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The relation between platelet reactivity and stent thrombosis, major bleeding, and other adverse events after coronary artery implantation of drug-eluting stents has been incompletely characterised. We aimed to determine the relation between platelet reactivity during dual therapy with aspirin and clopidogrel and clinical outcomes after successful coronary drug-eluting stent implantation. ADAPT-DES was a prospective, multicentre registry of patients successfully treated with one or more drug-eluting stents and given aspirin and clopidogrel at 10–15 US and European hospitals. We assessed platelet reactivity in those patients after successful percutaneous coronary intervention using VerifyNow point-of-care assays, and assigned different cutoffs to define high platelet reactivity. The primary endpoint was definite or probable stent thrombosis; other endpoints were all-cause mortality, myocardial infarction, and clinically relevant bleeding. We did a propensity-adjusted multivariable analysis to determine the relation between platelet reactivity and subsequent adverse events. This study is registered with ClinicalTrials.gov, number NCT00638794. Between Jan 7, 2008, and Sept 16, 2010, 8665 patients were prospectively enrolled at 11 sites, of which 8583 were eligible. At 1-year follow-up, stent thrombosis had occurred in 70 (0·8%) patients, myocardial infarction in 269 (3·1%), clinically relevant bleeding in 531 (6·2%), and death in 161 (1·9%) patients. High platelet reactivity on clopidogrel was strongly related to stent thrombosis (adjusted HR 2·49 [95% CI 1·43–4·31], p=0·001) and myocardial infarction (adjusted HR 1·42 [1·09–1·86], p=0·01), was inversely related to bleeding (adjusted HR 0·73 [0·61–0·89], p=0·002), but was not related to mortality (adjusted HR 1·20 [0·85–1·70], p=0·30). High platelet reactivity on aspirin was not significantly associated with stent thrombosis (adjusted HR 1·46 [0·58–3·64], p=0·42), myocardial infarction, or death, but was inversely related to bleeding (adjusted HR 0·65 [0·43–0·99], p=0·04). The findings from this study emphasise the counter-balancing effects of haemorrhagic and ischaemic complications after stent implantation, and suggest that safer drugs or tailored strategies for the use of more potent agents must be developed if the benefits of greater platelet inhibition in patients with cardiovascular disease are to be realised. Boston Scientific, Abbott Vascular, Medtronic, Cordis, Biosensors, The Medicines Company, Daiichi-Sankyo, Eli Lilly, Volcano, and Accumetrics

Dual antiplatelet therapy (DAPT) cessation increases the risk of adverse events after percutaneous coronary intervention (PCI). Whether risk changes over time, depends on the underlying reason for DAPT cessation, or both is unknown. We assessed associations between different modes of DAPT cessation and cardiovascular risk after PCI. The PARIS (patterns of non-adherence to anti-platelet regimens in stented patients) registry is a prospective observational study of patients undergoing PCI with stent implantation in 15 clinical sites in the USA and Europe between July 1, 2009, and Dec 2, 2010. Adult patients (aged 18 years or older) undergoing successful stent implantation in one or more native coronary artery and discharged on DAPT were eligible for enrolment. Patients were followed up at months 1, 6, 12, and 24 after implantation. Prespecified categories for DAPT cessation included physician-recommended discontinuation, brief interruption (for surgery), or disruption (non-compliance or because of bleeding). All adverse events and episodes of DAPT cessation were independently adjudicated. Using Cox models with time-varying covariates, we examined the effect of DAPT cessation on major adverse events (MACE [composite of cardiac death, definite or probable stent thrombosis, myocardial infarction, or target-lesion revascularisation]). Incidence rates for DAPT cessation and adverse events were calculated as Kaplan-Meier estimates of time to the first event. This study is registered with ClinicalTrials.gov, number NCT00998127. We enrolled 5031 patients undergoing PCI, including 5018 in the final study population. Over 2 years, the overall incidence of any DAPT cessation was 57·3%. Rate of any discontinuation was 40·8%, of interruption was 10·5%, and of disruption was 14·4%. The corresponding overall 2 year MACE rate was 11·5%, most of which (74%) occurred while patients were taking DAPT. Compared with those on DAPT, the adjusted hazard ratio (HR) for MACE due to interruption was 1·41 (95% CI 0·94–2·12; p=0·10) and to disruption was 1·50 (1·14–1.97; p=0·004). Within 7 days, 8–30 days, and more than 30 days after disruption, adjusted HRs were 7·04 (3·31–14·95), 2·17 (0·97–4·88), and 1·3 (0·97–1·76), respectively. By contrast with patients who remained on DAPT, those who discontinued had lower MACE risk (0·63 [0·46–0·86]). Results were similar after excluding patients receiving bare metal stents and using an alternative MACE definition that did not include target lesion revascularisation. In a real-world setting, for patients undergoing PCI and discharged on DAPT, cardiac events after DAPT cessation depend on the clinical circumstance and reason for cessation and attenuates over time. While most events after PCI occur in patients on DAPT, early risk for events due to disruption is substantial irrespective of stent type. Bristol-Myers Squibb and Sanofi-Aventis.

