The effect of obesity on repeat coronary revascularization and restenosis in patients who undergo stent implantation has not been reported. We therefore examined the database from the multicenter ...randomized TAXUS-IV trial to determine the effect of body mass index (BMI) on outcomes after bare-metal and drug-eluting stent implantation. In TAXUS-IV, patients were randomized to receive a slow-release, polymer-based, paclitaxel-eluting stent or a bare-metal stent. Outcomes were stratified by baseline BMI. Of the 1,307 randomized patients who had documented BMI, 233 (17.8%) had normal weight (BMI <25 kg/m
2), 531 (40.6%) were overweight (BMI ≤25 to 30 kg/m
2), and 543 (41.5%) were obese (BMI ≥30 kg/m
2). Patients who had been assigned to receive bare-metal stents and were overweight and obese compared with those who had normal weight had higher rates of 9-month binary restenosis (29.2% and 30.5% vs 9.3%, respectively; p = 0.01) and 1-year major adverse cardiac events (20.8% and 23.2% vs 11.1%, respectively; p = 0.02), whereas rates of these events did not differ significantly among those who received a paclitaxel-eluting stent (7.6% and 9.3% vs 4.9%, respectively for binary restenosis; p = 0.65; 11.3% and 10.4% vs 10.1%, respectively; p = 0.82 for major adverse cardiac events). By multivariate analysis, BMI ≥30.0 kg/m
2 independently predicted binary restenosis (hazard ratio 4.26, p = 0.005), 1-year target vessel revascularization (hazard ratio 1.95, p = 0.04), and major adverse cardiac events (hazard ratio 1.95, p = 0.004) in patients who received bare-metal stents but not paclitaxel-eluting stents. In conclusion, obesity is an important risk factor for clinical and angiographic restenosis and for composite major adverse cardiac events in patients who receive bare-metal stents. Paclitaxel-eluting stents attenuate the increased risk associated with obesity, such that the intermediate-term prognosis after percutaneous coronary intervention is independent of weight.
We sought to examine the short- and long-term outcomes of patients who developed contrast-induced acute kidney injury (CI-AKI; defined as an increase in serum creatinine of ≥0.5 mg/dL or a 25% ...relative rise within 48 h after contrast exposure) from the large-scale HORIZONS-AMI trial.
Multivariable analyses were used to identify predictors of CI-AKI, as well predictors of the primary and secondary endpoints. The incidence of CI-AKI in this cohort of ST-segment elevation myocardial infarction (STEMI) patients was 16.1% (479/2968). Predictors of CI-AKI were contrast volume, white blood cell count, left anterior descending infarct-related artery, age, anaemia, creatinine clearance <60 mL/min, and history of congestive heart failure. Patients with CI-AKI had higher rates of net adverse clinical events NACE; a combination of major bleeding or composite major adverse cardiac events (MACE; consisting of death, reinfarction, target vessel revascularization for ischaemia, or stroke) at 30 days (22.0 vs. 9.3%; P < 0.0001) and 3 years (40.3 vs. 24.6%; P < 0.0001). They also had higher rates of mortality at 30 days (8.0 vs. 0.9%; P < 0.0001) and 3 years (16.2 vs. 4.5%; P < 0.0001). Multivariable analysis confirmed CI-AKI as an independent predictor of NACE hazard ratio (HR), 1.53; 95% confidence interval (CI), 1.23-1.90; P = 0.0001, MACE (HR, 1.56; 95% CI, 1.23-1.98; P = 0.0002), non-coronary artery bypass grafting major bleeding (HR, 2.07; 95% CI, 1.57-2.73; P < 0.0001), and mortality (HR, 1.80; 95% CI, 1.19-2.73; P = 0.005) at 3-year follow-up.
Contrast-induced acute kidney injury is associated with poor short- and long-term outcomes after primary percutaneous coronary intervention in STEMI.
Objectives This study sought to assess the contemporary outcomes of patients with prior coronary artery bypass graft (CABG) who present with moderate and high-risk acute coronary syndromes (ACS) and ...are treated with an early invasive strategy and contemporary antithrombin regimens. Background The prognosis of patients with ACS and prior CABG in relation to triage strategy and contemporary antithrombotic regimens is unknown. Methods In the ACUITY (Acute Catheterization and Urgent Intervention Triage Strategy) trial, 2,475 of 13,764 patients (18.0%) with ACS managed with an early invasive strategy had previously undergone CABG. Their outcomes were examined according to treatment and randomized antithrombin regimen. Results Prior CABG was associated with older age, more frequent comorbidities, higher Thrombolysis In Myocardial Infarction risk score, and lower left ventricular ejection fraction. Patients with versus without prior CABG were less likely to undergo (repeat) CABG and were more likely to be managed medically. At 1 year, patients with versus without prior CABG had higher rates of major adverse cardiac events (MACE) (22.5% vs. 15.2%, p < 0.0001) due to greater mortality (5.4% vs. 3.9%, p < 0.0001), myocardial infarction (10.0% vs. 6.8%, p < 0.0001), and unplanned revascularization (13.1% vs. 8.2%, p < 0.0001). History of CABG was an independent predictor of MACE. The 1-year MACE rates were not significantly different after randomization to bivalirudin versus heparin plus a glycoprotein IIb/IIIa inhibitor (odds ratio: 1.24, 95% confidence interval: 0.90 to 1.70). Conclusions Despite the progress in the treatment of coronary artery disease, patients with prior CABG and ACS have a poor prognosis, substantially worse than for those without prior CABG. Whereas bivalirudin monotherapy was an acceptable treatment for these patients, it did not improve their prognoses.
