Favorable long-term outcome after drug-eluting stent implantation in nonbifurcation lesions that involve unprotected left main coronary artery: a multicenter registry.

BACKGROUND: The presence of a lumen narrowing at the ostium and the body of an unprotected left main coronary artery but does not require bifurcation treatment is a class I indication of surgical revascularization. METHODS AND RESULTS: A total of 147 consecutive patients who had a stenosis in the ostium and/or the midshaft of an unprotected left main coronary artery (treatment of the bifurcation not required) and were electively treated with percutaneous coronary intervention and sirolimus-eluting stents (n=107) or paclitaxel-eluting stents (n=40) in 5 centres were included in this registry. In 72 patients (almost 50%), intravascular ultrasound guidance was performed. Procedural success was achieved in 99% of the patients; in 1 patient with stenosis in the left main coronary artery ostium, a >30% residual stenosis persisted at the end of the procedure, and the patient was referred for coronary artery bypass graft surgery. During hospitalization, no patients experienced a Q-wave myocardial infarction or died. One patient died 19 days after the procedure because of pulmonary infection. At long-term clinical follow-up (886+/-308 days), 5 patients had died; 7 patients had target vessel revascularization (5 repeat percutaneous coronary interventions and 2 coronary artery bypass graft surgeries), and of these only 1 patient had a target lesion revascularization. Angiographic follow-up was performed in 106 patients (72%) with a late loss of -0.01 mm. Restenosis in the left main trunk occurred only in 1 patient (0.9%). CONCLUSIONS: Percutaneous coronary intervention with sirolimus-eluting stents or paclitaxel-eluting stents implantation in nonbifurcation left main coronary artery lesions appears safe with a long-term major adverse clinical event rate of 7.4% and a restenosis rate of 0.9%.

Outcomes After Percutaneous Coronary Intervention or Bypass Surgery in Patients With Unprotected Left Main Disease.

BACKGROUND: Currently available randomized data on the comparison between percutaneous coronary intervention (PCI) and coronary artery bypass graft (CABG) for the treatment of unprotected left main coronary disease (LMD) lacks statistical power due to low numbers of patients enrolled. OBJECTIVES: This study assessed long-term outcomes of PCI and CABG for the treatment of LMD in specific subgroups according to disease anatomic complexity. METHODS: We conducted a pooled analysis of individual patient-level data of the LMD patients included in the PRECOMBAT (Bypass Surgery Versus Angioplasty Using Sirolimus-Eluting Stent in Patients With Left Main Coronary Artery Disease) and SYNTAX (Synergy Between PCI With TAXUS and Cardiac Surgery) trials. Incidences of major adverse cardiac events were assessed at 5 years follow-up. RESULTS: Study population comprised 1,305 patients. The incidence of major adverse cardiac and cerebrovascular events at 5 years was 28.3% in the PCI group and 23.0% in the CABG group (hazard ratio [HR]: 1.23; 95% confidence interval [CI]: 1.01 to 1.55; p = 0.045). This difference is mainly driven by a higher rate of repeat revascularization associated with PCI (HR: 1.85; 95% CI: 1.38 to 2.47; p < 0.001). The 2 strategies showed similar rates of the safety composite endpoint of death, myocardial infarction, or stroke (p = 0.45). In patients with isolated LM or LM + 1-vessel disease, PCI was associated with a 60% reduction in all-cause mortality (HR: 0.40; 95% CI: 0.20 to 0.83; p = 0.029) and 67% reduction in cardiac mortality (HR: 0.33; 95% CI: 0.12 to 0.88; p = 0.025) when compared with CABG. CONCLUSIONS: In patients with unprotected LMD, CABG, and PCI result in similar rates of the safety composite endpoint of death, myocardial infarction, or stroke. In patients with isolated LM or LM + 1-vessel disease, PCI is associated with lower all-cause and cardiac mortality when compared to CABG.

Meta-Analysis of the Duration of Dual Antiplatelet Therapy in Patients Treated With Second-Generation Drug-Eluting Stents.

