Impact of preprocedural left ventricular systolic function on the safety and durability of percutaneous coronary intervention.

BACKGROUND: Percutaneous coronary intervention (PCI) is considered less safe in patients with reduced ejection fraction (EF), an impression based on older data. Whether the safety and durability of contemporary PCI are different in patients with reduced EF compared with normal EF patients is unknown. METHODS: Patients from the BIOFLOW II, IV and V clinical trials were grouped as normal EF (≥50%) and reduced EF (30%-50%). Using multivariable logistic regression and cox proportional hazards regression, we determined relations of EF category with procedural safety (a composite of cardiac death, myocardial infarction, stroke and urgent coronary artery bypass grafting within 30 days of PCI) and target lesion failure (TLF; comprising cardiac death, target vessel myocardial infarction, target vessel revascularization within 1 year of PCI) respectively. In sensitivity analyses, we regrouped patients into EF < 45% and ≥55% and repeated the aforementioned analyses. RESULTS: In 1685 patients with normal EF (mean age 65 years; 27% women; mean EF 61%) and 259 with low EF (mean age 64 years; 17% women; mean EF 41%), 101 safety and 148 TLF events occurred. Compared with patients in the normal EF group, those with reduced EF had neither a statistically significant higher proportion of safety events, nor a higher multivariable-adjusted risk for such events. Similarly, patients with reduced EF and normal EF did not differ in terms of TLF event proportions or multivariable-adjusted risk for TLF. The results were similar in sensitivity analyses with EF groups redefined to create a 10% between-group EF separation. CONCLUSION: PCI safety and durability outcomes are similar in patients with mild-moderately reduced EF and normal EF.

Percutaneous coronary intervention in patients undergoing transcatheter aortic valve implantation: a systematic review and meta-analysis.

OBJECTIVE: The importance of revascularisation of significant coronary artery disease (CAD) in patients undergoing transcatheter aortic valve implantation (TAVI) is unclear. Despite the lack of randomised controlled trials comparing different revascularisation strategies, guidelines currently recommend percutaneous coronary intervention (PCI) in patients with significant proximal CAD undergoing TAVI. METHODS: In this systematic review and meta-analysis, a systematic search was conducted to identify studies comparing TAVI with and without PCI in patients with significant CAD on pre-TAVI coronary angiography. Endpoints were all-cause mortality, cardiac death, stroke, myocardial infarction and major bleeding. RESULTS: In total, 14 studies were included, involving 3838 patients, of whom 1806 (47%) underwent PCI before TAVI. All-cause mortality did not differ significantly between TAVI with and without preceding PCI at 30 days, 1 year and > 1 year. There were no significant differences in risk of cardiac death, stroke or myocardial infarction between the groups. However, TAVI performed with PCI resulted in a higher risk of major bleeding within 30 days after TAVI (odds ratio: 0.66; 95% confidence interval: 0.46-0.94). CONCLUSION: This systematic review and meta-analysis showed no significant differences in clinical outcomes between patients with concomitant significant CAD who were treated with TAVI with and without preceding PCI at both short- and long-term follow-up. However, there was a higher risk of major bleeding at 30 days in patients undergoing TAVI with preceding PCI. In the context of serious risk of bias in the included studies, results of randomised controlled trials are warranted.

Targeted therapy with a localised abluminal groove, low-dose sirolimus-eluting, biodegradable-polymer coronary stent - five-year results of the TARGET All Comers randomised clinical trial.

