Therapeutic benefits of ACE inhibitors and other antihypertensive drugs in patients with type 2 diabetes

OBJECTIVE: To assess whether ACE inhibitors are superior to alternative agents for the prevention of cardiovascular events in patients with hypertension and type 2 diabetes. RESEARCH DESIGN AND METHODS: This study is a review and meta-analysis of randomized controlled trials that included patients with type 2 diabetes and hypertension who were randomized to an ACE inhibitor or an alternative drug, were followed for > or =2 years, and had adjudicated cardiovascular events. RESULTS: A total of 4 trials were eligible. The Appropriate Blood Pressure Control in Diabetes (ABCD) trial (n = 470) compared enalapril with nisoldipine, the Captopril Prevention Project (CAPPP) (n = 572) compared captopril with diuretics or beta-blockers, the Fosinopril Versus Amlodipine Cardiovascular Events Trial (FACET) (n = 380) compared fosinopril with amlodipine, and the U.K. Prospective Diabetes Study (UKPDS) (n = 758) compared captopril with atenolol. The cumulative results of the first 3 trials showed a significant benefit of ACE inhibitors compared with alternative treatments on the outcomes of acute myocardial infarction (63% reduction, P < 0.001), cardiovascular events (51% reduction, P < 0.001), and all-cause mortality (62% reduction, P = 0.010). These findings were not observed in the UKPDS. The ACE inhibitors did not appear to be superior to other agents for the outcome of stroke in any of the trials. None of the findings were explained by differences in blood pressure control. CONCLUSIONS: Compared with the alternative agents tested, ACE inhibitors may provide a special advantage in addition to blood pressure control. The question of whether atenolol is equivalent to captopril remains open. Conclusive evidence on the comparative effects of antihypertensive treatments will come from large prospective randomized trials.     

Hypopituitarism following external radiotherapy for pituitary tumours in adults

The development of anterior pituitary hormone deficiencies has been studied in a group of 165 patients who underwent external radiotherapy for tumours of the pituitary or closely related anatomical sites, and who have been observed for up to 10 years. One hundred and forty had undergone pituitary surgery before radiotherapy. All patients received external radiotherapy by a three-field technique, giving 3750-4250 cGy in 15 or 16 fractions over 20-22 days. A combined test of anterior pituitary function using insulin hypoglycaemia or glucagon stimulation in conjunction with thyrotrophin and gonadotrophin releasing hormone tests and basal estimations of prolactin, thyroid hormones and testosterone or oestradiol was performed before radiotherapy. This was repeated six and 12 months later and subsequently annually. Before radiotherapy, 18 per cent of patients had normal growth hormone secretion, 21 per cent had normal gonadotrophin secretion, 57 per cent had normal corticotrophin reserve and 80 per cent had normal thyrotrophin secretion. Life table analysis demonstrated increasing incidences of all anterior pituitary hormone deficiencies with time: by five years all patients were growth hormone deficient, 91 per cent were gonadotrophin deficient, 77 per cent were corticotrophin deficient and 42 per cent were thyrotrophin deficient. At eight years, respective incidences of deficiencies were 100, 96, 84 and 49 per cent. Radiation-induced hyperprolactinaemia was seen in 73 patients; mean serum prolactin concentration rose from 227 +/- 11 mU/l to a peak of 369 +/- 60 mU/l at two years and subsequently declined towards the basal value. The primary diagnosis, patient age, sex, irradiated tissue volume and previous surgery were examined as variables that might influence the rate of development of anterior pituitary hormone deficiencies, but none of these factors had a significant effect. The radiation induced hyperprolactinaemia was however more marked in female patients. Although anterior pituitary hormone deficiencies most commonly developed in the order growth hormone, gonadotrophin, corticotrophin, thyrotrophin (61 per cent of patients), other sequences were evident. Most notably corticotrophin deficiency occurred before gonadotrophin deficiency. There is a high incidence of anterior pituitary hormone deficiencies in patients treated surgically for pituitary tumours and the incidence increases after external radiotherapy. Deficiencies may occur in an unpredictable sequence and endocrine testing is recommended on an annual basis.     

