Abstract Background The prospective, randomized FREEDOM (Comparison of Two Treatments for Multivessel Coronary Artery Disease in Individuals With Diabetes) trial found coronary artery bypass graft ...surgery (CABG) was associated with better clinical outcomes than percutaneous coronary intervention (PCI) in patients with diabetes and multivessel disease, managed with or without insulin. Objectives In this subgroup analysis of the FREEDOM trial, we examined the association of long-term clinical outcomes after revascularization in patients with insulin-treated diabetes mellitus (ITDM) compared with patients not treated with insulin. Methods A total of 1,850 FREEDOM subjects had an index revascularization procedure performed: 956 underwent PCI with drug-eluting stents (DES), and 894 underwent CABG. A total of 602 patients (32.5%) had ITDM (PCI/DES n = 325, 34%; CABG n = 277, 31%). Subjects were classified according to ITDM versus non-ITDM, with comparison of PCI/DES versus CABG for each group. Interaction analyses were performed for treatment by diabetes mellitus (DM) status alone and for treatment by DM status by coronary lesion complexity. Analyses were performed for the primary outcome composite of death/stroke/myocardial infarction (MI) using all available follow-up data. Results The overall 5-year event rate of death/stroke/MI was significantly higher in ITDM versus non-ITDM patients (28.7% vs. 19.5%, p < 0.001), which persisted even after adjustment for multiple baseline factors, angiographic complexity, and revascularization treatment group (death/stroke/MI hazard ratio HR: 1.35, 95% confidence interval CI: 1.06 to 1.73, p = 0.014). With respect to the primary composite endpoint, CABG was superior to PCI/DES in both DM types and the magnitude of treatment effect was similar (interaction p = 0.40) for ITDM (PCI vs. CABG HR: 1.21; 95% CI: 0.87 to 1.69) and non-ITDM patients (PCI vs. CABG HR: 1.46; 95% CI 1.10 to 1.94), even after adjusting for the angiographic SYNTAX score level. Based on 5-year event rates, the number needed to treat with CABG versus PCI to prevent 1 event is 12.7 in ITDM and 13.2 in non-ITDM. Conclusions In patients with diabetes and multivessel coronary artery disease, the rate of major adverse cardiovascular events (death, MI, or stroke) is higher in patients treated with insulin than in those not treated with insulin. Furthermore, we did not detect a significant difference in the magnitude of PCI versus CABG treatment effect for patients treated with insulin and those not treated with insulin. (Comparison of Two Treatments for Multivessel Coronary Artery Disease in Individuals With Diabetes FREEDOM; NCT00086450 ).
The long-term risk associated with different coronary artery disease (CAD) presentations in women undergoing percutaneous coronary intervention (PCI) with drug-eluting stents (DES) is poorly ...characterized. We pooled patient-level data for women enrolled in 26 randomized clinical trials. Of 11,577 women included in the pooled database, 10,133 with known clinical presentation received a DES. Of them, 5,760 (57%) had stable angina pectoris (SAP), 3,594 (35%) had unstable angina pectoris (UAP) or non–ST-segment-elevation myocardial infarction (NSTEMI), and 779 (8%) had ST-segment-elevation myocardial infarction (STEMI) as clinical presentation. A stepwise increase in 3-year crude cumulative mortality was observed in the transition from SAP to STEMI (4.9% vs 6.1% vs 9.4%; p <0.01). Conversely, no differences in crude mortality rates were observed between 1 and 3 years across clinical presentations. After multivariable adjustment, STEMI was independently associated with greater risk of 3-year mortality (hazard ratio HR 3.45; 95% confidence interval CI 1.99 to 5.98; p <0.01), whereas no differences were observed between UAP or NSTEMI and SAP (HR 0.99; 95% CI 0.73 to 1.34; p = 0.94). In women with ACS, use of new-generation DES was associated with reduced risk of major adverse cardiac events (HR 0.58; 95% CI 0.34 to 0.98). The magnitude and direction of the effect with new-generation DES was uniform between women with or without ACS (pinteraction = 0.66). In conclusion, in women across the clinical spectrum of CAD, STEMI was associated with a greater risk of long-term mortality. Conversely, the adjusted risk of mortality between UAP or NSTEMI and SAP was similar. New-generation DESs provide improved long-term clinical outcomes irrespective of the clinical presentation in women.
