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Objectives The aim of this study was to assess race-based differences in patients undergoing percutaneous coronary intervention from a large pooled database of randomized controlled trials. Background Data on race-based outcomes after percutaneous coronary intervention are limited, deriving mainly from registries and single-center studies. Methods Baseline characteristics and outcomes at 30 days, 1 year, and 5 years were assessed across different races, from an individual patient data pooled analysis from 10 randomized trials. Endpoints of interest included death, myocardial infarction, and major adverse cardiac events (defined as cardiac death, myocardial infarction, or ischemia-driven target lesion revascularization). Multivariate Cox proportional hazards regression was performed to assess associations between race and outcomes, controlling for differences in 12 baseline covariates. Results Among 22,638 patients, 20,585 (90.9%) were white, 918 (4.1%) were black, 404 (1.8%) were Asian, and 473 (2.1%) were Hispanic. Baseline and angiographic characteristics differed among groups. Five-year major adverse cardiac event rates were 18.8% in white patients (reference group), compared with 23.9% in black patients (p = 0.0009), 11.2% in Asian patients (p = 0.0007), and 21.5% in Hispanic patients (p = 0.07). Multivariate analysis demonstrated an independent association between black race and 5-year risk for major adverse cardiac events (hazard ratio: 1.28; 95% confidence interval: 1.05 to 1.57; p = 0.01). Conclusions In the present large-scale individual patient data pooled analysis, comorbidities were significantly more frequent in minority-group patients than in white patients enrolled in coronary stent randomized controlled trials. After accounting for these differences, black race was an independent predictor of worse outcomes, whereas Hispanic ethnicity and Asian race were not. Further research examining race-based outcomes after percutaneous coronary intervention is warranted to understand these differences.
1. We compared the effects of two novel tachykinin receptor antagonists, FK888 (selective at the tachykinin NK1 receptor) and FK224 (dual antagonist at NK1 and NK2 tachykinin receptors) on stimulus-evoked airway plasma exudation, bronchoconstriction and systemic hypotension in guinea-pigs in vivo. Plasma exudation was induced by substance P (SP), synthetic tachykinin receptor agonists, platelet activating factor (PAF), electrical stimulation of the cervical vagus nerves or by inhalation of cigarette smoke. Changes in airway tone and in carotid artery blood pressure (BP) were induced by synthetic tachykinin agonists, PAF and vagal stimulation. 2. Both FK224 and FK888 dose-dependently inhibited SP-induced plasma exudation in the lower trachea and main bronchi (ID50 values respectively of 1.1 and 0.1 mumol kg-1 in lower trachea, and of 0.5 and 0.1 mumol kg-1 in main bronchi) with complete inhibition at both airway levels at 10 mumol kg-1 for FK224 and at 2 mumol kg-1 for FK888. 3. The NK1-selective tachykinin receptor agonist, [Sar9,Met(O2)11]substance P ([Sar]SP), induced plasma exudation, a response which was blocked by both FK888 and FK224. The NK2-selective agonist, [beta-Ala8]neurokinin A-(4-10) ([beta-Ala]NKA), did not induce plasma exudation: neither FK888 nor FK224 affected this lack of response to [beta-Ala]NKA. 4. [beta-Ala]NKA induced bronchoconstriction, a response which was blocked by FK224 but which was completely unaffected by FK888. [Sar]SP induced a small but significant bronchoconstriction which was completely inhibited by both tachykinin antagonists. 5. In animals pretreated with capsaicin to deplete sensory neuropeptides, PAF induced both plasma exudation and bronchoconstriction. Neither response to PAF was inhibited by either FK888 or FK224.6. Both FK888 and FK224 inhibited plasma exudation induced by vagus nerve stimulation or by cigarette smoke, with FK888 more potent than FK224.7. FK224 inhibited non-cholinergic bronchoconstriction induced by vagal stimulation, whereas FK888,at doses inhibiting vagally-induced plasma exudation, did not.8. Decreases in BP induced by SP or [Sar]SP were blocked by both FK888 and FK224. In contrast,neither antagonist had any significant inhibitory effect on the decrease in BP induced by vagal stimulation (in the presence of atropine) or PAF. [beta-Ala]NKA did not decrease BP and neither tachykinin antagonist had any significant effect on this lack of response.9. We conclude that in guinea-pig airways, plasma leakage induced by endogenous tachykinins is mediated predominantly via NK1-receptors, whereas bronchoconstriction is mediated predominantly via NK2-receptors. In addition, SP-evoked decreases in BP are also mediated via NK1 receptors, whereas the contribution of endogenous tachykinins to vagally-induced decreases in BP appears to be minimal.Development of selective tachykinin receptor antagonists will be important in understanding the involvement of tachykinins in airway physiology and pathophysiology, whereas potent dual tachykinin receptor antagonists such as FK224 may have greater therapeutic potential in certain airway diseases in which tachykinins have been implicated in pathogenesis, including asthma and chronic bronchitis associated with cigarette smoking.
BACKGROUND: Sputum induction is becoming more commonly used to assess airway inflammation. Since it is a relatively non-invasive procedure it may be useful for repeated measurements over a short period of time. METHODS: To assess the repeatability of the method over a 24 hour period, eight healthy, non-smoking, non-atopic subjects (four men) of mean age 30 years underwent sputum induction, repeated at eight hours and 24 hours. Sputum was induced by inhalation of 3.5% saline. Absolute and differential counts of inflammatory cells were performed on the whole sputum after dilution in Hank's balanced salt solution containing 1% dithiothreitol to solubilise the mucus content of the samples. RESULTS: There was a significant rise in the percentage of neutrophils in the eight hour sample compared with the baseline (57%, range 25-94% at eight hours compared with 28%, range 19-60%: median difference 26%). The median baseline percentage of macrophages was 55% (range 26-69%) which fell to 38% (range 3-56%: median difference 22%) at eight hours and 19% (range 14-59%: median difference 25%) at 24 hours. There was no significant change in the differential counts of eosinophils, lymphocytes or columnar epithelial cells, nor in any of the absolute cell counts, at any time point. CONCLUSIONS: Sputum induction may have limited utility in serial assessment of neutrophilic airway inflammation in normal subjects within a 24 hour period.
The earliest evidence supporting transcatheter aortic valve implantation (TAVI) was derived from its comparison with conservative therapy in inoperable patients and with surgical aortic valve replacement (SAVR) in extremely high risk patients. TAVI had a relative advantage in these situations being less invasive and hence less prone to the classic early postoperative devastating complications. To prove as effective in less fragile and less morbid patients, the long-term durability of the haemodynamic and clinical gains from TAVI needs to be confirmed. In this report we will discuss three aspects of the dilemma of expanding TAVI indications to lower-risk patients: first, available data on early and late outcomes after TAVI; second, durability issues; and third, TAVI complications and procedural refinements.
