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MULTI STRATEGY: 3-year Follow-up of the Comparison of Angioplasty with Infusion of Tirofiban or Abciximab and with Implantation of Sirolimus-Eluting or Uncoated Stents for Acute Myocardial Infarction

Cardiovascular Surgery
Interventional Cardiology and Cardiovascular Surgery

Marco Valgimigli
Presenter | see Discussant report Webcasts become available 24h after the presentation
Valgimigli, Marco
Open presentation slides

List of Authors:

Marco Valgimigli, MD, PhD, Gianluca Campo, MD, Stefania Gambetti, BSc, Leonardo Bolognese, MD, Flavio Ribichini, MD, Salvatore Colangelo, MD, Nicoletta de Cesare, MD, Alfredo E. Rodriguez, MD, PhD, Filippo Russo, MD, Raul Moreno, MD, Tommaso Piva, MD, Imad Sheiban, MD, Carlo Penzo, MD, Francesco Prati, MD, PhD, Marco S. Nazzaro, MD, PhD, José F. Díaz Fernández, MD, Giovanni Parrinello, PhD, Roberto Ferrari, MD, Ph.D, For the MULTIcentre evaluation of Single high-dose bolus TiRofiban versus Abciximab with sirolimus eluting sTEnt or Bare Metal Stent in Acute Myocardial Infarction studY (MULTISTRATEGY) investigators



Glycoprotein IIb/IIIa inhibitors (GPIs) remain today a cornerstone of treatment in ST-elevation myocardial infarction (STEMI) patients. Among GPIs, Abciximab still remains today the preferable treatment option in STEMI patients undergoing primary angioplasty (PCI). This largely reflects the results of three European studies in which the value of abciximab was shown to accrue overtime over unfractioned heparin alone. Similar to other GPIs available on the market, abciximab displays a potent inhibition of the glycoprotein (GP) IIb/IIIa platelet receptor. Yet, abciximab is unique in that it exerts an irreversible inhibition of the target reception and it concomitantly inhibits other ß3 integrins, such as the vitronectin and the activated MAC-1 receptors. Studies comparing abciximab to eptifibatide are scarce whereas comparisons of abciximab versus tirofiban are largely confined to short-term outcomes.

On the other hand, the long-term safety profile of drug-eluting stent implantation in patients with STEMI remains uncertain as only a limited number of controlled data exists beyond 2 years.

The STRATEGY, TYPHOON and SESAMI trials testing sirolimus-eluting (SES) over bare metal stent implantation in primary PCI reported no safety concern respectively at 5, 4 and 3 year follow-up. Yet, the DEDICATION study which tested a mixture of first and second generation DES showed a higher mortality rate at 3 years in the DES group which was not explained by the difference in myocardial infarction nor stent thrombosis between groups. The PASSION study, in which paclitaxel-eluting stent (PES) was compared to BMS in STEMI patients, recently corroborated the concerns around the use of DES in STEMI by showing a non-significant 49% increase in the rate of recurrent MI and a trend towards almost twice higher rate of definite stent thrombosis in the PES arm through five years.

To investigate whether the use of tirofiban, given at high-dose bolus, leads to comparable and endurable clinical outcomes over abciximab as well as the long-term safety/efficacy profile of SES over BMS in STEMI patients, the 3-year results of the MULTIcentre evaluation of Single high-dose bolus TiRofiban versus Abciximab with sirolimus eluting sTEnt or Bare Metal Stent in Acute Myocardial Infarction studY (MULTISTRATEGY) are reported here.


Complete data at 3 years was available for 736 patients (99%). All-cause mortality was 6.7% in the tirofiban and 7.8% in the abciximab (P=0.56) and 7.5% in the BMS vs 7.0% in the SES groups, P=0.79. The composite of all-cause death or MI was identical at 12.9% in tirofiban and abciximab groups, P=0.99 and it occurred in 13.2% in the BMS vs. 12.6% in the SES groups (P=0.83). The need for reintervention remained more than twice as common with BMS (13.7%; versus 6.2%, HR, 2.29; 95%CI, 1.4 to 3.7; P=0.0006). The cumulative rate of stent thrombosis (ST) did not differ.


The 3-year follow-up of MULTISTRATEGY demonstrated comparable outcomes with HDB Tirofiban or abciximab and a sustained efficacy of SES to reduce reintervention with no difference in death, repeat MI or ST.

Patrick Serruys, FESC
Discussant | see Presenter abstract Webcasts become available 24h after the presentation
Serruys, Patrick
Open presentation slides


At the time of his fellowship in Rotterdam, Dr. Valgimigli was already designing mentally this trial based on the concept of a maybe less effective IIb/IIIa inhibitor combined with an expensive and effective DES vs. a IIb/IIIa inhibitor considered more effective than other but more expensive combined with a cheap BMS.

Although the MULTISTRATEGY was designed some years ago, it is still contemporary from that point of view. The risk of a long-term follow-up is that a concept that seemed revolutionary and a major question mark at the time of the design may look somewhat more futile at the time of medium-long term report.

The strong points of the study are: 1) small difference between the number of patients assessed for the eligibility and the number of patients randomized; 2) small deviation between the number of patients “per protocol” and “intention to treat”; 3) excellent clinical follow-up (patients lost to follow-up range between 1 and 3 per cohort); 4) appropriate long-term and balanced treatment in the four arms; 5) the idea of checking the P2Y12 inhibition sequentially, although it remains unclear why in the first year there was a difference between DES and BMS arms, but not between abciximab and tirofiban arms. The duration of the use of clopidogrel maybe is a confounding factor in the analysis of this multifactor study.

Anyway, did the authors hypothesize that an early difference in ST-resolution (with impact on peri-procedural re-infarction and acute stent thrombosis, acute mortality, etc) could substantially affect the long-term results up to the point that the drug-effect would be supersede the difference between the two stents? From the other point of view, the efficacy of DES on BMS in terms of TVR reduction is overwhelming and superseded the potential subtle differences in IIb/IIIa inhibitors. The AMI related to TVR (more frequent in BMS), but not related to stent thrombosis (potentially more frequent in DES) is another complex confounding factor in the interpretation of the possible difference or absence of difference between the two IIb/IIIa at medium and long-term follow-up.


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Clinical Trial Update I
The content of this article reflects the personal opinion of the author/s and is not necessarily the official position of the European Society of Cardiology.