Cardiovascular outcomes after percutaneous coronary intervention on bifurcation lesions with moderate to severe coronary calcium: A single-center registry study.

BACKGROUND: Both target vessel calcification and target vessel bifurcation are associated with worse outcomes following percutaneous coronary intervention (PCI). Whether these entities in combination interact to influence outcomes after PCI of complex coronary disease is not known. OBJECTIVES: This study evaluated the association of target vessel bifurcation and target vessel calcification, alone and in combination, with adverse events following PCI. METHODS: Registry data from 21,165 patients who underwent PCI with drug-eluting stents (DES) between January 2009 and December 2017 were analyzed. Patients were divided into four groups according to the presence or absence of target vessel bifurcation and presence of none/mild or moderate/severe target vessel calcification on angiography. Associations between lesion groups and 1 year major adverse cardiac events (MACE) were examined using Cox regression analysis. RESULTS: At 1 year, unadjusted rates of MACE, death, myocardial infarction (MI), as well as stent thrombosis were highest in the group with both bifurcation lesion and moderate/severe calcification. After adjusting for confounders such as age, renal disease, and smoking, hazard ratios for MACE were 1.14 (95%CI 0.99-1.33) for bifurcation with none/mild calcification, 1.21 (95%CI 1.06-1.38) for no bifurcation and moderate/severe calcification, and 1.37 (95%CI 1.14-1.64) for bifurcation and moderate severe calcification, compared to patients with no bifurcation and none/mild calcification. CONCLUSIONS: The presence of a bifurcating target vessel with moderate/severe calcification is associated with a higher risk of adverse outcomes than either attribute alone. New approaches are needed to improve outcomes in this subset of patients with complex coronary artery disease.

Sex differences in 1-year clinical outcomes after percutaneous coronary intervention with COMBO stents: From the COMBO collaboration.

BACKGROUND: The COMBO drug eluting stent is a novel device with luminal endothelial progenitor cell capture technology for rapid homogeneous endothelialization. METHODS AND RESULTS: We examined for sex differences in 1-year outcomes after COMBO stenting from the COMBO collaboration, a pooled patient-level dataset from the MASCOT and REMEDEE multicenter registries. The primary endpoint was 1-year target lesion failure (TLF), composite of cardiac death, target vessel-myocardial infarction (TV-MI), or clinically driven target lesion revascularization (CD-TLR). Secondary outcomes included stent thrombosis (ST). Adjusted outcomes were assessed using Cox regression methods. The study included 861 (23.8%) women and 2,753 (76.2%) men. Women were older with higher prevalence of several comorbidities including diabetes mellitus. Risk of 1-year TLF was similar in both sexes (3.8% vs. 3.9%, HR 0.92, 95% CI 0.59-1.42, p = .70), without sex differences in the incidence of cardiac death (1.6% vs. 1.5%, p = .78), TV-MI (1.5% vs. 1.1%, p = .32), or CD-TLR (2.0% vs. 2.2%, p = .67). Definite or probable ST occurred in 0.4% women and 1.0% men (HR 0.26, 95% CI 0.06-1.11, p = .069). CONCLUSIONS: Despite greater clinical risks at baseline, women treated with COMBO stents had similarly low 1-year TLF and other ischemic outcomes compared to men.

One-Year COMBO Stent Outcomes in Acute Coronary Syndrome: from the COMBO Collaboration.

PURPOSE: The COMBO biodegradable polymer sirolimus-eluting stent includes endothelial progenitor cell capture (EPC) technology for rapid endothelialization, which may offer advantage in acute coronary syndromes (ACS). We sought to analyze the performance of the COMBO stent by ACS status and ACS subtype. METHODS: The COMBO collaboration (n = 3614) is a patient-level pooled dataset from the MASCOT and REMEDEE registries. We evaluated outcomes by ACS status, and ACS subtype in patients with ST segment elevation myocardial infarction (STEMI) or non-STEMI (NSTEMI) versus unstable angina (UA). The primary endpoint was 1-year target lesion failure (TLF), composite of cardiac death, target vessel myocardial infarction, or clinically driven target lesion revascularization. Secondary outcomes included stent thrombosis (ST). RESULTS: We compared 1965 (54%) ACS and 1649 (46.0%) non-ACS patients. ACS presentations included 40% (n = 789) STEMI, 31% (n = 600) NSTEMI, and 29% (n = 576) UA patients. Risk of 1-year TLF was greater in ACS patients (4.5% vs. 3.3%, HR 1.51 95% CI 1.01-2.25, p = 0.045) without significant differences in definite/probable ST (1.1% vs 0.5%, HR 2.40, 95% CI 0.91-6.31, p = 0.08). One-year TLF was similar in STEMI, NSTEMI, and UA (4.8% vs 4.8% vs. 3.7%, p = 0.60), but definite/probable ST was higher in STEMI patients (1.9% vs 0.5% vs 0.7%, p = 0.03). Adjusted outcomes were not different in MI versus UA patients. CONCLUSIONS: Despite the novel EPC capture technology, COMBO stent PCI was associated with somewhat greater risk of 1-year TLF in ACS than in non-ACS patients, without significant differences in stent thrombosis. No differences were observed in 1-year TLF among ACS subtypes.

