Design, baseline characteristics, and preliminary clinical results of the Organization to Assess Strategies for Ischemic Syndromes–2 (OASIS–2) trial

Design, Baseline Characteristics, andPreliminary Clinical Results of the

Organization to Assess Strategies forIschemic Syndromes–2 (OASIS–2) Trial

Salim Yusuf, DPhil, for the OASIS-2 Investigators*

Despite use of heparin and aspirin, 5–10% of patientswith unstable angina develop myocardial infarction (MI)or refractory angina in the hospital. We tested the hy-pothesis that recombinant hirudin (lepirudin), a directthrombin inhibitor, is superior to heparin, an indirectthrombin inhibitor, in patients with acute ischemic syn-dromes who were receiving aspirin. Patients (n 510,141) with unstable angina or suspected acute MIwithout ST-segment elevation were randomly assignedheparin (5,000-U bolus, then 15-U/kg per hour infu-sion; n 5 5,058) or hirudin (0.4-mg/kg bolus, then0.15-mg/kg per hour infusion; n 5 5,083) for 72 hoursin a double-blind trial. The primary outcome measurewas cardiovascular death or new MI at 7 days. Analysiswas by intention to treat. At 7 days, 213 patients (4.2%)in the heparin group and 182 (3.6%) in the hirudingroup had experienced cardiovascular death or new MI(relative risk 5 0.84; 95% CI 5 0.69–1.02; p 5 0.077).The number of patients with cardiovascular death, newMI, or refractory angina at 7 days was 340 (6.7%) with

heparin and 284 (5.6%) with hirudin (relative risk 50.82; 95% CI 5 0.70–0.96; p 5 0.0125). These differ-ences were primarily observed during the 72-hour treat-ment period (cardiovascular death or MI relative risk 50.76; 95% CI 5 0.59–0.99; p 5 0.039; cardiovasculardeath, MI, or refractory angina relative risk 5 0.78;95% CI 5 0.63–0.96; p 5 0.019). Although there wasan excess of major bleeding with hirudin requiringtransfusion (59 [1.2%] vs 34 [0.7%] with heparin; p 50.01), there was no excess in life-threatening episodes(20 in each group) or strokes (14 in each group). Datafrom the Organization to Assess Strategies for IschemicSyndromes (OASIS)-2 trial suggest that a direct thrombininhibitor, recombinant hirudin, is more effective than anindirect thrombin inhibitor, heparin, in preventing car-diovascular death, MI, or refractory angina. Recombi-nant hirudin also has an acceptable safety profile inpatients with unstable angina or acute MI without ST-segment elevation. Q1999 by Excerpta Medica, Inc.

Am J Cardiol 1999;84:20M–25M

There is significant evidence that unstable anginaand myocardial infarction (MI) are caused by cor-

onary thrombosis superimposed on a ruptured athero-sclerotic plaque.1 Recent investigations have focusedon the use of aspirin and heparin as antithrombotictherapy to decrease the incidence of cardiovascularevents in patients with ischemic syndromes.2 Never-theless, approximately 5–10% of patients with unsta-ble angina experience MI or refractory angina requir-ing revascularization. In addition, after being dis-charged from the hospital, patients still have anincreased risk of recurrent ischemic events over thenext few years.

The Organization to Assess Strategies for IschemicSyndromes (OASIS)-1 and OASIS-2 trials were de-signed to evaluate the use of hirudin—a potent andspecific thrombin inhibitor—in the treatment of pa-tients with unstable angina or acute MI without ST-segment elevation. Hirudin interacts directly withthrombin to inhibit clot-bound and circulating throm-bin3 and has been shown in animal experiments to be

a more effective antithrombotic agent than heparin.4

The OASIS-1 trial of 909 patients evaluated hirudin atlow and medium doses versus heparin and found adecreased incidence of cardiovascular death, new MI,or refractory angina at 7 days in the hirudin groupsversus the heparin group.5 In addition, fewer patientsin the hirudin groups required revascularization orcoronary artery bypass grafting, and long-term analy-ses at 35 days and 180 days showed fewer ischemicevents among hirudin patients compared with heparinpatients. The incidence of major bleeds was low andsimilar in all 3 groups, whereas the incidence of minorbleeds (bruising and puncture site oozing) was slightlyhigher in the hirudin groups than in the heparin group.

Based on these promising results, investigatorscontinued the OASIS program in a larger populationof .10,000 patients. This article reports the results ofthe OASIS-2 trial.

