Prognostic Impact of Prefrailty and Frailty in Women Undergoing TAVR: Insights From the WIN-TAVI Registry.

BACKGROUND: The risks of prefrail and frail women undergoing transcatheter aortic valve replacement (TAVR) have not been fully examined. The aim of the analysis was to assess the prognostic impact of prefrailty and frailty in women undergoing TAVR. METHODS: Women at intermediate or high surgical risk with severe aortic stenosis undergoing TAVR from the prospective multicentre WIN-TAVI (Women's International Transcatheter Aortic Valve Implantation) registry were stratified based on the number of Fried frailty criteria (weight loss, exhaustion, low physical activity, slow gait, weakness) met: nonfrail (no criteria), prefrail (1 or 2 criteria), or frail (3 or more criteria). The primary outcome at 1 year was the Valve Academic Research Consortium 2 (VARC-2) efficacy end point, a composite of mortality, stroke, myocardial infarction, hospitalisation for valve-related symptoms or heart failure, and valve-related dysfunction; secondary outcomes included the composite of VARC-2 life-threatening or major bleeding. RESULTS: Out of 1019 women, 297 (29.1%) met at least 1 frailty criterion: 264 (25.9%) had prefrailty and 33 (3.2%) frailty. The 1-year risk of the primary outcome was significantly higher in prefrail and frail (20.2%) than in nonfrail (14.9%) women (adjusted hazard ratio [aHR] 1.51, 95% confidence interval [CI] 1.07-2.12). The risk of VARC-2 life-threatening or major bleeding was higher in prefrail or frail (19.9%) than in nonfrail (10.0%) women (aHR 2.06, 95% CI 1.42-2.97). These risks were consistently increased in the prefrail and frail groups assessed separately. CONCLUSIONS: In women undergoing TAVR, the presence of prefrailty or frailty conferred an increased risk of the VARC-2 efficacy end point and of VARC-2 life-threatening or major bleeding.

Outcomes in Patients With Early Menopause Who Underwent Transcatheter Aortic Valve Implantation.

Early menopause is associated with an increased risk of cardiovascular diseases, including aortic stenosis (AS). We sought to investigate the prevalence and impact of early menopause on clinical outcomes in patients who underwent transcatheter aortic valve implantation (TAVI) for severe symptomatic AS. Women's International TAVI is a multinational, prospective, observational registry of women who underwent TAVI for severe symptomatic AS (n = 1,019). Patients were divided into 2 groups based on age of menopause: early menopause (age ≤45 years) and regular menopause (age >45 years). The primary outcome of interest was Valve Academic Research Consortium 2 efficacy end point, a composite of mortality, stroke, myocardial infarction, hospitalization for valve-related symptoms, or heart failure or valve-related dysfunction at 1-year follow-up. Of 732 patients with available data on menopause age, 173 (23.6%) were classified as having early menopause. These patients presented for TAVI at a younger age (81.6 ± 6.9 vs 82.7 ± 5.9, p = 0.05) and had a significantly lower Society of Thoracic Surgeons score (6.6 ± 4.8 vs 8.2 ± 7.1, p = 0.03) than those with regular menopause. However, the total valve calcium volume was smaller among patients with early versus regular menopause (731.8 ± 850.9 mm3 vs 807.6 ± 633.8 mm3, p = 0.002). Other co-morbidities were similar between the 2 groups. At 1-year follow-up, there were no significant differences in clinical outcomes between patients with early versus regular menopause (hazard ratio 1.00, 95% confidence interval 0.61 to 1.63, p = 1.00). In conclusion, despite presenting for TAVI at a younger age, patients with early menopause had a similar risk of adverse events as patients with regular menopause at 1 year after TAVI.

Pre-procedural oral anticoagulant use is associated with cardiovascular events in women after transcatheter aortic valve replacement: An analysis from the WIN-TAVI cohort.