Combined and independent impact of coronary artery calcification and inflammation on risk for adverse cardiovascular events after percutaneous coronary intervention: Results from a large single-center registry.

PURPOSE: Our study investigated the impact of coronary artery calcification (CAC) and systemic inflammation on risks for major adverse cardiovascular events (MACE) following percutaneous coronary intervention (PCI). BACKGROUND: CAC and systemic inflammation are known to be associated with an increased risk of cardiovascular events. METHODS: A total of 17,711 consecutive patients who underwent PCI in our hospital between January 1, 2009 and December 31, 2015 were categorized according to the degree of CAC (moderate/severe vs. none/mild) and high-sensitivity C-reactive protein (hsCRP) level (≥2 vs. <2 mg/L). MACE was defined as death, myocardial infarction (MI), or target vessel revascularization (TVR) occurring over 1 year. RESULTS: Within the four groups, patients with both moderate/severe CAC and elevated hsCRP (n = 1,814 [10.2%]) were older with more comorbid risk factors compared to those with moderate/severe CAC alone (n = 1,687 [9.5%]), elevated hsCRP alone (n = 7,597 [42.9%]) or neither abnormality (n = 6,613 [37.3%]). The analogous 1-year MACE rates were 21.2, 14.9, 11.5, and 7.8%, respectively (p-trend < .001). Results were unchanged after multivariable adjustment, suggesting synergistic adverse effects in patients with both CAC and elevated hsCRP. CONCLUSIONS: The presence of both moderate/severe CAC and systemic inflammation confers a synergistic effect on risk for MACE following PCI, indicating the need for novel or more intense therapeutic interventions to mitigate risk in such patients.

One-year clinical outcomes in patients with chronic kidney disease treated with COMBO stents: From the COMBO collaboration.

BACKGROUND: Chronic kidney disease (CKD) patients undergoing percutaneous coronary intervention (PCI) experience greater ischemic events including clinically driven target lesion revascularization (CD-TLR). Whether the COMBO biodegradable-polymer sirolimus-eluting stent promotes better outcomes in these patients by virtue of endothelial progenitor cell capture technology is unknown. OBJECTIVE: We examined one-year outcomes by CKD status from the COMBO collaboration. METHODS: The COMBO collaboration was a patient-level pooled dataset from the REMEDEE and MASCOT registries (3,614 patients) of all-comers undergoing attempted COMBO stent PCI. The primary endpoint was one-year target lesion failure (TLF), composite of cardiac death, target-vessel myocardial infarction (TV-MI) or CD-TLR. Secondary endpoints included stent thrombosis (ST). RESULTS: The study included 6.4% (n = 231) CKD and 93.6% (n = 3,361) non-CKD patients. CKD patients were older and included more women with greater prevalence of several comorbidities but similar rate of acute coronary syndrome (50.6% vs. 54.5%, p = .26). CKD patients underwent radial PCI less often (56.1% vs. 70.3%, p < .001) and received clopidogrel (78.6% vs. 68.3%) more often (p = .004). One-year TLF occurred in 7.9% CKD vs. 3.7% non-CKD patients, p = .001. CKD patients also demonstrated greater incidence of cardiac death (6.2% vs. 1.2%, p < .0001), TV-MI (2.7% vs. 1.1%, p = .04) but similar CD-TLR (2.7% vs 2.2%, p = .61) and definite/probable ST (1.4% vs. 0.8%, p = .42), compared to non-CKD patients. CONCLUSIONS: CKD patients treated with COMBO stents had significantly greater incidence of one-year TLF compared to non-CKD patients driven by cardiac death and to a lesser extent TV-MI but not CD-TLR. They had similar rates of definite/probable ST.

Impact of insulin treated and non-insulin-treated diabetes compared to patients without diabetes on 1-year outcomes following contemporary PCI.