BACKGROUND: In the prospective, multicentre, randomised TARGET All Comers study, percutaneous coronary intervention (PCI) with the FIREHAWK biodegradable-polymer sirolimus-eluting stent (BP-SES) was non-inferior to the durable-polymer everolimus-eluting stent (DP-EES) for the primary endpoint of target lesion failure (TLF) at 12 months. AIMS: We aimed to report the final study outcomes at 5 years. METHODS: Patients referred for PCI were randomised to receive either a BP-SES or DP-EES in a 1:1 ratio in 10 European countries. Randomisation was stratified by centre and ST-elevation myocardial infarction (STEMI) presentation, and clinical follow-up extended to 5 years. The primary endpoint was TLF (composite of cardiac death, target vessel myocardial infarction [MI], or ischaemia-driven target lesion revascularisation). Secondary endpoints included patient-oriented composite events (POCE; composite of all-cause death, all MI, or any revascularisation and its components). RESULTS: From December 2015 to October 2016, 1,653 patients were randomly assigned to the BP-SES or DP-EES groups, of which 93.8% completed 5-year clinical follow-up or were deceased. At 5 years, TLF occurred in 17.1% of the BP-SES group and in 16.3% of the DP-EES group (p=0.68). POCE occurred in 34.0% of the BP-SES group and 32.7% of the DP-EES group (p=0.58). Revascularisation was the most common POCE, occurring in 19.3% of patients receiving BP-SES and 19.2% receiving DP-EES, of which less than one-third was ischaemia-driven target lesion-related. In the landmark analysis, there were no differences in the rates of TLF and POCE between groups from 1 to 5 years, and these results were consistent across all subgroups. CONCLUSIONS: In an all-comers population requiring stent implantation for myocardial ischaemia, the BP-SES was non-inferior to the DP-EES for the primary endpoint of TLF at 12 months, and results were sustained at 5 years, confirming the long-term safety and efficacy of the FIREHAWK BP-SES.

EXpansion of stents after intravascular lithoTripsy versus conventional predilatation in CALCified coronary arteries.

BACKGROUND: Coronary artery calcification is a strong predictor for procedural failure and is independently associated with adverse events after percutaneous coronary intervention (PCI). An important contributor to the impaired outcome is the inability to achieve optimal results due to stent underexpansion or stent deformation/fracture. Intravascular lithotripsy (IVL) has emerged as an alternative technique to change the integrity of calcified plaques. AIMS: Our aim was to investigate if pre-treatment with IVL in severely calcified lesions increases stent expansion, assessed by optical coherence tomography (OCT), when compared to predilatation with conventional and/or specialty balloon strategy. METHODS: EXIT-CALC was a prospective, single-centre, randomised controlled study. Patients with an indication for PCI and severe calcification of the target lesion were allocated to predilatation with conventional angioplasty balloons or pre-treatment with IVL, followed by drug-eluting stenting and mandatory postdilatation. Primary endpoint was stent expansion assessed by OCT. Secondary endpoints were the occurrence of peri-procedural events and major adverse cardiac events (MACE) in hospital and during follow-up. RESULTS: A total of 40 patients were included. The minimal stent expansion in the IVL-group (n = 19) was 83.9 ± 10.3% and 82.2 ± 11.5% in the conventional group (n = 21) (p = 0.630). Minimal stent area was 6.6 ± 1.5 mm2 and 6.2 ± 1.8 mm2, respectively (p = 0.406). No peri-procedural, in-hospital and 30-day follow-up MACE were reported. CONCLUSIONS: In severely calcified coronary lesions we found no significant difference in stent expansion measured by OCT when comparing IVL, as plaque modification, with conventional and/or specialty angioplasty balloons.

Ticagrelor Monotherapy or Dual Antiplatelet Therapy After Drug-Eluting Stent Implantation: Per-Protocol Analysis of the GLOBAL LEADERS Trial.

Background In the GLOBAL LEADERS trial, ticagrelor monotherapy beyond 1 month compared with standard antiplatelet regimens after coronary stent implantation did not improve outcomes at intention-to-treat analysis. Considerable differences in treatment adherence between the experimental and control groups may have affected the intention-to-treat results. In this reanalysis of the GLOBAL LEADERS trial, we compared the experimental and control treatment strategies in a per-protocol analysis of patients who did not deviate from the study protocol. Methods and Results Baseline and postrandomization information were used to classify whether and when patients were deviating from the study protocol. With logistic regressions, we derived time-varying inverse probabilities of nondeviation from protocol to reconstruct the trial population without protocol deviation. The primary end point was a composite of all-cause mortality or nonfatal Q-wave myocardial infarction at 2 years. At 2-year follow-up, 1103 (13.8%) of 7980 patients in the experimental group and 785 (9.8%) of 7988 patients in the control group qualified as protocol deviators. At per-protocol analysis, the rate ratio for the primary end point was 0.88 (95% CI, 0.75-1.03; P=0.10) on the basis of 274 versus 325 events in the experimental versus control group. The rate ratio for the key safety end point of major bleeding was 1.00 (95% CI, 0.79-1.26; P=0.99). The per-protocol and intention-to-treat effect estimates were overall consistent. Conclusions Among patients who complied with the study protocol in the GLOBAL LEADERS trial, ticagrelor plus aspirin for 1 month followed by ticagrelor monotherapy was not superior to 1-year standard dual antiplatelet therapy followed by aspirin alone at 2 years after coronary stenting. Registration URL: https://www.clinicaltrials.gov; Unique identifier: NCT01813435.