BACKGROUND: Transcatheter aortic valve implantation (TAVI) has become an accepted treatment for patients with severe aortic stenosis (AS). Predicting which patients are at risk for adverse clinical outcomes after TAVI remains difficult, especially in women. AIM: To identify predictors of adverse events in the WIN-TAVI cohort. METHODS: The WIN-TAVI study is an observational registry of 1019 women undergoing TAVI for severe symptomatic AS. Follow-up was 1 year. The primary outcome was defined according to VARC-2: a composite of mortality, stroke, myocardial infarction or hospitalization for valve-related symptoms or heart failure. The secondary outcome was a composite of cardiovascular mortality or hospitalization for valve-related symptoms or heart failure. RESULTS: We included 1019 women with severe AS (mean age of 82.5 ± 6.3 years). At 1 year, 16.4% of the patients experienced the primary endpoint and 12.6% the secondary endpoint. The use of oral anticoagulants (OAC) was the strongest independent predictor of the primary outcome (adjusted hazard ratio [aHR] 1.51, 95% confidence interval [CI] 1.079-2.106, p = 0.016). Independent predictors of the secondary endpoint were age (aHR 1.04 per year, 95% CI 1.01-1.074, p = 0.016) and use of OAC (aHR: 1.79, 95% CI 1.24-2.60, p = 0.002). OAC use was not associated with higher bleeding risk. CONCLUSION: Pre-procedural use of OAC was the strongest predictor of adverse outcomes during 1-year follow-up, likely reflecting a combination of high-risk factors and comorbidities, but was not related to increased bleeding risk.

[The importance of intensive lipid-lowering therapy after acute coronary syndrome: changing the paradigm to improve the achievement of targets]. / L'importanza di una terapia ipolipemizzante intensiva dopo sindrome coronarica acuta: cambiare il paradigma per migliorare il raggiungimento dei target.

BACKGROUND: Despite the availability of effective lipid-lowering drugs, only few high-risk patients attain their LDL cholesterol (LDL-C) guideline-recommended risk-based goal because of underprescription of combination therapy. We present an 18-month experience with variation of prescription protocols after publication of the 2019 ESC/EAS guidelines for the management of dyslipidemias. METHODS: Overall, 621 consecutive patients hospitalized for acute coronary syndrome at Mauriziano Hospital in Turin, Italy, between January 2020 and June 2021 were enrolled. Lipid-lowering therapy recommended at discharge was registered to evaluate how many patients received statin monotherapy, statin plus ezetimibe combination or triple therapy with high-intensity statin plus ezetimibe and proprotein convertase subtilisin/kexin type 9 inhibitor (PCSK9i). At 6-month follow-up, the reduction in LDL-C, adverse events, compliance and cardiovascular recurrences was analyzed. RESULTS: Of 621 patients enrolled, 7 died during hospitalization. During the entire study period, 33% of patients received statin monotherapy, 50% were discharged on statin-ezetimibe combination, and PCSK9i (evolocumab) was prescribed to 17% of patients. Between April 2020 and June 2021, when new recommendations were introduced into clinical practice, 20% of patients received evolocumab, 56% combination therapy and only 24% were discharged on statin monotherapy. At the beginning of observation, evolocumab was prescribed to 3% of patients hospitalized for acute coronary syndrome, while at the end of the study period 27% of patients were discharged on PCSK9i, with an increase of the prescription rate by 759%; in the same period, prescription of statin monotherapy decreased by 75%. At 6-month follow-up, LDL-C reduction was 77% in patients treated with PCSK9i vs 48% in patients taking statin-ezetimibe combination therapy (p<0.001). All patients on evolocumab reached the guideline-directed goals and a low rate of adverse events was reported, mainly represented by local injection site reactions. Six patients experienced acute coronary syndrome recurrence; only one of them was treated with evolocumab. CONCLUSION: Prescription of intensive lipid-lowering therapy after acute coronary syndrome, eventually with introduction of PCSK9i during hospitalization or at discharge, leads to attainment of guideline-recommended goals for all patients, with a low incidence of adverse events and optimal compliance.