Primary results of the HORIZONS-AMI trial have been previously reported. In this final report, we aimed to assess 3-year outcomes. HORIZONS-AMI was a prospective, open-label, randomised trial undertaken at 123 institutions in 11 countries. Patients aged 18 years or older were eligible for enrolment if they had ST-segment elevation myocardial infarction (STEMI), presented within 12 h after onset of symptoms, and were undergoing primary percutaneous coronary intervention. By use of a computerised interactive voice response system, we randomly allocated patients 1:1 to receive bivalirudin or heparin plus a glycoprotein IIb/IIIa inhibitor (GPI; pharmacological randomisation; stratified by previous and expected drug use and study site) and, if eligible, randomly allocated 3:1 to receive a paclitaxel-eluting stent or a bare metal stent (stent randomisation; stratified by pharmacological group assignment, diabetes mellitus status, lesion length, and study site). We produced Kaplan-Meier estimates of major adverse cardiovascular events at 3 years by intention to treat. This study is registered with ClinicalTrials.gov, number NCT00433966. Compared with 1802 patients allocated to receive heparin plus a GPI, 1800 patients allocated to bivalirudin monotherapy had lower rates of all-cause mortality (5·9% vs 7·7%, difference −1·9% [−3·5 to −0·2], HR 0·75 [0·58–0·97]; p=0·03), cardiac mortality (2·9% vs 5·1%, −2·2% [−3·5 to −0·9], 0·56 [0·40–0·80]; p=0·001), reinfarction (6·2% vs 8·2%, −1·9% [−3·7 to −0·2], 0·76 [0·59–0·99]; p=0·04), and major bleeding not related to bypass graft surgery (6·9% vs 10·5%, −3·6% [−5·5 to −1·7], 0·64 [0·51–0·80]; p=0·0001) at 3 years, with no significant differences in ischaemia-driven target vessel revascularisation, stent thrombosis, or composite adverse events. Compared with 749 patients who received a bare-metal stent, 2257 patients who received a paclitaxel-eluting stent had lower rates of ischaemia-driven target lesion revascularisation (9·4% vs 15·1%, −5·7% [−8·6 to −2·7], 0·60 [0·48–0·76]; p<0·0001) after 3 years, with no significant differences in the rates of death, reinfarction, stroke or stent thrombosis. Stent thrombosis was high (≥4·5%) in both groups. The effectiveness and safety of bivalirudin monotherapy and paclitaxel-eluting stenting are sustained at 3 years for patients with STEMI undergoing primary percutaneous coronary intervention. Boston Scientific and The Medicines Company.

