High Bleeding Risk Patients Treated with Very Thin-Strut Biodegradable Polymer or Thin-Strut Durable Polymer Drug-Eluting Stents in the BIO-RESORT Trial

Purpose: Patients with high bleeding risk (HBR) who undergo percutaneous coronary intervention also have an increased risk of ischemic events and represent an overall high-risk population. The coating of durable polymer drug-eluting stents (DP-DES) may induce inflammation and delay arterial healing, which might be reduced by novel biodegradable polymer DES (BP-DES). We aimed to evaluate the safety and efficacy of treating HBR patients with very thin-strut BP-DES versus thin-strut DP-DES. Methods: Participants in BIO-RESORT (NCT01674803), an investigator-initiated multicenter, randomized all-comers trial, were treated with very thin-strut BP-DES (Synergy or Orsiro) or thin-strut DP-DES (Resolute Integrity). For the present analysis, patients were classified following HBR criteria based on previous trials. The primary endpoint was target vessel failure: a composite of cardiac death, target vessel-related myocardial infarction, or target vessel revascularization at 1 year. Results: Of all 3514 patients, 1009 (28.7%) had HBR. HBR patients were older (p < 0.001) and had more co-morbidities than non-HBR patients (p < 0.001). At 1-year follow-up, HBR patients had significantly higher rates of target vessel failure (6.7 vs. 4.2%, p = 0.003), cardiac death (1.9 vs. 0.4%, p < 0.001), and major bleeding (3.3 vs. 1.5%, p = 0.001). Of all 1009 HBR patients, 673 (66.7%) received BP-DES and 336 (33.3%) had DP-DES. The primary endpoint was met by 43/673 (6.5%) patients treated with BP-DES and 24/336 (7.3%) treated with DP-DES (HR 0.88 [95%CI 0.54–1.46], p = 0.63). There were no significant between-group differences in the most global patient-oriented clinical endpoint (9.7 vs. 10.5%, HR 0.92 [95%CI 0.61–1.39], p = 0.69) and other secondary endpoints. Conclusions: At 1-year follow-up, very thin-strut BP-DES showed similar safety and efficacy for treating HBR patients as thin-strut DP-DES

Evolution of renal function and predictive value of serial renal assessments among patients with acute coronary syndrome:BIOMArCS study

Background: Impaired renal function predicts mortality in acute coronary syndrome (ACS), but its evolution immediately following index ACS and preceding next ACS has not been described in detail. We aimed to describe this evolution using serial measurements of creatinine, glomerular filtration rate [eGFRCr] and cystatin C [CysC]. Methods: From 844 ACS patients included in the BIOMArCS study, we analysed patient-specific longitudinal marker trajectories from the case-cohort of 187 patients to determine the risk of the endpoint (cardiovascular death or hospitalization for recurrent non-fatal ACS) during 1-year follow-up. Study included only patients with eGFRCr ≥ 30 ml/min/1.73 m2. Survival analyses were adjusted for GRACE risk score and based on data >30 days after the index ACS (mean of 8 sample per patient). Results: Mean age was 63 years, 79% were men, 43% had STEMI, and 67% were in eGFR stages 2–3. During hospitalization for index ACS (median [IQR] duration: 5 (3–7) days), CysC levels indicated deterioration of renal function earlier than creatinine did (CysC peaked on day 3, versus day 6 for creatinine), and both stabilized after two weeks. Higher CysC levels, but not creatinine, predicted the endpoint independently of the GRACE score within the first year after index ACS (adjusted HR [95% CI] per 1SD increase: 1.68 [1.03–2.74]). Conclusion: Immediately following index ACS, plasma CysC levels deteriorate earlier than creatinine-based indices do, but neither marker stabilizes during hospitalization but on average two weeks after ACS. Serially measured CysC levels predict mortality or recurrence of ACS during 1-year follow-up independently of patients' GRACE risk score

Bioresorbable Polymer-Coated Orsiro Versus Durable Polymer-Coated Resolute Onyx Stents (BIONYX):Rationale and design of the randomized TWENTE IV multicenter trial