OBJECTIVE: We compared 1-year outcomes in insulin-treated diabetes mellitus (ITDM) and non-ITDM patients compared to nondiabetic (DM) patients following contemporary percutaneous coronary intervention (PCI). BACKGROUND: ITDM is associated with extensive atherosclerotic disease and worse cardiovascular prognosis compared to non-ITDM patients. METHODS: We evaluated PCI patients at a large tertiary center from 2010 to 2016, grouped according to diabetes and treatment status at baseline. One-year major adverse cardiac events (MACE) were defined as a composite of death, myocardial infarction (MI), or target vessel revascularization. Outcomes were adjusted using multivariable Cox regression methods. RESULTS: During the study period, 16,889 patients underwent PCI including 13.7% ITDM, 34.0% non-ITDM, and 52.3% non-DM patients. Patients with DM were younger, including more females and non-white patients, with higher body mass index and greater prevalence of prior revascularization and chronic kidney disease. Compared to others, ITDM patients more often presented with acute coronary syndrome, in-stent restenosis, or severe lesion calcification. There were no differences in discharge rates of dual antiplatelet therapy and statins, whereas beta-blockers were more commonly prescribed in DM patients. At 1-year, both ITDM and non-ITDM patients had greater risk of MACE compared with non-DM patients, and ITDM conferred greater adjusted risk than non-ITDM (ITDM = HR: 2.11, 95% CI [1.79,2.50]; non-ITDM = HR: 1.27, 95%CI [1.09,1.47]). CONCLUSIONS: The negative prognostic effect of DM following contemporary PCI is heightened in the presence of insulin treatment, compared to non-DM patients. Focus on secondary prevention, prescription of and adherence to optimal medical therapy is necessary for post-PCI risk reduction.

Impact of stent diameter on outcomes following percutaneous coronary intervention with second-generation drug-eluting stents: Results from a large single-center registry.

BACKGROUND: In patients treated with bare metal stents and first-generation drug-eluting stents (DES) smaller stent diameter (SD) has been associated with worse long term outcomes after percutaneous coronary intervention (PCI). Data on the impact of small SD on outcomes after PCI with second-generation DES is scarce. METHODS: Consecutive patients treated with second-generation DES between 2010 and 2016 were included in a single tertiary center. Patients were grouped according to SD: ≤2.50 mm, 2.75 ≤ 3.00 mm, 3.25 ≤ 3.50 mm, and >3.50 mm. One-year event rates were estimated using the Kaplan-Meier method and adjusted hazard ratios were generated using Cox regression analysis. The primary endpoint was major adverse cardiac events (MACE; death, myocardial infarction [MI], or target vessel revascularization [TVR]). RESULTS: Of the 17,607 patients who underwent PCI with second-generation DES, 32.6% (n = 5,741) had SD ≤2.5 mm, 39.1% (n = 6,890) had SD 2.75 ≤ 3.0 mm, 22.2% (n = 3,910) had SD 3.25 ≤ 3.5 mm, and 6.1% (n = 1,066) had SD >3.5 mm. At 1 year, MACE rates were 10.5%, 9.5%, 8.0%, and 8.0%, respectively, with increasing SD (p = .006). TVR rates decreased with increasing SD (7.2%, 5.8%, 4.7%, and 3.3%, respectively [p < .0001]) whereas rates of MI across SD groups were comparable (1.7%, 1.9%, 2.0%, and 1.5%, respectively [p = .60]). After multivariable adjustment, smaller SD remained associated with higher rates of MACE, TVR, and target lesion revascularization. CONCLUSION: In a large cohort of patients undergoing PCI with second-generation DES, smaller SD was associated with increased MACE, driven by higher rates of repeat revascularization. Further research into the optimal treatment of small coronary arteries is warranted.

Incidence, predictors and impact of stroke on mortality among patients with acute coronary syndromes following percutaneous coronary intervention-Results from the PROMETHEUS registry.

BACKGROUND: Stroke represents a potentially calamitous complication among patients with acute coronary syndrome (ACS) undergoing percutaneous intervention (PCI). Data on the distribution of stroke occurrence post-PCI and its impact on mortality are scarce. OBJECTIVES: We sought to determine the incidence, predictors and impact of stroke on mortality in ACS patients undergoing PCI. METHODS: A total of 19,914 ACS patients underwent PCI in the PROMETHEUS multicenter observational study. We calculated the cumulative stroke incidence at 30 days and 1 year using the Kaplan Meier method. We also compared the distribution of stroke, myocardial infarction (MI), and bleeding across time and evaluated their overlap. Predictors of stroke were identified through multivariable Cox-regression. Stroke, MI, and bleeding were assessed as time-updated covariates to estimate how each impacts subsequent mortality. RESULTS: We found that 244 patients had a stroke within 1 year, a cumulative incidence of 1.5%. Previous cerebrovascular disease was the strongest predictor for post-PCI stroke, followed by ST-elevation MI presentation, hypertension, non-ST-elevation MI presentation, smoking, female sex, and age. Mortality risk was significantly higher among those who had a stroke versus those who did not (adjusted HR 4.84, p < .0001). However, the association attenuated over time with a much larger effect in the first 30 days of its occurrence (adjusted HR 17.7; 95% CI: 12.3-25.4, p < .0001) versus beyond 30 days (adjusted HR 1.22; 95% CI: 0.6-2.46, p = .58). CONCLUSIONS: Stroke occurrence within 1 year was not uncommon for ACS patients undergoing PCI. When compared with MI and bleeding, stroke had a substantial impact on mortality that attenuated rapidly over time.