PRECISE-DAPT score for bleeding risk prediction in patients on dual or single antiplatelet regimens: insights from the GLOBAL LEADERS and GLASSY.

AIMS: The five-item PRECISE-DAPT, integrating age, haemoglobin, white-blood-cell count, creatinine clearance, and prior bleeding, predicts bleeding risk in patients on dual antiplatelet therapy (DAPT) after stent implantation. We sought to assess whether the bleeding risk prediction offered by the PRECISE-DAPT remains valid among patients receiving ticagrelor monotherapy from 1 month onwards after coronary stenting instead of standard DAPT and having or not having centrally adjudicated bleeding endpoints. METHODS AND RESULTS: The PRECISE-DAPT was calculated in 14 928 and 7134 patients from GLOBAL LEADERS and GLASSY trials, respectively. The ability of the score to predict Bleeding Academic Research Consortium 3 or 5 bleeding was assessed and compared among patients on ticagrelor monotherapy (experimental strategy) or standard DAPT (reference strategy) from 1 month after drug-eluting stent implantation. Bleeding endpoints were investigator-reported or centrally adjudicated in GLOBAL LEADERS and GLASSY, respectively. At 2 years, the c-indexes for the score among patients treated with the experimental or reference strategy were 0.67 [95% confidence interval (CI): 0.63-0.71] vs. 0.63 (95% CI: 0.59-0.67) in GLOBAL LEADERS (P = 0.27), and 0.67 (95% CI: 0.61-0.73) vs. 0.66 (95% CI: 0.61-0.72) in GLASSY (P = 0.88). Decision curve analysis showed net benefit using the PRECISE-DAPT to guide bleeding risk assessment under both treatment strategies. Results were consistent between investigator-reported and adjudicated endpoints and using the simplified four-item PRECISE-DAPT. CONCLUSION: The PRECISE-DAPT offers a prediction model that proved similarly effective to predict clinically relevant bleeding among patients on ticagrelor monotherapy from 1 month after coronary stenting compared with standard DAPT and appears to be unaffected by the presence or absence of adjudicated bleeding endpoints.

Two-Year Clinical Outcomes of the REVELATION Study: Sustained Safety and Feasibility of Paclitaxel-Coated Balloon Angioplasty Versus Drug-Eluting Stent in Acute Myocardial Infarction.

OBJECTIVES: The randomized REVELATION (REVascularization With PaclitaxEL-Coated Balloon Angioplasty Versus Drug-Eluting Stenting in Acute Myocardial InfarcTION) trial showed that in the setting of ST-segment elevation myocardial infarction (STEMI), a drug-coated balloon (DCB) strategy was non-inferior to a drug-eluting stent (DES) strategy in terms of fractional flow reserve assessed at 9 months. The aim of the present study is to evaluate the long-term clinical outcome of this treatment strategy. METHODS: Between October 2014 and November 2017, a total of 120 patients with a non-severely calcified culprit lesion in a native coronary artery and a residual stenosis of <50% after predilation were randomized to treatment with DCB or DES. Primary clinical endpoint was the occurrence of major adverse cardiac events, defined as death, recurrent myocardial infarction, or target-lesion revascularization, the occurrence of definite ST, and non-coronary artery bypass grafting (CABG) major bleeding. RESULTS: Complete clinical follow-up at 2 years was available for 109 patients (91%). A major adverse cardiac event occurred in 3 patients (5.4%) in the DCB group and 1 patient (1.9%) in the DES group (hazard ratio, 2.86; 95% confidence interval, 0.30-27.53; P=.34). Between 9 months and 2 years, only 1 additional event occurred (target-lesion revascularization in a patient randomized to DCB). CONCLUSION: In this randomized study of DCB vs DES in selected patients presenting with STEMI, 2-year clinical outcome was excellent and comparable between the DCB and DES groups.

