Effects of esomeprazole 40 mg twice daily on asthma: a randomized placebo-controlled trial

RATIONALE: Gastroesophageal reflux disease (GERD) is common in patients with asthma, suggesting an interaction between the two conditions. OBJECTIVES: To assess the effect of gastric acid suppression with the proton pump inhibitor esomeprazole on asthma outcomes in subjects with persistent moderate to severe asthma treated with antiinflammatory asthma medication. METHODS: In this double-blind study, subjects were randomized to receive esomeprazole 40 mg or placebo twice daily for 16 wk. According to nocturnal respiratory symptoms (NOC) and GERD, subjects were divided into three strata: GERD-/NOC+, GERD+/NOC-, and GERD+/NOC+. MEASUREMENTS AND MAIN RESULTS: A total of 770 subjects were randomized. There was no statistically significant improvement in morning peak expiratory flow (PEF) over placebo in the overall study population: 6.3 L/min (p = 0.061). Over the whole treatment period, in GERD+/NOC+ subjects (n = 350), esomeprazole provided an 8.7-L/min improvement (p = 0.03) in morning PEF, and a 10.2-L/min improvement (p = 0.012) in evening PEF over placebo. Among 307 subjects taking long-acting beta2-agonists, improvements over placebo were observed in morning PEF (12.2 L/min, p = 0.017) and in evening PEF (11.1 L/min, p = 0.024); these improvements were more pronounced in GERD+/NOC+ subjects. Esomeprazole 40 mg twice daily was well tolerated and no safety concerns were noted. CONCLUSIONS: Esomeprazole improved PEF in subjects with asthma who presented with both GERD and NOC. In subjects without both GERD and NOC, no improvement could be detected.     

Fluvastatin treatment and withdrawal: effects on endothelial function

Fluvastatin lowers lipids and protects endothelial function. This study investigated how 2 preparations of fluvastatin would affect endothelial function after treatment and early after its discontinuation. Twenty-seven patients received 80 mg extended-release fluvastatin every day, 40 mg immediate-release fluvastatin twice a day, or placebo for 5 weeks. Fasting lipids and flow-mediated dilation were measured at baseline and after each treatment period. In 21 patients, flow-mediated vasodilation was also measured 24 hours after discontinuation of therapy. Both forms of fluvastatin improved flow-mediated vasodilation (extended release: P < .037 and immediate release: P < .001). However, this improvement occurred preferentially in patients with low baseline flow-mediated vasodilation (<5%). Twenty-four hours after treatment discontinuation, the flow-mediated vasodilation deteriorated again to baseline (extended release and immediate release: P < .001). Fluvastatin improved flow-mediated vasodilation only in patients with low baseline values. Twenty-four hours after discontinuation, the flow-mediated vasodilation deteriorated again, surprisingly irrespective of prior improvement.     

每日40 mg阿托伐他汀对预防2型糖尿病患者颈动脉硬化影响的观察

目的 观察40 mg/d阿托伐他汀对预防T2DM患者颈动脉硬化的影响. 方法 将T2DM合并颈动脉斑块患者随机分为给予40 mg/d阿托伐他汀治疗的观察（n=31）组和给予常规剂量阿托伐他汀治疗的对照（n=30）组,分别于治疗前和治疗后12周检测血脂指标、颈动脉斑块情况及内皮功能情况. 结果 观察组TG、TC、LDL-C、载脂蛋白B水平、颈动脉内=中膜厚度、血管内径和斑块面积均低于对照组（P＜0.05）;载脂蛋白A-I水平以及内皮依赖性血管舒张功能均高于对照组（P＜0.05）;两组HDL-C比较差异无统计学意义. 结论 40mg/d阿托伐他汀有助于改善血脂代谢水平、颈动脉斑块情况以及内皮舒张功能,对于预防T2DM患者颈动脉硬化有积极价值.     

