title: Tradeoff between bleeding and stent thrombosis in different dual antiplatelet therapy regimes: Importance of case fatality rates and effective treatment durations.
abstract: BACKGROUND
  The tradeoff between stent thrombosis (ST) and major bleeding (MB) of 12- versus 6-month dual antiplatelet therapy (DAPT) after coronary stent implantation has not been clearly defined.
  
  
  METHODS
  Definite/probable ST and MB (TIMI major and Bleeding Academic Research Consortium (BARC) ≥ 3) were compared in 2 subsequent trials with similar inclusion criteria but different DAPT duration, that is, BASKET (6 months; n = 557) and BASKET-PROVE (12 months; n = 2,314), between months 0 to 6 (DAPT in both trials), 7 to 12 (DAPT in BASKET-PROVE only), and 13 to 24 (aspirin in both trials) using propensity score-adjusted, time-stratified Cox proportional hazard models.
  
  
  RESULTS
  Overall, event rates were low with fewer ST but similar MB in prolonged DAPT. Analysis of the 3 periods showed a uniform pattern for ST (interaction DAPT/period; P = .145) but an inconsistent pattern for MB (interaction DAPT/period; P < .001 for TIMI major and P = .046 for BARC ≥ 3), with more MB occurring during months 7 to 12 with prolonged DAPT. Considering observed case fatality rates of 31% with ST and 11% with MB, the extrapolated prevention of 27 ST deaths and the excess of 5 MB deaths resulted in an expected benefit of 22 survivors/10,000 patients treated over 2 years with prolonged DAPT.
  
  
  CONCLUSIONS
  Despite overall low event rates, prolonged DAPT was associated with more MB during months 7 to 12 according to the interaction DAPT/period. Given the higher observed case fatality rates of ST versus MB, 12- versus 6-month DAPT was associated with an extrapolated reduction in mortality. Effective treatment periods and case fatality rates seem important in the analysis of different DAPT durations, specifically with regard to ongoing trials.
authors.affiliation: University Hospital Basel, Basel, Switzerland. Electronic address: raban.jeger@usb.ch.
authors.forename: Raban V
authors.initials: RV
authors.lastname: Jeger
authors.affiliation: University Hospital Basel, Basel, Switzerland.
authors.forename: Matthias E
authors.initials: ME
authors.lastname: Pfisterer
authors.affiliation: Copenhagen University Hospital, Gentofte, Denmark.
authors.forename: Rikke
authors.initials: R
authors.lastname: Sørensen
authors.affiliation: University Hospital Basel, Basel, Switzerland.
authors.forename: Stefanie
authors.initials: S
authors.lastname: von Felten
authors.affiliation: Innsbruck Medical University, Innsbruck, Austria.
authors.forename: Hannes
authors.initials: H
authors.lastname: Alber
authors.affiliation: Cantonal Hospital, Chur, Switzerland.
authors.forename: Piero O
authors.initials: PO
authors.lastname: Bonetti
authors.affiliation: Triemli City Hospital, Zürich, Switzerland.
authors.forename: Franz
authors.initials: F
authors.lastname: Eberli
authors.affiliation: Cantonal Hospital, Luzern, Switzerland.
authors.forename: Paul
authors.initials: P
authors.lastname: Erne
authors.affiliation: Cardiocentro Ticino, Lugano, Switzerland.
authors.forename: Giovanni
authors.initials: G
authors.lastname: Pedrazzini
authors.affiliation: Cantonal Hospital, St Gallen, Switzerland.
authors.forename: Hans
authors.initials: H
authors.lastname: Rickli
authors.affiliation: Copenhagen University Hospital, Gentofte, Denmark.
authors.forename: Søren
authors.initials: S
authors.lastname: Galatius
authors.affiliation: University Hospital Basel, Basel, Switzerland.
authors.forename: Christoph A
authors.initials: CA
authors.lastname: Kaiser
mesh_terms: D000368:Aged; D000787:Angina Pectoris / Q000628:therapy*; D001241:Aspirin / Q000627:therapeutic use*; D000077144:Clopidogrel; D003328:Coronary Thrombosis / Q000517:prevention & control*; D004359:Drug Therapy, Combination; D054855:Drug-Eluting Stents; D005260:Female; D006470:Hemorrhage / Q000139:chemically induced*; D006801:Humans; D060046:Maintenance Chemotherapy; D008297:Male; D008875:Middle Aged; D009203:Myocardial Infarction / Q000628:therapy*; D062645:Percutaneous Coronary Intervention; D010975:Platelet Aggregation Inhibitors / Q000627:therapeutic use*; D011475:Prosthesis Failure; D018570:Risk Assessment; D020123:Sirolimus; D013988:Ticlopidine / Q000031:analogs & derivatives* / Q000627:therapeutic use; D013997:Time Factors; D016896:Treatment Outcome
chemical_list: D010975:Platelet Aggregation Inhibitors; D000077144:Clopidogrel; D013988:Ticlopidine; D001241:Aspirin; D020123:Sirolimus