Courtesy of Dr. Cristian Jesús Rodríguez.

Most stents currently used in percutaneous coronary intervention (PCI) are durable-polymer second-generation drug-eluting stents (DP-DES, with everolimus or zotarolimus). However, it has been argued that the persistence of such a polymer after complete drug elution is one of the main factors for a dangerous complication: stent thrombosis (ST). After DP-DES implantation, ST takes place partly due to a general inflammatory process generated by the polymer inside coronary vessels.

Since the biodegradable-polymer everolimus-eluting stent (BP-DES) SYNERGY was first approved, being aimed at solving a theoretical polymer-mediated prothrombotic inflammation, there has been much expectation amongst the interventional community as regards its potential advantages compared with metallic stents (DP-DES). The approval of the BP-DES was based on the results of EVOLVE and EVOLVE II, with an ST incidence of 0%-0.4%.

This work analyzed the US Food and Drugs Administration (FDA) Manufacturer and User Facility Device Experience (MAUDE) database, which is a public-use database listing complications reported by patients, healthcare providers, or device manufacturers. Such complications frequently caused lesions or death.

Also read: “Everolimus DES Are More Effective and Less Costly than Conventional BMS.”

This database was searched for adverse events reported between October, 2015, and December, 2016, encountered after the placement of either BP-DES or DP-DES through PCI, reported through the MAUDE server. Of all adverse events reported, the event of interest was ST. ST was defined as the presence of acute coronary syndrome [ACS] with evidence of thrombus in an angiography or autopsy. Probable ST was defined as unexplained death within a month from the procedure or myocardial infarction involving the culprit vessel without angiographic confirmation. As regards the time to the event, acute ST took place between 0 and 24 h after PCI; subacute ST, between 24 h and 30 days after PCI; late ST, between 31 and 365 days after the procedure, and extremely late ST took place beyond 365 days after PCI.

Results

A total of 951 adverse events with BP-DES and DP-DES were identified. Among these, 309 (32.5%) were experienced by patients treated with BP-DES and 642 (67.5%), by patients with DP-DES- Furthermore, ST occurred in 48/951 patients (31 with BP-DES and 17 with DP-DES, p = 0.00001). Among these 48 events, 44 were defined STs and 4 were probable STs. Over half the ST events were reported in patients with BP-DES.

Most ST events with BP-DES occurred within less than 24 h (21/31) and over half of them (16/31) occurred within less than 2 h from the procedure. There were 6 reported deaths with BP-DES and a similar amount with DP-DES, all of which resulted from ST complications. Among the 6 deaths reported with BP-DES, 4 occurred within 24 h from the procedure. Similarly, among the 6 death reported with DP-DES, 2 occurred within 24 h.

The authors concluded that in their analysis of the FDA MAUDE database, there was a higher incidence of ST with the use of the bioresorbable-polymer stent SYNERGY (Boston Sci) (BP-DES) compared with permanent-polymer stents Xience, Promus, and Resolute (DP-DES).

Also read: “Biodegradable-Polymer Stents Are as Safe as Permanent-Polymer Stents in a 5-Year Follow-Up.”

ST events reported with BP-DES took place mainly between the first 2 to 24 h after implantation, and death cases reported with BP-DES mainly occurred within the first 24 h after ST.

This is the first report assessing the safety of BP-DES compared with DP-DES in the United States. These results could be comparable to a meta-analysis of 126 trials published by Bangalore S, Toklu B, Amoroso N, et al in 2013, in which results for BP-DES were lower than for second-generation DP-DES as regards ST and mortality rates (although that meta-analysis did not include the SYNERGY device).

Different factors may have influenced the results, including the initial experience with a new device and its learning curve, as opposed to results for randomized studies involving experienced operators.

As indicated, over half the ST cases reported occurred within the first 2 h after the procedure. In consequence, one may infer that the source for the mechanism of thrombosis is derived from mechanic factors as opposed to being directly related to the bioresorbable polymer per se. Lack of experience with the device, changes in design and structure of the BP-DES (particularly ultra thin struts) may have caused inadvertent mistakes during stent implantation. The lack of a standardized implantation protocol, especially for a new device structurally different from those currently used, may have affected the results as well.

This study presents several limitations, including the inability to the determine the cause of ST, the inability to provide clean data on the actual rate of ST, factors affecting ST with bioresorbable scaffolds, or the comparative risk among different stent types.

Editorial

Stent thrombosis (ST) is an unusual but serious complication. Results obtained from this analysis offer the possibility of a higher risk for ST with the use of BP-DES (SYNERGY) compared with second-generation DP-DES, which means that they are significantly different from results obtained from EVOLVE and EVOLVE II. While the mechanism for ST is not well-defined in this analysis, and no clean data on the actual rate of ST can be obtained, results call for strict monitoring and surveillance of the analyzed device.

Courtesy of Dr. Cristian Jesús Rodríguez.

Original title: Stent Thrombosis with Bioabsorbable Polymer Drug-Eluting Stents: Insights from the Food and Drug Administration Database.

Reference: Coron Artery Dis. 2017 Jul 20. doi: 10.1097/MCA.0000000000000539.

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