Impact of Small Valve Size on 1-Year Outcomes After Transcatheter Aortic Valve Implantation in Women (from the WIN-TAVI Registry).

Although most patients with small aortic annulus are women, there is paucity of data on the prognostic impact of small aortic prosthesis in women who underwent transcatheter aortic valve implantation (TAVI). Therefore, we aimed to evaluate the impact of small valve size on 1-year clinical outcomes after TAVI in women. The Women's INternational Transcatheter Aortic Valve Implantation is an all-women registry evaluating patients with severe aortic stenosis who underwent TAVI. Based on the size of the aortic bioprosthesis implanted, women were stratified into small (≤23 mm) and nonsmall (>23 mm) valve. The primary efficacy endpoint was the Valve Academic Research Consortium-2 composite of all-cause death, stroke, myocardial infarction, hospitalization for valve-related symptoms or heart failure or valve-related dysfunction at 1-year follow-up. Of 934 women who underwent TAVI, 388 (41.5%) received a small valve. Women with a small valve size had a lower body mass index, lower surgical risk scores, were less likely to suffer from atrial fibrillation, less often required postdilation and had a lower rate of residual aortic regurgitation grade ≥2. The occurrence of the Valve Academic Research Consortium-2 efficacy endpoint was similar between women treated with small and nonsmall valve (16.0% vs 16.3%, p = 0.881; adjusted hazard ratio 1.34, 95% confidence interval 0.90 to 2.00). Likewise, there were no significant differences in the occurrence of other secondary endpoints after multivariable adjustment. In conclusion, women with severe aortic stenosis who underwent TAVI with the implantation of a small valve bioprosthesis had similar 1-year outcomes as those receiving a nonsmall bioprosthesis.

"No-Reflow" Phenomenon: A Contemporary Review.

Primary percutaneous angioplasty (pPCI), represents the reperfusion strategy of choice for patients with STEMI according to current international guidelines of the European Society of Cardiology. Coronary no-reflow is characterized by angiographic evidence of slow or no anterograde epicardial flow, resulting in inadequate myocardial perfusion in the absence of evidence of mechanical vessel obstruction. No reflow (NR) is related to a functional and structural alteration of the coronary microcirculation and we can list four main pathophysiological mechanisms: distal atherothrombotic embolization, ischemic damage, reperfusion injury, and individual susceptibility to microvascular damage. This review will provide a contemporary overview of the pathogenesis, diagnosis, and treatment of NR.

Sex Differences in Outcomes After Percutaneous Coronary Intervention or Coronary Artery Bypass Graft for Left Main Disease: From the DELTA Registries.

Background Controversy exists over whether sex has significant interaction with revascularization strategy for unprotected left main coronary artery disease. Higher mortality has been reported among women treated with percutaneous coronary intervention compared with coronary artery bypass grafting. Methods and Results The DELTA (Drug-Eluting Stents for Left Main Coronary Artery Disease) and DELTA-2 registries are international, multicentric registries evaluating the outcomes of subjects undergoing coronary revascularization for unprotected left main coronary artery disease. The primary outcome was a composite of death, myocardial infarction, or cerebrovascular accidents. The population consisted of 6253 patients, including 1689 (27%) women. Women were older and more likely to have diabetes and chronic kidney disease than men (P<0.05). At a median follow-up of 29 months (interquartile range 12-49), a significant interaction between sex and revascularization strategy was observed for the primary end point (pint=0.012) and all-cause death (pint=0.037). Among women, compared with percutaneous coronary intervention, coronary artery bypass grafting was associated with lower risk of the primary end point (event rate 9.5% versus 15.3%; adjusted hazard ratio [AHR], 0.53; 95% CI, 0.35-0.79, P<0.001) and all-cause death (event rate 5.6% versus 11.7% AHR, 0.50; 95% CI, 0.30-0.82) and no significant differences were observed in men. Conclusions In women undergoing coronary revascularization for unprotected left main coronary artery disease, coronary artery bypass grafting was associated with lower risk of death, myocardial infarction, or cerebrovascular accidents whereas no significant differences between coronary artery bypass grafting and percutaneous coronary intervention were observed in men. Further dedicated studies are needed to determine the optimal revascularization strategy in women with unprotected left main coronary artery disease.