Temporal trends, determinants, and impact of high-intensity statin prescriptions after percutaneous coronary intervention: Results from a large single-center prospective registry.

BACKGROUND: High-intensity statins (HIS) are recommended for secondary prevention following percutaneous coronary intervention (PCI). We aimed to describe temporal trends and determinants of HIS prescriptions after PCI in a usual-care setting. METHODS: All patients with age ≤75 years undergoing PCI between January 2011 and May 2016 at an urban, tertiary care center and discharged with available statin dosage data were included. HIS were defined as atorvastatin 40 or 80 mg, rosuvastatin 20 or 40 mg, and simvastatin 80 mg. RESULTS: A total of 10,495 consecutive patients were included. Prevalence of HIS prescriptions nearly doubled from 36.6% in 2011 to 60.9% in 2016 (P < .001), with a stepwise increase each year after 2013. Predictors of HIS prescriptions included ST-segment elevation myocardial infarction/non-ST-segment elevation myocardial infarction (odds ratio [OR] 4.60, 95% CI 3.98-5.32, P < .001) and unstable angina (OR 1.31, 95% CI 1.19-1.45, P < .001) as index event, prior myocardial infarction (OR 1.48, 95% CI 1.34-1.65, P < .001), and co-prescription of ß-blocker (OR 1.26, 95% CI 1.12-1.43, P < .001). Conversely, statin treatment at baseline (OR 0.86, 95% CI 0.77-0.96, P = .006), Asian races (OR 0.73, 95% CI 0.65-0.83, P < .001), and older age (OR 0.90, 95% CI 0.88-0.92, P < .001) were associated with reduced HIS prescriptions. There was no significant association between HIS prescriptions and 1-year rates of death, myocardial infarction, or target-vessel revascularization (adjusted hazard ratio 0.98, 95% CI 0.84-1.15, P = .84), although there was a trend toward reduced mortality (adjusted hazard ratio 0.71, 95% CI 0.50-1.00, P = .05). CONCLUSION: Although the rate of HIS prescriptions after PCI has increased in recent years, important heterogeneity remains and should be addressed to improve practices in patients undergoing PCI.

Small-vessel PCI outcomes in men, women, and minorities following platinum chromium everolimus-eluting stents: Insights from the pooled PLATINUM Diversity and PROMUS Element Plus Post-Approval studies.

OBJECTIVE: We evaluated 1-year outcomes after platinum chromium everolimus-eluting stents (PtCr-EES) in small versus non-small coronary arteries within a large, diverse sample of men, women, and minorities. BACKGROUND: There exists limited outcomes data on the use of second-generation drug-eluting stent to treat small diameter coronary arteries. METHODS: We pooled patients from the PLATINUM Diversity and PROMUS Element Plus stent registries. Small-vessel percutaneous coronary intervention (SV-PCI) was defined as ≥1 target lesion with reference vessel diameter (RVD) ≤2.5 mm. Endpoints included major adverse cardiac event (MACE; death, myocardial infarction [MI] or target vessel revascularization [TVR]), target vessel failure (TVF; death related to the target vessel, target vessel MI or TVR) and definite/probable stent thrombosis (ST). Multivariable Cox regression was used to risk-adjust outcomes. RESULTS: We included 4,155/4,182 (99%) patients with available RVD, of which 1,607 (39%) underwent small-vessel PCI. SV-PCI was not associated with increased MACE (adjHR 1.02; 95%CI 0.81-1.30) or TVF (adjHR 1.07; 95%CI 0.82-1.39). MI risk was lower in white men compared to women and minorities, both in the setting of SV-PCI (adjHR 0.41; 95%CI 0.23-0.74 and adjHR 0.39; 95%CI 0.20-0.75, respectively) and for non-SV-PCI (adjHR 0.61; 95%CI 0.38-0.99 and adjHR 0.45; 95%CI 0.27-0.74, respectively). There was no significant interaction between RVD and sex or minority status for any endpoint. CONCLUSION: In a large diverse contemporary PCI outcomes database, SV-PCI with PtCr-EES was not associated with increased MACE or TVR and did not account for the increased MI risk noted in women and minorities compared to white men.