Prevention of duodenal ulcer recurrence by pirenzepine 50 mg twice daily

Eighty-four patients with healed duodenal ulcers were treated for 1 year with pirenzepine, 50 mg twice daily, or placebo in this double-blind, randomized, multicenter trial. Clinical follow-up and endoscopy were performed before and after 3, 6, and 12 months of treatment. Endoscopy was also carried out whenever symptoms compatible with ulcer recurrence were present for more than 2 days. Both groups were well matched for age, sex, duration of peptic ulcer disease, and smoking habits. There were 21 drop-outs due to lack of compliance. Therefore, 32 patients treated with pirenzepine and 31 with placebo were included in the analysis. Expressed in cumulative percentage of recurrence, with pirenzepine, 28% of the patients had a relapse at 3 months, 41% at 6 months, and 53% at 12 months; with placebo, the recurrence rates were 58% at 3 months, 68% at 6 months, and 71% at 12 months. The mean success time at 1 year is also longer for pirenzepine (7.38 months) than for placebo (5.52 months). These differences are significantly in favor of pirenzepine (p less than 0.05). Both treatments were well tolerated. Dry mouth was more frequently observed with pirenzepine (14 versus 5 patients). We conclude that pirenzepine, 50 mg twice daily, significantly reduces the relapse rate of duodenal ulcers during a 1-year maintenance treatment.     

阿托伐他汀40 mg/d用于急性冠状动脉综合征患者冠状动脉介入术后调脂的疗效

目的探讨阿托伐他汀40mg/d在急性冠状动脉综合征(ACS)患者行经皮冠状动脉介入术(PCI)后强化降脂治疗的效果,不同剂量阿托伐他汀的血脂降低程度及血脂降低的时间曲线,不良反应和对急性临床心脏事件的影响。方法92例PCI术后的ACS患者随机分配为阿托伐他汀常规剂量(10mg/d)A组和大剂量阿托伐他汀(40mg/d)B组各46例,观察用药后1,4,12,24周两组的结果。结果失访率A组6·5%(3例),B组8·6%(4例)。(1)两组患者用药后1~4周为丙氨酸转氨酶(ALT)出现异常的高峰期,1周异常例数A组20·9%比B组45·2%(P=0·011)发生比例少,多数ALT<正常值的3倍,观察后恢复正常;而A组有2例(4·7%)、B组有3例(7·1%)的患者ALT>正常值的3倍,需停药;两组各有2例肾功能异常。(2)A、B组患者的血脂下降率,在给药12周后TC下降率12·3%比21·7%(P=0·042),给药24周后TC下降率11·1%比23·4%(P=0·005),低密度脂蛋白(LDL)下降率10·0%比29·5%(P=0·000),以及24周LDL≤1·8mmol/L比例为19·5%比51·2%(P=0·005),差异均有统计学意义。(3)随访期内A、B两组心脏事件差异无统计学意义。结论(1)阿托伐他汀40mg/d是安全的。(2)服用阿托伐他汀40mg/d可显著提高ACS患者PCI术后调脂的达标率,特别是LDL降至1·8mmol/L及以下的比例更高。     

A comparison of enalapril 20 mg once daily versus 10 mg twice daily in terms of blood pressure lowering and patient compliance

OBJECTIVE: To compare enalapril 20 mg once daily with 10 mg twice daily in terms of blood pressure reduction and patient compliance. DESIGN: Cross-over study of patients randomly assigned to a sequence of enalapril 20 mg once daily or 10 mg twice daily in three 4-week periods following a 4-week placebo run-in. SETTING: General practices in the greater Belfast and Lisburn area in Northern Ireland. PATIENTS: Twenty-five hypertensive patients who had a mean diastolic blood pressure of between 90 and 110 mm Hg after receiving placebo for 4 weeks. MAIN OUTCOME MEASURES: Reduction in blood pressure and estimation of patient compliance. RESULTS: Patient compliance was superior on the once daily regimen. However, the twice daily regimen was associated with a greater blood pressure reduction which almost reached statistical significance at the 5% level. CONCLUSIONS: Enalapril 20 mg should be prescribed as 10 mg twice daily and measures taken to improve patient compliance.     