METHODSPatients: Patients eligible for randomization in-

cluded those admitted to the hospital within 12 hoursof an episode of chest pain suspected to be due tounstable angina or MI without ST-segment elevation,as determined by the admission electrocardiogram. Adiagnosis of unstable angina included symptoms thatwere new, worsening, or occurring with minimal ac-tivity. Symptoms had to be associated with admissionelectrocardiographic evidence of ischemia or docu-

From the Division of Cardiology, McMaster University, Hamilton Gen-eral Hospital, Hamilton, Ontario, Canada.

Address for correspondence: Salim Yusuf, DPhil, Division of Car-diology, McMaster University, Hamilton General Hospital, 237 Bar-ton Street East, Hamilton, Ontario, L8L 2X2 Canada. Reprints are notavailable from the author.

*See Appendix for complete list of participating investigators.

20M ©1999 by Excerpta Medica, Inc. 0002-9149/99/$20.00All rights reserved. PII S0002-9149(99)00549-4

mented coronary artery disease. MI without ST-seg-ment elevation was diagnosed based on characteristicchest pain lasting$20 minutes with ST depression asshown by electrocardiograph. Patients meeting thefollowing criteria were excluded: contraindication toheparin or hirudin, stroke within the last 12 months,renal impairment, cardiogenic shock, angina not dueto cardiovascular disease, other diseases limiting lifeexpectancy to,6 months, creatinine levels.175mmol/L (.2.0 mg/dL), long-term anticoagulant ther-apy, percutaneous transluminal coronary angioplastywithin the previous 6 months, pregnancy, or,21 and.85 years of age.

Study design: The OASIS-2 trial was a double-blind, randomized study (n5 10,141), comparingheparin with hirudin conducted in 360 centers in 16countries over 20 months. The heparin group (n55,058) received a bolus of 5,000 U of heparin, fol-lowed by a 15-U/kg per hour infusion plus hirudinplacebo for 72 hours. In the hirudin group (n55,083), patients received a bolus of 0.4 mg/kg ofhirudin, followed by a 0.15-mg/kg per hour infusionplus heparin placebo for 72 hours.

Patients in both groups who had received heparinbefore randomization did not receive a bolus if theactivated partial thromboplastin time (aPTT) was$60seconds or if a heparin bolus was administered duringthe previous 2 hours. The aPTT was monitored within8 hours after initiation of therapy and then dailythroughout treatment. The study protocol allowed ad-justment of hirudin or heparin doses to maintain aPTTbetween 60 and 100 seconds.

The primary endpoint was the incidence of thecombined outcome of cardiovascular death or new MIat 7 days. The secondary endpoint was cardiovasculardeath, MI, or refractory angina at 7 days. New MI wasdefined as recurrent symptoms with new electrocar-diographic changes or new enzyme elevation levels.Refractory angina was defined as recurrent ischemicpain of$5 minutes’ duration with new electrocardio-graphic changes while receiving maximum medicaltherapy and requiring urgent intervention within 24hours. Intervention included thrombolytic therapy, in-tra-aortic balloon pump, urgent cardiac catheteriza-tion, or transfer to a tertiary-care center for possibleinvasive procedures, including coronary artery bypassgrafting or percutaneous transluminal coronary angio-plasty. After discharge from the hospital, refractoryangina was defined as readmission for unstable anginabased on electrocardiographic evidence of ischemia oradmission to a monitoring unit. Safety outcomes in-cluded the incidence of stroke (ischemic or hemor-rhagic) and major bleeding events, classified as requir-ing a transfusion of#3 U of blood or judged to bedisabling or life-threatening (i.e., fatal, intracranial,requiring surgical intervention, or requiring a transfu-sion of $4 U of blood).

Data were analyzed at 72 hours (end of studyperiod) and again at 7 days to determine whether therewere rebound effects or loss of benefit between the72-hour end-of-treatment point and the 7-day end-point. In addition, a follow-up review of the incidence

of cardiovascular death and new MI occurred 35 daysafter the end of treatment. However, the study was notdesigned to determine statistically significant differ-ences between treatment groups at this point.

Statistical methods: Primary and secondary out-comes were compared on an intent-to-treat basis usingMantel–Haenszel (log-rank) tests stratified by centerto determine the number of events and when theyoccurred during the 7-day evaluation period. To assessthe consistency of results, 2 other analyses were con-ducted, including a modified intent-to-treat analysisexcluding patients who received no study medication,and outcomes at the end of the 72-hour evaluationperiod (end of treatment). Three additional interimanalyses were conducted to determine combined effi-cacy outcomes.

