Year : 2015 | Volume
: 1 | Issue : 2 | Page : 182--184
Journal review: The BASKET PROVE II study
Suraj Khanal, Ramesh Patel
Department of Cardiology, Post Graduate Institute of Medical Education and Research, Chandigarh, India
Dr. Suraj Khanal
Department of Cardiology, 3rd Floor; Block-C; Advanced Cardiac Center, Post Graduate Institute of Medical Education and Research, Chandigarh - 160 012
|How to cite this article:|
Khanal S, Patel R. Journal review: The BASKET PROVE II study.J Pract Cardiovasc Sci 2015;1:182-184
|How to cite this URL:|
Khanal S, Patel R. Journal review: The BASKET PROVE II study. J Pract Cardiovasc Sci [serial online] 2015 [cited 2020 May 30 ];1:182-184
Available from: http://www.j-pcs.org/text.asp?2015/1/2/182/166314
Kaiser C, Galatius S, Jeger R, Gilgen N, Skov Jensen J, Naber C, et al. for the BASKET-PROVE II study group. Long-term efficacy and safety of biodegradable-polymer biolimus-eluting stents: Main results of the Basel Stent Kosten-Effektivitäts Trial-PROspective Validation Examination II (BASKET-PROVE II), a randomized, controlled noninferiority 2-year outcome trial. Circulation 2015;131:74-81.
Polymers are drug carrier molecules and are large compounds consisting of repeating structural units typically connected by covalent chemical bondsIt has been demonstrated that the coating of stents with inert polymers may reduce the surface reactivity and thrombosis Both the first and the second-generation of drug-eluting stents (DES) are using a nonbiodegradable polymer such as polystyrene-b-isobutylene-b-styrene (Taxus) and fluoropolymer (Xience) to control the drug elutionHowever, polymers by disintegration and absorption, may induce local inflammation, hypersensitivity reactions, neoatherosclerosis and very late stent thrombosis (VLST), myocardial infarction, or cardiac death As nonbiodegradable polymers may lead to an inflammatory response, biodegradable polymers are being investigated such as polylactic acid (PLA) and polyglycolic acidThe rationale postulated for biodegradable polymer DES was that they would reduce the risk of VLST or late clinical events related to stent thrombosis beyond the 1st year, when the polymer has dissolved while remaining as effective as a second-generation durable polymer DES (DP-DES) and as safe >1-year as bare-metal stents (BMS)This particular study has used PLA-based biodegradable polymer.
The aim of this study was to evaluate the long-term performance profile of a biodegradable polymer DES compared with DP-DES for efficacy and safety, and comparison with thin-strut coated BMS for late safety on a background of dual antiplatelet therapy, including prasugrelThe primary end point was major adverse cardiac eventsThe main secondary end point, the safety end point, was a combination of definite or probable stent thrombosis, myocardial infarction, or cardiac death.
BASKET-PROVE II was a randomized, multicenter, single- and assessor-blind, noninferiority trial with primary end point assessment after 2 yearsEligible patients were presented between April 1, 2010 and May 21, 2012Eight centers in Switzerland, Denmark, Germany, and Austria were contributed patientsA total of 2299 patients were enrolled in the trial.
Eligible patients with chronic or acute coronary artery disease requiring stenting with stents ≥3.0 mm in diameter by visual assessmentPatients were randomized in a 1:1:1 ratio to either: Biolimus-A9–eluting biodegradable polymer stainless steel DES (Nobori), everolimus-eluting DP cobalt-chromium DES (Xience Prime), or a newest-generation thin-strut BMS coated with a biocompatible silicone-carbide layer (prokinetic)Eight hundred patients per group was the primary goal, expecting a loss to follow-up rate of 10%However, actual loss was only 2% and hence 765/arm were includedAll the patients were prescribed acetylsalicylic acid 75–100 mg daily for long-termA loading dose of 60 mg prasugrel with a maintenance dose of 10 mg daily, risk-adjusted to 5 mg in patients aged >75 years, or body weight <60 kgPrasugrel for 12 months after stenting with DES and for patients with acute coronary syndrome and for 4 weeks after elective stenting with BMS.
