Marlies M. Kok

Five-year outcome after implantation of zotarolimus- and everolimus-eluting stents in randomized trial participants and nonenrolled eligible patients : A secondary analysis of a randomized clinical trial

Importance Long-term follow-up after a clinical trial of 2 often-used, newer-generation drug-eluting stents (DESs) in a broad patient population is of interest. Comprehensive long-term outcome of eligible nonenrolled patients has never been reported. Objective To assess 5-year safety and efficacy of 2 newer-generation DESs in randomized participants with non–ST-elevation acute coronary syndromes or stable angina and to evaluate long-term outcomes of nonenrolled eligible patients treated with the same DESs. Design, Setting, and Participants The TWENTE (Real-World Endeavor Resolute vs Xience V Drug-Eluting Stent Study in Twente) trial is an investigator-initiated, patient-blinded, randomized, comparative DES trial that enrolled patients from June 18, 2008, to August 26, 2010. Most patients had non–ST-elevation acute coronary syndromes and complex lesions. Of all 1709 eligible patients, 1391 (81.4%) were treated in the TWENTE trial with zotarolimus-eluting (ZES, n = 697) or everolimus-eluting (EES, n = 694) cobalt-chromium stents. The remaining 318 eligible patients (18.6%) were not enrolled but underwent nonrandomized treatment with the same DESs. Data were analyzed from August 26, 2015, to October 11, 2016. Event rates (percentages) were derived from log-rank analysis and may differ from straightforward calculation (nominator/denominator). The 5-year follow-up of the TWENTE participants was prespecified in the trial protocol; that of the nonenrolled participants was ad hoc. Main Outcomes and Measures Target vessel failure (TVF), a composite of cardiac death, target vessel–related myocardial infarction, or target vessel revascularization. Results Of 1709 eligible participants, 1233 (72.1%) were men, 476 (27.9%) were women, and mean (SD) age was 64.6 (10.6) years. Among the 1370 of 1391 TWENTE trial participants (98.5% follow-up), TVF was similar between those in the ZES (16.1%) and EES (18.1%) groups (P = .36). Stent thrombosis rates were low: definite (7 of 697 [1.0%] vs 4 of 694 [0.6%]; P = .37) and occurred after more than 1 year in 3 (0.4%) with ZES vs 4 (0.6%) with EES (P = .69). The 318 nonenrolled eligible patients (308 patients [96.9%] of whom were followed up) were older and had more advanced disease than trial participants. Their TVF rate was higher than that of trial participants (71 of 318 [23.3%] vs 233 of 1391 [17.1%]; P = .02), which partly reflects a difference in cardiac mortality (23 of 318 [7.7%] vs 60 of 1391 [4.5%]; P = .03). Similar 5-year rates were found for myocardial infarction (91 of 1391 [6.7%] vs 22 of 318 [7.2%]; P = .80) and target vessel revascularization (129 of 1391 [9.7%] vs 34 of 318 [11.4%]; P = .36) between trial participants and nonenrolled eligible patients. In all eligible patients (ie, trial participants plus nonenrolled eligible patients), the TVF rate was only slightly higher than in trial participants only (18.3% vs 17.1%). Conclusions and Relevance Long-term outcome data from nonenrolled eligible patients support the validity of the TWENTE trial findings and present, with the trial, a strong case for the long-term safety and efficacy of the newer-generation DESs used. Trial Registration clinicaltrials.gov Identifier: NCT01066650

Impact of severe lesion calcification on clinical outcome of patients with stable angina, treated with newer generation permanent polymer-coated drug-eluting stents: A patient-level pooled analysis from TWENTE and DUTCH PEERS (TWENTE II)

BACKGROUND The outcome of percutaneous coronary intervention with newer generation permanent polymer-coated drug-eluting stents (DES) in patients with severely calcified lesions is greatly unknown. We assessed the impact of severe lesion calcification on clinical outcome in patients with stable angina who underwent percutaneous coronary intervention with newer generation DES. METHODS TWENTE and DUTCH PEERS randomized trials enrolled 1423 patients with stable angina, who were categorized into patients with versus without severe target lesion calcification. A patient-level pooled analysis assessed clinical outcome, including target vessel failure (TVF), a composite of cardiac death, target vessel-related myocardial infarction, or target vessel revascularization (TVR). RESULTS Patients with severe calcification (n = 342) were older (66.6 ± 9.1 vs 64.2 ± 9.8 years, P < .001) and had more diabetes (25.7% vs 20.4%, P = .04) than other patients (n = 1081). Patients with calcified lesions had higher rates of TVF (16.4% vs 9.8%, pLogrank = .001), cardiac death (4.4% vs 1.5%, P = .03), target vessel myocardial infarction (7.6% vs 3.4%, P = .001), and definite stent thrombosis (1.8% vs 0.4%, P = .02). Multivariate analysis demonstrated that severe calcification was an independent risk factor of 2-year TVF (HR 1.42, 95% CI: 1.02-1.99, pLogrank = .04); landmark analysis showed that this was based on a difference during the first year (periprocedural: 5.8% vs. 3.1%, pLogrank = .02; first year: 7.5% vs. 3.8%, pLogrank = .007; second year: 4.1% vs. 3.3%, pLogrank = .54). CONCLUSION In patients with stable angina, severe target lesion calcification is associated with an increased risk of adverse cardiovascular events following treatment with newer generation permanent polymer-coated DES. This increase in risk is restricted to the first year of follow-up, which is an encouraging finding.