RESULTSA total of 10,141 patients with unstable angina or

suspected acute MI without ST-segment elevationwere randomized to receive either heparin or hirudin.Of this total, 62% were men and 38% were women.The mean age was 64 years. Eighty-seven percent hadunstable angina, 12% had MI without ST-segmentelevation, and 90% had abnormal electrocardio-graphic readings. Median time from onset of pain torandomization was 6 hours.

Of the 5,058 patients in the heparin group,.90%received therapy for$48 hours, compared with 86%of the 5,083 patients in the hirudin group. The medianduration of treatment in both groups was 71–73 hours,indicating investigator compliance with the study pro-tocol. There were more discontinuations due to bleed-ing or adverse events in the hirudin group (2.8%)compared with the heparin group (1.3%, p,0.001).There were also more discontinuations for raisedaPTT in the hirudin group (5.3%) compared with theheparin group (1.5%, p,0.001). However, there weremore discontinuations for low aPTT in the heparingroup (0.3%) versus the hirudin group (0.1%, p50.003).

Infusion adjustments: Dose adjustments could bemade, according to protocol guidelines, to maintainaPTT between 60 and 100 seconds. Of all patients inthe trial, 12% required no dose adjustments; about halfthe patients in the hirudin group required no adjust-ments. Only single-infusion adjustments were gener-ally required in the hirudin group, whereas multipleadjustments were more common in the heparin group.

Infusion was adjusted upward in 33% of heparinpatients but in only 21% of hirudin patients, whereasinfusion was adjusted downward in 24% of the hirudingroup versus 10% of the heparin group. Adjustmentsin both directions for the same patient occurred morefrequently with heparin than with hirudin.

Mean aPTT rates were comparable for both treat-ment groups. Figure 1 presents aPTT levels for the 2treatment groups throughout the 72-hour treatmentperiod. At 6 hours, aPTT was approximately 100seconds in the heparin group and 85–90 seconds in thehirudin group. At 12–24 hours, aPTT rates were sim-ilar for the 2 groups. At 24–72 hours, aPTT rates were

A SYMPOSIUM: TREATMENT OF UNSTABLE ANGINA PECTORIS WITH LEPIRUDIN 21M

slightly higher in the hirudin group compared with theheparin group. Mean aPTT was approximately 85seconds in the heparin group; this was achieved usinga weight-adjusted, dose-planned, aPTT-adjusted regi-men.

Primary and secondary outcomes: The primary end-point was the incidence of cardiovascular death ornew MI at 7 days. These events occurred in 3.6% (n5182) of the hirudin group versus 4.2% (n5 213) of theheparin group (p5 0.077). There was no furthersignificant divergence at the 35-day follow-up period.Figure 2 presents all effects for the 2 treatment groupsfor each time period.6

The secondary endpoint was cardiovascular death,new MI, or refractory angina at 7 days. As expected,secondary endpoint results were consistent with pri-mary endpoint results, occurring in 5.6% (n5 284) ofthe hirudin group compared with 6.7% (n5 340) ofthe heparin group (p5 0.0125). Refractory anginaoccurred in 2.2% (n5 111) of the hirudin group andin 2.8% (n5 141) of the heparin group. The primarycontributing factor to the difference in the incidence ofrefractory angina was the need for intervention. Forexample, 24 patients in the heparin group requiredurgent revascularization, compared with only 11 in thehirudin group. Table I summarizes the total incidence

FIGURE 2. Pooled analysis of large trials of hirudin versus heparin in acute ischemic syn-dromes at 72 hours (end of treatment), 7 days, and at 35 days. Note that the early reduc-tion of about 100 patients with events persists during long-term follow up. (Reproduced withpermission from Lancet.6)

FIGURE 1. Average of mean aPTT levels for both treatment groups throughout the 72-hourtreatment period. aPTT 5 activated partial thromboplastin time; STD 5 standard deviation;pre 5 pretreatment.