We sought to examine the intravascular ultrasound (IVUS) findings of stent fracture. Stent fracture has been implicated as a cause of drug-eluting stent failure. IVUS is more likely to identify ...mechanisms of stent failure—including stent fracture—than angiography. Twenty stent fractures diagnosed by IVUS in 17 patients were evaluated. Eighteen stent fractures (90%) occurred in sirolimus-eluting Cypher stents, and 2 stent fractures (10%) occurred in bare metal stents, but none occurred in paclitaxel-eluting Taxus stents. Half of the stent fractures presented ≤1 year after implantation, and ½ presented >1 year after implantation. IVUS analysis showed that 9 stent fractures were complete (45%) and 11 were partial (55%); 10 (50%) were adjacent to stent metal overlap; and 5 occurred in a coronary aneurysm accompanied by malapposition (all Cypher stents) despite the absence of an aneurysm at index stenting. Compared with 60 matched control segments in patients without stent fracture, but with similar clinical events, the stent fracture group had longer stent segments (45.2 ± 23.0 vs 28.5 ± 14.9 mm, p = 0.003). Comparing stent fractures associated with an aneurysm (n = 5) with those that did not occur in association with an aneurysm (n = 15) showed that complete stent fracture was more frequent (100% vs 27%, p = 0.008), and all presented >1 year after index stenting (vs 33%, p = 0.03). In conclusion, IVUS is helpful to identify stent fracture as a cause of stent failure and to understand possible mechanisms of stent fracture such as aneurysm formation.
COVID-19 has proven to be particularly challenging given the complex pathogenesis of SARS-CoV-2. Early data have demonstrated how the host response to this novel coronavirus leads to the ...proliferation of pro-inflammatory cytokines, massive endothelial damage, and generalized vascular manifestations. While SARS-CoV-2 primarily targets the upper and lower respiratory tract, other organ systems are also affected. SARS-CoV-2 relies on 2 host cell receptors for successful attachment: angiotensin-converting enzyme 2 and transmembrane protease serine 2. Clinicopathologic reports have demonstrated associations between severe COVID-19 and viral coagulopathy, resulting in pulmonary embolism; venous, arterial, and microvascular thrombosis; lung endothelial injury; and associated thrombotic complications leading to acute respiratory distress syndrome. Viral coagulopathy is not novel given similar observations with SARS classic, including the consumption of platelets, generation of thrombin, and increased fibrin degradation product exhibiting overt disseminated intravascular coagulation–like syndrome. The specific mechanism(s) behind the thrombotic complications in COVID-19 patients has yet to be fully understood. Parenteral anticoagulants, such as heparin and low-molecular-weights heparins, are widely used in the management of COVID-19 patients. Beyond the primary (anticoagulant) effects of these agents, they may exhibit antiviral, anti-inflammatory, and cytoprotective effects. Direct oral anticoagulants and antiplatelet agents are also useful in the management of these patients. Tissue plasminogen activator and other fibrinolytic modalities may also be helpful in the overall management. Catheter-directed thrombolysis can be used in patients developing pulmonary embolism. Further investigations are required to understand the molecular and cellular mechanisms involved in the pathogenesis of COVID-19-associated thrombotic complications.