Effect of colchicine (0.5 mg twice daily) on high-sensitivity C-reactive protein independent of aspirin and atorvastatin in patients with stable coronary artery disease

In patients with stable coronary artery disease, elevated levels of biomarkers of inflammation, including high-sensitivity C-reactive protein (hs-CRP) > or = 2.0 mg/L, are predictors of future vascular events. Because long-term low-dose colchicine is a safe and effective means of dampening inflammation, we conducted an open-label pilot study to determine whether it could significantly lower hs-CRP in patients with stable coronary artery disease in whom hs-CRP was > or = 2.0 mg/L despite taking both aspirin and high-dose atorvastatin therapy. Plasma hs-CRP was measured in 200 patients with clinically stable coronary artery disease who were taking aspirin and atorvastatin. In 64 patients, hs-CRP was > or = 2.0 mg/L. In 20 of these patients, hs-CRP was measured again at 2 weeks (no treatment group), and in 44 patients, hs-CRP was measured again after 4 weeks of open-label colchicine 0.5 mg twice daily (treatment group). In the no treatment group, mean baseline hs-CRP did not decrease significantly, measuring 4.28 +/- 2.03 mg/L at baseline and 3.70 +/- 2.30 mg/L after repeated measurement (mean change 11.0%, 95% confidence interval [CI] -30% to +9%, p = NS). In contrast, hs-CRP decreased in all patients administered colchicine, with mean baseline hs-CRP decreasing from 4.58 +/- 2.05 to 1.78 +/- 1.38 mg/L (p <0.001), an absolute decrease of 2.80 mg/L (95% CI 2.40 to 3.65 mg/L) and a relative decrease of 60% (95% CI 54% to 67%). In 28 patients (64%) in this group, the decrease in hs-CRP was >50% from baseline, and in 31 patients (70%), hs-CRP decreased to <2.0 mg/L. No significant side effects were reported. In conclusion, low-dose colchicine (0.5 mg twice daily) can effectively decrease hs-CRP in patients with clinically stable coronary artery disease and increased hs-CRP independent of aspirin and atorvastatin use. Additional controlled studies are warranted to confirm this observation and determine whether long-term use of low-dose colchicine can improve clinical outcomes in patients with advanced vascular disease.     

Effects of atorvastatin and atorvastatin withdrawal on soluble CD40L and adipocytokines in patients with hypercholesterolaemia

OBJECTIVE: Beyond lipid lowering, statins have pleiotropic effects with favourable benefits against atherogenesis.Withdrawal of statin therapy has been demonstrated to abrogate vascular protective activity and even increase the incidence of thrombotic vascular events.The purpose of this study is to investigate the serial changes of soluble CD40 ligand (sCD40L) and two adipocytokines, adiponectin and resistin, after short-term atorvastatin therapy and withdrawal in patients with hypercholesterolaemia. METHODS AND RESULTS: Thirty-two patients with hypercholesterolaemia received atorvastatin 10 mg/day for 3 months. Serum lipid profiles, and levels of sCD40L, adiponectin and resistin, were assessed before and immediately after 3 months' statin therapy. Serum levels of sCD40L and adiponectin were also measured on the 3 consecutive days after statin withdrawal.After 3 months' statin therapy, levels of sCD40L (1.93 +/- 1.13 vs. 1.30 +/- 0.97 ng/mL), total cholesterol and low-density lipoprotein cholesterol (LDL-C) were all reduced significantly (p < 0.05). However, sCD40L level tended to increase towards baseline on the first and second days after statin withdrawal, but was not significantly elevated until the third day after withdrawal (1.89 +/- 1.28 vs. 1.30 +/- 0.97 ng/mL, p < 0.05).Total cholesterol and LDL-C levels did not increase during the 3 days of statin withdrawal. No significant changes of adiponectin and resistin levels were shown after statin therapy. CONCLUSIONS: These results indicate that the effect of statin on sCD40L level was abrogated after therapy withdrawal, and was independent of serum cholesterol level. Statin therapy did not significantly alter levels of adiponectin and resistin.     