One-year mortality in NSTEMI patients is unaffected by timing of PCI within the first week of admission: Results of a real-world cohort analysis.

OBJECTIVES: We aimed to explore the impact of time to percutaneous coronary intervention (PCI) (T2P) on 1-year mortality in non-ST-elevation myocardial infarction (NSTEMI) patients. BACKGROUND: The current guidelines recommend an early invasive strategy for NSTEMI patients. However, impact of an early invasive strategy on mortality is a matter of debate. For that reason, real world data are of great value to determine the optimal treatment window. METHODS: This retrospective single center cohort study was performed in a high-volume PCI center in Amsterdam, The Netherlands. Intermediate- and high-risk NSTEMI patients undergoing PCI were included. The main discriminant was timing of PCI after admission (T2P), stratified according to different time windows (<24 h, 24-72 h, 72 h-7 days or >7 days). We analyzed 1-year mortality and the time distribution of overall survival. RESULTS: In total, 848 patients treated between January 1, 2016 and January 1, 2018 were included in the analysis. T2P was <24 h in 145 patients, 24-72 h in 192 patients, 72 h-7 days in 275 patients, and >7 days in 236 patients. The mean GRACE-risk score was 127.1 (SD 28.7), 130.0 (33.1), 133.8 (32.1), and 148.7 (34.6) respectively, p = <0.001. After adjusting for confounders, 1-year mortality in patients with T2P <24 h did not significantly differ when compared with T2P 24-72 h (OR = 1.08; 95% CI = 0.33-3.51) and T2P 72 h-7 days (OR 1.72; 95% CI = 0.57-5.21) but was significantly higher in T2P >7 days (OR = 3.20; 95% CI = 1.06-9.68). CONCLUSIONS: In an unselected cohort of patients with NSTEMI, treatment by PCI <24 h did not lead to improved survival as compared to aT2P <7 days strategy. Delay in PCI >7 days after admission resulted in worse outcome.

Impact of Coronary Calcification on Clinical Outcomes After Implantation of Newer-Generation Drug-Eluting Stents.

Background Percutaneous coronary intervention of calcified lesions was associated with worse outcomes in the era of bare-metal and first-generation drug-eluting stents. Data on percutaneous coronary intervention of calcified lesions with newer-generation drug-eluting stents are scarce. Therefore, we investigated the impact of lesion calcification on clinical outcomes in patients undergoing percutaneous coronary intervention with a bioresorbable-polymer sirolimus-eluting stent or a durable-polymer everolimus-eluting stent. Methods and Results Patients (n=2361) from BIOFLOW II, IV, and V trials were categorized into moderate/severe versus none/mild lesion calcification by a core laboratory. End points were target-lesion failure (TLF) (cardiac death, target-vessel myocardial infarction, or target-lesion revascularization) and probable/definite stent thrombosis at 2 years. The agreement in calcification assessment between the operator and the core laboratory was weak (weighted κ, 0.23). Patients with moderate/severe calcification (n=303; 16%) had higher TLF (13.5% versus 8.4%; P=0.003) and stent thrombosis rates (2.1% versus 0.2%; P<0.0001), whereas target-lesion revascularization was not different between the groups (5.0% versus 3.9%; P=0.302). After adjustment, calcification did not emerge as an independent predictor of TLF (adjusted hazard ratio [aHR], 1.37; 95% CI, 0.89-2.08; P=0.148) but did for target-vessel myocardial infarction (aHR, 1.66; 95% CI, 1.03-2.68; P=0.037). TLF rates were similar between bioresorbable-polymer sirolimus-eluting stent and durable-polymer everolimus-eluting stent (12.6% versus 15.4%, P=0.482) in moderate/severe calcification. In none/mild calcification, the bioresorbable-polymer sirolimus-eluting stent showed lower TLF (7.5% versus 10.3%, P=0.045). Conclusions With newer-generation drug-eluting stents, moderate/severe lesion calcification was not associated with more TLF after adjustment for the higher risk of patients with coronary calcification, whereas the rate of target-vessel myocardial infarction was higher. The bioresorbable-polymer sirolimus-eluting stent and durable-polymer everolimus-eluting stent were equally effective and safe in calcified lesions. Registration URL: https://www.clinicaltrials.gov; Unique identifiers: NCT01356888, NCT01939249, NCT02389946.