To propose standardized consensus definitions for important clinical endpoints in transcatheter aortic valve implantation (TAVI), investigations in an effort to improve the quality of clinical ...research and to enable meaningful comparisons between clinical trials. To make these consensus definitions accessible to all stakeholders in TAVI clinical research through a peer reviewed publication, on behalf of the public health.
Transcatheter aortic valve implantation may provide a worthwhile less invasive treatment in many patients with severe aortic stenosis and since its introduction to the medical community in 2002, there has been an explosive growth in procedures. The integration of TAVI into daily clinical practice should be guided by academic activities, which requires a harmonized and structured process for data collection, interpretation, and reporting during well-conducted clinical trials.
The Valve Academic Research Consortium established an independent collaboration between Academic Research organizations and specialty societies (cardiology and cardiac surgery) in the USA and Europe. Two meetings, in San Francisco, California (September 2009) and in Amsterdam, the Netherlands (December 2009), including key physician experts, and representatives from the US Food and Drug Administration (FDA) and device manufacturers, were focused on creating consistent endpoint definitions and consensus recommendations for implementation in TAVI clinical research programs. Important considerations in developing endpoint definitions included (i) respect for the historical legacy of surgical valve guidelines; (ii) identification of pathophysiological mechanisms associated with clinical events; (iii) emphasis on clinical relevance. Consensus criteria were developed for the following endpoints: mortality, myocardial infarction, stroke, bleeding, acute kidney injury, vascular complications, and prosthetic valve performance. Composite endpoints for TAVI safety and effectiveness were also recommended.
Although consensus criteria will invariably include certain arbitrary features, an organized multidisciplinary process to develop specific definitions for TAVI clinical research should provide consistency across studies that can facilitate the evaluation of this new important catheter-based therapy. The broadly based consensus endpoint definitions described in this document may be useful for regulatory and clinical trial purposes.
Objectives The objective of this study is to investigate the incidence and clinical implications of thrombus on baseline angiography among patients presenting with non–ST-segment elevation acute ...coronary syndromes (ACS) undergoing percutaneous coronary intervention (PCI). Background Given current advances in the pharmacological and mechanical treatment of ACS patients managed with an early invasive strategy, the incidence and prognostic importance of pre-procedural lesion thrombus is warranted. Methods In the ACUITY (Acute Catheterization and Urgent Intervention Triage strategY) trial, a total of 3,627 patients with moderate- and high-risk ACS undergoing PCI had their baseline and final post-PCI angiograms analyzed by an independent angiographic core laboratory. Results Patients with thrombus (n = 530 15%) compared with those without thrombus had higher rates of impaired final epicardial coronary flow (final Thrombolysis In Myocardial Infarction TIMI flow grade 3: 89.6% vs. 97.1%, p < 0.0001). Thrombus was an independent predictor of 30 day death (odds ratio OR: 3.16 95% confidence interval (CI): 1.20 to 8.37, p = 0.02), and myocardial infarction (MI) at 30 days (OR: 1.62 95% CI: 1.17 to 2.24, p = 0.003) and at 1 year (OR: 1.56 95% CI: 1.16 to 2.08, p = 0.003). Patients with thrombus had significantly higher rates of stent thrombosis (ST) compared with patients without thrombus at 30 days (2.8% vs. 1.1%, p = 0.002) and at 1 year (3.7% vs. 1.8%, p = 0.003), and thrombus was an independent predictor of ST at both 30 days (OR: 2.61 95% CI: 1.38 to 4.91) and 1 year (OR: 2.98 95% CI: 1.64 to 5.42). Conclusions Pre-procedural thrombus was present in 15% of moderate- and high-risk ACS patients undergoing PCI in the ACUITY trial. Baseline thrombus predicts increased ischemic complications at 30 days including a 3-fold increased risk of death as well as MI up to 1 year. Further evaluation of adjunctive pharmacotherapy is needed in this high-risk population.