Three-year clinical outcome of patients with bifurcation treatment with second-generation Resolute and Xience V stents in the randomized TWENTE trial

BACKGROUND Only limited data from large randomized clinical trials have been published on the long-term performance of second-generation drug-eluting stents in bifurcation lesions. METHODS We investigated in patients in the randomized TWENTE trial the long-term safety and efficacy of treating bifurcation lesions with 2 widely applied second-generation drug-eluting stents, the zotarolimus-eluting Resolute stent (Medtronic Inc, Santa Rosa, CA) and the everolimus-eluting Xience V stent (Abbott Vascular, Santa Clara, CA). Three-year follow-up was available in 99.3%. Patients were categorized into treatment for ≥1 bifurcation lesion versus treatment for nonbifurcation lesions only. RESULTS Among the 1,391 patients of the TWENTE trial, 362 (26%) were treated for bifurcation lesions. At 3-year follow-up, target-vessel failure did not differ between patients treated for bifurcation versus nonbifurcation lesions (13.1% vs 12.6%; P = .84), whereas the periprocedural myocardial infarction rate was higher in patients with bifurcation lesions (6.9% vs 3.1%; P < .01). Of the 362 patients with bifurcation lesion treatment, 179 (49.4%) were treated with Resolute and 183 (50.6%) with Xience V. There was no significant difference in target-vessel failure between the Resolute and Xience V groups with bifurcation treatment (13.6% vs 12.6%; P = .78), and their incidence of definite-or-probable stent thrombosis was low and similar (1.1% vs 0.5%, respectively; P = .62). CONCLUSION Despite a significant difference in periprocedural myocardial infarction, 3-year clinical outcome after implantation of second-generation stents was favorable and similar for patients with and without bifurcation lesions. In addition, we observed no difference in long-term clinical outcome after bifurcation lesion treatment with Resolute and Xience V stents.

Patient preference for radial versus femoral vascular access for elective coronary procedures: The PREVAS study

To explore patient preference for vascular access site in percutaneous coronary procedures, the perceived importance of benefits and risks of transradial access (TRA) and transfemoral access (TFA) were assessed. In addition, direct preference for vascular access and preference for shared decision making (SDM) were evaluated.

Sex Difference in Chest Pain After Implantation of Newer Generation Coronary Drug-Eluting Stents: A Patient-Level Pooled Analysis From the TWENTE and DUTCH PEERS Trials

OBJECTIVES This study sought to assess sex differences in chest pain after percutaneous coronary intervention (PCI) with newer generation drug-eluting stents (DES). BACKGROUND Sex-based data on chest pain after PCI with DES are scarce. METHODS The authors performed a patient-level pooled analysis of the TWENTE and DUTCH PEERS randomized trials, in which patients were treated with newer generation permanent polymer-coated DES. At 1 and 2 years, clinical follow-up was available in 99.8% and patient-reported chest pain data in 94.1% and 93.6%, respectively. RESULTS Among all 3,202 patients, the 871 (27.2%) women were older (67.5 ± 10.2 years vs. 62.8 ± 10.6 years; p < 0.001) and had more cardiovascular risk factors: diabetes (24.2% vs. 17.8%; p < 0.001), hypertension (63.6% vs. 51.6%; p < 0.001), and positive family history (54.5% vs. 50.1%; p = 0.03). At 1- and 2-year follow-up, women reported more clinically relevant chest pain (16.3% vs. 10.5%; p < 0.001, and 17.2% vs. 11.1%; p < 0.001, respectively). Multivariate analysis demonstrated that female sex independently predicted clinically relevant chest pain at 1- and 2-year follow-up both during daily activities and at minimum physical exertion/at rest (1 year adjusted odds ratio [OR]: 1.7; 95% confidence interval [CI]: 1.2 to 2.4; p = 0.002; and adjusted OR: 1.8; 95% CI: 1.3 to 2.5; p < 0.001; 2-year adjusted OR: 1.8; 95% CI: 1.3 to 2.6; p < 0.001; and adjusted OR: 1.7; 95% CI: 1.3 to 2.3; p = 0.001). Nevertheless, the 2-year rates of death, myocardial infarction, revascularization, stent thrombosis, and various composite clinical endpoints were similar for both sexes. CONCLUSIONS Although the incidence of adverse cardiovascular events was low and similar for both sexes, women showed a statistically significantly higher prevalence of clinically relevant chest pain, which might be largely related to mechanisms other than epicardial coronary obstruction.