Rabeprazole, 20 mg once daily or 10 mg twice daily, is equivalent to omeprazole, 20 mg once daily, in the healing of erosive gastrooesophageal reflux disease

BACKGROUND: Proton pump inhibitors are the most potent pharmacologic inhibitors of gastric acid secretion currently available, and have proven effective in the treatment of gastro-oesophageal reflux disease (GERD). The object of this study was to compare the efficacy and tolerability of a new proton pump inhibitor, rabeprazole at two different dosages, with that of omeprazole in the healing of erosive GERD. METHODS: Rabeprazole 20 mg once daily (QD) and 10 mg twice daily (BID) were compared with omeprazole 20 mg QD in a double-blind, multicentre, parallel group study involving 310 patients with erosive GERD. The primary efficacy endpoint was oesophageal mucosal healing determined by endoscopy. Secondary endpoints included reduction in symptoms and improvements in quality-of-life scores. RESULTS: The healing rates between both rabeprazole groups and the omeprazole group were equivalent in both the per-protocol and intent-to-treat populations. In the per-protocol population, rabeprazole 20 mg was noted to have a numerical trend toward more rapid daytime heartburn relief. However, by 4 and 8 weeks of treatment, no significant differences were found between groups for secondary endpoints, adverse events, or laboratory abnormalities including elevation of serum gastrin levels. CONCLUSIONS: Rabeprazole 20 mg in two different dosing schedules is as effective as omeprazole 20 mg QD with regard to efficacy and tolerability in patients with erosive GERD.     

Effect of omeprazole 20 mg twice daily on duodenogastric and gastro-oesophageal bile reflux in Barrett's oesophagus

Background—Both acid and duodenal contents arethought to be responsible for the mucosal damage in Barrett'soesophagus, a condition often treated medically. However, little isknown about the effect of omeprazole on duodenogastric reflux (DGR) andduodenogastro-oesophageal reflux (DGOR).
Aims—To study the effect of omeprazole 20 mgtwice daily on DGR and DGOR, using the technique of ambulatorybilirubin monitoring.
Methods—Twenty three patients with Barrett'soesophagus underwent manometry followed by 24 hour oesophageal andgastric pH monitoring. In conjunction with pH monitoring, 11 patients(group 1) underwent oesophageal bilirubin monitoring and 12 patients (group 2) underwent gastric bilirubin monitoring, both before andduring treatment with omeprazole 20 mg twice daily.
Results—In both groups there was a significantreduction in oesophageal acid (pH<4) reflux (p<0.005) and asignificant increase in the time gastric pH was above 4 (p<0.005). Ingroup 1, median total oesophageal bilirubin exposure was significantlyreduced from 28.9% to 2.4% (p<0.005). In group 2, median totalgastric bilirubin exposure was significantly reduced from 24.9% to7.2% (p<0.005).
Conclusions—Treatment of Barrett's oesophaguswith omeprazole 20 mg twice daily results in a notable reduction in theexposure of the oesophagus to both acid and duodenal contents. Inaddition, delivery of duodenal contents to the upper gastric body is reduced.

Keywords:bilirubin monitoring; Barrett's oesophagus; omeprazole; pH monitoring; duodenogastric reflux; duodenogastro-oesophageal reflux

     

Efficacy of famotidine 20 mg twice a day versus 40 mg twice a day in the treatment of erosive or ulcerative reflux esophagitis