22M THE AMERICAN JOURNAL OF CARDIOLOGYT VOL. 84 (5A) SEPTEMBER 2, 1999

of refractory angina as well as the incidence by inter-vention category.6

The most marked differences between groups werefor patients requiring intervention other than catheter-ization or for readmission for unstable angina withdocumented electrocardiographic changes. However,there was little difference in outcomes between groupsfor patients requiring catheterization or who had noelectrocardiographic changes and were readmitted to along-term unit. For all cardiac interventions, 6.9% ofthe hirudin group and 8% of the heparin group re-quired some intervention at 7 days. Table II presentsthe total incidence of all cardiac interventions at 7days.6

When reviewing radiologic evidence of heart fail-ure, there were no differences between the treatmentgroups within the first 24 hours; however, after 24hours, the hirudin group showed fewer events than theheparin group (1.8% vs 2.6%; p5 0.006). Assessmentof both primary and secondary endpoints at 35 daysshowed a continuing trend toward fewer events in thehirudin group compared with the heparin group, withthe exception of refractory angina, where there wereslightly more events in the hirudin group.

Safety: The overall rate of major bleeding episodeswas low (1.2% in the hirudin group and 0.7% in theheparin group; p5 0.01). The higher incidence ofmajor bleeding in the hirudin group was attributed to

an increased risk of gastrointestinal bleeding. Life-threatening bleeding episodes were defined as intra-cranial bleeds, bleeds requiring surgical intervention,or those requiring inotropic therapy or a transfusion of$4 U of blood. There was no difference in the rates oflife-threatening bleeds, which was low in both groups(0.4%).

The rate of stroke was equal in the 2 treatmentgroups with 14 in each. There was 1 hemorrhagicstroke in the heparin group and none in the hirudingroup.

Combined results of OASIS-1 and OASIS-2: TheOASIS-1 and OASIS-2 trials using hirudin plus aspi-rin versus heparin plus aspirin in.11,000 patientshave shown promising results. The combined inci-dence of death or MI for the 2 trials is shown in TableIII. 6 These significant results demonstrate consistencybetween the OASIS-1 and OASIS-2 studies.

DISCUSSIONAspirin and heparin have been used as antithrom-

botic therapy with the goal of decreasing mortality andcardiovascular events.2 However, despite decreasingevents to some degree, the risk of cardiovascularevents such as MI in patients with ischemic syn-dromes can still be improved. The OASIS-2 trial un-derscored the promising results shown in the OASIS-1trial using a larger patient population. In the combined

TABLE II Cardiac Interventions by Day 7

Heparin(n 5 5,058)

Hirudin(n 5 5,083)

Relative Risk(95% CI) p Value

PTCA 261 (5.2%) 215 (4.2%) 0.82 (0.69–0.98) 0.027CABG 98 (1.9%) 96 (1.9%) 0.97 (0.74–1.29) 0.856PTCA/CABG 358 (7.1%) 309 (6.1%) 0.86 (0.74–0.99) 0.042Intra-aortic balloon pump 33 (0.7%) 33 (0.6%) 0.99 (0.62–1.61) 0.983Thrombolytic therapy 54 (1.1%) 43 (0.8%) 0.79 (0.53–1.18) 0.251Any of the above 411 (8.1%) 349 (6.9%) 0.84 (0.74–0.97) 0.016

CABG 5 coronary artery bypass graft; CI 5 confidence interval; PTCA 5 percutaneous transluminal coronaryangioplasty.

Reproduced with permission from Lancet.6

TABLE I Details of Patients with Refractory Angina up to Day 7

Type of Intervention*Heparin

(n 5 5,058)Hirudin

(n 5 5,083)Relative Risk

(95% CI)

All interventions 141 (2.8%) 111 (2.2%) 0.77 (0.60–0.99)Catheterization 49 48 0.97 (0.66–1.45)PTCA 14 6 0.43 (0.16–1.11)CABG 10 5 0.50 (0.17–1.45)Intra-aortic balloon pump 8 4 0.50 (0.15–1.65)Thrombolytic therapy 4 2 0.50 (0.09–2.71)Transfer to tertiary center 35 20 0.57 (0.33–0.98)Readmission for unstable angina 14 8 0.57 (0.24–1.35)With ECG changes 6 0Without ECG changes but

admitted to a monitoring unit8 8 0.99 (0.37–2.65)

CABG 5 coronary artery bypass graft; ECG 5 electrocardiogram; CI 5 confidence interval; PTCA 5

percutaneous transluminal coronary angioplasty.*Patients may be included in more than 1 category.Reproduced with permission from Lancet.6


analysis of OASIS trial data, the risk of death, newMI, or refractory angina was approximately 20%lower at 7 days.6

There is also consistency in results between theOASIS trials and the Global Use of Strategies to OpenOccluded Coronary Arteries in Acute Coronary Syn-dromes (GUSTO)-IIb and Thrombolysis and Throm-bin Inhibition in Myocardial Infarction (TIMI)-9B tri-als, the 2 largest studies of acute coronary endpoints,with an estimated 24,000 patients.7,8 When comparingdata from these trials at 72 hours to data from theOASIS-1 pilot study, the results reinforce the superi-ority of hirudin, a direct thrombin inhibitor, over hep-arin. When administered with aspirin, hirudin is 15–20% more effective than heparin with aspirin in de-creasing mortality and the incidence of MI at 7 days.During the treatment period, the difference in relativerisk was about one-quarter.