A periprocedural myocardial infarction, defined as the advent of new Q-waves or a creatine kinase-MB elevation >8× normal has been previously validated as predictive of subsequent mortality. We ...examined the effects of using this clinically relevant definition of periprocedural myocardial infarction instead of the original protocol definition on outcomes in the recent PROTECT II A Prospective, Multi-center, Randomized Controlled Trial of the IMPELLA RECOVER LP 2.5 System Versus Intra Aortic Balloon Pump (IABP) in Patients Undergoing Non Emergent High Risk PCI trial. In this trial, patients who were undergoing high-risk percutaneous coronary intervention (PCI) were randomized to either an intra-aortic balloon pump (IABP, n = 211) or a left ventricular assist device (Impella, n = 216). All eligible patients per study protocol were included in the analysis. Patient outcomes were compared up to 90 days, the longest available follow-up, on the composite end points of major adverse events (MAE) and major adverse cardiac and cerebral events (MACCE = death, stroke, myocardial infarction, and repeat revascularization). At 90 days, the rates of both composite end points were lower in the Impella group compared with the IABP group (MAE, 37% vs 49%, p = 0.014 respectively; MACCE, 22% vs 31%, p = 0.034 respectively). There were no differences in death or large myocardial infarction between the 2 arms. By multivariable analysis, treatment with Impella as opposed to IABP was an independent predictor for freedom from MAE (odds ratio = 0.75 95% confidence interval 0.61 to 0.92, p = 0.007) and MACCE (odds ratio = 0.76 95% confidence interval 0.61 to 0.96, p = 0.020) at 90 days postprocedure. In conclusion, hemodynamic support with Impella compared with IABP during high-risk PCI in the PROTECT-II trial resulted in improved event-free survival at 3-month follow-up; this finding was further supported by multivariate analyses.
Objectives This study sought to develop a practical risk score to predict the risk of stent thrombosis (ST) after percutaneous coronary intervention (PCI) for acute coronary syndromes (ACS). ...Background ST is a rare, yet feared complication after PCI with stent implantation. A risk score for ST after PCI in ACS can be a helpful tool to personalize risk assessment. Methods This study represents a patient-level pooled analysis of 6,139 patients undergoing PCI with stent implantation for ACS in the HORIZONS-AMI (Harmonizing Outcomes With Revascularization and Stents in Acute Myocardial Infarction) and ACUITY (Acute Catheterization and Urgent Intervention Triage Strategy) trials who were randomized to treatment with bivalirudin versus heparin plus a glycoprotein IIb/IIIa inhibitor. The cohort was randomly divided into a risk score development cohort (n = 4,093) and a validation cohort (n = 2,046). Cox regression methods were used to identify clinical, angiographic, and procedural characteristics associated with Academic Research Consortium–defined definite/probable ST at 1 year. Each covariate in this model was assigned an integer score based on the regression coefficients. Results Variables included in the risk score were type of ACS (ST-segment elevation myocardial infarction, non-ST-segment elevation ACS with ST deviation, or non–ST-segment elevation ACS without ST changes), current smoking, insulin-dependent diabetes mellitus, prior PCI, baseline platelet count, absence of early (pre-PCI) anticoagulant therapy, aneurysmal/ulcerated lesion, baseline TIMI (Thrombolysis In Myocardial Infarction) flow grade 0/1, final TIMI flow grade <3, and number of treated vessels. Risk scores 1 to 6 were considered low risk, 7 to 9 intermediate risk, and 10 or greater high risk for ST. Rates of ST at 1 year in low-, intermediate-, and high-risk categories were 1.36%, 3.06%, and 9.18%, respectively, in the development cohort (p for trend <0.001), and 1.65%, 2.77%, and 6.45% in the validation cohort (p for trend = 0.006). The C-statistic for this risk score was over 0.65 in both cohorts. Conclusions The individual risk of ST can be predicted using a simple risk score based on clinical, angiographic, and procedural variables. (Harmonizing Outcomes With Revascularization and Stents in Acute Myocardial Infarction HORIZONS-AMI; NCT00433966 ) (Comparison of Angiomax Versus Heparin in Acute Coronary Syndromes ACUITY; NCT00093158 )
