Aircraft noise exposure and risk for recurrent cardiovascular events after acute coronary syndrome: A prospective patient cohort study.

In several population based cohort studies associations between aircraft noise and various diagnoses of cardiovascular disease were observed. However, no study has yet addressed the risk of recurrences in relation to transportation noise in patients with acute coronary heart disease. We conducted a prospective patient cohort study of 737 individuals recruited from eleven cardiac centers in the Rhine-Main region in the vicinity of Frankfurt Airport. All patients had an angiographically confirmed acute coronary syndrome diagnosed between July 2013 and November 2018. Individual aircraft noise exposure at the place of residence was calculated using Soundplan software, and exposure to road traffic and railway noise was obtained from noise maps provided by the Hessian State Agency. Data was analyzed by means of Cox regression adjusted for relevant confounders. Recurrent event as non-fatal endpoint was defined as myocardial infarction, stroke, bypass surgery or percutaneous coronary intervention with stent implantation. In addition, all-cause mortality was evaluated. Follow-up data including socioeconomic and confounder information was obtained from 663 (90%) patients covering a mean follow-up period of 42 (range: 1-80) months. Mean Lden aircraft noise exposure was 48.1 dB. Adjusted hazard ratio (HR) for recurrence was 1.24 (95%-CI: 0.97-1.58) per 10 dB increase in Lden aircraft noise exposure. A combined analysis of recurrence and all-cause mortality yielded a HR of 1.31 (95%-CI: 1.03-1.66). Similar HRs were found for Lday and Lnight aircraft noise exposure. HRs for road traffic and railway noise were above unity but less pronounced and not significant. Observed exposure-response associations for aircraft noise were more pronounced than previously observed in population-based cohort studies suggesting that acute coronary heart disease patients are particularly vulnerable to effects from transportation noise. Measures to reduce environmental noise exposure may thus be helpful in improving clinical outcome of patients with coronary heart disease.

Dose comparisons of clopidogrel and aspirin in acute coronary syndromes.

BACKGROUND: Clopidogrel and aspirin are widely used for patients with acute coronary syndromes and those undergoing percutaneous coronary intervention (PCI). However, evidence-based guidelines for dosing have not been established for either agent. METHODS: We randomly assigned, in a 2-by-2 factorial design, 25,086 patients with an acute coronary syndrome who were referred for an invasive strategy to either double-dose clopidogrel (a 600-mg loading dose on day 1, followed by 150 mg daily for 6 days and 75 mg daily thereafter) or standard-dose clopidogrel (a 300-mg loading dose and 75 mg daily thereafter) and either higher-dose aspirin (300 to 325 mg daily) or lower-dose aspirin (75 to 100 mg daily). The primary outcome was cardiovascular death, myocardial infarction, or stroke at 30 days. RESULTS: The primary outcome occurred in 4.2% of patients assigned to double-dose clopidogrel as compared with 4.4% assigned to standard-dose clopidogrel (hazard ratio, 0.94; 95% confidence interval [CI], 0.83 to 1.06; P=0.30). Major bleeding occurred in 2.5% of patients in the double-dose group and in 2.0% in the standard-dose group (hazard ratio, 1.24; 95% CI, 1.05 to 1.46; P=0.01). Double-dose clopidogrel was associated with a significant reduction in the secondary outcome of stent thrombosis among the 17,263 patients who underwent PCI (1.6% vs. 2.3%; hazard ratio, 0.68; 95% CI, 0.55 to 0.85; P=0.001). There was no significant difference between higher-dose and lower-dose aspirin with respect to the primary outcome (4.2% vs. 4.4%; hazard ratio, 0.97; 95% CI, 0.86 to 1.09; P=0.61) or major bleeding (2.3% vs. 2.3%; hazard ratio, 0.99; 95% CI, 0.84 to 1.17; P=0.90). CONCLUSIONS: In patients with an acute coronary syndrome who were referred for an invasive strategy, there was no significant difference between a 7-day, double-dose clopidogrel regimen and the standard-dose regimen, or between higher-dose aspirin and lower-dose aspirin, with respect to the primary outcome of cardiovascular death, myocardial infarction, or stroke. (Funded by Sanofi-Aventis and Bristol-Myers Squibb; ClinicalTrials.gov number, NCT00335452.)