Use of prasugrel and clinical outcomes in African-American patients treated with percutaneous coronary intervention for acute coronary syndromes.

OBJECTIVE: To investigate the use of prasugrel after percutaneous coronary intervention (PCI) in African American (AA) patients presenting with acute coronary syndrome (ACS). BACKGROUND: AA patients are at higher risk for adverse cardiovascular outcomes after PCI and may derive greater benefit from the use of potent antiplatelet therapy. METHODS: Using the multicenter PROMETHEUS observational registry of ACS patients treated with PCI, we grouped patients by self-reported AA or other races. Clinical outcomes at 90-day and 1-year included non-fatal myocardial infarction (MI), major adverse cardiac events (composite of death, MI, stroke, or unplanned revascularization) and major bleeding. RESULTS: The study population included 2,125 (11%) AA and 17,707 (89%) non-AA patients. AA patients were younger, more often female (46% vs. 30%) with a higher prevalence of diabetes mellitus, chronic kidney disease, and prior coronary intervention than non-AA patients. Although AA patients more often presented with troponin (+) ACS, prasugrel use was much less common in AA vs. non-AA (11.9% vs. 21.4%, respectively, P = 0.001). In addition, the use of prasugrel increased with the severity of presentation in non-AA but not in AA patients. Multivariable logistic regression showed AA race was an independent predictor of reduced use of prasugrel (0.42 [0.37-0.49], P < 0.0001). AA race was independently associated with a significantly higher risk of MI at 90-days and 1 year after PCI. CONCLUSIONS: Despite higher risk clinical presentation and worse 1-year ischemic outcomes, AA race was an independent predictor of lower prasugrel prescription in a contemporary population of ACS patients undergoing PCI.

Residual inflammatory risk and the impact on clinical outcomes in patients after percutaneous coronary interventions.

Aims: It remains unknown what percentage of patients treated with percutaneous coronary artery intervention (PCI) have high residual inflammatory risk (RIR). Moreover, the impact of RIR on clinical outcomes has not been established. The objective of this study is to determine the prevalence of patients with persistent high levels of inflammation after PCI and to evaluate clinical outcomes according to inflammatory response. Methods and results: This is a retrospective cohort study assessing patients undergoing PCI between 2009 and 2016 with serial inflammatory status assessment from a large, prospective, and single-centre PCI registry. Assessment of inflammation status with at least two high sensitive C-reactive protein (hsCRP) measurements at baseline and follow-up with >4 weeks apart. High RIR was defined as an hsCRP≥ 2 mg/L. Patients were divided into four groups: persistent high RIR, increased RIR (first low-, then high hsCRP), attenuated RIR (first high-, then low hsCRP), or persistent low RIR. The primary endpoint was all-cause mortality at 1 year follow-up. Occurrence of myocardial infarction (MI) was assessed as secondary outcome. Seven thousand and twenty-six patients were identified with serial hsCRP measurements (30.8% of all PCI patients). Of these patients 2654 (38%) had persistent high RIR, 719 patients (10%) had increased RIR, 1088 patients (15%) had attenuated RIR, and persistent low RIR was seen in 2565 patients (37%). All-cause mortality at 1 year was 2.6% in patients with persistent high RIR, compared with 1.0% in increased RIR, 0.3% in attenuated RIR, and 0.7% in persistent low RIR patients, P < 0.01. MI at 1 year was observed in 7.5% of persistent high RIR, compared with 6.4% in increased RIR, 4.6% in attenuated RIR, and 4.3% in persistent low RIR, P < 0.01. In an adjusted model, including accounting for diabetes mellitus, acute coronary syndrome, and baseline low-density lipoprotein, results were sustained. Conclusion: Persistent high RIR is observed frequently in patients undergoing PCI. In these patients, significantly higher all-cause mortality and MI rates are observed at 1 year follow-up. Residual inflammatory risk in patients undergoing PCI should be identified and treatment options should be further explored.

Prevalence, correlates, and impact of coronary calcification on adverse events following PCI with newer-generation DES: Findings from a large multiethnic registry.