Incidence, predictors and clinical impact of permanent pacemaker insertion in women following transcatheter aortic valve implantation: Insights from a prospective multinational registry.

OBJECTIVES: To describe the incidence, predictors, and clinical impact of permanent pacemaker insertion (PPI) following transcatheter aortic valve replacement (TAVR) in women. BACKGROUND: Data on pacemaker insertion complicating TAVR in women are scarce. METHODS: The Women's International Transcatheter Aortic Valve implantation (WIN-TAVI) is a prospective registry evaluating the safety and efficacy of TAVR in women. We included patients without preprocedural pacemakers and divided them into two groups: (1) PPI and (2) no-PPI. We identified PPI predictors using logistic regression and studied its clinical impact on the Valve Academic Research Consortium (VARC)-2 efficacy and safety endpoints. RESULTS: Out of 1019 patients, 922 were included in the analysis. Post-TAVR PPI occurred in 132 (14.3%) patients. Clinical and procedural characteristics were similar in both groups. Pre-existing right bundle branch block (RBBB) was associated with a high risk of post-TAVR PPI (OR 3.62, 95% CI 1.85-7.06, p < 0.001), while implantation of balloon-expandable prosthesis was associated with a lower risk (OR 0.47, 95% CI 0.30-0.74, p < 0.001). Post-TAVR PPI prolonged in-hospital stay by a median of 2 days (11 [9-16] days in PPI vs. 9 [7-14] days in no-PPI, p = 0.005), yet risks of VARC-2 efficacy and safety endpoints at 1 year were similar in both groups (adj HR 0.95, 95% CI 0.60-1.52, p = 0.84 and adj HR 1.22, 95% CI 0.83-1.79, p = 0.31, respectively). CONCLUSION: Pacemaker implantation following TAVR is frequent among women and is associated with pre-existing RBBB and valve type. PPI prolongs hospital stay, albeit without any significant impact on 1-year outcomes.

Prevalence, predictors, and outcomes of patient prosthesis mismatch in women undergoing TAVI for severe aortic stenosis: Insights from the WIN-TAVI registry.

OBJECTIVE: To evaluate the incidence, predictors and outcomes of female patients with patient-prosthesis mismatch (PPM) following transcatheter aortic valve intervention (TAVI) for severe aortic stenosis (AS). BACKGROUND: Female AS TAVI recipients have a significantly lower mortality than surgical aortic valve replacement (SAVR) recipients, which could be attributed to the potentially lower PPM rates. TAVI has been associated with lower rates of PPM compared to SAVR. PPM in females post TAVI has not been investigated to date. METHODS: The WIN-TAVI (Women's INternational Transcatheter Aortic Valve Implantation) registry is a multicenter registry of women undergoing TAVR for severe symptomatic AS. Two hundred and fifty patients with detailed periprocedural and follow-up echocardiographic investigations were included in the WIN-TAVI echocardiographic sub-study. PPM was defined as per European guidelines stratified by the presence of obesity. RESULTS: The incidence of PPM in our population was 32.8%. Patients with PPM had significantly higher BMI (27.4 ± 6.1 vs. 25.2 ± 5.0, p = .002), smaller sized valves implanted (percentage of TAVI ≤23 mm 61% vs. 29.2%, PPM vs. no PPM, p < .001) and were more often treated with balloon expandable valves (48.3 vs. 32.5%, p < .001) rather than self expanding ones (26.3 vs. 52.8%, <.001). BMI (OR = 1.08; 95%CI 1.02-1.14, p = .011) and valve size ≤23 mm (OR = 3.00 95%CI 1.14-7.94, p = .027) were the only independent predictors of PPM. There was no significant interaction between valve size and valve type (p = .203). No significant differences were observed in 1-year mortality or major adverse cardiovascular events. CONCLUSIONS: PPM in females undergoing TAVI occurs in one third of patients. BMI and valve size ≤23 mm are independent predictors. Larger registries are required to determine the impact of PPM on future clinical outcomes.