Comparison of Investigator-Reported and Clinical Event Committee-Adjudicated Outcome Events in GLASSY.

BACKGROUND: Event adjudication by a clinical event committee (CEC) provides a standardized, independent outcome assessment. However, the added value of CEC to investigators reporting remains debated. GLASSY (GLOBAL LEADERS Adjudication Sub-Study) implemented, in a subset of the open-label, investigator-reported (IR) GLOBAL LEADERS trial, an independent adjudication process of reported and unreported potential outcome events (triggers). We describe metrics of GLASSY feasibility and efficiency, diagnostic accuracy of IR events, and their concordance with corresponding CEC-adjudicated events. METHODS: We report the proportion of myocardial infarction, bleeding, stroke, and stent thrombosis triggers with sufficient evidence for assessment (feasibility) that were adjudicated as outcome events (efficiency), stratified by source (IR or non-IR). Using CEC-adjudicated events as criterion standard, we describe sensitivity, specificity, positive and negative predictive value, and global diagnostic accuracy of IR events. Using Gwet AC coefficient, we examine the concordance between IR- and corresponding CEC-adjudicated triggers. There was sufficient evidence for assessment for 2592 (98.3%) of 2636 triggers. RESULTS: Overall, the adjudicated end point-to-trigger ratio was high and similar between IR- (88%) and non-IR-reported (87%) triggers. The global diagnostic accuracy and concordance between IR-reported and CEC-adjudicated outcome events was 0.70 (95% CI, 0.65-0.74) and 0.54 (95% CI, 0.45-0.62), respectively, for myocardial infarction; 0.77 (95% CI, 0.75-0.79) and 0.71 (95% CI, 0.68-0.74) for bleeding; 0.70 (95% CI, 0.62-0.79) and 0.59 (95% CI, 0.43-0.74) for stroke; 0.59 (95% CI, 0.52-0.66) and 0.39 (95% CI, 0.25-0.53) for stent thrombosis. For IR bleedings, the concordance with the CEC on type of events was generally weak. CONCLUSIONS: Implementing CEC adjudication in a pragmatic open-label trial with IR events is feasible and efficient. Our findings of modest global diagnostic accuracy for IR events and generally weak concordance between investigators and CEC support the role for CEC adjudication in such settings. Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT03231059.

Biodegradable polymer sirolimus-eluting stents vs durable polymer everolimus-eluting stents in patients undergoing percutaneous coronary intervention: A meta-analysis of individual patient data from 5 randomized trials.

BACKGROUND: Newest generation drug-eluting stents combine biodegradable polymers with ultrathin stent platforms in order to minimize vessel injury and inflammatory response. Evidence from randomized controlled trials suggested that differences in stent design translate into differences in clinical outcome. The aim of the present study was to evaluate the safety and efficacy of ultrathin strut, biodegradable polymer sirolimus eluting stents (BP SES) compared with thin strut, durable polymer everolimus-eluting stents (DP EES) among patients undergoing percutaneous coronary intervention (PCI). METHODS: We pooled individual participant data from 5 randomized trials (NCT01356888, NCT01939249, NCT02389946, NCT01443104, NCT02579031) including a total of 5,780 patients, and performed a one-stage meta-analysis using a mixed effects Cox regression model. RESULTS: At a median duration of follow-up of 739 days (interquartile range 365-1,806 days), target-lesion failure occurred in 337 (10.3%) and 304 (12.2%) patients treated with BP SES and DP EES (HR 0.86, 95%CI 0.71-1.06, P = .16). There were no significant differences between BP SES and DP EES with regards to cardiac death (111 (3.4%) vs 102 (4.1%); HR 1.05, 95%CI 0.80-1.37, P = .73), target-vessel myocardial infarction (136 (4.1%) vs 126 (5.0%), HR 0.79, 95%CI 0.62-1.01, P = .061), and clinically-driven target-lesion revascularization (163 (5.0%) vs 147 (5.9%); HR 0.94, 95%CI 0.75-1.18, P = .61). The effect was consistent across major subgroups. In a landmark analysis, there was no significant interaction between treatment effect and timing of events. CONCLUSIONS: In this patient-level meta-analysis of 5 randomized controlled trials, BP SES were associated with a similar risk of target-lesion failure compared with DP EES among patients undergoing PCI. STUDY REGISTRATION: PROSPERO registry (CRD42018109098).