The Utility of the Beck Depression Inventory in a Bariatric Surgery Population

Background  

The Beck Depression Inventory (BDI) is commonly used in bariatric surgery psychological assessments. However, several items may be measuring physical consequences of obesity (e.g., sleep disturbance, chronic pain, or sexual dysfunction) rather than depressive symptoms.     

Evaluation of the effects of everolimus‐eluting and paclitaxel‐eluting stents on target lesions with jailed side branches: 2‐year results from the SPIRIT III randomized trial

Objective: To evaluate whether an everolimus‐eluting stent (EES) with thinner stent struts and polymer results in less periprocedural myonecrosis and adverse outcomes. Background: Higher periprocedural myocardial infarction (MI) rates have been reported with the TAXUS® EXPRESS² paclitaxel‐eluting stent (PES) compared to the bare metal EXPRESS²® stent due to more frequent side branch compromise, presumably attributable to the thickness of the stent/polymer on the PES. Methods: In the SPIRIT III trial, we identified 113 patients in the XIENCE V® EES group and 63 patients in the TAXUS EXPRESS² PES group who met the criteria of having a lesion with a jailed side branch (<2 mm diameter, and <50% stenosis). Two‐year clinical outcomes were evaluated. Results: A periprocedural increase in Creatine Kinase‐MB >1× upper normal level occurred in 9.0% of EES compared to 29.7% of PES patients with jailed side branches, P = 0.01. Through 2 years, major adverse cardiac events (MACE; cardiac death, MI, or target lesion revascularization [TLR]) occurred in 6.8% of EES and 19.0% of PES jailed side branch patients (P = 0.03), with numerically lower rates of MI (2.9% vs. 10.3%, P = 0.07) and TLR (3.9% vs. 10.3%, P = 0.17) in the EES group, with comparable rates of cardiac death (1.9% vs. 1.7%, P = 1.00). Conclusions: In this post‐hoc analysis of the SPIRIT III RCT, patients undergoing stenting of target lesions with jailed side branches with the thin strut and polymer XIENCE V EES compared to the thicker strut TAXUS PES had lower rates of MACE through 2 years due to fewer MIs and TLRs. © 2010 Wiley‐Liss, Inc.     

Clinical and angiographic outcomes with an everolimus‐eluting stent in large coronary arteries: The SPIRIT III 4.0 mm registry

Objective : This study evaluates the safety and efficacy of the XIENCE V® 4.0 mm stent for the treatment of de novo native coronary artery lesions. Background : In the SPIRIT III trial, the XIENCE V® everolimus‐eluting stent (EES), compared with the TAXUS EXPRESS² paclitaxel‐eluting stent (PES) in 2.5–3.75 mm diameter coronary arteries, resulted in reduced angiographic late loss (LL), noninferior rates of target vessel failure (TVF), and fewer major adverse cardiac events (MACE). Methods : The SPIRIT III 4.0 mm registry was a concurrent arm of the SPIRIT III trial consisting of 69 nonrandomized patients with lesions ≤28 mm in length and reference vessel diameter 3.75–4.25 mm treated with a 4.0 mm EES. The primary endpoint was 8‐month in‐segment LL compared with the randomized PES arm. Results : In‐segment LL was 0.17 ± 0.38 mm in the 4.0 mm EES registry compared with 0.28 ± 0.48 mm in the PES arm (P < 0.0001 for noninferiority). The 1‐year rates of ischemia‐driven TVF (cardiac death, myocardial infarction [MI], or target vessel revascularization) and MACE (cardiac death, MI, or target lesion revascularization [TLR]) were numerically, but not statistically, lower in the 4.0 mm EES patients compared with the randomized PES patients (5.9 vs. 11.3%, P = 0.27 and 5.9 vs. 10.3%, P = 0.36, respectively). There was no difference in 8‐month LL or 1‐year TVF or MACE between the 4.0 mm EES and randomized EES patients. Conclusions : In large coronary arteries, the 4.0 mm EES results in low rates of LL at 8 months and adverse clinical events at 1 year. © 2009 Wiley‐Liss, Inc.     