The purpose of the study was to evaluate the optimal duration of dual antiplatelet therapy (DAPT) after percutaneous coronary intervention, especially in the era of second-generation drug-eluting stents (DES). The work was conducted from November 2014 to April 2015. All randomized controlled trials comparing short (<12 months) versus long (≥12 months) DAPT in patients treated with second-generation DES were analyzed. Sensitivity analyses were performed for length of DAPT and type of DES. All-cause death was the primary end point, whereas cardiovascular death, myocardial infarction (MI), stent thrombosis (ST), and major bleeding were secondary end points. Results were pooled and compared with random-effect models and meta-regression analysis. Eight randomized controlled trials with 18,810 randomized patients were included. The studies compared 3 versus 12 months of DAPT (2 trials), 6 versus 12 months (3 trials), 6 versus 24 months (1 trial), 12 versus 24 months (1 trial), and 12 versus 30 months (1 trial). Comparing short versus long DAPT, there were no significant differences in all-cause death (odds ratio [OR] 0.87; 95% confidence interval [CI] 0.66 to 1.44), cardiovascular death (OR 0.95; 95% CI 0.65 to 1.37), and ST (OR 1.20; 95% CI 0.79 to 1.83), and no differences were present when considering everolimus-eluting and fast-release zotarolimus-eluting stents separately. Shorter DAPT was inferior to longer DAPT in preventing MI (OR 1.35; 95% CI 1.03 to 1.77). Conversely, major bleeding was reduced by shorter DAPT (OR 0.60; 95% CI 0.42 to 0.96). Baseline features did not influence these results in meta-regression analysis. In conclusion, DAPT for ≤6 months is reasonable for patients treated with everolimus-eluting and fast-release zotarolimus-eluting stents, with the benefit of less major bleeding at the cost of increased MI, with similar survival and ST rates. An individualized patient approach to DAPT duration should take into account the competing risks of bleeding and ischemic complications after present-generation DES.

Murine cytomegalovirus infection increases aortic expression of proatherosclerotic genes.

BACKGROUND: The possible etiologic role of infection in cardiovascular disease is still debated. Having previously demonstrated that murine cytomegalovirus (MCMV) infection of apolipoprotein (apo) E-/- mice increases atherosclerotic lesion size, we determined if MCMV infection produces proatherogenic changes in aortic gene expression. Additionally, in cholesterol-fed C57BL/6J mice, we examined the effects of MCMV infection on aortic lesion area. METHODS AND RESULTS: C57BL/6J apoE-/- and wild-type C57BL/6J mice were infected with MCMV. At various time points, aortas were collected and pooled. Total RNA was extracted and hybridized to Affymetrix murine chips or analyzed for specific gene expression using TaqMan reverse transcription-polymerase chain reaction. Data from infected and uninfected mice were compared. A separate group of cholesterol-fed C57BL/6J mice were infected with MCMV, and lesion area in the aortic sinus was assessed using oil red O staining. Acute MCMV infection altered aortic expression of atherogenic genes in young apoE-/- and C57BL/6J mice-specifically, monocyte chemoattractant protein-1, monokine induced by interferon-gamma, and interferon-gamma inducible protein 10. Acute infection in adult 9-month-old apoE-/- mice with well-established lesions increased aortic expression of monocyte chemoattractant protein-1. Atherosclerotic lesion area in cholesterol-fed C57BL/6J mice was increased after infection with MCMV. CONCLUSIONS: MCMV infection significantly increases atherosclerotic lesion area and aortic expression of atherogenic genes. These infection-induced effects indicate mechanisms by which cytomegalovirus may contribute to atherosclerotic disease initiation and progression and to the precipitation of clinical events. These results additionally add to data compatible with the concept that infection does play an important role in atherosclerotic disease.

The potential role of resistin in atherogenesis.

Resistin, an adipocyte-derived cytokine linked to insulin resistance and obesity, has recently been shown to activate endothelial cells (ECs). Using microarrays, we found that along with numerous other pro-atherosclerotic genes, resistin expression levels are elevated in the aortas of C57BL/6J apoE-/- mice; these findings led us to further explore the relation between resistin and atherosclerosis. Using TaqMan PCR and immunohistochemistry, we found that ApoE-/- mice had significantly higher resistin mRNA and protein levels in their aortas, and elevated serum resistin levels, compared to C57BL/6J wild-type mice. Incubation of murine aortic ECs with recombinant resistin increased monocyte chemoattractant protein (MCP)-1 and soluble vascular cell adhesion molecule (sVCAM)-1 protein levels in the conditioned medium. Furthermore, human carotid endarterectomy samples stained positive for resistin protein, while internal mammary artery did not show strong staining. Patients diagnosed with premature coronary artery disease (PCAD) were found to have higher serum levels of resistin than normal controls. In summary, resistin protein is present in both murine and human atherosclerotic lesions, and mRNA levels progressively increase in the aortas of mice developing atherosclerosis. Resistin induces increases in MCP-1 and sVCAM-1 expression in murine vascular endothelial cells, suggesting a possible mechanism by which resistin might contribute to atherogenesis. Finally, PCAD patients exhibited increased serum levels of resistin when compared to controls. These findings suggest a possible role of resistin in cardiovascular disease.