In addition, the effects of hirudin versus low-mo-lecular-weight heparin on arterial function should beexplored further. No direct comparator trials are avail-able in arterial disease. However, in a comparison ofenoxaparin and recombinant hirudin for treatment ofdeep vein thrombosis, there was a 28% risk reductionin the total number of deep vein thromboses in thehirudin group and a 40% reduction in the number ofproximal deep vein thromboses with no excessivebleeding.9 Therefore, perhaps the differences betweenhirudin and unfractionated heparin are due to thedifference in direct versus indirect thrombin inhibi-tion. Additional trials directly comparing hirudin andlow-molecular-weight heparin are needed to ascertainif hirudin is superior to low-molecular-weight heparinin preventing arterial complications. However, giventhe inconsistent results when comparing low-molecu-lar-weight heparin with unfractionated heparin and theclear superiority of hirudin over unfractionated hepa-rin, as well as the clear superiority of hirudin over

low-molecular-weight heparin in venous trials, it ishighly likely that hirudin will prove superior to hep-arin.

CONCLUSIONResults from the OASIS trials are consistent across

a range of related outcomes in treatment effects. Theresults of these trials reinforce the conclusion that adirect thrombin inhibitor is superior to an indirectthrombin inhibitor in controlling ischemic syndromes.However, it is important to note that only about 40%of events occurred within the first 3 days of treatment,suggesting that antithrombotic agents should be usedfor .3 days and should be studied in regard to use aslong-term therapy.

APPENDIX: OASIS INVESTIGATORSAND HOSPITALSAustralia: C. Aroney, Prince Charles Hospital,Chermside, Queensland; G.Aroney, Gold Coast Hospital,Southport, Queensland; F. Bates, Gosford Hospi-tal, Gosford, New South Wales; P. Bradshaw, Sir Charles Gairdner Hospital,Nedlands, Western Australia; H. Briggs, Alfred Healthcare Group,Prahran,Victoria; M. Brooks, Royal Perth Hospital,Perth, Western Australia; L. Brown,Austin and Repatriation Medical Centre,Melbourne, Victoria; A. Carle, PrinceCharles Hospital,Chermside, Queensland; B. Conway, Gosford Hospital,Gos-ford, New South Wales; D. Cross, Royal Brisbane Hospital,Brisbane, Queens-land; M. Firmin, St. George’s Hospital,Kew, Victoria; L. Fitzpatrick, RoyalBrisbane Hospital,Brisbane, Queensland; J. Garrett, Fremantle Hospital,Fremantle, Western Australia; J. E. Gault, Bendigo Hospital,Bendigo, Victoria;H. Hamilton, Illawarra Regional Hospital,Wollongong, New South Wales; P.Hicks, Gold Coast Hospital,Southport, Queensland; B. Hockings, Royal PerthHospital, Perth, Western Australia; D. Hunt, Royal Melbourne Hospital,Parkville, Victoria; I. Jeffery, Canberra Hospital,Garran, Australian CapitalTerritory; B. Johnson, Wangaratta District Hospital,Wangaratta, Victoria; A.Kerney, Gosford Hospital,Gosford, New South Wales; R. Kimber, Royal HobartHospital, Hobart, Tasmania; M. Knight, Manning Base Hospital,Taree, NewSouth Wales; G. K. Lane, Fremantle Hospital,Fremantle, Western Australia;Y. L. Lim, Box Hill Hospital, Box Hill, Victoria; P. G. Macleish, WangarattaDistrict Hospital, Wangaratta, Victoria; L. Morgan, Mildura Base Hospital,Mildura, Victoria; P. Neid, Royal Hobart Hospital,Hobart, Tasmania; C. Newitt,Prince Charles Hospital,Chermside, Queensland; R. A. Newman, Manning BaseHospital,Taree, New South Wales; E. O’Sullivan, St. George’s Hospital,Kew,Victoria; D. Owensby, Illawarra Regional Hospital,Wollongong, New SouthWales; C. Parsons, Box Hill Hospital,Box Hill, Victoria; A. Pitt, Alfred Health-care Group,Prahran, Victoria; L. Pittard, Bendigo Hospital,Bendigo, Victoria;