Aim: The aim was to compare in a noninferiority trial the efficacy and safety of 2 contemporary drug-eluting stents (DESs): a novel, durable polymer-coated stent versus an established bioabsorbable polymer-coated stent. Methods and results: The BIONYX trial (ClinicalTrials.gov-no.NCT02508714) is an investigator-initiated, prospective, randomized, patient- and assessor-blinded, international, multicenter study in all-comer patients with all types of clinical syndromes and lesions who require percutaneous coronary interventions with DES. Patients at 7 study sites in the Netherlands, Belgium, and Israel were randomly assigned (1:1, stratified for gender and diabetes mellitus) to treatment with the novel, zotarolimus-eluting, durable polymer-coated Resolute Onyx stent that has a radiopaque, thin-strut, CoreWire stent platform versus the sirolimus-eluting, bioresorbable polymer-coated Orsiro stent (reference device) that has a very thin-strut, cobalt-chromium stent backbone. The primary end point is the 1-year incidence of the composite clinical end point target vessel failure consisting of cardiac death, target vessel–related myocardial infarction, or clinically indicated target vessel revascularization. A power calculation, assuming a target vessel failure rate of 6.0% (noninferiority margin 2.5%), revealed that 2,470 study patients would give the study 80% power (α level 5%), allowing for up to 3% loss to follow-up. The first patient was enrolled on October 7, 2015; on December 23, 2016, the last patient entered the study. Conclusions: BIONYX is a large-scale, prospective, randomized, international, multicenter trial comparing a novel DES with durable coating versus a reference DES with biodegradable coating in all-comers. The study is the first randomized assessment of the Resolute Onyx stent, which is an often-used DES outside the United States

Final 5-Year Report of the Randomized BIO-RESORT Trial Comparing 3 Contemporary Drug-Eluting Stents in All-Comers

BACKGROUND: In a previous trial, higher 5‐year mortality was observed following treatment with biodegradable polymer Orsiro sirolimus‐eluting stents (SES). We assessed 5‐year safety and efficacy of all‐comers as well as patients with diabetes treated with SES or Synergy everolimus‐eluting stents (EES) versus durable polymer Resolute Integrity zotarolimus‐eluting stents (ZES). METHODS AND RESULTS: The randomized BIO‐RESORT (Comparison of Biodegradable Polymer and Durable Polymer Drug‐Eluting Stents in an All Comers Population) trial enrolled 3514 all‐comer patients at 4 Dutch cardiac centers. Patients aged ≥18 years who required percutaneous coronary intervention were eligible. Participants were stratified for diabetes and randomized to treatment with SES, EES, or ZES (1:1:1). The main end point was target vessel failure (cardiac mortality, target vessel myocardial infarction, or target vessel revascularization). Five‐year follow‐up was available in 3183 of 3514 (90.6%) patients. The main end point target vessel failure occurred in 142 of 1169 (12.7%) patients treated with SES, 130 of 1172 (11.6%) treated with EES, versus 157 of 1173 (14.1%) treated with ZES (hazard ratio [HR], 0.89 [95% CI, 0.71–1.12], P (log‐rank)=0.31; and HR, 0.82 [95% CI, 0.65–1.04], P (log‐rank)=0.10, respectively). Individual components of target vessel failure showed no significant between‐stent difference. Very late definite stent thrombosis rates were low and similar (SES, 1.1%; EES, 0.6%; ZES, 0.9%). In patients with diabetes, target vessel failure did not differ significantly between stent‐groups (SES, 19.8%; EES, 19.2%; versus ZES, 21.1% [P (log‐rank)=0.69 and P (log‐rank)=0.63]). CONCLUSIONS: Orsiro SES, Synergy EES, and Resolute Integrity ZES showed similar 5‐year outcomes of safety and efficacy, including mortality. A prespecified stent comparison in patients with diabetes also revealed no significant differences in 5‐year clinical outcomes. REGISTRATION: URL: https://www.clinicaltrials.gov; Unique identifier: NCT01674803

Serially measured high-sensitivity cardiac troponin T, N-terminal-pro-B-type natriuretic peptide, high-sensitivity C-reactive protein, and growth differentiation factor 15 for risk assessment after acute coronary syndrome: the BIOMArCS cohort

Aims: Evidence regarding the role of serial measurements of biomarkers for risk assessment in post-acute coronary syndrome (ACS) patients is limited. The aim was to explore the prognostic value of four, serially measured biomarkers in a large, real-world cohort of post-ACS patients.// Methods and results: BIOMArCS is a prospective, multi-centre, observational study in 844 post-ACS patients in whom 12 218 blood samples (median 17 per patient) were obtained during 1-year follow-up. The longitudinal patterns of high-sensitivity cardiac troponin T (hs-cTnT), N-terminal-pro-B-type natriuretic peptide (NT-proBNP), high-sensitivity C-reactive protein (hs-CRP), and growth differentiation factor 15 (GDF-15) were analysed in relation to the primary endpoint (PE) of cardiovascular mortality and recurrent ACS using multivariable joint models. Median age was 63 years, 78% were men and the PE was reached by 45 patients. The average biomarker levels were systematically higher in PE compared with PE-free patients. After adjustment for 6-month post-discharge Global Registry of Acute Coronary Events score, 1 standard deviation increase in log[hs-cTnT] was associated with a 61% increased risk of the PE [hazard ratio (HR) 1.61, 95% confidence interval (CI) 1.02–2.44, P = 0.045], while for log[GDF-15] this was 81% (HR 1.81, 95% CI 1.28–2.70, P = 0.001). These associations remained significant after multivariable adjustment, while NT-proBNP and hs-CRP were not. Furthermore, GDF-15 level showed an increasing trend prior to the PE (Structured Graphical Abstract).// Conclusion: Longitudinally measured hs-cTnT and GDF-15 concentrations provide prognostic value in the risk assessment of clinically stabilized patients post-ACS.// Clinical Trial Registration: The Netherlands Trial Register. Currently available at URL https://trialsearch.who.int/; Unique Identifiers: NTR1698 and NTR1106