Objectives The aim of this study was to evaluate long-term clinical outcomes after percutaneous coronary intervention (PCI) for chronic total occlusions (CTO). Background Despite technical ...advancements, there is a paucity of data on long-term outcomes after PCI of CTO. Methods We evaluated long-term clinical outcomes in 1,791 patients who underwent PCI of 1,852 CTO at 3 tertiary care centers in the United States, South Korea, and Italy between 1998 and 2007. Median follow-up was 2.9 years (interquartile range: 1.5 to 4.6 years). Results Procedural success was obtained in 1,226 (68%) patients. Stents were implanted in 1,160 patients (95%); 396 patients (34%) received bare-metal stents (BMS), and 764 patients (66%) received drug-eluting stents (DES). After multivariable analysis, successful CTO PCI was an independent predictor of a lower cardiac mortality (hazard ratio HR: 0.40, 95% confidence interval CI: 0.21 to 0.75, p < 0.01) and reduced need for coronary artery bypass graft surgery (HR: 0.21, 95% CI: 0.13 to 0.40, p < 0.01); it also correlated with a strong trend toward lower all-cause mortality (HR: 0.63, 95% CI: 0.40 to 1.00, p = 0.05) at 5-year follow-up. Among patients who underwent stent implantation, treatment with DES rather than BMS resulted in less target vessel revascularization at long-term follow-up (17.2% vs. 31.1%, p < 0.01); definite/probable stent thrombosis rates were similar (DES 1.7%, BMS 2.3%, p = 0.58). Within the DES subgroup, patients treated with paclitaxel-eluting stents and sirolimus-eluting stents had similar clinical outcomes. Conclusions Successful CTO PCI is associated with reduced long-term cardiac mortality and need for coronary artery bypass graft surgery. Treatment of CTO with DES rather than BMS is associated with a significant reduction in target vessel revascularization with similar rates of stent thrombosis. Paclitaxel-eluting stents and sirolimus-eluting stents had similar long-term safety and efficacy outcomes.
Background Thrombocytopenia (TP) is a common abnormality in patients presenting with acute coronary syndrome. Whether baseline TP has any influence on the outcome of patients treated with primary ...angioplasty for acute myocardial infarction is unknown. Methods We sought to detect the impact of baseline TP on the early and late outcomes of patients with ST-elevation myocardial infarction in the HORIZONS-AMI trial that included a protocol of immediate angiography and primary percutaneous coronary intervention. Results Baseline TP was found in 4.2% of patients and was associated with a higher incidence of cardiovascular mortality, major bleeding, and major cardiovascular events at short- and long-term follow-up. The 30-day rates of death, major bleeding, major cardiac events, and major cardiac events plus major bleeding were 6.2%, 11.9%, 9.6%, and 18.5% in the TP group, respectively, compared with 2.1%, 7%, 5.2%, and 10.8% in those without TP ( P < .05 for all). Similarly, event rates at 2 years were 11.3%, 12.7%, 24.7%, and 30.8% compared with 5.1%, 7.9%, 18.5%, and 23.3% ( P < .05). By multivariate analysis, baseline TP was an independent predictor of 30-day net adverse clinical events but not of any 2-year events. Conclusions We found that baseline TP in patients with ST-elevation myocardial infarction undergoing routine angiography and primary percutaneous coronary intervention is strongly associated with early adverse events and is a maker of late events, related to both ischemia and bleeding.