Impact of diabetes mellitus on female subjects undergoing transcatheter aortic valve implantation: Insights from the WIN-TAVI international registry.

BACKGROUND: Female subjects constitute half of all transcatheter aortic valve implantation (TAVI) candidates, but the association between important comorbidities such as diabetes mellitus (DM) and clinical outcomes after TAVI remains unclear in this group. METHOD: WIN-TAVI is a real-world international registry of exclusively female subjects undergoing TAVI. The study population was stratified into those with (DM) and those without DM (NDM). Valve Academic Research Consortium (VARC)-2 efficacy (composite of all-cause death, stroke, myocardial infarction, hospitalization for valve-related symptoms or worsening congestive heart failure, or valve-related dysfunction) was the primary endpoint for this analysis. RESULTS: Of the 1012 subjects included in this study, 264 (26.1%) had DM at baseline. DM patients were younger but had a higher burden of comorbidities. There were no differences in VARC-2 efficacy events between DM and NDM patients at 30 days or 1 year. Conversely, patients with DM had a lower risk of VARC-2 life threatening bleeding at 30 days and 1 year after TAVI compared to NDM patients, which remained significant even after multivariable adjustment (HR, 0.34, 95% CI, 0.12-0.99; p = .047). In the subgroup analysis, insulin-dependent DM was not associated with an increased risk of adverse outcomes. CONCLUSIONS: Among female patients undergoing TAVI, more than one-fourth of the subjects presented with DM. At 1-year follow-up, DM was associated with lower bleeding complications and no increase in the risk of other adverse events, including mortality, after TAVI.

Preprocedural anemia in females undergoing transcatheter aortic valve implantation: Insights from the WIN-TAVI registry.

OBJECTIVES: To assess the impact of anemia on clinical outcomes in female patients enrolled in the Women's InterNational transcatheter aortic valve implantation (WIN-TAVI) registry. BACKGROUND: Anemia is highly prevalent among females who constitute half of TAVI candidates, yet, its clinical significance remains poorly investigated. METHODS: Patients were divided into three groups according to preprocedural hemoglobin (Hb) level: (1) no anemia (Hb ≥12 g/dl), (2) mild-to-moderate anemia (10 ≤ Hb <12 g/dl), and (3) severe anemia (Hb <10 g/dl). The primary outcome was the occurrence of Valve Academic Research Consortium (VARC)-2 efficacy endpoint, a composite of mortality, stroke, myocardial infarction (MI), hospitalization for valve-related symptoms or heart failure or valve-related dysfunction at 1-year follow-up. RESULTS: Hemoglobin level was available in 877 (86.1%) patients: 412 (47.0%) had no anemia, 363 (41.4%) had mild-to-moderate anemia, and 102 (11.6%) had severe anemia. The latter group had a higher prevalence of cardiovascular risk factors. Compared with patients without anemia, severe anemia was associated with a greater risk of VARC-2 efficacy endpoint (adj HR 1.71, 95% CI: 1.02-2.87, p = .04), all-cause death (adj HR 2.36, 95% CI: 1.31-4.26, p = .004) and a composite of death, MI or stroke (adj HR 1.88, 95% CI: 1.10-3.22, p = .02) at 1 year. Moreover, an increased risk of late mortality (adj HR 1.15, 95% CI: 1.02-1.30, p = .03) was observed with every 1 g/dl decrease in hemoglobin level. CONCLUSION: Severe anemia in females undergoing TAVI was independently associated with increased rates of VARC-2 efficacy endpoint and mortality at 1 year.