OBJECTIVES: We sought to determine the prevalence, predictors, and clinical impact of target lesion calcification in patients undergoing percutaneous coronary intervention (PCI) with newer generation drug-eluting stents (DES) and devices. BACKGROUND: Coronary calcification is independently associated with adverse outcomes following PCI. While newer DES and contemporary devices are considered safer and more efficacious, their influence on outcomes following PCI of heavily calcified lesions is unknown. METHODS: We performed a retrospective analysis of a large, multiethnic cohort of patients undergoing PCI with new generation DES at an academic center between 2009 and 2013. Coronary calcification was qualitatively assessed as none/mild, moderate, or severe. Independent demographic, clinical, and anatomic predictors of moderate/severe calcification were identified using logistic regression. Associations between coronary calcification and 1-year MACE (death, myocardial infarction, or target vessel revascularization) were examined using Cox modeling. RESULTS: Compared to patients with none/mild (n = 10,180; 82.0%), those with moderate (n = 1,271; 10.0%) or severe (n = 994; 8.0%) calcification were older, more often Caucasian, had more complex target lesions, and worse renal function. The strongest demographic, clinical, and anatomic correlates of moderate/severe calcification were age, Caucasian race, renal dysfunction, lesion length, and left main location. Unadjusted MACE rates among those with none/mild, moderate, and severe calcification were 8.3, 14.6, and 17.8%, respectively (P < 0.001). After multivariable adjustment, the hazard ratio (95% CI) for MACE associated with moderate or severe coronary calcification was 1.63. CONCLUSIONS: Target lesion calcification remains independently associated with adverse outcomes in patients treated with newer generation DES and modern devices.

Use of prasugrel vs clopidogrel and outcomes in patients with acute coronary syndrome undergoing percutaneous coronary intervention in contemporary clinical practice: Results from the PROMETHEUS study.

BACKGROUND AND OBJECTIVES: We sought to determine the frequency of use and association between prasugrel and outcomes in acute coronary syndrome patients undergoing percutaneous coronary intervention (PCI) in clinical practice. METHODS: PROMETHEUS was a multicenter observational registry of acute coronary syndrome patients undergoing PCI from 8 centers in the United States that maintained a prospective PCI registry for patient outcomes. The primary end points were major adverse cardiovascular events at 90days, a composite of all-cause death, nonfatal myocardial infarction, stroke, or unplanned revascularization. Major bleeding was defined as any bleeding requiring hospitalization or blood transfusion. Hazard ratios (HRs) were generated using multivariable Cox regression and stratified by the propensity to treat with prasugrel. RESULTS: Of 19,914 patients (mean age 64.4years, 32% female), 4,058 received prasugrel (20%) and 15,856 received clopidogrel (80%). Prasugrel-treated patients were younger with fewer comorbid risk factors compared with their counterparts receiving clopidogrel. At 90days, there was a significant association between prasugrel use and lower major adverse cardiovascular event (5.7% vs 9.6%, HR 0.58, 95% CI 0.50-0.67, P<.0001) and bleeding (1.9% vs 2.9%, HR 0.65, 95% CI 0.51-0.83, P<.001). After propensity stratification, associations were attenuated and no longer significant for either outcome. Results remained consistent using different approaches to adjusting for potential confounders. CONCLUSIONS: In contemporary clinical practice, patients receiving prasugrel tend to have a lower-risk profile compared with those receiving clopidogrel. The lower ischemic and bleeding events associated with prasugrel use were no longer evident after accounting for these baseline differences.

Sex-related differences in outcomes among men and women under 55 years of age with acute coronary syndrome undergoing percutaneous coronary intervention: Results from the PROMETHEUS study.

BACKGROUND: Young women undergoing percutaneous coronary intervention (PCI) for acute coronary syndrome (ACS) experience greater adverse events than men, potentially due to under-treatment. We sought to compare the 1-year outcomes by sex in patients ≤55 years of age from a contemporary PCI cohort. METHODS: PROMETHEUS was a retrospective multicenter observational US study comparing outcomes in clopidogrel and prasugrel treated patients following ACS PCI. MACE was defined as a composite of death, myocardial infarction, stroke or unplanned revascularization. Clinically significant bleeding was defined as bleeding requiring transfusion or hospitalization. Hazard ratios were generated using multivariable Cox proportional hazards regression. RESULTS: The study cohort included 4,851 patients of which 1,162 (24.0%) were women and 3,689 (76.0%) were men. In this cohort, the prevalence of diabetes (41.0 vs. 27.9%) and chronic kidney disease (12.7 vs. 7.2%) was higher among women compared with men. Irrespective of sex, prasugrel was used in less than one-third of patients (31.8% in men vs. 28.1% in women, P = 0.01). Unadjusted, 1-year MACE (21.1% vs. 16.2%, P < 0.001) and bleeding (3.6% vs. 2.2%, P = 0.01) was significantly higher in women compared with men, but these results were no longer significant after adjustment for risk (HR 1.13, 95% CI 0.94-1.36 for MACE and HR 1.31, 95% CI 0.85-2.04 for bleeding). CONCLUSION: Women ≤ 55 years of age undergoing ACS PCI have significantly greater comorbidities than young men. Despite a higher risk clinical phenotype in women, prasugrel use was significantly lower in women than men. Female sex was associated with a significantly higher risk of 1-year MACE and bleeding than male sex, findings that are attributable to baseline differences. © 2016 Wiley Periodicals, Inc.