Two different doses of famotidine (20 mg twice a day versus 40 mg twice a day) were evaluated in a double-blind, randomized multicenter study in 474 symptomatic patients with erosive ulcerative reflux esophagitis. A total of 238 patients were treated with famotidine 20 mg and 236 patients with 40 mg at breakfast and dinnertime. Relief of symptoms was significant in all patients after six and 12 weeks and not different in both treatment groups. Overall endoscopic healing was significantly better in the famotidine 40 mg twice a day group compared with 20 mg twice a day at week 6 (58% versus 43%;P<0.05) and at week 12 (76% versus 67%;P<0.05). Extending treatment to 24 weeks with 40 mg of famotidine twice a day in those patients not healed after 12 weeks did not result in further symptom relief or in significantly better overall healing. The differences in efficacy of these two doses were more pronounced with increasing severity of esophagitis. Analyzed by grade of esophagitis at entrance, healing was significantly better with famotidine 40 mg twice a day at week 6 for grade II, at week 12 for grades III and IV, and at week 24 for grade IV esophagitis. The results show that in the treatment of erosive/ ulcerative reflux patients famotidine 40 mg twice a day is more effective and achieves faster healing than famotidine 20 mg twice a day.for the Dutch Esophagitis Study Group.Participating physicians: P. Batenburg, J. Beker, J. Bellaar Spruijt, L. van Bergeijk, J. Bergmann, W. Bode, J. de Boer, H. Boot, G. Dorrepaal, J. Douma, J. Drapers, J. Ferwerda, H. Festen, A. Geraedts, J. Götz, E. van der Hoek, R. van Hogezand, J. Juttmann, M. Kloppenburg, F. Lalisang, W. Lesterhuis, D. van der Linde, G. van der Linden, J. van Maanen, J. Minkema, C. Mulder, I. van Munster, J. Nadorp, G. Nelis, J. Nicolai, R. Ouwendijk, D. Overbosch, A. van der Putten, J. Raats, F. Schuitemaker, J. Sindram, G. Slagboom, P. Snel, P. Stijnen, J. Thies, J. Thijs, H. Tuynman, B. Uyterlinde, J. ten Veen, K. te Velde, M. Vidakovic-Vukic, F. Vismans, A. Vogten, G. Vosmaer, P. de Vries, H. Walinga, S. van der Werf, I. Wesdorp, B. Westerveld, A. Wolff, R. Ypma.This study was supported by a grant from Merck Sharp & Dohme, The Netherlands.This study was presented in part at the annual meeting of the American Gastroenterology Association, May 1991 (Gastroenterology 100:63A, 1991).     

Safety and efficacy of switching to nilotinib 400 mg twice daily for patients with chronic myeloid leukemia in chronic phase with suboptimal response or failure on front-line imatinib or nilotinib 300 mg twice daily

In a randomized, phase III trial of nilotinib versus imatinib in patients with newly diagnosed Philadelphia chromosome positive chronic myeloid leukemia in chronic phase, more patients had suboptimal response or treatment failure on front-line imatinib than on nilotinib. Patients with suboptimal response/treatment failure on imatinib 400 mg once or twice daily or nilotinib 300 mg twice daily could enter an extension study to receive nilotinib 400 mg twice daily. After a 19-month median follow up, the safety profile of nilotinib 400 mg twice daily in patients switching from imatinib (n=35) was consistent with previous reports, and few new adverse events occurred in patients escalating from nilotinib 300 mg twice daily (n=19). Of patients previously treated with imatinib or nilotinib 300 mg twice daily, respectively, 15 of 26 (58%) and 2 of 6 (33%) without complete cytogenetic response at extension study entry, and 11 of 34 (32%) and 7 of 18 (39%) without major molecular response at extension study entry, achieved these responses at any time on nilotinib 400 mg twice daily. Estimated 18-month rates of freedom from progression and overall survival after entering the extension study were lower for patients switched from imatinib (85% and 87%, respectively) versus nilotinib 300 mg twice daily (95% and 94%, respectively). Nilotinib dose escalation was generally well tolerated and improved responses in about one-third of patients with suboptimal response/treatment failure. Switch to nilotinib improved responses in some patients with suboptimal response/treatment failure on imatinib, but many did not achieve complete cytogenetic response (clinicaltrials.gov identifiers:00718263, 00471497 - extension).     

Efficacy of rosuvastatin (5 mg and 10 mg) twice a week in patients intolerant to daily statins

The aim of this study was to evaluate the efficacy of rosuvastatin twice weekly in 40 patients intolerant to daily statins. Rosuvastatin twice weekly alone or added to other lipid-lowering medications decreased total cholesterol by 19%, low-density lipoprotein cholesterol by 26%, and triglycerides by 14% (p<0.01 for all). High-density lipoprotein cholesterol did not change. Eight of the 40 patients (20%) discontinued twice-weekly rosuvastatin treatment because of muscle-related symptoms, during an average of 8 weeks of treatment. In conclusion, rosuvastatin twice weekly reduced total cholesterol, low-density lipoprotein cholesterol, and triglycerides and was well tolerated, but determining long-term tolerability requires more prolonged treatment.     

