Bivalirudin or Unfractionated Heparin in Acute Coronary Syndromes.
BACKGROUND
Conflicting evidence exists on the efficacy and safety of bivalirudin administered as part of percutaneous coronary intervention (PCI) in patients with an acute coronary syndrome.


METHODS
We randomly assigned 7213 patients with an acute coronary syndrome for whom PCI was anticipated to receive either bivalirudin or unfractionated heparin. Patients in the bivalirudin group were subsequently randomly assigned to receive or not to receive a post-PCI bivalirudin infusion. Primary outcomes for the comparison between bivalirudin and heparin were the occurrence of major adverse cardiovascular events (a composite of death, myocardial infarction, or stroke) and net adverse clinical events (a composite of major bleeding or a major adverse cardiovascular event). The primary outcome for the comparison of a post-PCI bivalirudin infusion with no post-PCI infusion was a composite of urgent target-vessel revascularization, definite stent thrombosis, or net adverse clinical events.


RESULTS
The rate of major adverse cardiovascular events was not significantly lower with bivalirudin than with heparin (10.3% and 10.9%, respectively; relative risk, 0.94; 95% confidence interval [CI], 0.81 to 1.09; P=0.44), nor was the rate of net adverse clinical events (11.2% and 12.4%, respectively; relative risk, 0.89; 95% CI, 0.78 to 1.03; P=0.12). Post-PCI bivalirudin infusion, as compared with no infusion, did not significantly decrease the rate of urgent target-vessel revascularization, definite stent thrombosis, or net adverse clinical events (11.0% and 11.9%, respectively; relative risk, 0.91; 95% CI, 0.74 to 1.11; P=0.34).


CONCLUSIONS
In patients with an acute coronary syndrome, the rates of major adverse cardiovascular events and net adverse clinical events were not significantly lower with bivalirudin than with unfractionated heparin. The rate of the composite of urgent target-vessel revascularization, definite stent thrombosis, or net adverse clinical events was not significantly lower with a post-PCI bivalirudin infusion than with no post-PCI infusion. (Funded by the Medicines Company and Terumo Medical; MATRIX ClinicalTrials.gov number, NCT01433627.).
From the Swiss Cardiovascular Center Bern, Bern University Hospital (M.V.), Clinical Trials Unit and Institute of Social and Preventive Medicine (M.R., D.H.), and Institute of Primary Health Care (P.J.), University of Bern, Bern, Switzerland; Thoraxcenter, Erasmus Medical Center, Rotterdam (M.V.), and Isala Klinieken, Zwolle (A.H.) - both in the Netherlands; EUSTRATEGY Association, Forli (E.F.), Unità Operativa Complessa Cardiologia, Dipartimento CardioToracoVascolare, Fondazione IRCCS Policlinico San Matteo, Pavia (S.L., A.R.), Cardiology Unit, Ospedali Riuniti di Rivoli (A.G., F.V.), and San Giovanni Bosco Hospital (R.G., G.B.), Turin, Division of Cardiology, Department of Cardiothoracic Sciences, Second University of Naples (P.C.), Department of Advanced Biomedical Sciences, Division of Cardiology, Federico II University of Naples (G.E.), and Clinica Mediterranea (C.B.), Naples, Azienda Ospedaliera Ospedale Civile di Vimercate, Desio (S.G.), Department of Cardiology, ASL3 Ospedale Villa Scassi (P.R.), and IRCCS Azienda Ospedaliera Universitaria San Martino (A.Z.), Genoa, Azienda Ospedaliera Universitaria Policlinico Gaetano Martino, University of Messina, Messina (G.A.), Unità Operativa Cardiologia, ASL 9 Grosseto, Grosseto (U.L.), Azienda Ospedaliera Ospedale Treviglio-Caravaggio, Treviglio (P.S.), Azienda Ospedaliera Sant'Anna, Como (F.R.), University Hospital Maggiore della Carita, Novara (A.L.), Ospedale Fatebenefratelli, Milan (B.C.), Casa di Cura Villa Verde, Taranto (A.A.), Ospedale Sirai-Carbonia, Carbonia (S.I.), IRCCS Humanitas, Rozzano (P.P.), Cardiovascular Department, Infermi Hospital, Rimini (A.S.), Policlinico Umberto I, Sapienza University of Rome (G.S.), and Interventional Cardiology Unit, Sandro Pertini Hospital Rome (S.R.), Rome, Azienda Ospedaliera Ospedale di Desio, Desio (S.T.), Policlinico San Marco, Zingonia (N.C.), and Mater Salutis Hospital, Legnago (P.T.) - all in Italy; Sahlgrenska University Hospital, Göteborg, Sweden (E.O.); Hospi
Marco
M
Valgimigli
Enrico
E
Frigoli
Sergio
S
Leonardi
Martina
M
Rothenbühler
Andrea
A
Gagnor
Paolo
P
Calabrò
Stefano
S
Garducci
Paolo
P
Rubartelli
Carlo
C
Briguori
Giuseppe
G
Andò
Alessandra
A
Repetto
Ugo
U
Limbruno
Roberto
R
Garbo
Paolo
P
Sganzerla
Filippo
F
Russo
Alessandro
A
Lupi
Bernardo
B
Cortese
Arturo
A
Ausiello
Salvatore
S
Ierna
Giovanni
G
Esposito
Patrizia
P
Presbitero
Andrea
A
Santarelli
Gennaro
G
Sardella
Ferdinando
F
Varbella
Simone
S
Tresoldi
Nicoletta
N
de Cesare
Stefano
S
Rigattieri
Antonio
A
Zingarelli
Paolo
P
Tosi
Arnoud
A
van 't Hof
Giacomo
G
Boccuzzi
Elmir
E
Omerovic
Manel
M
Sabaté
Dik
D
Heg
Peter
P
Jüni
Pascal
P
Vranckx
D054058:Acute Coronary Syndrome / Q000188:drug therapy* / Q000401:mortality; D000368:Aged; D000925:Anticoagulants / Q000009:adverse effects / Q000627:therapeutic use*; D003131:Combined Modality Therapy; D003328:Coronary Thrombosis / Q000517:prevention & control; D005260:Female; D006493:Heparin / Q000009:adverse effects / Q000627:therapeutic use*; D006629:Hirudins / Q000009:adverse effects; D006801:Humans; D015994:Incidence; D007262:Infusions, Intravenous; D008297:Male; D008875:Middle Aged; D009203:Myocardial Infarction / Q000453:epidemiology; D010446:Peptide Fragments / Q000009:adverse effects / Q000627:therapeutic use*; D062645:Percutaneous Coronary Intervention / Q000706:statistics & numerical data; D011994:Recombinant Proteins / Q000009:adverse effects / Q000627:therapeutic use; D015607:Stents; D020521:Stroke / Q000453:epidemiology
D000925:Anticoagulants; D006629:Hirudins; D010446:Peptide Fragments; D011994:Recombinant Proteins; D006493:Heparin; C074619:bivalirudin