TABLE III Combined Results of OASIS-1 and OASIS-2 Studies at 7 Days and 35 Days

No. of Events/Patients (%)Relative Risk

(95% CI)p Value

(unadjusted)Heparin Hirudin

Cardiovascular death/MI at 7 days

OASIS-1 18/371 (4.9) 14/538 (2.6) 0.54 (0.27–1.06) 0.07OASIS-2 213/5,058 (4.2) 182/5,083 (3.6) 0.84 (0.69–1.02) 0.077Total 231/5,429 (4.3) 196/5,621 (3.5) 0.81 (0.67–0.98) 0.039

Cardiovascular death/MI/refractory angina at 7 days


Need for intervention at 7 days


Death/MI at 35 days


CI 5 confidence interval; MI 5 myocardial infarction.Reproduced with permission from Lancet.6

24M THE AMERICAN JOURNAL OF CARDIOLOGYT VOL. 84 (5A) SEPTEMBER 2, 1999

K. Roberts, Logan Hospital,Lonanholme, Queensland; M. Sallaberger, RoyalMelbourne Hospital,Parkville, Victoria; J. Sampson, Logan Hospital,Lonan-holme, Queensland; J. Shepherd, Launceston General Hospital,Launceston,Tasmania; C. Singh, Launceston General Hospital,Launceston, Tasmania; A.Soward, Mildura Base Hospital,Mildura, Victoria; J. Stickland, Ballarat BaseHospital,Ballarat, Victoria; K. Tankard, Mildura Base Hospital,Mildura, Vic-toria; C. Tauschke, Ballarat Base Hospital,Ballarat, Victoria; P. Taverner,Canberra Hospital,Garran, Australian Capital Territory; L. Taylor, BallaratBase Hospital,Ballarat, Victoria; P. L. Thompson, Sir Charles Gairdner Hospital,Nedlands, Western Australia; A. Thomson, Royal Hobart Hospital,Hobart,Tasmania; A. Tonkin, Austin and Repatriation Medical Centre,Melbourne,Victoria; A. Trotter, Austin and Repatriation Medical Centre,Melbourne, Victo-ria; T. Young, Royal Perth Hospital,Perth, Western Australia; Brazil: J. A.Abrantes, Santa Case de Miserico´rdia de Pelotas, Pelotas, Rio Grande do Sul;A. C. Assumpçao, Santa Casa de Miserico´rdia de Araras,Araras, Saõ Paulo;M. A. O. Barbosa, Hospital do Coraçao da Associaçao Sanato´rio Sırio, SaoPaulo, Saõ Paulo; C. Blacher, Santa Casa de Miserico´rdia de Porto Alegre,PortoAlegre, Rio Grande do Sul; A. C. C. Carvalho, Hospital Saõ Paulo,Sao Paulo,Sao Paulo; C. Costa de Oliveira, Fundaçao Hospital da Agro Indu´stria do Acuare do Alcool,Maceio, Alagoas; J.P. Esteves, Hospital Portugueˆs,Salvador, Bahia;B. Filho Markham, Proca´rdio, Recife, Pernambuco; C. Garcia, Hospital Univer-sitario de Santa Catarina Floriano´polis, Santa Catarina; T. Kawamura, SantaCasa de Miserico´rdia de Araçatuba,Aracatuba, Saõ Paulo; A. Labrunie, SantaCasa de Miserico´rdia de Marı´la, Marıla, Sao Paulo; A. P. Lichter, HospitalFelicio Rocho,Belo Horizonte, Minas Gerais; J. A. Marin Neto, Hospital dasClınicas da Faculta de Medicina de Ribeiraõ Preto,Ribeirao Preto, Saõ Paulo;R. L. Marino, Hospital Madre Teresa,Belo Horizonte, Minas Gerais; J. C.Nicolau, Instituto de Mole´stias Cardiovasculares,Sao Josedo Rio Preto, SaõPaulo; P. Pimentel Filho, Hospital Nossa Senhora da Conceiçao, Porto Alegre,Rio Grande do Sul; R. F. Ramos, Instituto Dante Pazzanese de Cardiologia,SaoPaulo, Saõ Paulo; J. M. Rossi Neto, Instituto Dante Pazzanese de Cardiologia,Sao Paulo, Saõ Paulo; L. A. Silva, Hospital Unicor,Sao Paulo, Saõ Paulo; F. R.Silveira, Prontocor,Belo