Early versus delayed invasive intervention in acute coronary syndromes.

BACKGROUND: Earlier trials have shown that a routine invasive strategy improves outcomes in patients with acute coronary syndromes without ST-segment elevation. However, the optimal timing of such intervention remains uncertain. METHODS: We randomly assigned 3031 patients with acute coronary syndromes to undergo either routine early intervention (coronary angiography < or = 24 hours after randomization) or delayed intervention (coronary angiography > or = 36 hours after randomization). The primary outcome was a composite of death, myocardial infarction, or stroke at 6 months. A prespecified secondary outcome was death, myocardial infarction, or refractory ischemia at 6 months. RESULTS: Coronary angiography was performed in 97.6% of patients in the early-intervention group (median time, 14 hours) and in 95.7% of patients in the delayed-intervention group (median time, 50 hours). At 6 months, the primary outcome occurred in 9.6% of patients in the early-intervention group, as compared with 11.3% in the delayed-intervention group (hazard ratio in the early-intervention group, 0.85; 95% confidence interval [CI], 0.68 to 1.06; P=0.15). There was a relative reduction of 28% in the secondary outcome of death, myocardial infarction, or refractory ischemia in the early-intervention group (9.5%), as compared with the delayed-intervention group (12.9%) (hazard ratio, 0.72; 95% CI, 0.58 to 0.89; P=0.003). Prespecified analyses showed that early intervention improved the primary outcome in the third of patients who were at highest risk (hazard ratio, 0.65; 95% CI, 0.48 to 0.89) but not in the two thirds at low-to-intermediate risk (hazard ratio, 1.12; 95% CI, 0.81 to 1.56; P=0.01 for heterogeneity). CONCLUSIONS: Early intervention did not differ greatly from delayed intervention in preventing the primary outcome, but it did reduce the rate of the composite secondary outcome of death, myocardial infarction, or refractory ischemia and was superior to delayed intervention in high-risk patients. (ClinicalTrials.gov number, NCT00552513.)

[Surgical procedures in patients treated with platelet function inhibitors]. / Therapie mit Thrombozytenfunktionshemmern bei operativen Eingriffen.

The platelet function inhibitors (PFI) acetylsalicylic acid (ASA) and clopidogrel are widely used in a broad spectrum of atherothrombotic diseases, either as mono- or dual antiplatelet therapy. Platelet function is inhibited for the whole lifespan of platelets (10 days). In case of surgical procedures the bleeding risk under continued antiplatelet therapy has to be balanced against the risk of ischemic complications due to withdrawal of antiplatelet therapy. Especially after stent implantation, the high risk and unfavorable prognosis of stent thrombosis have to be considered. Whereas surgical procedures with a low bleeding risk may be performed with continued antiplatelet therapy, there is a need for partial or total discontinuation of antiplatelet therapy in surgical procedures with higher bleeding risks.

Bivalirudin for patients with acute coronary syndromes.