First in human evaluation of a novel Sirolimus-eluting ultra-high molecular weight bioresorbable scaffold: 9-, 24-and 36-months imaging and clinical results from the multi-center RENASCENT study.

BACKGROUND: RENASCENT is a prospective, multi-center first-in-human clinical study to evaluate the clinical performance of the novel sirolimus-eluting 150-µm strut thickness FORTITUDE® BRS for percutaneous coronary intervention of single de novo coronary lesions. METHODS: FORTITUDE® BRS was tested in a prospective study in Italy and Colombia. Study objectives were in-scaffold angiographic late lumen loss (LLL) measured by quantitative coronary angiography and target vessel failure (TVF) defined as the composite rate of cardiac death, target vessel myocardial infarction or ischemia driven target lesion revascularization (TLR) at 9- and 24-months with clinical results up to 36-months. RESULTS: A total of 63 patients were enrolled. All patients underwent lesion pre-dilatation and 22 patients (34.9%) underwent post-dilatation. Clinical device and procedural success was 98.4% (62/63 patients) and 96.8% (61/63 patients) respectively. At 9-months, TVF occurred in 3/61 (4.9%) of the patients including 2 peri-procedural MI and one ischemia-driven TLR. Between 9- to 24-months, ischemia-driven TLR occurred in 3 additional patients (4.9%) including 1 patient who presented with very late ST after stopping all medications. There were no further TVF between 24- and 36-months. CONCLUSIONS: In this multi-center prospective study, the FORTITUDE® BRS was shown to be safe and effective in the treatment of single coronary lesions with low levels of TVF and LLL at 9- and 24-months. It was shown to be clinically safe upto 36-months follow-up.

Edwards SAPIEN Versus Medtronic Aortic Bioprosthesis in Women Undergoing Transcatheter Aortic Valve Implantation (from the Win-TAVI Registry).

We sought to analyze outcomes of women receiving balloon-expandable valves (BEV) or self-expanding valves (SEV) in contemporary transcatheter aortic valve implantation (TAVI). WIN TAVI (Women's INternational Transcatheter Aortic Valve Implantation) is the first all-female TAVI registry to study the safety and performance of TAVI in women. We compared women treated with BEV (n = 408, 46.9%) versus those treated with SEV (n = 461, 53.1%). The primary efficacy end point was the Valve Academic Research Consortium-2 (VARC-2) composite of 1-year all-cause death, stroke, myocardial infarction, hospitalization for valve-related symptoms or heart failure or valve-related dysfunction. Women receiving SEV had higher surgical risk scores, higher rate of previous stroke and pulmonary hypertension whereas women receiving BEV were more frequently denied surgical valve replacement due to frailty. BEV patients were less likely to require post-dilation and had significantly lower rates of residual aortic regurgitation grade ≥2 (9.8% vs 4.7%, p = 0.007). At 1 year, the crude incidence and adjusted risk of the primary VARC-2 efficacy end point was similar between groups (17.1% with SEV and 14.3% with BEV, p = 0.25; hazards ratio 1.09, 95% confidence interval 0.68 to 1.75). Conversely the crude rate and adjusted risk of new pacemaker implantation was higher with SEV than BEV (15% vs 8.6%, p = 0.001; hazards ratio 1.97, 95% confidence interval 1.13 to 3.43). A subanalysis on new generation valves showed no difference in the need for pacemaker implantation between the 2 devices (10.1% vs 8.0%, p = 0.56). In conclusion, in contemporary TAVI, SEV are used more frequently in women with greater co-morbidities. While there were no differences in unadjusted and adjusted risk of 1-year primary efficacy end point between the valve types, there was a greater need for permanent pacemakers after SEV implantation.

New-generation drug-eluting stents for left main coronary artery disease according to the EXCEL trial enrollment criteria: Insights from the all-comers, international, multicenter DELTA-2 registry.