Comparison of the effects of combination atorvastatin (40 mg) + ezetimibe (10 mg) versus atorvastatin (40 mg) alone on secretory phospholipase A2 activity in patients with stable coronary artery disease or coronary artery disease equivalent

Secretory phospholipase A2 (sPLA2) is an enzyme that plays an important role in the pathogenesis of atherosclerosis and of adverse cardiovascular events. It is currently the target of emerging therapeutic agents. Our study was designed to investigate the effect of aggressive lowering of low-density lipoprotein (LDL) cholesterol with ezetimibe and atorvastatin on sPLA2 activity. We randomized 100 patients with stable coronary artery disease (CAD) or CAD equivalent (diabetes, stroke, or peripheral vascular disease) to receive ezetimibe 10 mg/day in association with atorvastatin 40 mg/day (combination therapy group) versus atorvastatin 40 mg/day and placebo (monotherapy group). Patients on statin therapy before inclusion were allowed to enter the study as long as the potency of the statin was lower than atorvastatin 40 mg/day. Lipid profile, high-sensitivity C-reactive protein (hs-CRP), and sPLA activity were measured at baseline and after 8 weeks of therapy. The decrease in LDL cholesterol was more significant in the combination therapy group, but the decrease in hs-CRP was similar. sPLA2 activity significantly decreased in the ezetimibe/atorvastatin group from 29 U/ml (interquartile range 23 to 35) to 26 U/ml (23 to 29, p = 0.001) but remained similar in the placebo/atorvastatin group (23 U/ml, 19 to 32, vs 22 U/ml, 19 to 28, p = NS). In a multivariate stepwise linear regression model, change in sPLA2 correlated with change in hs-CRP (p <0.001), baseline LDL cholesterol level (p = 0.001), body mass index (p = 0.003), diabetes mellitus (p = 0.04) and combination therapy with ezetimibe/atorvastatin (p = 0.05). In conclusion, this study demonstrates that coadministration of ezetimibe and atorvastatin decreases sPLA2 activity.     

A single-centre study of gastric ulcer healing with 300 mg ranitidine at night versus 150 mg ranitidine twice daily

In a single-centre study 59 patients with gastric ulcer were treated either with 300 mg ranitidine at night or with 150 mg ranitidine twice daily. After 4 and 8 weeks 73% and 97%, respectively, of those treated with 300 mg at night and 59% and 86% of those treated with 150 mg twice daily had complete ulcer healing. These differences between the two groups were not statistically significant. No serious side effects were seen. Ranitidine, 300 mg at night, appears to be at least as effective as the standard 150 mg twice daily regimen in the treatment of gastric ulcer.     

阿托伐他汀40 mg对急性冠状动脉综合征介入术后患者的影响

目的 研究给予急性冠状动脉综合征（ACS）行经皮冠状动脉介入术（PCI）后患者40 mg/d阿托伐他汀强化调脂,探讨该治疗方案对炎症因子、调脂疗效及临床心脏事件的影响,同时观察不良反应.方法 92例ACS患者行PCI后,随机分为阿托伐他汀常规剂量（10 mg/d,A组）和大剂量阿托伐他汀（40 mg/d,B组）各46例,用药后4 、12 、24周抽外周静脉血,统一用ELISA法检测血清中高敏C-反应蛋白（hs-CRP）和金属蛋白酶-9（MMP-9）浓度,分析两组间差异,及其与调脂疗效的关系,并观测对肝功能、临床冠状动脉事件等影响.结果 失访率A组6.5%（3例）,B组8.6%（4例）.（1） 两组患者用药后1～12周为丙氨酸氨基转移酶（ALT）出现异常的高峰期,1周,4周,12周异常例数A 组比B组发生率少（P＜0.05）;多数ALT＜3倍正常值,观察4周后恢复正常;而A组有2例（4.7%）、B组有3例（7.1%）的患者ALT＞3倍正常值,需停药,两组各有2例肾功能异常.（2） A、B组患者的血脂下降率在给药12周后总胆固醇（TC） 为12.3%比21.7%（P＜0.05）,给药24周后TC为 11.1%比23.4%（P＜0.05）,低密度脂蛋白胆固醇（LDL-C）为 10.0%比29.5%（P＜0.05）,差异有统计学意义.（3） A、B两组患者血清hs-CRP在服药后下降率分别为4周30.5%比21.8%、12周46.8%比64.3%、24周55.5%比71.7%（P＜0.05）;血清MMP-9 下降率分别为4周49.1%比50.0%、12 周72.7%比84.2%（P＜0.05）;二变量相关分析发现血清hs-CRP浓度下降与TC、LDL-C的变化呈线性相关;血清MMP-9浓度下降与TC、LDL变化也呈线性相关.（4） 随访期内A、B两组不良心脏事件发生率差异无统计学意义.结论 （1） 阿托伐他汀40 mg/d是安全的;（2） 服用阿托伐他汀40 mg/d可显著提高冠心病患者二级预防调脂的达标率,特别是LDL-C降至≤1.8 mmol/L的目标值比例更高 ;（3） 调脂强度与患者的血清hs-CRP与MMP-9的浓度下降趋势有线性相关.     