BACKGROUND: Current guidelines for patients with moderate- or high-risk acute coronary syndromes recommend an early invasive approach with concomitant antithrombotic therapy, including aspirin, clopidogrel, unfractionated or low-molecular-weight heparin, and glycoprotein IIb/IIIa inhibitors. We evaluated the role of thrombin-specific anticoagulation with bivalirudin in such patients. METHODS: We assigned 13,819 patients with acute coronary syndromes to one of three antithrombotic regimens: unfractionated heparin or enoxaparin plus a glycoprotein IIb/IIIa inhibitor, bivalirudin plus a glycoprotein IIb/IIIa inhibitor, or bivalirudin alone. The primary end points were a composite ischemia end point (death, myocardial infarction, or unplanned revascularization for ischemia), major bleeding, and the net clinical outcome, defined as the combination of composite ischemia or major bleeding. RESULTS: Bivalirudin plus a glycoprotein IIb/IIIa inhibitor, as compared with heparin plus a glycoprotein IIb/IIIa inhibitor, was associated with noninferior 30-day rates of the composite ischemia end point (7.7% and 7.3%, respectively), major bleeding (5.3% and 5.7%), and the net clinical outcome end point (11.8% and 11.7%). Bivalirudin alone, as compared with heparin plus a glycoprotein IIb/IIIa inhibitor, was associated with a noninferior rate of the composite ischemia end point (7.8% and 7.3%, respectively; P=0.32; relative risk, 1.08; 95% confidence interval [CI], 0.93 to 1.24) and significantly reduced rates of major bleeding (3.0% vs. 5.7%; P<0.001; relative risk, 0.53; 95% CI, 0.43 to 0.65) and the net clinical outcome end point (10.1% vs. 11.7%; P=0.02; relative risk, 0.86; 95% CI, 0.77 to 0.97). CONCLUSIONS: In patients with moderate- or high-risk acute coronary syndromes who were undergoing invasive treatment with glycoprotein IIb/IIIa inhibitors, bivalirudin was associated with rates of ischemia and bleeding that were similar to those with heparin. Bivalirudin alone was associated with similar rates of ischemia and significantly lower rates of bleeding. (ClinicalTrials.gov number, NCT00093158 [ClinicalTrials.gov].).

13-year follow-up of the German angioplasty bypass surgery investigation.

AIMS: The German Angioplasty Bypass Surgery Investigation was designed to compare symptomatic efficacy and safety of percutaneous coronary balloon angioplasty (PTCA) with coronary artery bypass surgery (CABG) in patients with symptomatic multi-vessel disease. This follow-up study was performed to determine the long-term outcome of patients following these interventions. METHODS AND RESULTS: From 1986 to 1991, 359 patients with angina CCS class II-IV, age below 75 years, and coronary multi-vessel disease requiring revascularization of at least two major coronary vessels were recruited at eight German centres and randomized to PTCA or CABG. From 337 patients undergoing the planned procedure, 324 patients could be followed-up (96%). Baseline parameters were identical in both groups, 2.2+/-0.6 vessels were treated in CABG patients, whereas 1.9+/-0.5 vessels were treated in PTCA patients. Thirty-seven per cent of surgical patients received internal mammary artery grafts, while no stents were used in patients undergoing PTCA. At the end of the 13-year follow-up period, the degree of angina, the degree of dyspnea, and the utilization of nitrates were comparable in both groups. With a total number of 76 deaths, Kaplan-Meier analysis revealed a comparable distribution in both groups. Although time to first re-intervention was significantly shorter in the PTCA group, P<0.001, frequencies of re-intervention (CABG, n=94; PTCA, n=136) and crossover rates (CABG to PTCA, n=49; PTCA to CABG, n=51) were comparable in both groups. CONCLUSION: The results of our 13-year follow-up suggest that in patients with symptomatic multi-vessel disease, both PTCA and CABG are associated with a comparable long-term survival and symptomatic efficacy. How far these results may be altered by developments such as drug-eluting stents or off-pump surgery remains to be determined.

Angiographic outcome in multivessel disease (GABI II study) using new coronary device interventions and comparison with GABI I trial results.

Percutaneous coronary interventions using stents were investigated in patients with multivessel disease. Acute and long-term results were compared with those of the German Angioplasty Bypass Surgery Investigation trial in a prospective multicenter study. The study included 134 patients in whom 277 lesions were treated. Angiographic success and procedural success were achieved in 268 of 277 lesions (97%) and 118 of 134 patients (88%), respectively. Control angiography performed in 90 of 118 eligible patients (76%) exhibited restenosis in 43 of 182 lesions (24%). Multivariate regression analysis found that a diffuse lesion, the lesion and stent length, and the final luminal diameter were predictive for restenosis. Thus, immediate and long-term results of multivessel coronary intervention utilizing stents were improved compared to percutaneous transluminal coronary angioplasty of multivessel lesions. However, there is still need for improvement of long-term results, especially in particular lesion subgroups.