Acute ST-segment elevation myocardial infarction is often treated with immediate coronary stenting of the infarct-related artery. The use of a paclitaxel-eluting stent, as compared with a bare-metal stent, reduced the risk of restenosis and was equally safe. Acute ST-segment elevation myocardial infarction is often treated with immediate coronary stenting of the infarct-related artery. The use of a paclitaxel-eluting stent, as compared with a bare-metal stent, reduced the risk of restenosis and was equally safe. By enlarging luminal dimensions and sealing dissection planes at the site of coronary-artery occlusion in patients with evolving ST-segment elevation myocardial infarction, bare-metal stents reduce the risk of early and late recurrent ischemia and reocclusion of the infarct-related artery, as compared with balloon angioplasty alone, decreasing the need for subsequent revascularization of the target lesion with repeat percutaneous coronary intervention (PCI) or coronary-artery bypass grafting. 1 , 2 Nonetheless, restenosis occurs in more than 20% of patients in whom bare-metal stents are implanted during primary PCI, and implantation of bare-metal stents, as compared with balloon angioplasty, has not reduced the rates of . . .

Congestive heart failure (CHF) is a major source of morbidity, mortality, and health-care resource consumption. However, the incidence of symptomatic CHF after primary percutaneous coronary intervention (PCI) for ST-segment elevation myocardial infarction (STEMI) has rarely been fully reported. We therefore examined the early and late incidence, predictors, and implications of CHF in the large-scale, prospective, randomized HORIZONS-AMI trial. New York Heart Association (NYHA) functional classification was prospectively collected from patient-level data at baseline, 30 days, 6 months, and at 1 and 2 years from 3,343 patients with STEMI undergoing PCI at 123 centers in 11 countries. The baseline incidence of CHF (before the index STEMI) was 2.6%, increasing to 4.6% 1 month after primary PCI ( P < .0001), 4.7% at 1 year, and 5.1% at 2 years. The incidence of NYHA class III/IV symptoms was 0.4% at baseline and 0.8% at 2 years ( P = .03). CHF at 1 year was associated with diabetes ( P < .0001), dyslipidemia ( P = .009), previous MI ( P < .0001), previous revascularization ( P = .01), anterior STEMI ( P = .02), and baseline TIMI grade 0 flow ( P = .01) but not procedural anticoagulation with bivalirudin versus heparin + GPIIb/IIIa inhibitors ( P = .93) or use of drug-eluting versus bare metal stents ( P = .66). Among patients in whom CHF was not present at baseline but developed after PCI, the rate of all-cause mortality was significantly higher during 2-year follow-up (7.3% vs 2.0%, P < .0001), as was cardiac mortality (2.4% vs 0.8%, P = .004), reinfarction (9.4% vs 5.2%, P = .0009), stent thrombosis (7.0% vs 3.8%, P = .007), and ischemic target vessel revascularization (19.4% vs 11.8%, P < .0001). In the HORIZONS-AMI trial, the development of new-onset CHF within 2 years after contemporary PCI, although infrequent, was associated with significantly increased rates of mortality and major adverse ischemic events.