Horizonte, Minas Gerais; J. E. M. R. Sousa, InstitutoDante Pazzanese de Cardiologia,Sao Paulo, Saõ Paulo; R. C. Vaz, Instituto deCardiologia do Rio Grande do Sul,Porto Alegre, Rio Grande do Sul;Canada:P. Auger, Hotel Dieu de Levis,Levis, Que´bec; L. Balleza, Sunnybrook HealthSciences,Toronto, Ontario; M. Bartoshyk, Lethbridge Regional Hospital,Leth-bridge, Alberta; I. Bata, Camp Hill Medical Centre,Halifax, Nova Scotia;V. Carr,St. Boniface Hospital,Winnipeg, Manitoba; T. Cochran, Holy Cross Hospital,Calgary, Alberta; L. Crossman, Colchester Regional Hospital-Annex,Truro,Nova Scotia; C. Darveau, Hotel Dieu de Que´bec City,Quebec City, Que´bec; F.Dumont, Hotel Dieu de Levis,Levis, Que´bec; T. Fawcett, Camp Hill MedicalCentre,Halifax, Nova Scotia; D. Folkins, Colchester Regional Hospital-Annex,Truro, Nova Scotia; C. Girard, McKellar General Hospital,Thunder Bay, On-tario; C. Joyner, Sunnybrook Health Sciences,Toronto, Ontario; K. S. C.Kwiatkowski, General Hospital of Port Arthur/St. Joseph’s, Thunder Bay, andThunder Bay Hospital, Thunder Bay, Ontario; C. Lai, General Hospital of PortArthur/St. Joseph’s, Thunder Bay, and Thunder Bay Hospital,Thunder Bay,Ontario; R. Lesoway, Calgary District Hospital Group,Calgary, Alberta; M.McFarlane, Camp Hill Medical Centre,Halifax, Nova Scotia; A. Morris, St.Boniface Hospital,Winnipeg, Manitoba; G. Proulx, Hotel Dieu de Que´bec City,Quebec City, Que´bec; M. Schillberg, St. Boniface Hospital,Winnipeg, Manitoba;R. Schuld, Lethbridge Regional Hospital,Lethbridge, Alberta; B. Smith, HeritageClinic, Calgary, Alberta; H. Smith, Concordia Hospital,Winnipeg, Manitoba; M.Sokulski, Concordia Hospital,Winnipeg, Manitoba; J. Warnica, Heritage Clinic,Calgary, Alberta; A. Weeks, McKellar General Hospital,Thunder Bay, Ontario;Hungary: T. Acs, Mentokorhaz,Budapest; G. Buday, Bajcsy Korhaz Cardiol-ogy, Budapest; J. Csillag, Megyei Korhaz II Bel,Veszprem; A. Janosi, SzentJanos Korhaz Kardiologiai Osztaly,Budapest; M. Mezofi, Buda Military Hospitalof the Hungarian Army,Budapest; P. Polgar, University Medical School ofDebrecen,Debrecen; M. Rusznak, B. A. 7 Megyei Korhaz III Belosztaly,Nyiregyhaza; F. Salamon, Szent Janos Korhaz II Belosztaly, Budapest; I. Sarosi,Pecsi Orvostudomanyiegyetem Anesthesio`logiai, Pecs; E. Sitkei, Orszagos Kar-diologiai Intezet,Budapest; F. Szaboky, Mav Korhaz,Budapest; H. Tamas,Varosi Korhaz,Nagykanizsa; S. Timar, Kecskemeti Megyei Korhaz,Kecskemet;Poland: P. Achremczyk, Wojewodzki Szpital Zespolony,Radom; J. Barylak,Szpital im J. Dietla,Krakow; R. Bubinski, Szpital Rejonowy im Jana Pawla II,Belchatow; A. Budaj, Szpital Grochowski,Warszawa; J. Burkot, Szpital Spec-jalistyczny Rydygiera, Krakow; L. Ceremuzynski, Szpital Grochowski,Warszawa; A. Cieslinski, Instytut Kardiologii A. M.,Poznan; M. Dalkowski,Szpital Gorniczo-Hutniczy,Lubin; M. Dowgird, Wojewodzki Szpital Zespolony,Olsztyn; K. Duda, Wojewodzki Szpital Zespolony,Radom; J. Dziubinska, KlinikaKardiologii-C. S. K. M. S.W.,Warszawa; H. Falkowska, Szpital Rejonowy imJana Pawla II,Belchatow; J. Frycz, Szpital Miejski nr I,Gliwice; J. Gessek,