BACKGROUND: Percutaneous coronary intervention (PCI) has been established as an alternative treatment option to coronary artery by-pass graft (CABG) surgery in patients with left main coronary artery disease (LMCAD). Whether the findings of randomized controlled trials are applicable to a real-world patient population is unclear. METHODS: We compared the outcomes of PCI with new-generation DES in the all-comer, international, multicenter DELTA-2 registry retrospectively evaluating mid-term clinical outcomes with the historical CABG cohort enrolled in the DELTA-1 registry according to the EXCEL key inclusion or exclusion criteria. The primary endpoint was the composite of death, myocardial infarction, or stroke at the median time of follow-up time of 501 days. The consistency of the effect of DELTA-2 PCI versus DELTA-1 CABG according to the EXCEL enrollment criteria was tested using propensity score-adjusted Cox regression models. RESULTS: Out of 3986 patients enrolled in the DELTA-2 PCI registry, 2418 were EXCEL candidates and 1568 were not EXCEL candidates. The occurrence of the primary endpoint was higher among non-EXCEL candidates compared with EXCEL candidates (15.4% vs. 6.9%; hazard ratio 2.52; 95% confidence interval 2.00-3.16; p < 0.001). Among 901 patients enrolled in the historical DELTA-1 CABG cohort, 471 were EXCEL candidates and 430 were not EXCEL candidates. When comparing the DELTA-2 PCI with the DELTA-1 CABG cohort, the occurrence of the primary endpoint was lower in the PCI group compared with the historical CABG cohort among EXCEL candidates (6.9% vs. 10.7%; adjusted hazard ratio: 0.65; 95% confidence interval: 0.45-0.92), while no significant difference was observed among non-EXCEL candidates (15.4% vs. 12.5%; adjusted hazard ratio: 0.94; 95% confidence interval: 0.67-1.33) with evidence of statistical interaction (adjusted interaction p-value = 0.002). CONCLUSIONS: In a real-world population, PCI can be selected more favorably as an alternative to CABG in patients fulfilling the enrollment criteria of the EXCEL trial.

Impact of angiographic coronary artery disease complexity on ischemic and bleeding risks and on the comparative effectiveness of zotarolimus-eluting vs. bare-metal stents in uncertain drug-eluting stent candidates.

BACKGROUND: The impact of coronary artery disease (CAD) extension/complexity on outcomes and on the comparative benefits/risks of zotarolimus-eluting stent (ZES) versus bare-metal stents (BMS) remains unclear in patients at high risk of bleeding or thrombosis or at low restenosis risk. METHODS: We performed a post-hoc analysis of the ZEUS trial. The impact of coronary anatomic complexity measured by the SYNTAX score on the differences in outcomes following ZES and BMS was assessed at 1 year. RESULTS: The mean SYNTAX score was 16.3 ±â€¯13.1 with a median of 12 (IQR: 7 to 22). We stratified patients according to SYNTAX tertiles (0-8: n = 563; >8-19 n = 532; >19: n = 511), and observed that the higher the score, the correspondingly higher was the rate of the primary endpoint of major adverse cardiovascular events (MACE) and other ischemic events, but not bleeding after adjustment. The superior efficacy of ZES versus BMS for MACE was consistent across SYNTAX tertiles (tertile 1: HR 0.71, 95% CI 0.44-1.13; tertile 2: HR 0.71, 95% CI 0.46-1.09; tertile 3: HR 0.83, 95% CI 0.61-1.10) without significant heterogeneity (p for trend = 0.55). This between-groups difference mainly reflected a reduction in MI and TVR without effect on mortality. There was no significant interaction between the SYNTAX score and allocated stent type with respect to ischemic and bleeding endpoints. CONCLUSIONS: The SYNTAX score was predictor of major adverse cardiovascular events but not bleeding and ZES provided superior efficacy and safety than BMS across the whole spectrum of CAD complexity. SYNTAX score may be routinely used for the assessment of the ischemic risk (but not bleeding) after PCI and should not guide the decision-making for DES versus BMS in patients undergoing PCI.