An immediate or early invasive strategy in non-ST-elevation acute coronary syndrome: The OPTIMA-2 randomized controlled trial.

BACKGROUND: In intermediate- and high-risk non-ST elevated acute coronary syndrome (NSTE-ACS) patients, a routine invasive approach is recommended. The timing of coronary angiography remains controversial. To assess whether an immediate (<3 hours) invasive treatment strategy would reduce infarct size and is safe, compared with an early strategy (12-24 hours), for patients admitted with NSTE-ACS while preferably treated with ticagrelor. METHODS: In this single-center, prospective, randomized trial an immediate or early invasive strategy was randomly assigned to patients with NSTE-ACS. At admission, the patients were preferably treated with a combination of aspirin, ticagrelor and fondaparinux. The primary endpoint was the infarct size as measured by area under the curve (AUC) of CK-MB in 48 hours. Secondary endpoints were bleeding outcomes and major adverse cardiac events (MACE): composite of all-cause death, MI and unplanned revascularization. Interim analysis showed futility regarding the primary endpoint and trial inclusion was terminated. RESULTS: In total 249 patients (71% of planned) were included. The primary endpoint of in-hospital infarct size was a median AUC of CK-MB 186.2 ng/mL in the immediate group (IQR 112-618) and 201.3 ng/mL in the early group (IQR 119-479). Clinical follow-up was 1-year. The MACE-rate was 10% in the immediate and 10% in the early group (hazard ratio [HR] 1.13, 95% CI: 0.52-2.49). CONCLUSIONS: In NSTE-ACS patients randomized to either an immediate or an early-invasive strategy the observed median difference in the primary endpoint was about half the magnitude of the expected difference. The trial was terminated early for futility after 71% of the projected enrollment had been randomized into the trial.

Dedicated plug based closure for large bore access -The MARVEL prospective registry.

OBJECTIVES: To study safety and performance of the MANTA Vascular closure device (VCD) under real world conditions in 10 centers. BACKGROUND: The MANTA is a novel plug-based device for large bore arteriotomy closure. METHODS: We included all eligible patients who underwent transfemoral large bore percutaneous procedures. Exclusion criteria were per operator's discretion and included severe calcification or marked tortuosity of the access vessel, presence of marked obesity/cachexia or a systolic blood pressure above 180 mmHg. The primary performance endpoint was time to hemostasis. Primary and secondary safety endpoints were major and minor access site related vascular complications up to 30 days, respectively. Vascular complications were adjudicated by an independent clinical event committee according to VARC-2 criteria. We performed multivariable logistic regression to estimate the effect of baseline and procedural characteristics on any and major vascular complications. RESULTS: Between February 2018 and July 2019 500 patients were enrolled undergoing Transcatheter aortic valve replacement (TAVR, N = 496), Balloon aortic valvuloplasty (BAV, N = 2), Mechanical circulatory support (MCS, N = 1) or Endovascular aneurysm repair (EVAR, N = 1). Mean age was 80.8 ± 6.6 years with a median STS-score of 2.7 [IQR 2.0-4.3] %. MANTA access site complications were major in 20 (4%) and minor in 28 patients (5.6%). Median time to hemostasis was 50 [IQR 20-120] sec. Severe femoral artery calcification, scar presence in groin, longer procedure duration, female gender and history of hypertension were independent predictors for vascular complications. CONCLUSION: In this study, MANTA appeared to be a safe and effective device for large bore access closure under real-world conditions.

