN infarction|NN .|. 
In|IN the|DT first|JJ four|CD months|NNS ,|, patients|NNS will|MD be|VB randomized|JJ to|TO simvastatin|NN 40|CD mg|NN daily|NN or|CC placebo|NN .|. 
Thereafter|RB ,|, those|DT patients|NNS treated|VBN with|IN simvastatin|NN in|IN the|DT first|JJ phase|NN will|MD receive|VB 80|CD mg|NN of|IN simvastatin|NN daily|JJ and|CC those|DT treated|VBN with|IN placebo|NN ,|, 40|CD mg|NN of|IN simvastatin|NN daily|RB .|. 
The|DT primary|JJ composite|JJ endpoint|NN is|VBZ the|DT occurrence|NN of|IN cardiovascular|JJ death|NN ,|, non-fatal|JJ myocardial|NN infarction|NN ,|, or|CC rehospitalization|NN for|IN an|DT acute|JJ coronary|JJ syndrome|NN (|( ACS|NNP )|) at|IN one|CD year|NN .|. 
If|IN A-|NNP 2|CD -|: Z|NNP demonstrates|VBZ significant|JJ reductions|NNS in|IN the|DT incidence|NN of|IN adverse|JJ events|NNS during|IN the|DT first|JJ four|CD months|NNS ,|, it|PRP would|MD suggest|VB an|DT incremental|JJ clinical|JJ benefit|NN from|IN initiating|VBG these|DT agents|NNS early|RB after|IN an|DT acute|JJ coronary|JJ syndrome|NN .|. 
If|IN benefits|NNS accrue|VB ,|, but|CC do|VBP so|RB later|RB during|IN follow|VB up|RB ,|, it|PRP would|MD be|VB difficult|JJ to|TO discriminate|JJ between|IN the|DT effects|NNS of|IN more|RBR aggressive|JJ vs.|NN earlier|JJR lipid|NN lowering|VBG therapy|NN .|. 

The|DT Pravastatin|NNP or|CC Atorvastatin|NNP Evaluation|NNP and|CC Infection|NNP Therapy|NNP (|( PROVE|NNP IT|PRP )|) trial|NN is|VBZ looking|VBG at|IN 4,000|CD patients|NNS within|IN 10|CD days|NNS of|IN an|DT acute|JJ coronary|JJ syndrome|NN and|CC randomizing|VBG them|PRP to|TO either|CC pravastatin|NN 40|CD mg|NN or|CC atorvastatin|NN 80|CD mg|NN daily|JJ [|NN 29|CD ]|NN .|. 
Patients|NNS will|MD be|VB observed|VBN over|IN at|IN least|JJS 1.5|CD years|NNS for|IN the|DT occurrence|NN of|IN myocardial|NN infarction|NN or|CC other|JJ cardiovascular|JJ events|NNS .|. 
Unlike|IN ,|, MIRACL|NNP and|CC the|DT A-|NNP 2|CD -|: Z|NNP trials|NNS ,|, this|DT study|NN will|MD not|RB assess|VB the|DT efficacy|NN of|IN early|JJ statin|NN therapy|NN after|IN an|DT acute|JJ coronary|JJ syndrome|NN ;|: rather|RB ,|, it|PRP will|MD examine|VB the|DT role|NN of|IN more|JJR vs.|NN less|RBR aggressive|JJ lipid-lowering|JJ in|IN this|DT setting|VBG .|. 

In|IN 2002|CD ,|, many|JJ would|MD consider|VB it|PRP unethical|JJ to|TO withhold|VB statins|NNS from|IN patients|NNS with|IN established|VBN coronary|JJ disease|NN .|. 
This|DT makes|VBZ it|PRP unlikely|JJ that|IN additional|JJ placebo-controlled|JJ trials|NNS will|MD be|VB carried|VBN out|IN in|IN this|DT area|NN .|. 
Future|NNP secondary|JJ prevention|NN studies|NNS should|MD look|VB at|IN patients|NNS with|IN stable|JJ or|CC unstable|JJ disease|NN and|CC will|MD need|VB to|TO address|VB the|DT comparative|JJ efficacy|NN of|IN different|JJ statins|NNS (|( or|CC newer|JJR agents|NNS )|) ,|, assess|VBP the|DT incremental|JJ benefit|NN of|IN combination|NN therapy|NN [|NN 30|CD ]|NN and|CC determine|VB whether|IN there|EX is|VBZ a|DT serum|NN cholesterol|NN '|'' floor|NN '|'' below|IN which|WDT reductions|NNS are|VBP unlikely|JJ to|TO provide|VB further|JJ clinical|JJ benefit|NN .|. 

Competing|VBG interests|VBZ Dr|NNP Aronow|NNP has|VBZ received|VBN honoraria|NN as|IN a|DT speaker|NN and|CC advisory|JJ board|NN member|NN for|IN Pfizer|NNP and|CC as|IN a|DT speaker|NN for|IN Merck|NNP .|. 

Abbreviations|NNP HMG|NNP CoA|NNP =|SYM 3-Hydroxy-3-methylgluatryl|NN coenzyme|NN A|DT ;|: MIRACL|NNP =|SYM Myocardial|NNP Ischemia|NNP Reduction|NNP with|IN Aggressive|NNP Cholesterol|NNP Lowering|NNP ;|: LDL|NNP =|SYM low|JJ density|NN lipoprotein|NN ;|: RR|NNP =|SYM relative|JJ risk|NN ;|: CI|NNP =|SYM confidence|NN interval|NN ;|: HDL|NNP =|SYM high|JJ density|NN lipoprotein|NN ;|: PTCA|NNP =|SYM percutaneous|JJ transluminal|NN coronary|JJ angioplasty|NN ;|: CABG|NNP =|SYM coronary|JJ artery|NN bypass|NN graft|NN ;|: ECG|NNP =|SYM electrocardiogram|NN ;|: A-|NNP 2|CD -|: Z|NNP =|SYM Aggrastat|NNP to|TO Zocor|NNP ;|: ACS|NNP =|SYM acute|JJ coronary|JJ syndrome|NN ;|: PROVE|NNP IT|PRP =|SYM Pravastatin|NNP or|CC Atorvastatin|NNP Evaluation|NNP and|CC Infection|NNP Therapy|NNP .|. 