High bleeding risk patients with acute coronary syndromes treated with contemporary drug-eluting stents and Clopidogrel or Ticagrelor: Insights from CHANGE DAPT

BACKGROUND The prospective observational CHANGE DAPT study compared clopidogrel versus ticagrelor-based dual antiplatelet (DAPT) regimens in consecutive patients with acute coronary syndrome (ACS), treated with percutaneous coronary intervention (PCI) with contemporary drug-eluting stents (DES). During the ticagrelor period (TP, May 2014-August 2015) there were more major bleedings than during the clopidogrel period (CP, December 2012-April 2014). METHODS AND RESULTS To evaluate whether the excess of major bleedings during TP may be limited to high bleeding risk (HBR) patients, we performed an explorative analysis of all 2062 CHANGE DAPT participants, of whom 547(26.5%) were classified as HBR (CP, n = 245; TP, n = 302). In HBR and non-HBR patients, we assessed the impact of CP versus TP on propensity score-adjusted rates of major bleeding and a pre-defined ischemic endpoint (composite of cardiac death, myocardial infarction, or stroke) at 1-year follow-up. Among HBR patients, the rate of major bleeding was significantly higher during TP (1.7% vs. 5.0%; HRadjusted 3.70 [95% CI 1.18-11.67], p = 0.03), while there was no significant difference in the ischemic endpoint (6.6% vs. 8.0%, HRadjusted 1.23 [95% CI 0.63-2.42], p = 0.54). In non-HBR patients, the rates of major bleeding (1.1% vs. 1.7%; HRadjusted 2.13 [95% CI 0.84-5.43], p = 0.11) and the ischemic endpoint (2.8% vs. 3.4%, HRadjusted 1.38 [95% CI 0.74-2.57], p = 0.32) were similar between both periods. CONCLUSIONS Among consecutive ACS patients, the increased risk of major bleeding during ticagrelor-based DAPT was limited to HBR patients. In both HBR and non-HBR patients, ticagrelor-based DAPT did not reduce ischemic outcomes following treatment with contemporary DES implantation.

Three-Year Clinical Outcome of Patients with Coronary Disease and Increased Event Risk Treated with Newer-Generation Drug-Eluting Stents: From the Randomized DUTCH PEERS Trial

Objective: Limited data is available on the long-term outcome of patients with increased cardiovascular event risk, treated with newer-generation durable polymer drug-eluting stents (DES). Methods: We therefore assessed 3-year follow-up data of high-risk versus low- to intermediate-risk patients of the randomized DUTCH PEERS trial (NCT01331707). In both risk groups we also compared patients treated with Resolute Integrity versus Promus Element DES. Patients were categorized as “high-risk” if they met ≥1 of the following criteria: (1) diabetes (17.9%); (2) previous myocardial infarction (21.9%); (3) previous coronary revascularization (25.8%); (4) chronic renal failure (3.5%); (5) left ventricular ejection fraction ≤30% (1.5%); and (6) age ≥75 years (17.3%). Results: At the 3-year follow-up, the incidence of the composite endpoint target vessel failure (TVF) (13.2 vs. 7.5%; logrank p < 0.001) and 2 of its components - cardiac death (4.7 vs. 1.5%; logrank p < 0.001) and target vessel revascularization (7.3 vs. 4.7%; logrank p = 0.03) - was higher in high-risk (n = 957) versus low- to intermediate-risk patients (n = 854). Among high-risk patients, treatment with Resolute Integrity (n = 481) and Promus Element stents (n = 476) was similarly safe and efficacious (TVF: 13.3 vs. 13.1%; logrank p = 0.95; definite-or-probable stent thrombosis: 1.7 vs. 1.7%; logrank p = 1.00). Conclusions: The newer-generation Resolute Integrity and Promus Element stents showed similar results in terms of safety and efficacy for treating high-risk patients, who had significantly higher event rates than patients with low-to-intermediate risk.