Influence of Bleeding Risk on Outcomes of Radial and Femoral Access for Percutaneous Coronary Intervention: An Analysis From the GLOBAL LEADERS Trial.

BACKGROUND: Radial artery access has been shown to reduce mortality and bleeding events, especially in patients with acute coronary syndromes. Despite this, interventional cardiologists experienced in femoral artery access still prefer that route for percutaneous coronary intervention. Little is known regarding the merits of each vascular access in patients stratified by their risk of bleeding. METHODS: Patients from the Global Leaders trial were dichotomized into low or high risk of bleeding by the median of the PRECISE-DAPT score. Clinical outcomes were compared at 30 days. RESULTS: In the overall population, there were no statistical differences between radial and femoral access in the rate of the primary end point, a composite of all-cause mortality, or new Q-wave myocardial infarction (MI) (hazard ratio [HR] 0.70, 95% confidence interval [CI] 0.42-1.15). Radial access was associated with a significantly lower rate of the secondary safety end point, Bleeding Academic Research Consortium (BARC) 3 or 5 bleeding (HR 0.55, 95% CI 0.36-0.84). Compared by bleeding risk strata, in the high bleeding score population, the primary (HR 0.47, 95% CI 0.26-0.85; P = 0.012; Pinteraction = 0.019) and secondary safety (HR 0.57, 95% CI 0.35-0.95; P = 0.030; Pinteraction = 0.631) end points favoured radial access. In the low bleeding score population, however, the differences in the primary and secondary safety end points between radial and femoral artery access were no longer statistically significant. CONCLUSIONS: Our findings suggest that the outcomes of mortality or new Q-wave MI and BARC 3 or 5 bleeding favour radial access in patients with a high, but not those with a low, risk of bleeding. Because this was not a primary analysis, it should be considered hypothesis generating.

Individual patient data analysis of the BIOFLOW study program comparing safety and efficacy of a bioresorbable polymer sirolimus eluting stent to a durable polymer everolimus eluting stent.

OBJECTIVES: This analysis of pooled individual patient data (IPD) aimed to evaluate the safety and efficacy of a bioresorbable polymer sirolimus eluting stent system (BP-SES; Orsiro) compared to a durable polymer everolimus eluting stent system (DP-EES; Xience) in the pooled population as well as in subgroups. METHODS: IPD with up to 12 months follow-up of the randomized controlled trials BIOFLOW-II (NCT01356888), -IV (NCT01939249), and -V (NCT02389946) as well as the all comers registry BIOFLOW-III (NCT01553526) were pooled. A total of 3,717 subjects (2,923 in BP-SES and 794 in DP-EES) with 5,328 lesions (4,225 lesions in BP-SES and 1,103 in DP-EES) were included in the IPD. The primary endpoint was target lesion failure (TLF) at 12 months follow-up. Subgroups analyzed included diabetes, age (≥65 years), gender, complex lesions (B2/C), small vessels (reference vessel diameter ≤2.75 mm), multivessel treatment, renal disease, and patients with acute coronary syndrome. RESULTS: Overall, TLF at 12 months was significantly lower with 5.2%in the BP-SES group versus 7.6% in the DP-EES group (p = .0098). Similarly, target vessel myocardial infarction (TV-MI) was 3.1 versus 5.7% (p = .0005). The rate of stent thrombosis was similar in both groups (0.004%). By regression analysis, an independent stent effect in favor of BP-SES was observed for TLF (p = .0043) and TV-MI (p = .0364) in small vessels. CONCLUSION: Results of this IPD analysis suggest that the BP-SES with ultrathin struts is as safe as and more efficacious than DP-EES in the overall cohort and especially in small vessels.

Regional variation in patients and outcomes in the GLOBAL LEADERS trial.