The sample size for the trial was estimated based on the findings of the BASKET-PROVE trialBased on the BASKET-PROVE results, a noninferiority margin of 3.8% absolute risk difference compared with the DES group was prespecified, considering a 50% relative excess of events or more in the biodegradable polymer biolimus-A9–eluting stent patients as inferiorBaseline characteristics are reported as counts and percentages or means ± standard deviationAll the analyses were performed on the intention-to-treat populationTime-to-event analyses were carried out using the Kaplan–Meier estimator and Cox proportional hazards models, stratifying for the centerAll the analyses were performed by an independent statistical team using the Statistical Software System R, version 3.1.0 (NOBORI stent, Terumo Corp., Japan).
The primary end point occurred in 7.6% of patients receiving biodegradable polymer, 6.8% of those receiving DP, and 12.7% with BMSNoninferiority of the biodegradable polymer stent compared with the DP-DES was established with an absolute risk difference of 0.78% (95% confidence interval [CI], −1.93% to 3.50% P for noninferiority, 0.042)Biodegradable polymer stent was superior to the BMS regarding the primary end point after 2 years (absolute risk difference − 5.16, 95% CI, −8.32 to − 2.01, P + 0.0011)The combined safety end points were not significantly different among the three stent groups.
In the present study, the biodegradable polymer biolimus-A9–eluting stent proved to be as effective and noninferior by intention-to-treat to the best-in-class second-generation DP everolimus-eluting stent to prevent restenosisBiodegradable polymer DES did not further reduce the rate of VLST, myocardial infarction, or cardiac death beyond 1-yearStent thrombosis rates were very low with all three stents, possibly because of the prasugrel based dual antiplatelet therapy in this studySimilar results in DES in 1st year reflect similar antiproliferative efficacy of the different “limus” drugsThe lack of a reduction of VLST with biodegradable polymer observed in this study seems to question the concept that DP are key in late stent thrombosis formationThis study enrolled patients in need of large coronary stents ≥3 mm in diameter, a population expected to have lower restenosis rates and higher rates of myocardial infarction, and death related to stent thrombosis.
The trial was not powered for late safety, the main secondary end pointPresent results suggest that a trial of >20,000 patients would be required to demonstrate a significant benefit of biodegradable polymer DES given the observed differences in VLSTBecause the priori definition of a noninferiority margin is somewhat arbitrary, the authors based their assumptions on the results of the predecessor BASKET-PROVE trial with similar designInconsistent findings for noninferiority depending on whether the intention-to-treat or the per-protocol set was usedFinally, the fact that all the patients were treated with prasugrel-based dual antiplatelet therapy may question the generalizability, regarding VLST and ischemic end points.
No trial evaluating biodegradable polymer versus DP second-generation stents had a primary outcome assessment beyond 1-year up to the present trial Findings of four meta-analyses indicate that the biodegradable polymer DES are superior in efficacy and safety compared with the BMS and first-generation DES ,,,Three meta-analyses found the increased rates of stent thrombosis for biodegradable polymer stents within 1-year, and 2 found a higher myocardial infarction rate, whereas others described the biodegradable polymer stents as noninferior in these outcomesWith respect to the events after 1-year, the conclusions remain vague in view of the lack of direct trial comparisonsBASKET-PROVE II adds important new information: It is the first trial with a 2-year primary endpoint and the first with a BMS control arm.
Apparent noninferiority of biodegradable polymer biolimus-eluting DES compared with DP everolimus-eluting DES in the intention-to-treat analysis confirms the similar findings of early 1-year outcomes and extends them to a 2-year primary assessmentPresent data do not offer any evidence, however, that VLST and related myocardial infarction or cardiac death may be reduced by the biodegradable polymer biolimus-eluting compared to the best-in-class DP everolimus-eluting stentsThese findings challenge the concept that the polymer should be a key in the perceived late deficiency of DP-DES (i.e. their propensity to VLST).
Financial support and sponsorship
Conflicts of interest
There are no conflicts of interest.
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