Objectives This study sought to develop a risk score predictive of bleeding in patients undergoing percutaneous coronary intervention (PCI) and to investigate the impact of bleeding on subsequent ...mortality. Background Bleeding complications after PCI have been independently associated with early and late mortality. Methods This study represents a patient-level pooled analysis including 17,034 patients undergoing PCI from 3 large, randomized trials of bivalirudin versus heparin plus glycoprotein IIb/IIIa inhibitors, including the REPLACE-2 (Randomized Evaluation of PCI Linking Angiomax to Reduced Clinical Events), ACUITY (Acute Catheterization and Urgent Intervention Triage Strategy), and HORIZONS-AMI (Harmonizing Outcomes With Revascularization and Stents in Acute Myocardial Infarction) trials. We developed a risk score to predict noncoronary artery bypass graft (CABG)–related TIMI (Thrombolysis In Myocardial Infarction) major bleeding and evaluated the impact of various types of bleeding on 1-year mortality. Results A non-CABG–related TIMI major bleed occurred within 30 days in 267 patients (1.6%), and death occurred in 497 patients (2.9%) within 1 year. A risk score was developed to predict the bleeding risk of patients undergoing PCI, consisting of 7 variables (serum creatinine, age, sex, presentation, white blood cell count, cigarette smoking, and randomized treatment). The TIMI major bleeding rates increased by bleeding risk score groups: from 0.4% for those in the lowest to 5.8% for those in the highest risk group. Non-CABG–related TIMI major bleeding and the occurrence of myocardial infarction within 30 days were independent predictors of subsequent mortality, with respective hazard ratios of 4.2 and 2.9, each p < 0.001. Ranked in order of severity, TIMI major bleeding, blood transfusion without TIMI bleed, TIMI minor bleeding requiring blood transfusion, and TIMI minor bleeding not requiring blood transfusion were independent predictors of subsequent mortality with hazard ratios of 4.89, 2.91, 2.73, and 1.66, respectively. Isolated hematomas were not predictive of subsequent mortality. Conclusions Non-CABG–related bleeding within 30 days is strongly associated with an increased risk of subsequent mortality at 1 year in patients undergoing PCI for all indications. A risk score was established to calculate the bleeding risk for patients undergoing PCI, allowing therapeutic decision making to minimize the incidence of bleeding.
Coronary artery disease is a major cause of morbidity and mortality worldwide, and is a consequence of acute thrombotic events involving activation of platelets and coagulation proteins. Factor Xa ...inhibitors and aspirin each reduce thrombotic events but have not yet been tested in combination or against each other in patients with stable coronary artery disease.
In this multicentre, double-blind, randomised, placebo-controlled, outpatient trial, patients with stable coronary artery disease or peripheral artery disease were recruited at 602 hospitals, clinics, or community centres in 33 countries. This paper reports on patients with coronary artery disease. Eligible patients with coronary artery disease had to have had a myocardial infarction in the past 20 years, multi-vessel coronary artery disease, history of stable or unstable angina, previous multi-vessel percutaneous coronary intervention, or previous multi-vessel coronary artery bypass graft surgery. After a 30-day run in period, patients were randomly assigned (1:1:1) to receive rivaroxaban (2·5 mg orally twice a day) plus aspirin (100 mg once a day), rivaroxaban alone (5 mg orally twice a day), or aspirin alone (100 mg orally once a day). Randomisation was computer generated. Each treatment group was double dummy, and the patients, investigators, and central study staff were masked to treatment allocation. The primary outcome of the COMPASS trial was the occurrence of myocardial infarction, stroke, or cardiovascular death. This trial is registered with ClinicalTrials.gov, number NCT01776424, and is closed to new participants.
Between March 12, 2013, and May 10, 2016, 27 395 patients were enrolled to the COMPASS trial, of whom 24 824 patients had stable coronary artery disease from 558 centres. The combination of rivaroxaban plus aspirin reduced the primary outcome more than aspirin alone (347 4% of 8313 vs 460 6% of 8261; hazard ratio HR 0·74, 95% CI 0·65–0·86, p<0·0001). By comparison, treatment with rivaroxaban alone did not significantly improve the primary outcome when compared with treatment with aspirin alone (411 5% of 8250 vs 460 6% of 8261; HR 0·89, 95% CI 0·78–1·02, p=0·094). Combined rivaroxaban plus aspirin treatment resulted in more major bleeds than treatment with aspirin alone (263 3% of 8313 vs 158 2% of 8261; HR 1·66, 95% CI 1·37–2·03, p<0·0001), and similarly, more bleeds were seen in the rivaroxaban alone group than in the aspirin alone group (236 3% of 8250 vs 158 2% of 8261; HR 1·51, 95% CI 1·23–1·84, p<0·0001). The most common site of major bleeding was gastrointestinal, occurring in 130 2% patients who received combined rivaroxaban plus aspirin, in 84 1% patients who received rivaroxaban alone, and in 61 1% patients who received aspirin alone. Rivaroxaban plus aspirin reduced mortality when compared with aspirin alone (262 3% of 8313 vs 339 4% of 8261; HR 0·77, 95% CI 0·65–0·90, p=0·0012).
