Medical Device Daily
BARCELONA, Spain – "There is only so much I can retain, and then there is only so much I can care about," complained one cardiologist following a "Late-Breaking Trial" session at EuroPCR 2009 here last week.
A signature feature of this annual congress for interventional cardiologists, the trials sessions reflect the fierce competition to introduce or promote bare-metal (BMS) and drug-eluting stents (DES) to capture a piece of that lucrative market.
And the marathon sessions can prove to be a trial for participants, as reflected in the cardiologist's comment.
While sales have fallen a third from their peak of $6 billion globally in 2006 following reports raising safety questions about DES, there has been no let-up in the waves of clinical trials proving, or merely promoting, the virtues of each product.
Adding to the confusion is the emergence of regional players who are introducing me-too stents at attractive price points, furthering the pressure on major manufacturers.
Continuing the storm of trial results, Cordis (Miami Lakes, Florida) presented at EuroPCR four-year results from its trial to assess the use of the Cypher stent in acute myocardial infarction treated with balloon angioplasty, the TYPHOON study.
TYPHOON closed in 2006 after one-year of follow-up, but due to the concerns about stent thrombosis, raised in a 2006 article in the New England Journal of Medicine, the trial re-opened in 2007 to demonstrate longer-term effectiveness.
Neo-TYPHOON was conducted at 48 sites in 15 countries across Europe, Israel and Australia with 501 patients available for the follow up.
The first-year results, showed a significant reduction of 7.3% for patients receiving the Cordis Cypher stent against 14.3% for those receiving a bare metal stent (BMS) in a composite end point of target vessel revascularization (TVR), myocardial infarction (MI), or target vessel-related cardiac death among patients.
Christian Spaulding, MD, of René Descartes University Hospital (Paris), reported that four years after implantation patients receiving the Cypher stent remained 53% less likely to experience target lesion revascularisation than those receiving a BMS.
Specifically, he said, patients in the Cypher study arm had a target lesion revascularization (TLR) rate of 7.2% against 15.2% with BMS.
The reduction of TVR in the Cypher patients was also maintained with a 44% reduction at four years compared with BMS, or 9.6% against 17.2%.
There continued to be no differences in the key safety parameters of cardiac death, MI or stent thrombosis in the four-year follow-up.
He stated pointedly that these findings do not support the earlier concerns on the long-term safety and efficacy of the DES, and Cypher specifically in primary angioplasty for acute MI.
In the discussion of the results by a disinterested third-party, a feature of the EuroPCR trials sessions Manel Sabate, MD, of Hospital de Sant Pau (Barcelona), noted the trial had exclusion criteria that avoided the kinds of patients that were the subject of criticisms of DES and added that a third of real-world patients were filtered out of the TYPHOON trial.
On the whole he agreed with Spaulding that the results were reassuring, while noting that 28% of original patients could not be contacted or else refused to participate.
New wave of next-generation stents
The performance of a next-generation DES, the BioMatrix III from Biosensors Europe (Morges, Switzerland), were reported with results of these two subgroup analyses of the landmark LEADERS trial (Limus Eluted from A Durable versus ERodable Stent coating).
The biolimus A9-eluting stent with abluminal biodegradable polymer was compared to the Cypher Select from Cordis in patients with acute coronary syndrome (ACS) and bifurcation lesions.
In the first subgroup, 470 ACS patients treated with the Biosensors stent and 473 treated with Cypher after 12 months, showed an incidence of MACE of 9.4% with the BioMatrix III stent and 11.2% for the Cypher stent.
Further parsing the results, presenter Stephan Windecker, MD, of University Hospital (Bern, Switzerland), principal investigator for the trial, said that when only patients with STEMI were considered, there was a more significant 50% reduction in the incidence of MACE at 12 months with 6.7% for the biolimus A9 stent against 15.7% for the Cypher's sirolimus.
Zooming further into the data with a sub-subgroup of 135 patients receiving the biolimus A9 therapy and 140 patients receiving the sirolimus effects, this difference was seen to be driven not only by clinically-indicated TVR but also by the composite of cardiac death and MI that shows a significant reduction for the Biosensors stent at 3.7% vs. 10.0% for Cypher, he said.
Results from a second subgroup of 258 patients with bifurcations, after 12 months, patients given the Biosensors stent experienced similar levels of MACE to patients given the Cypher stent (12.8% vs. 16.%, he reported).
Yet, he noted, the need for revascularization as measured by TVR was significantly lower with the Biolimus A9-eluting stent at 12 months.
While LEADERS is an all-comers trial gathering a respectable 1,707 patients eligible for percutaneous coronary intervention for symptomatic coronary disease, Laura Mauri from the Harvard Clinical Research Institute (Cambridge, Massachusetts) commented following Windecker's presentation of nine-month results at the European Society of Cardiology (Sophia Antipolis, France) meeting in Munich, Germany last September that "there is not sufficient power to determine the safety or efficacy in these subgroups (Medical Device Daily; Sept. 5, 2008)."
Acknowledging that a fully biodegradable polymer may have a unique advantage over a durable polymer, "the hypothesis that the new biolimus-eluting stent has improved late safety and preserved efficacy compared to sirolimus-eluting stent remains to be proven in further follow-up," she said.
The TITAX-AMI trial presented by its co-principal investigator, Pasi Karjalainen, MD, of Satakunta Hospital Pori Hospital in Finland, compared a novel coating for a stent against a traditional pharmaceutical-based therapy.
The TiTAN2 Bio Active stent from Hexacath (Paris) is coated with titanium-nitride-oxide, a compound which has demonstrated mechanisms of action such as inhibiting platelet and fibrin deposition, promoting re-endothelialization and minimizing inflammation.
The Hexcath stent is compared in an ongoing, multicentre randomized trial with the paclitaxel-eluting stent Taxus Liberté from Boston Scientific (Natick, Massachusetts) among 245 patients presenting with ST-elevated myocardial infarction (STEMI) as well as non-STEMI.
The primary endpoint is major adverse cardiac events (MACE) at 12 and 24 months and clinical follow up was an exceptional 100% after two years.
Karjalainen reported the cumulative incidence of MACE for TiTAN2 was 10.3% against 12.8% for Taxus Liberté at 12 months, but that the gap grew significantly wider at 24 months with 11.2% vs. 21.8%, respectively.
The growing differences were attributed to a lower 5.1% rate of MI reduced for Hexcath's stent vs. 15.6%for the Boston Scientific stent and cardiac death that was reported less than 1% for TiTAN2 while Taxus reported 4.7%.
Definite stent thrombosis occurred in 0.5% patients with TiTAN2, he said, but 6.2% for Taxus Liberté.
Karjalainen concluded the TITAX-AMI trial is providings fresh data confirming the efficacy and safety of the Bio Active coating stent and that "Interestingly, the outcomes of patients presenting with NSTEMI and STEMI were similar at follow up confirming the fact that although NSTEMI and STEMI are usually considered to be different entities, the prognosis of either subgroup of MI is similar."