Patients with atrial fibrillation (AF) who underwent percutaneous coronary intervention (PCI) are at elevated risk for bleeding and thromboembolic ischemic events. Currently, guidelines on ...antithrombotic treatment for these patients are based on weak consensus. We describe patterns and determinants of antithrombotic prescriptions in this population. The Antithrombotic Strategy Variability in Atrial Fibrillation and Obstructive Coronary Disease Revascularized with PCI Registry was an international observational study of 859 consecutive patients with AF who underwent PCI from 2009 to 2011. Patients were stratified by treatment at discharge with either dual antiplatelet therapy (DAPT; aspirin plus clopidogrel) or triple therapy (TT; warfarin plus DAPT). Bleeding and thromboembolism risks were assessed by the HAS-BLED and CHADS2 scores, respectively, and predictors of TT prescription at discharge were identified. Major adverse cardiovascular events and clinically relevant bleeding (Bleeding Academic Research Consortium score ≥2) at 1-year follow-up were compared across antithrombotic regimens. Compared with patients on DAPT (n = 488; 57%), those given TT (n = 371; 43%) were older, with higher CHADS2 scores, lower left ventricular ejection fraction, and more often had permanent AF, single-vessel coronary artery disease, and bare-metal stents. In multivariate analysis, increasing thromboembolic risk (CHADS2 ) was associated with a higher rate of TT prescription at discharge (intermediate vs low CHADS2 : odds ratio 2.2, 95% confidence interval CI 2.0 to 3.3, p <0.01; high vs low CHADS2 : odds ratio 1.6, 95% CI 2.6 to 4.3, p <0.01 for TT). However, there was no significant association between bleeding risk and TT prescription in the overall cohort or within each CHADS2 risk stratum. The rates of major adverse cardiovascular events were similar for patients discharged on TT or DAPT (20% vs 17%, adjusted hazard ratio 0.8, 95% CI 0.5 to 1.1, p = 0.19), whereas the rate of Bleeding Academic Research Consortium ≥2 bleeding was higher in patients discharged on TT (11.5% vs 6.4%, adjusted hazard ratio 1.8, 95% CI 1.1 to 2.9, p = 0.02). In conclusion, the choice of the intensity of antithrombotic therapy correlated more closely with the risk of ischemic rather than bleeding events in this cohort of patients with AF who underwent PCI.
Objectives The study sought to determine whether rapid access to medical care and reperfusion results in a better prognosis in patients with in-hospital compared with out-of-hospital stent thrombosis ...(ST) in patients with ST-segment elevation myocardial infarction (STEMI) in the HORIZONS-AMI (Harmonizing Outcomes with Revascularization and Stents in Acute Myocardial Infarction) trial. Background Whether the prognosis of in-hospital and out-of-hospital ST are similar is uncertain, with conflicting data reported from prior studies. Methods A total of 3,602 STEMI patients undergoing primary percutaneous coronary intervention (PCI) were randomized to bivalirudin (n = 1,800) versus unfractionated heparin (UFH) plus a glycoprotein IIb/IIIa inhibitor (GPI) (UFH+GPI; n = 1,802). Stents were implanted in 3,202 patients, 156 (4.9%) of whom developed Academic Research Consortium definite/probable ST during 3-year follow-up. We investigated the 1-year clinical outcomes after ST in 54 patients with in-hospital ST compared with 102 patients with out-of-hospital ST. Results One year after the ST event, patients with in-hospital compared with out-of-hospital ST had significantly greater mortality (27.8% vs. 10.8%, p < 0.01); most deaths in both groups occurred within 1 week of the ST event. Patients with in-hospital ST also had higher rates of major bleeding (21.2% vs. 6.0%, p < 0.01), but a lower rate of myocardial infarction (56.6% vs. 77.5%, p < 0.01). Subgroup analysis within both in-hospital and out-of-hospital ST groups indicated that subacute ST had the highest mortality. By multivariable analysis, 1-year mortality was significantly increased in patients with in-hospital compared with out-of-hospital ST (adjusted hazard ratio: 4.62, 95% confidence interval: 1.98 to 10.77, p < 0.01). Additional correlates of increased mortality after an ST event included diabetes and randomization to UFH+GPI (vs. bivalirudin). Conclusions Following primary PCI for STEMI, more than one-third of all ST events during 3-year follow-up occurred during the index hospital phase. Mortality and major bleeding were significantly higher after in-hospital ST compared with out-of-hospital ST. (Harmonizing Outcomes With Revascularization and Stents in Acute Myocardial Infarction; NCT00433966 )
PDF