In the HORIZONS-AMI trial, patients with acute ST-segment elevation myocardial infarction (STEMI) undergoing percutaneous coronary intervention (PCI) who were treated with the thrombin inhibitor bivalirudin had substantially lower 30-day rates of major haemorrhagic complications and net adverse clinical events than did patients assigned to heparin plus a glycoprotein IIb/IIIa inhibitor (GPI). Here, we assess whether these initial benefits were maintained at 1 year of follow-up. Patients aged 18 years or older were eligible for enrolment in this multicentre, open-label, randomised controlled trial if they had STEMI, presented within 12 h after the onset of symptoms, and were undergoing primary PCI. 3602 eligible patients were randomly assigned by interactive voice response system in a 1:1 ratio to receive bivalirudin (0·75 mg/kg intravenous bolus followed by 1·75 mg/kg per h infusion; n=1800) or heparin plus a GPI (control; 60 IU/kg intravenous bolus followed by boluses with target activated clotting time 200–250 s; n=1802). The two primary trial endpoints were major bleeding and net adverse clinical events (NACE; consisting of major bleeding or composite major adverse cardiovascular events [MACE; death, reinfarction, target vessel revascularisation for ischaemia, or stroke]). This prespecified analysis reports data for the 1-year follow-up. Analysis was by intention to treat. Patients with missing data were censored at the time of withdrawal from the study or at last follow-up. This trial is registered with ClinicalTrials.gov, number NCT00433966. 1-year data were available for 1696 patients in the bivalirudin group and 1702 patients in the control group. Reasons for participant dropout were loss to follow-up and withdrawal of consent. The rate of NACE was lower in the bivalirudin group than in the control group (15·6% vs 18·3%, hazard ratio [HR] 0·83, 95% CI 0·71–0·97, p=0·022), as a result of a lower rate of major bleeding in the bivalirudin group (5·8% vs 9·2%, HR 0·61, 0·48–0·78, p<0·0001). The rate of MACE was similar between groups (11·9% vs 11·9%, HR 1·00, 0·82–1·21, p=0·98). The 1-year rates of cardiac mortality (2·1% vs 3·8%, HR 0·57, 0·38–0·84, p=0·005) and all-cause mortality (3·5% vs 4·8%, HR 0·71, 0·51–0·98, p=0·037) were lower in the bivalirudin group than in the control group. In patients with STEMI undergoing primary PCI, anticoagulation with bivalirudin reduced the rates of net adverse clinical events and major bleeding at 1 year compared with treatment with heparin plus a GPI. This finding has important clinical implications for the selection of optimum treatment strategies for patients with STEMI. Cardiovascular Research Foundation, with unrestricted grant support from Boston Scientific Corporation and The Medicines Company.

The association between anemia at admission and adverse outcomes in patients with acute coronary syndrome (ACS) has been incompletely studied. Anemia was defined as serum hemoglobin <12 g/dl in women or <13 g/dl in men in 2 large trials of patients with ACS. We plotted hazard functions for major bleeding at 30 days and all-cause mortality, myocardial infarction, and stent thrombosis at 1 year according to baseline hemoglobin. Among 16,318 patients, 3070 (18.8%) had anemia at baseline. All-cause death at 1 year (2.9% vs 1.5%), major bleeding (7.6% vs 3.6%, p <0.001), and transfusions (6.7% vs 1.5%, p <0.001) were more common in patients with baseline anemia. Spline transformations of the hazard for adverse events as a function of hemoglobin level on admission showed that adverse outcomes increased in a nonlinear fashion with lower levels of baseline hemoglobin; the lowest rates were observed at a level of ∼14 g/dl. Baseline hemoglobin and anemia were independent predictors of major bleeding and death. In conclusion, in patients with ACS, baseline hemoglobin carries important independent prognostic information and demonstrates a nonlinear association with major bleeding and mortality.

The clinical outcome of acute cardiovascular events may be more favorable in patients with a high body mass index (BMI), although obesity increases the risk for cardiovascular diseases. The authors sought to define the association between BMI and acute and long-term outcome of patients presenting within 12 hours of ST-segment myocardial infarction (STEMI) in a large multinational cohort. A total of 3,579 patients enrolled in the Harmonizing Outcomes with Revascularization and Stents in Acute Myocardial Infarction trial were stratified according to BMI quartiles: <24.5, 24.5 to <27.1, 27.1 to 30.1, and >30.1 kg/m2 (quartiles 1, 2, 3, and 4, respectively). Death, myocardial reinfarction, ischemia-driven target vessel revascularization, stroke, and noncoronary artery bypass grafting-related major bleeding events were centrally adjudicated for the acute, 30 days, and yearly follow-up. Patients with a BMI in the highest quartile were younger than patients in the lower BMI quartiles and more frequently had hypertension, hyperlipidemia, and diabetes mellitus. Complete occlusions and noncalcified lesions were more common in patients with a high BMI. In-hospital mortality decreased with increasing BMI due to lower cardiac mortality (2.9%, 2.3%, 1.2%, and 1.0% for quartiles 1, 2, 3, and 4, respectively, p <0.05). Out-of-hospital 3-year mortality was also lower in higher-weight patients due to lower noncardiac mortality (4.2%, 2.6%, 2.3%, and 1.7% for quartiles 1 to 4, respectively, p = 0.01). After adjustment for covariates, BMI was no longer predictive of acute or long-term mortality after STEMI. In conclusion, as BMI increases, patients have a more extensive adjusted cardiovascular risk profile and disease burden and premature STEMI onset but similar adjusted acute and long-term outcomes.