Serially measured high-sensitivity cardiac troponin T, N-terminal-pro-B-type natriuretic peptide, high-sensitivity C-reactive protein, and growth differentiation factor 15 for risk assessment after acute coronary syndrome:the BIOMArCS cohort

Aims: Evidence regarding the role of serial measurements of biomarkers for risk assessment in post-acute coronary syndrome (ACS) patients is limited. The aim was to explore the prognostic value of four, serially measured biomarkers in a large, real-world cohort of post-ACS patients. Methods and results: BIOMArCS is a prospective, multi-centre, observational study in 844 post-ACS patients in whom 12 218 blood samples (median 17 per patient) were obtained during 1-year follow-up. The longitudinal patterns of high-sensitivity cardiac troponin T (hs-cTnT), N-terminal-pro-B-type natriuretic peptide (NT-proBNP), high-sensitivity C-reactive protein (hs-CRP), and growth differentiation factor 15 (GDF-15) were analysed in relation to the primary endpoint (PE) of cardiovascular mortality and recurrent ACS using multivariable joint models. Median age was 63 years, 78% were men and the PE was reached by 45 patients. The average biomarker levels were systematically higher in PE compared with PE-free patients. After adjustment for 6-month post-discharge Global Registry of Acute Coronary Events score, 1 standard deviation increase in log[hs-cTnT] was associated with a 61% increased risk of the PE [hazard ratio (HR) 1.61, 95% confidence interval (CI) 1.02-2.44, P = 0.045], while for log[GDF-15] this was 81% (HR 1.81, 95% CI 1.28-2.70, P = 0.001). These associations remained significant after multivariable adjustment, while NT-proBNP and hs-CRP were not. Furthermore, GDF-15 level showed an increasing trend prior to the PE (Structured Graphical Abstract). Conclusion: Longitudinally measured hs-cTnT and GDF-15 concentrations provide prognostic value in the risk assessment of clinically stabilized patients post-ACS. Clinical Trial Registration: The Netherlands Trial Register. Currently available at URL https://trialsearch.who.int/; Unique Identifiers: NTR1698 and NTR1106.</p

Impact of premature coronary artery disease on adverse event risk following first percutaneous coronary intervention

ObjectivesWe assessed differences in risk profile and 3-year outcome between patients undergoing percutaneous coronary intervention (PCI) for premature and non-premature coronary artery disease (CAD).BackgroundThe prevalence of CAD increases with age, yet some individuals develop obstructive CAD at younger age.MethodsAmong participants in four randomized all-comers PCI trials, without previous coronary revascularization or myocardial infarction (MI), we compared patients with premature (men &lt;50 years; women &lt;55 years) and non-premature CAD. Various clinical endpoints were assessed, including multivariate analyses.ResultsOf 6,171 patients, 887(14.4%) suffered from premature CAD. These patients had fewer risk factors than patients with non-premature CAD, but were more often smokers (60.7% vs. 26.4%) and overweight (76.2% vs. 69.8%). In addition, premature CAD patients presented more often with ST-segment elevation MI and underwent less often treatment of multiple vessels, and calcified or bifurcated lesions. Furthermore, premature CAD patients had a lower all-cause mortality risk (adj.HR:0.23, 95%-CI: 0.10–0.52; p &lt; 0.001), but target vessel revascularization (adj.HR:1.63, 95%-CI: 1.18–2.26; p = 0.003) and definite stent thrombosis risks (adj.HR:2.24, 95%-CI: 1.06–4.72; p = 0.034) were higher. MACE rates showed no statistically significant difference (6.6% vs. 9.4%; adj.HR:0.86, 95%-CI: 0.65–1.16; p = 0.33).ConclusionsAbout one out of seven PCI patients was treated for premature CAD. These patients had less complex risk profiles than patients with non-premature CAD; yet, their risk of repeated revascularization and stent thrombosis was higher. As lifetime event risk of patients with premature CAD is known to be particularly high, further efforts should be made to improve modifiable risk factors such as smoking and overweight.Clinical Trial Registration[clinicaltrials.gov], TWENTE [NCT01066650]; DUTCH PEERS [NCT01331707]; BIO-RESORT [NCT01674803]; BIONYX [NCT02508714]