BACKGROUND: Despite the overall neutral results of the GLOBAL-LEADERS trial, results from a prespecified subgroup analysis showed that patients from Western Europe had a significantly lower rate of the primary endpoint when treated with ticagrelor monotherapy. Therefore, we aimed to examine the regional disparities in patients' baseline characteristics and their response to ticagrelor monotherapy. METHODS: Patients' baseline characteristics and the treatment effects of ticagrelor combined with aspirin for 1 month, followed by ticagrelor monotherapy for 23-months versus 12-months of standard dual antiplatelet therapy (DAPT) were compared according to participating countries. The primary endpoint was a composite endpoint of all-cause death or new Q-wave myocardial infarction at two years. RESULTS: Significant variances in patients' baseline characteristics were found between participating countries. The primary endpoint varied significantly according to the country (Pinteraction = 0.027). Patients from France (1.6% versus 5.2%, HR: 0.31, 95%CI: 0.13-0.73) and The Netherlands (2.4% versus 4.8%, HR, 0.50, 95%CI: 0.26-0.94) had lower rates of the primary endpoint when allocated to ticagrelor monotherapy, compared with the standard DAPT regimen. Of the 26 baseline and post-randomization factors explored, variance in the rate of complex PCI between countries was identified as the top contributor to this regional interaction. CONCLUSIONS: Patients' baseline characteristics varied between participating countries in the GLOBAL-LEADERS trial. There is a significant regional variance in the treatment effect of ticagrelor monotherapy, which could partly be explained by the differences in complex PCI being performed. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov (NCT01813435).

Ticagrelor monotherapy in patients with concomitant diabetes mellitus and chronic kidney disease: a post hoc analysis of the GLOBAL LEADERS trial.

BACKGROUND: Patients with both diabetes mellitus (DM) and chronic kidney disease (CKD) are a subpopulation characterized by ultrahigh ischemic and bleeding risk after percutaneous coronary intervention. There are limited data on the impact of ticagrelor monotherapy among these patients. METHODS: In this post hoc analysis of the GLOBAL-LEADERS trial, the treatment effects of the experimental (one-month dual-antiplatelet therapy [DAPT] followed by 23-month ticagrelor monotherapy) versus the reference regimen (12-month DAPT followed by 12-month aspirin alone) were analyzed according to DM/CKD status. The primary endpoint was a composite endpoint of all-cause death or new Q-wave myocardial infarction at 2-years. The patient-oriented composite endpoint (POCE) was defined as the composite of all-cause death, any stroke, site-reported MI and any revascularization, whereas net adverse clinical events (NACE) combined POCE with BARC type 3 or 5 bleeding events. RESULTS: At 2 years, the DM + /CKD + patients had significantly higher incidences of the primary endpoint (9.5% versus 3.1%, adjusted HR 2.16; 95% CI [1.66-2.80], p < 0.001), BARC type 3 or 5 bleeding events, stroke, site-reported myocardial infraction, all revascularization, POCE, and NACE, compared with the DM-/CKD- patients. Among the DM + /CKD + patients, after adjustment, there were no significant differences in the primary endpoints between the experimental and reference regimen; however, the experimental regimen was associated with lower rates of POCE (20.6% versus 25.9%, HR 0.74; 95% CI [0.55-0.99], p = 0.043, pinteraction = 0.155) and NACE (22.7% versus 28.3%, HR 0.75; 95% CI [0.56-0.99], p = 0.044, pinteraction = 0.310), which was mainly driven by a lower rate of all revascularization, as compared with the reference regimen. The landmark analysis showed that while the experimental and reference regimen had similar rates of all the clinical endpoints during the first year, the experimental regimen was associated with significantly lower rates of POCE (5.8% versus 11.0%, HR 0.49; 95% CI [0.29-0.82], p = 0.007, pinteraction = 0.040) and NACE (5.8% versus 11.2%, HR 0.48; 95% CI [0.29-0.82], p = 0.007, pinteraction = 0.013) in the second year. CONCLUSION: Among patients with both DM and CKD, ticagrelor monotherapy was not associated with lower rates of all-cause death or new Q-wave, or major bleeding complications; however, it was associated with lower rates of POCE and NACE. These findings should be interpreted as hypothesis-generating. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov (NCT01813435).