A Medical Device Daily

Though late thrombosis is rare following the use of a drug-eluting stent (DES), such an event can be extremely severe, resulting in death in up to 45% of all cases, according to a report issued at this year's Congress of the European Society of Cardiology (Sophia Antipolis), ongoing this week in Vienna.

Professor Gabriel Steg of H pital Bichat-Claude Bernard (Paris) reported that late stent thrombosis can occur abruptly more than one year after DES placement and thus offset the benefits of DES devices in preventing restenosis.

Steg's analysis used the database from the Global Registry of Acute Coronary syndromEs (GRACE), collected in 94 hospitals in 14 countries across four continents (Americas, Europe, Australia/NZ) to compare the survival up to two years of patients treated with bare metal stents (BMS) only or receiving at least one DES. Survival appeared similar in the six-months following discharge, but thereafter mortality was greater in patients treated with DES. This difference was entirely related to patients treated for acute myocardial infarction and was associated with an increased risk of late reinfarction, suggesting that it may indeed be related to late stent thrombosis, according to Steg.

The risk of such late stent thrombosis may be greater in the context of acute coronary syndromes, but, in fact, little information is available so far from rigorous randomized clinical trials comparing DES and BMS, in the context of acute coronary syndromes, particularly in the context of acute myocardial infarction. The randomized clinical trials which have compared DES and BMS in the context of acute myocardial infarction are relatively small (totaling less than 1,000 patients with DES) and most have only reported one year of follow-up.

The ESC urged caution in analyzing an observation study such as GRACE (noting that the patients in the DES and BMS groups were not similar), this survival difference (which persists after statistical adjustment for the differences in baseline characteristics between the two types of patients) suggests that DES should be used with caution in patients with acute myocardial infarction, at least until more evidence is accumulated of their long term safety from large studies with long term follow up.

Ongoing since 1999, the GRACE registry is supported by sanofi-aventis and coordinated by the Center for Outcomes Research, University of Massachusetts Medical School (Worcester) in another study focused on the issue of late thrombosis following stent implantation:

Researchers at Hospital, Catholic University of the Sacred Heart (Rome) reported on the OPTIMIST study which looked at the use of percutaneous coronary intervention with stent implantation (angioplasty/stenting), particularly the outcomes of PCI for stent thrombosis in the contemporary DES era.

A primary goal of the OPTIMIST was to collect data on the clinical outcome of patients with stent thrombosis undergoing urgent PCI in the contemporary, the researchers saying that this is generally unknown. "We discovered," they said, "that the clinical outcome during the six-month follow-up, despite good utilization of all the best pharmacological and technical resources, was a disappointing 17% mortality rate and 29% rate of major adverse coronary or cerebral events (death or myocardial infarction or stroke or necessity of a new interventional procedure). These results show that stent thrombosis is not a benign disease and emergency PCI in this setting is still associated with [an] unsatisfactory outcome."

OPTIMIST is an independent, large-scale, multi-centere study conducted by 11 hospitals in urban Rome. During the years 2005 and 2006 all patients who were admitted to participating hospitals with stent thrombosis and treated by PCI were enrolled. The clinical and procedural data was recorded on a detailed questionnaire and the clinical outcome up to six months after intervention was assessed by ambulatory visit or phone contact, and the efficacy of the procedure to re-establish optimal coronary blood flow was assessed by performing detailed analyses in an independent core laboratory.

During the study, 110 patients were enrolled. This constituted, the researchers said, the largest series of patients with stent thrombosis ever collected.

One of the initial observations arising from the study, the researchers said, is that stent thrombosis, even if it is a rare event, accounted for 3.6% of the emergency PCI performed in patients with acute myocardial infarction. "This data reinforces the perception that stent thrombosis has more than a negligible impact on the contemporary health system and further investigations on its causes and management are called for."

They said that the data collected did not provide any clarifying look at whether thrombosis is higher for DES vs. BMS implantation, but the researchers said that the supported the hypothesis that stent thrombosis "may have different mechanisms of occurrence in different types of stents.

"Indeed DES thrombosis, compared to BMS, happened more often after 30 days of implantation or after 15 days of anti-platelet drug therapy withdrawal. On the other hand, once stent thrombosis has occurred, we observed that the clinical manifestations, the procedural and the clinical outcomes, are not influenced by the type [DES or BMS] of previously implanted stent."

Additional analysis of OPTIMIST showed:

• that mortality is significantly higher when stent thrombosis occurred one year after stent implantation ("very late" thrombosis);

• when the attempted PCI result was not optimal and

• when a further stent was implanted during the PCI.

The data concerning mortality was interpreted by the investigators as indicating that clinical surveillance after a successful PCI should not be reduced after one year and that the possible value of long-term anti-thrombotic drug administration should be investigated.

"The other two factors may together provide some interesting suggestions to the interventional cardiologists who must perform emergency PCI procedures in patients with stent thrombosis. Indeed, it seems that they should aim to re-establish optimal coronary blood flow and not to eliminate any residual coronary vessel narrowing by further stent implantations," the investigators said.

OPTIMIST also evaluated the efficacy of novel techniques of PCI in the high risk scenario of stent thrombosis. Previous studies have suggested that thrombus removal by devices specifically designed for this procedure may facilitate restoration of coronary blood flow in thrombotic lesions by reducing thrombotic debris.

In OPTIMIST, one of every four patients was treated using thrombectomy devices as a first strategy. Though the patients treated by thrombectomy were sicker than the others, the data should no increase in adverse events.

Patients with absence of shock treated by thrombectomy had a five-fold improved rate of optimal coronary flow restoration, "suggesting that the role of distal embolization and its prevention may be important only before advanced heart damage has been established," according to the researchers.