Impact of proton pump inhibitors and dual antiplatelet therapy cessation on outcomes following percutaneous coronary intervention: Results From the PARIS Registry.

BACKGROUND: Proton pump inhibitors (PPI) may decrease the availability of clopidogrel by competitive antagonism, leading to a potential increase in ischemic events. METHODS: We evaluated patients from the all-comer PARIS registry treated with dual antiplatelet therapy (DAPT) with aspirin and clopidogrel following coronary stenting for outcomes stratified by PPI use. Two-year major adverse cardiovascular events (MACE), composite of cardiac death, myocardial infarction, definite or probable stent thrombosis or target lesion revascularization (TLR), and net adverse cardiac events (NACE), composite of MACE or Bleeding Academic Research consortium (BARC) type 3 or 5 bleeding were assessed. We also explored associations between PPI use and patterns of 2-year DAPT cessation. RESULTS: The cohort comprised 4635 patients (23% PPI users) with mean age 64.4 ±11.4 years. Two year adjusted risk of MACE (HR: 1.27, 95% CI: 1.04-1.55), NACE (HR: 1.21, 95% CI: 1.01-1.44) and TLR (HR: 1.33, 95% CI: 1.04-1.71) were significantly higher in PPI users vs. non-users, without a difference in bleeding. Although the incidence of 2-year DAPT discontinuation and interruption was similar, DAPT disruption was significantly lower among PPI users vs. non-users (10.0% vs. 14.7%, P <0.0001). Compared to non-PPI users on continued DAPT, disruption was associated with higher MACE in both PPI users (HR: 2.34, 95% CI: 1.38-3.97) and non-users (HR: 1.41, 95% CI: 1.02-1.94) but greater BARC 3,5 bleeding only in non-PPI users (HR: 2.06, 95% CI: 1.21-3.51). CONCLUSIONS: In clopidogrel treated PCI patients, the 2-year adjusted risk of MACE and NACE was significantly higher in PPI users driven by higher TLR compared to non-PPI users, without a difference in bleeding. PPI use was associated with lower incidence of DAPT disruption without an increase in disruption related bleeding compared to non-PPI users on DAPT. © 2016 Wiley Periodicals, Inc.

Mid-term outcomes of consecutive 998 cases of coronary atherectomy in contemporary clinical practice.

OBJECTIVES: To compare clinical and safety endpoints with use of rotational (RA) and orbital (OA) atherectomy in a large patient population with moderate to severely calcified lesions undergoing percutaneous coronary intervention (PCI). BACKGROUND: Coronary artery calcification (CAC) has been recognized as a risk factor for adverse outcomes with coronary artery disease (CAD). Though atheroablative techniques, RA and OA have been used extensively, comparison of their clinical and safety endpoints is lacking. Comparison of these two modalities formed the basis of our study. METHODS AND RESULTS: Of 12 001 patients who underwent PCI at our institution between January 2013-December 2015, we studied 998 consecutive patients with severe calcification treated with atheroablation. We assessed clinical outcomes including death, myocardial infarction (MI) and target lesion revascularization (TLR) at 30 days and 6 months in addition to post-procedural complications. Device perforation occurred more frequently with use of OA at high burr speed versus RA (1.9%, n = 3 vs. 0.2%, n = 2, P = 0.03). Rates of composite adverse events were similar between groups at 6 months (18.55 vs. 11.46%; P = 0.11) CONCLUSION: In this retrospective, single center study, we observed no significant differences in 6-month rates of adverse events associated with use of OA vs. RA in patients with moderate to severe calcification undergoing PCI. Larger, prospective studies are needed to confirm our findings.

TGF-ß1-induced PAI-1 contributes to a profibrotic network in patients with eosinophilic esophagitis.