Nickel release after implantation of the Amplatzer occluder.

BACKGROUND: Transcatheter closure of atrial septal defects is a new and less traumatic technique than open heart surgery. In recent years, patients with a patent foramen ovale sustaining potential paradoxical embolism have also become candidates for interventional closure devices. One of the more popular occluding devices is the Amplatzer septal occluder, which, like many other occluders, is made of nitinol. Nitinol-based alloys are widely used in medical products, for example, in orthopedics and orthodontics. However, the clinical use of nitinol, which contains 55% nickel, is still controversial because of concerns about its biocompatibility. Therefore, we examined the systemic nickel release after implantation of the Amplatzer occluder. METHODS AND RESULTS: In 67 patients with no history of nickel sensitivity, blood samples were taken 24 hours before and 24 hours, 1, 3, and 12 months after occluder implantation. Nickel serum concentrations were measured by atomic absorption spectrometry; a value of <2 ng/mL of nickel was considered to be normal. A rise in mean serum levels of nickel was observed, from 0.47 ng/mL before implantation to 1.27 ng/mL (24 hours after), to a maximum of 1.50 ng/mL 1 month after implantation, which was statistically significant (P =.008 and P = 0.022, Wilcoxon Test). During follow-up, the values decreased to those measured before implantation. CONCLUSIONS: Nickel seems to be released from the device, causing a systemic rise in serum levels of nickel, possibly until a calcium-phosphate layer has formed on the passive oxide film of the device or until endothelialization is complete. Possible biological effects should be considered, particularly in young patients or patients with nickel hypersensitivity.

Comparison of ReoPro((R)) (abciximab) versus intracoronary thrombolysis for early coronary stent thrombosis.

AIMS: This study evaluated the treatment of early coronary stent thrombosis with intracoronary urokinase or the platelet glycoprotein IIb/IIIa receptor inhibitor ReoPro (abciximab). METHODS AND RESULTS: Seventy-four patients (126 stents) were treated immediately after identification of early (0-30 days) coronary stent thrombosis. Twenty-nine patients were treated with intracoronary urokinase (UK) (UK alone in 19; UK and additional balloon angioplasty in 10) and another 45 patients were given ReoPro((R)) (abciximab) (0.25 mg/kg as a bolus alone in 26, abciximab with additional balloon angioplasty in 19) within 30 days of stent implantation. TIMI grade 3 flow was obtained in 23 patients (79%) in the UK group and in 38 (84%) in the abciximab group (nonsignificant). Three patients (10%) in the UK group and one (2%) in the abciximab group underwent repeat percutaneous transluminal coronary angioplasty (PTCA) (nonsignificant). Five patients (17%) in the UK group and three (7%) in the abciximab group were referred for urgent coronary artery bypass graft surgery (CABG) because of residual thrombus and refractory ischemia (nonsignificant). Repeat revascularization was necessary in eight patients (28%) in the UK group versus four (9%) in the abciximab group (p < 0.05). Five patients (17%) in the UK group and eight (18%) in the abciximab group developed myocardial infarction (nonsignificant). Five patients (17%) in the UK group (cardiogenic shock (three), cerebral hemorrhage (one) and pneumonia (one)) and three (6.6%) in the abciximab group (cardiogenic shock (two), heart failure (one)) died within 30 days (nonsignificant). Overall, noncardiac complications (bleeding including surgical repair of groin) were observed in 11 patients (38%) in the UK group and three (7%) in the abciximab group (p < 0.001). CONCLUSION: Compared to urokinase, abciximab reduced the need for repeat revascularization procedures and the risk of noncardiac events, including bleeding complications in patients with early coronary stent thrombosis.