Vascular closure devices: the second decade

Vascular closure devices (VCDs) introduce a novel means for improving patient comfort and accelerating ambulation after invasive cardiovascular procedures performed via femoral arterial access. Vascular closure devices have provided simple, rapid, and reliable hemostasis in a variety of clinical settings. Despite more than a decade of development, however, VCD utilization has neither been routine in the U.S. nor around the world. Their limited adoption reflects concerns of higher costs for cardiac procedures and a lack of data confirming a significant reduction in vascular complications compared with manual compression. Recent data, however, suggest that VCD are improving, complication rates associated with their use may be decreasing, and their utilization may improve the process of care after femoral artery access. Challenges in the second decade of VCD experience will include performing definitive randomized trials, evaluating outcomes in higher-risk patients, and developing more ideal closure devices.     

ABO blood types: influence on infarct size, procedural characteristics and prognosis

Introduction

Patients with non-O blood groups have higher plasma von Willebrand factor (vWF) levels than those with type O. vWF mediates platelet adhesion, aggregation and thrombosis. These considerations likely explain the prior observations that non-O patients have higher rates of arterial and venous thromboembolic events. However, the effect of blood group status on size of MI, procedural findings and outcomes after PCI for MI have not been reported.

Methods

We analyzed 1198 patients who underwent percutaneous coronary intervention for acute myocardial infarction between 10/03 and 8/06, and who had ABO blood group status and clinical follow-up.

Results and conclusions

Patients with O blood type were slightly older (62 ± 13 vs. 60 ± 13years; p = 0.017) had a higher prevalence of hypercholesterolemia (67% vs. 58%; p = 0.002), and had a higher burden of atherosclerosis with more vascular disease (17% vs. 13%; p = 0.017) and higher prevalence of previous PCI (22% vs. 17%; p = 0.025). Non-O blood group patients had larger infarcts as measured by median peak troponin (33 vs. 24; p = 0.037), total CK (721 vs. 532; p = 0.012) and CK-MB (101 vs. 68; p = 0.010). At PCI, non-O patients had increased visible thrombus and reduced TIMI flow pre-procedure. However, there were no differences in procedural success, in-hospital blood transfusion or occurrence of MACE at 1year follow-up. Our data demonstrate that non-O compared to O blood groups patients have higher thrombus burden despite less extensive atherosclerosis. Nevertheless, outcomes at 1year were similar.     

Human fetal bone cells associated with ceramic reinforced PLA scaffolds for tissue engineering

Fetal bone cells were shown to have an interesting potential for therapeutic use in bone tissue engineering due to their rapid growth rate and their ability to differentiate into mature osteoblasts in vitro. We describe hereafter their capability to promote bone repair in vivo when combined with porous scaffolds based on poly(l-lactic acid) (PLA) obtained by supercritical gas foaming and reinforced with 5 wt.% beta-tricalcium phosphate (TCP). Bone regeneration was assessed by radiography and histology after implantation of PLA/TCP scaffolds alone, seeded with primary fetal bone cells, or coated with demineralized bone matrix. Craniotomy critical size defects and drill defects in the femoral condyle in rats were employed. In the cranial defects, polymer degradation and cortical bone regeneration were studied up to 12 months postoperatively. Complete bone ingrowth was observed after implantation of PLA/TCP constructs seeded with human fetal bone cells. Further tests were conducted in the trabecular neighborhood of femoral condyles, where scaffolds seeded with fetal bone cells also promoted bone repair. We present here a promising approach for bone tissue engineering using human primary fetal bone cells in combination with porous PLA/TCP structures. Fetal bone cells could be selected regarding osteogenic and immune-related properties, along with their rapid growth, ease of cell banking and associated safety.