BACKGROUND: Eosinophilic esophagitis (EoE) is an allergic disease of increasing worldwide incidence. Complications are due to tissue remodeling and involve TGF-ß1-mediated fibrosis. Plasminogen activator inhibitor 1 (PAI-1/serpinE1) can be induced by TGF-ß1, but its role in EoE is not known. OBJECTIVE: We sought to understand the expression and role of PAI-1 in patients with EoE. METHODS: We used esophageal biopsy specimens and plasma samples from control subjects and patients with EoE, primary human esophageal epithelial cells, and fibroblasts from patients with EoE in immunohistochemistry, quantitative PCR, and immunoassay experiments to understand the induction of PAI-1 by TGF-ß1, the relationship between PAI-1 and esophageal fibrosis, and the role of PAI-1 in fibrotic gene expression. RESULTS: PAI-1 expression was significantly increased in epithelial cells of biopsy specimens from patients with active EoE compared with that seen in biopsy specimens from patients with inactive EoE or control subjects (P < .001). Treatment of primary esophageal epithelial cells with recombinant TGF-ß1 increased PAI-1 transcription, intracellular protein expression, and secretion. Esophageal PAI-1 expression correlated with basal zone hyperplasia, fibrosis, and markers of esophageal remodeling, including vimentin, TGF-ß1, collagen I, fibronectin, and matrix metalloproteases, and plasma PAI-1 levels correlated with plasma TGF-ß1 levels. PAI-1 inhibition significantly decreased baseline and TGF-ß1-induced fibrotic gene expression. CONCLUSIONS: PAI-1 expression is significantly increased in the epithelium in patients with EoE and reflects fibrosis, and its inhibition decreases TGF-ß1-induced gene expression. Epithelial PAI-1 might serve as a marker of EoE severity and form part of a TGF-ß1-induced profibrotic network.

Ticagrelor with aspirin or alone in high-risk patients after coronary intervention: Rationale and design of the TWILIGHT study.

BACKGROUND: Dual antiplatelet therapy (DAPT) is necessary to prevent thrombosis yet increases bleeding after percutaneous coronary intervention (PCI) with drug-eluting stents (DES). Antiplatelet monotherapy with a potent P2Y12 receptor antagonist may reduce bleeding while maintaining anti thrombotic efficacy compared with conventional DAPT. METHODS: TWILIGHT is a randomized, double-blind placebo-controlled trial evaluating the comparative efficacy and safety of antiplatelet monotherapy versus DAPT in up to 9000 high-risk patients undergoing PCI with DES. Upon enrollment after successful PCI, all patients will be treated with open label low-dose aspirin (81-100 mg daily) plus ticagrelor (90 mg twice daily) for 3 months. Event-free patients will then be randomized in a double-blind fashion to low-dose aspirin versus matching placebo with continuation of open-label ticagrelor for an additional 12 months. The primary hypothesis is that a strategy of ticagrelor monotherapy will be superior with respect to the primary endpoint of bleeding academic research consortium type 2, 3 or 5, while maintaining non-inferiority for ischemic events compared with ticagrelor plus ASA. CONCLUSIONS: TWILIGHT is the largest study to date that is specifically designed and powered to demonstrate reductions in bleeding with ticagrelor monotherapy versus ticagrelor plus ASA beyond 3 months post-procedure in a high-risk PCI population treated with DES. The trial will provide novel insights with respect to the potential role of ticagrelor monotherapy as an alternative for long-term platelet inhibition in a broad population of patients undergoing PCI with DES.

Impact of an integrated treatment algorithm based on platelet function testing and clinical risk assessment: results of the TRIAGE Patients Undergoing Percutaneous Coronary Interventions To Improve Clinical Outcomes Through Optimal Platelet Inhibition study.

Assessment of platelet reactivity alone for thienopyridine selection with percutaneous coronary intervention (PCI) has not been associated with improved outcomes. In TRIAGE, a prospective multicenter observational pilot study we sought to evaluate the benefit of an integrated algorithm combining clinical risk and platelet function testing to select type of thienopyridine in patients undergoing PCI. Patients on chronic clopidogrel therapy underwent platelet function testing prior to PCI using the VerifyNow assay to determine high on treatment platelet reactivity (HTPR, ≥230 P2Y12 reactivity units or PRU). Based on both PRU and clinical (ischemic and bleeding) risks, patients were switched to prasugrel or continued on clopidogrel per the study algorithm. The primary endpoints were (i) 1-year major adverse cardiovascular events (MACE) composite of death, non-fatal myocardial infarction, or definite or probable stent thrombosis; and (ii) major bleeding, Bleeding Academic Research Consortium type 2, 3 or 5. Out of 318 clopidogrel treated patients with a mean age of 65.9 ± 9.8 years, HTPR was noted in 33.3 %. Ninety (28.0 %) patients overall were switched to prasugrel and 228 (72.0 %) continued clopidogrel. The prasugrel group had fewer smokers and more patients with heart failure. At 1-year MACE occurred in 4.4 % of majority HTPR patients on prasugrel versus 3.5 % of primarily non-HTPR patients on clopidogrel (p = 0.7). Major bleeding (5.6 vs 7.9 %, p = 0.47) was numerically higher with clopidogrel compared with prasugrel. Use of the study clinical risk algorithm for choice and intensity of thienopyridine prescription following PCI resulted in similar ischemic outcomes in HTPR patients receiving prasugrel and primarily non-HTPR patients on clopidogrel without an untoward increase in bleeding with prasugrel. However, the study was prematurely terminated and these findings are therefore hypothesis generating.