The effects of atorvastatin on coronary endothelial function in patients with recent myocardial infarction

BACKGROUND: Endothelial dysfunction is a key early event in atherosclerosis that occurs in acute coronary syndrome. It was reported that atorvastatin improves the endothelial function of skeletal muscle vessels, but the effect on the coronary artery is unknown. HYPOTHESIS: The purpose of this study is to determine the effects of atorvastatin on coronary endothelial function in humans. METHODS: Non-infarct-related coronary arteries of 48 patients with acute myocardial infarction who had undergone successful percutaneous transluminal coronary angioplasty were examined. Three groups were studied: hyperlipidemia with use of atorvastatin (Group 1, n=17), hyperlipidemia without statin use (Group 2, n=18), and normal cholesterol level controls (Group 3, n=13). Statin treatment was started at discharge. Acetylcholine (Ach) was infused into the coronary artery and the diameter was assessed by quantitative angiography at baseline and after 6 months. RESULTS: Acetylcholine given in doses of 1, 3, 10, and 30 mg/min increased the coronary artery diameter change in a dose-dependent manner. In the initial study, patients in the three groups had similar responses to Ach. The mean diameter change after 6 months was significantly improved in Group 1 compared with Groups 2 and 3 (-11 +/- 3% vs. -20 +/- 7% and -21 +/- 6%, respectively; p < 0.01 in each case). Multivariate regression analysis showed that atorvastatin (p < 0.01) was the significant determinant for improvement of endothelial function. CONCLUSIONS: These findings suggest that atorvastatin improves endothelial function of the coronary artery in patients with myocardial infarction.     

Efficacy of the dosing regimen of pantoprazole 40 mg, amoxicillin 1000 mg and clarithromycin 500 mg, twice daily for 7 days, in the eradication of Helicobacter pylori in patients with peptic ulcer

AIM: This is an open label, multicenter trial to determine the efficacy of the association of pantoprazole, clarithromycin and amoxicillin to eradicate Helicobacter pylori in patients with peptic ulcer. MATERIAL AND METHODS: Seventy-one patients (36 females, 35 males, average age 41.9 years) from three Brazilian university centers (located in the cities of Belo Horizonte and Porto Alegre), with peptic ulcers confirmed by endoscopy, and infections by H. pylori proven by at least two diagnostic testings were admitted in the trial. An association of pantoprazole 40 mg, clarithromycin 500 mg and amoxicillin 1.0 g was administered to patients twice daily for 7 days. RESULTS: By the end of treatment all patients were examined for digestive symptoms, presence of adverse events, and treatment adherence. Sixty days after the end of the treatment a new endoscopy with biopsies and respiratory function testing with 13C-urea breath test was performed in order to determine the eradication rates of that microorganism. Patients showing negative results at least in the 13C-urea breath test and in one other test (urease or histology) were considered H. pylori-negative. By the end of the trial, 60/69 (87%, CI 95% = 78.9-94.8) patients had the H. pylori eradicated in the per protocol analysis and 60/71 (84.5%, CI 95% = 76-92.9) in the intention-to-treat analysis. One patient was withdrawn from the trial due to a diarrhea. Twelve (16.9%) patients showed adverse symptoms that were deemed as mild symptoms. CONCLUSION: Our conclusion is that the association of pantoprazole, amoxicillin and clarithromycin administered during 7 days is an effective and well-tolerated alternative as regards the eradication of H. pylori in patients with peptic ulcer in Brazil.