Hypertension is associated with vascular and endothelial dysfunction that may result in a greater propensity for reactive platelets to cause thrombosis. We sought to assess whether the risk of major adverse cardiac events (MACE) after percutaneous coronary intervention (PCI) in patients with on-clopidogrel residual high platelet reactivity (HPR) varies in patients with versus without hypertension. Assessment of dual antiplatelet therapy with drug eluting stents (ADAPT-DES) was a prospective, multicenter registry of patients successfully treated with coronary drug-eluting stents (DES). HPR was defined as P2Y12 reaction units (PRU) >208, as assessed by the VerifyNow point-of-care assay. Multivariable Cox proportional hazards regression was used to assess whether the adjusted association between HPR and 2-year risk of MACE (cardiac death, myocardial infarction [MI], or stent thrombosis) was different in patients with versus without hypertension. A total of 6833 of 8582 patients (79.6%) had a history of hypertension. Patients with compared with those without hypertension were older, more likely to have other cardiovascular risk factors, and had higher PRU (190.1 ± 97.3 vs 179.5 ± 94.3; p <0.0001). Patients with hypertension had significantly higher 2-year rates of MACE (7.0% vs 4.4%, p <0.001), all-cause death (4.2% vs 2.5%, p = 0.001), and MI (5.2% vs 3.2%, p <0.001), and had nominally higher rates of stent thrombosis (1.0% vs 0.5%, p = 0.059). A significant interaction was present between hypertension and HPR regarding 2-year MACE risk (adjusted hazard ratio for HPR vs no HPR 1.38, 95% confidence interval 1.14 to 1.68 for patients with hypertension vs 0.81, 95% confidence interval 0.50 to 1.33 for patients without hypertension, p = 0.046). In conclusion, following successful PCI with DES, 2-year MACE rates are increased in patients with both hypertension and residual HPR on clopidogrel. HPR had a greater effect on the risk of adverse events among patients with versus without hypertension.

The clinical features and prognosis of patients with ST-segment elevation myocardial infarction (STEMI) and no significant coronary artery disease (CAD) have not been well studied. We examined the outcomes of patients with STEMI in the Harmonizing Outcomes with Revascularization and Stents in Acute Myocardial Infarction (HORIZONS-AMI) trial according to the presence or absence of significant CAD. “No-CAD” was defined by the absence of any lesion with a diameter stenosis of ≥30% on quantitative coronary angiography of the baseline coronary angiogram. Of 3,602 patients, 127 (3.5%) had no-CAD. Of these, 86 (67.7%) had angiographically normal coronary arteries, and 41 (32.3%) had mild disease (diameter stenosis <30%). Eight patients had previously been treated with coronary artery bypass grafting. Compared to patients with CAD, patients with no-CAD were younger, had a lower body mass index, were more frequently black, had a lower prevalence of smoking and previous angina, and had a greater left ventricular ejection fraction. Cardiac enzymes were elevated in fewer patients with no-CAD than in those with CAD (63.2% vs 98.7%, p <0.001). At 3 years of follow-up, the patients with no-CAD versus CAD had lower rates of major adverse cardiovascular events (7.7% vs 22.2%, p = 0.002), net adverse clinical events (major adverse cardiovascular events or major bleeding not related to coronary artery bypass grafting, 12.5% vs 26.9%, p = 0.005), and postprocedure coronary revascularization (0% vs 19.5%, p <0.001). The differences in the rates of death or reinfarction, stroke, and major bleeding were not statistically significant. In conclusion, 3.5% of patients with STEMI had no significant CAD. The 3-year prognosis for these patients was favorable compared to that of patients with STEMI and with obstructive CAD.