Szpital ZOZ im M. Kopernika,Torun; J. Hanzlik, Klinika Chorob WewnetrznychA. M., Lublin; W. Jastnzebski, Szpital Gorniczo-Hutniczy,Lubin; M. Jaworska,Klinika Kardiologii-C. S. K. M. S.W.,Warszawa; J. Juza, Wojewodzki SzpitalZespolony,Tarnow; D. Kawka, Szpital Rejonowy Z. O. Z.,Kolobrzeg; T.Kawka-Urbanek, Wojewodzki Szpital Zespolony,Skierniewice; E. Kocot, SzpitalMiejski nr 2, Z. O. Z., Sosnowiec; X. Kruszewska, Szpital Grochowski,Warszawa; J. Lech, Centralny Szpital Kolejowy,Warszawa-Miedzylesie; R.Lysek, Szpital Z. O. Z. im M. Kopernika,Torun; J. Maciejewicz, Szpital im J.Dietla, Krakow; S. Motyka, Szpital Miejski nr 2, Z. O. Z.,Sosnowiec; E.Nartowicz, Klinika Kardiologii A. M., Bydgoszcz; R. Ochotny, Instytut Kardi-ologii A. M., Poznan; L. Pietchota, Szpital Zespolony im G. Narutowicza,Krakow; W. Piotrowski, Szpital Specjalistyczny Rydygiera,Krakow; M. Popiel,Instytut Kardiologii A. M., Poznan; B. Przywoska-Para, Wojewodzki SzpitalZespolony,Skierniewice; R. Ronkowski, Szpital Rejonowy Z. O. Z.,Kolobrzeg;S. Slowinski, Wojewodzki Szpital Zespolony,Tarnow; W. Smielak-Korombel,Szpital Zespolony im G. Narutowicza,Krakow; B. Sobkowicz, WojewodzkiSzpital Specjalistyczny,Wroclaw; M. Swiatkowski, Szpital Grochowski,Warszawa; M. Ukleja-Adamowicz, Klinika Kardiologii A. M.,Bydgoszcz; A.Witczak, Klinika Chorob Wewnetrznych A. M.,Lublin; K. Wrabec, WojewodzkiSzpital Specjalistyczny,Wroclaw; M. Zach, Wojewodzki Szpital Zespolony,Olsztyn; T. Zaleska, Centralny Szpital Kolejowy,Warszawa-Miedzylesie; A.Zukielewica, Szpital Miejski nr I,Gliwice; United States of America:A. Allen,L. D. S. Hospital,Salt Lake City, Utah; J. Anderson, L. D. S. Hospital,Salt LakeCity, Utah; M. Bonora, Buffalo General Hospital,Buffalo, New York; J. Calvin,Rush Presbyterian—St. Luke’s Medical Center,Chicago, Illinois; T. Cantrell,Heart Institute of Spokane,Spokane, Washington; L. Christie, Oregon HeartCenter,Eugene, Oregon; G. Cohen, Kingston Hospital,Kingston, New York; M.Gagnon, Kingston Hospital,Kingston, New York; R. M. Kohn, Buffalo GeneralHospital, Buffalo, New York; E. Lader, Benedictine Hospital,Kingston, NewYork; M. Lind, Oregon Heart Center,Eugene, Oregon; J. Nawarskas, Philadel-phia College of Pharmacy and Science and V. A. Hospital,Philadelphia, Penn-sylvania; S. North, Benedictine Hospital,Kingston, New York; S. A. Spinler,Philadelphia College of Pharmacy and Science and V. A. Hospital,Philadelphia,Pennsylvania; D. T. Spokas, Rush Presbyterian—St. Luke’s Medical Center,Chicago, Illinois; K. Tuttle, Heart Institute of Spokane,Spokane, Washington; H.Zimmerman, Pennsylvania State University,Hershey, Pennsylvania.

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Documents

Design, baseline characteristics, and preliminary clinical results of the Organization to Assess Strategies for Ischemic Syndromes–2 (OASIS–2) trial