Two-year outcome after treatment of severely calcified lesions with newer-generation drug-eluting stents in acute coronary syndromes: A patient-level pooled analysis from TWENTE and DUTCH PEERS

BACKGROUND Data on medium-term outcome of patients with acute coronary syndrome (ACS), treated with newer-generation durable polymer drug-eluting stents (DES) in severely calcified coronary lesions, are scarce. We aimed to assess the impact of severe coronary lesion calcification on clinical outcome of patients with ACS, treated with newer-generation DES. METHODS The TWENTE and DUTCH PEERS randomized trials comprise 1779 ACS patients, who were categorized into patients with versus without severe target lesion calcification. We performed a patient-level pooled analysis to assess 2-year outcome, including target vessel failure (TVF), a composite of cardiac death, target vessel-related myocardial infarction (MI), or target vessel revascularization (TVR). RESULTS Patients with severe target lesion calcification (n=340, 19.1%) were older (66.8±10.6 years vs. 62.8±11.5 years, p<0.001) and had more often diabetes (22.1% vs. 16.8%, p=0.02) and hypercholesterolemia (51.5% vs. 42.9%, p=0.005) than other patients (n=1439, 79.9%). In addition they showed a higher TVF rate (12.4% vs.7.0%, p=0.001), mainly related to a difference in TVR (6.8% vs. 3.3%, p=0.003). There was a borderline significant between-group difference in cardiac death (3.6% vs. 1.8%, p=0.05), but not in target vessel MI (3.8% vs.2.6%, p=0.23) and definite stent thrombosis (0.9% vs. 0.6%, p=0.71). Multivariate analysis demonstrated that severe lesion calcification was an independent risk factor of TVF (adjusted HR; 1.58, 95% CI: 1.23-2.03; p<0.001). CONCLUSIONS In patients with ACS, treatment of severely calcified lesions with newer-generation DES was associated with an overall higher clinical event risk - related in particular to a higher TVR rate, while the risk of MI was low.

Clinical outcomes after percutaneous coronary intervention with the COMBO stent versus Resolute Integrity and PROMUS Element stents: a propensity-matched analysis

AIMS The COMBO stent combines sirolimus elution with an endothelial progenitor cell-capturing layer to promote early endothelialisation. There has not been a head-to-head comparison of this novel device with any other currently used drug-eluting stent (DES). We sought to compare clinical outcome at two years after COMBO stent placement with the Resolute Integrity or PROMUS Element stent in an all-comers cohort. METHODS AND RESULTS Patients from the REMEDEE registry (COMBO, n=1,000) were matched with patients from the DUTCH PEERS trial (PROMUS Element/Resolute Integrity, n=1,811). Propensity score matching on 13 baseline characteristics was applied to create two balanced cohorts of patients treated with COMBO versus PROMUS Element/Resolute Integrity. Propensity score matching yielded 771 patient pairs, representing all-comers patients, with a median age of 65 years, 27% female and more than 50% of patients presenting with acute coronary syndrome. Target lesion failure (TLF), a composite of cardiac death, target vessel MI and any target lesion revascularisation, at two-year follow-up was 7.9% in COMBO and 6.4% in PROMUS Element/Resolute Integrity, HR 1.24 (95% CI: 0.85-1.81), p=0.26. Definite stent thrombosis (ST) was not significantly different between groups (0.8% vs. 0.9%, p=0.79). CONCLUSIONS In a propensity-matched analysis, the COMBO stent showed similar rates of TLF and ST at two-year follow-up compared to Resolute Integrity and PROMUS Element.

Patient preference regarding assessment of clinical follow-up after percutaneous coronary intervention: the PAPAYA study.

AIMS To keep patients in long-term clinical follow-up programmes after percutaneous coronary intervention (PCI), knowledge of the patient-preferred mode for follow-up assessment is crucial. We systematically assessed patient preference, and explored potential relationships with age and gender. METHODS AND RESULTS In the prospective, observational PAPAYA study (ClinicalTrials.gov: NCT02189070), 2,566 patients, treated by PCI between June 2008 and May 2012, were invited to participate in a postal survey on the patient-preferred mode (postal questionnaire, telephone or e-mail consultation) and frequency of follow-up assessment. A total of 1,797 (70.0%) patients responded. The vast majority preferred completing postal questionnaires (1,248 [69.9%]) as compared to telephone (240 [13.4%]) or e-mail-based approaches (227 [12.7%]) (p<0.001). With increasing age, there was a gradual decline in preference for e-mail (p<0.001); the youngest patients (≤60 years) preferred e-mail-based follow-up more often than the oldest (21.1% vs. 3.1%). Nevertheless, 79.9% of the youngest preferred to be approached in ways other than by e-mail. Women more often preferred approaches other than e-mail (94.1% vs. 87.3%, p<0.001). CONCLUSIONS Patients showed a distinct preference for completing postal questionnaires rather than being approached by telephone or e-mail. Younger patients accepted e-mail-based follow-up more often, but the majority of the youngest patients still preferred approaches other than by e-mail.