In patients with stable coronary artery disease, addition of rivaroxaban to aspirin lowered major vascular events, but increased major bleeding. There was no significant increase in intracranial bleeding or other critical organ bleeding. There was also a significant net benefit in favour of rivaroxaban plus aspirin and deaths were reduced by 23%. Thus, addition of rivaroxaban to aspirin has the potential to substantially reduce morbidity and mortality from coronary artery disease worldwide.
Bayer AG.
Objectives Five-year clinical follow-up has been scheduled per protocol by the 4 Cypher (Cordis/Johnson & Johnson, Warren, New Jersey) sirolimus-eluting stent (SES) versus bare-metal stent (BMS) ...randomized trials. Background A delayed arterial healing response after drug-eluting stent implantation has raised concerns about the long-term safety of drug-eluting stents. Methods In a pooled analysis of 4 randomized trials, 1,748 patients were assigned to receive either an SES (n = 878) or BMS (n = 870). Results At 5 years, there was no significant difference in the rate of death, myocardial infarction (MI), or the composite of death/MI between the 2 groups (15.1% in the SES group vs. 13.6% in the BMS group; p = 0.36). The 5-year incidence of stent thrombosis by the Academic Research Consortium definition did not differ between SES and BMS (definite/probable stent thrombosis, 2.1% vs. 2.0%; p = 0.99). The incidence of very late stent thrombosis was also similar between the SES and BMS groups (1.4% vs. 0.7%; p = 0.22). The annualized rates of definite/probable stent thrombosis after 1 year were 0.4% for SES and 0.2% for BMS. The 5-year incidence of target vessel revascularization was significantly lower in the SES group (15.2% vs. 30.1%; p < 0.0001). Conclusions In this patient-level pooled analysis, overall use of SES compared with BMS demonstrated persistent superior efficacy at 5 years in terms of a reduction in target vessel revascularization, without an increase in rates of death, MI, or stent thrombosis. (The Initial Double-Blind Drug-Eluting Stent vs Bare-Metal Stent Study, NCT00233805 ; The Study of the BX Velocity Stent in the Treatment of De Novo Artery Lesions, NCT00381420 ; Study of Sirolimus-Coated BX VELOCITY Balloon-Expandable Stent in Treatment of de Novo Native Coronary Artery Lesions SIRIUS, NCT00232765 ; The Study of the BX VELOCITY Stent In Patients With De Novo Coronary Artery Lesions, NCT00235144 )
Objectives The purpose of this study was to compare a one-time primary percutaneous coronary intervention (PCI) of the culprit and nonculprit lesions with PCI of only the culprit lesion and staged ...nonculprit PCI at a later date in patients with ST-segment elevation myocardial infarction (STEMI) and multivessel disease. Background In patients with STEMI and multivessel disease, it is unknown whether it is safe or even desirable to also treat the nonculprit vessel during the primary PCI procedure. Methods In the HORIZONS-AMI (Harmonizing Outcomes With Revascularization and Stents in Acute Myocardial Infarction) trial, 668 of the 3,602 STEMI patients enrolled (18.5%) underwent PCI of culprit and nonculprit lesions for multivessel disease. Patients were categorized into a single PCI strategy (n = 275) versus staged PCI (n = 393). The endpoints analyzed included the 1-year rates of major adverse cardiovascular events and its components, death, reinfarction, target-vessel revascularization for ischemia, and stroke. Results Single versus staged PCI was associated with higher 1-year mortality (9.2% vs. 2.3%; hazard ratio HR: 4.1, 95% confidence interval CI: 1.93 to 8.86, p < 0.0001), cardiac mortality (6.2% vs. 2.0%; HR: 3.14, 95% CI: 1.35 to 7.27, p = 0.005), definite/probable stent thrombosis (5.7% vs. 2.3%; HR: 2.49, 95% CI: 1.09 to 5.70, p = 0.02), and a trend toward greater major adverse cardiovascular events (18.1% vs. 13.4%; HR: 1.42, 95% CI: 0.96 to 2.1, p = 0.08). The mortality advantage favoring staged PCI was maintained in a subgroup of patients undergoing truly elective multivessel PCI. Also, the staged PCI strategy was independently associated with lower all-cause mortality at 30 days and at 1 year. Conclusions A deferred angioplasty strategy of nonculprit lesions should remain the standard approach in patients with STEMI undergoing primary PCI, as multivessel PCI may be associated with a greater hazard for mortality and stent thrombosis. (Harmonizing Outcomes With Revascularization and Stents in Acute Myocardial Infarction HORIZONS-AMI; NCT00433966 )
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