Effects of Anacetrapib in Patients with Atherosclerotic Vascular Disease

BACKGROUND: Patients with atherosclerotic vascular disease remain at high risk for cardiovascular events despite effective statin-based treatment of low-density lipoprotein (LDL) cholesterol levels. The inhibition of cholesteryl ester transfer protein (CETP) by anacetrapib reduces LDL cholesterol levels and increases high-density lipoprotein (HDL) cholesterol levels. However, trials of other CETP inhibitors have shown neutral or adverse effects on cardiovascular outcomes. METHODS: We conducted a randomized, double-blind, placebo-controlled trial involving 30,449 adults with atherosclerotic vascular disease who were receiving intensive atorvastatin therapy and who had a mean LDL cholesterol level of 61 mg per deciliter (1.58 mmol per liter), a mean non-HDL cholesterol level of 92 mg per deciliter (2.38 mmol per liter), and a mean HDL cholesterol level of 40 mg per deciliter (1.03 mmol per liter). The patients were assigned to receive either 100 mg of anacetrapib once daily (15,225 patients) or matching placebo (15,224 patients). The primary outcome was the first major coronary event, a composite of coronary death, myocardial infarction, or coronary revascularization. RESULTS: During the median follow-up period of 4.1 years, the primary outcome occurred in significantly fewer patients in the anacetrapib group than in the placebo group (1640 of 15,225 patients [10.8%] vs. 1803 of 15,224 patients [11.8%]; rate ratio, 0.91; 95% confidence interval, 0.85 to 0.97; P=0.004). The relative difference in risk was similar across multiple prespecified subgroups. At the trial midpoint, the mean level of HDL cholesterol was higher by 43 mg per deciliter (1.12 mmol per liter) in the anacetrapib group than in the placebo group (a relative difference of 104%), and the mean level of non-HDL cholesterol was lower by 17 mg per deciliter (0.44 mmol per liter), a relative difference of -18%. There were no significant between-group differences in the risk of death, cancer, or other serious adverse events. CONCLUSIONS: Among patients with atherosclerotic vascular disease who were receiving intensive statin therapy, the use of anacetrapib resulted in a lower incidence of major coronary events than the use of placebo. (Funded by Merck and others; Current Controlled Trials number, ISRCTN48678192 ; ClinicalTrials.gov number, NCT01252953 ; and EudraCT number, 2010-023467-18 .)

Does implementation of a paediatric asthma clinical practice guideline worksheet change clinical practice?

Background: Despite the development of evidence-based practice guidelines in many countries for asthma treatment in children, there is limited evidence that using such guidelines improves patient care. Aims: Our aim was to evaluate whether the implementation of an evidence-based asthma clinical practice guideline (CPG) worksheet changes clinical practice. Methods: The study was a before and after study of the implementation of a paediatric asthma CPG in a tertiary paediatric emergency department (ED). All children aged 2–16 years who had a diagnosis of asthma were included. Clinical data were obtained by retrospective chart review for time periods before (May to September 2003) and after (May to September 2005) the introduction of the CPG worksheet. Primary outcomes were: use of spacers for salbutamol instead of nebulisers, use of ipratropium and use of corticosteroids. Secondary outcomes were use of an ED action plan, ordering chest X-rays (CXR) and admission rate. Results: Before implementation, 240 children presented with asthma and after implementation, 286 children presented. The two groups had similar ages, asthma severity, admission respiratory rate (RR) and oxygen saturation. Following implementation there was an increase in spacer use from 17 to 26% [+9%; 95% confidence interval (CI): 2–16%; p = 0.015] and a reduction in ipratropium use from 58 to 44% (−13%; 95% CI: −22 to −5%; p = 0.0029). The proportion of patients treated with corticosteroids did not change. The number of patients with an ED action plan increased. The number of CXR ordered decreased and the hospital admission rate decreased. Conclusions: The study demonstrates that implementation of an asthma CPG worksheet in a tertiary paediatric ED resulted in modest changes in clinical practice, mainly by increasing clinician adherence to the guidelines

Ensaio clínico, aberto, controlado sobre a adição de brometo de ipratrópio ao fenoterol no tratamento da crise de asma em adultos Open, controlled clinical assay of the addition of ipratropium bromide to fenoterol in the treatment of acute asthma crisis in adults

No tratamento da crise de asma, empregam-se doses repetidas de drogas b2-agonistas por via inalatória. O efeito da adição do brometo de ipratrópio (BI) ao b2-agonistas é controverso em adultos. OBJETIVO: Avaliar se adição de BI ao fenoterol, em tratamentos inalatórios repetidos, induz a maior broncodilatação, com reversibilidade da crise e alta da emergência em pacientes em crise grave de asma. LOCAL DO ESTUDO: Serviço de Pronto-Atendimento de Pneumologia, Disciplina de Pneumologia da Unifesp-Hospital São Paulo, no período de julho de 1995 a fevereiro de 1997. TIPO DE ESTUDO: Aberto, randomizado, paralelo. Alta da emergência determinada pelo VEF1 e PFE > 60% do previsto. CASUÍSTICA E MÉTODOS: Cento e vinte pacientes em crise de asma foram divididos em dois grupos (N = 60): fenoterol (F) e brometo de ipratrópio + fenoterol (BIF) com VEF1 e PFE < 50% do previsto. Cada grupo recebeu três tratamentos inalatórios, através de nebulímetro e câmara de expansão, administrados em intervalos de 30 minutos. No grupo F foram administrados 4 jatos de fenoterol (400mcg) e no grupo BIF, 160mcg de BI e 400mcg de fenoterol (4 jatos). RESULTADOS: A média (± DP) do PFE basal (F = 36 ± 7% vs. BIF = 35 ± 9% previsto) e do VEF1 basal (F = 33 ± 9% vs. BIF = 32 ± 9%). Trinta e dois pacientes no grupo F e 33 pacientes no grupo BIF tiveram alta após tratamentos inalatórios. O VEF1 e PFE ao final dos tratamentos inalatórios foram, respectivamente, F = 60 ± 13% vs. BIF = 61 ± 11% e F = 74 ± 18% vs. BIF = 77 ± 13% (NS). CONCLUSÃO: A adição de brometo de ipratrópio ao fenoterol resulta em efeito funcional insignificante e sem impacto clínico no tratamento da crise de asma em adultos.<br>Repeated dosis of inhaled b2-agonists have been used in the treatment of acute asthma. The effect of added ipratropium bromide (IB) to b2-agonist is controversial in adults. OBJECTIVE: To evaluate if addition of IB to fenoterol, in repeated doses, induces a greater bronchodilation, a greater reversion of the attack, and discharge from emergency unit in adults with acute severe asthma. SETTING: Pneumology Emergency Department, Unifesp-Hospital São Paulo, in the period from July 1995 to February 1997. TYPE OF STUDY: Open, randomized and parallel study. Discharge from the hospital: FEV1 and PEF > 60% of the predicted value. METHODS: 120 patients with FEV1 and PEF < 50% of the predicted value were divided into two groups (N = 60): fenoterol (F) and ipratropium bromide + fenoterol (IBF). Each group received inhalation treatment through a metered-dose inhaler (MDI) attached to a holding chamber, administered at 30-minute interval, for a total of three treatments. In the group F four puffs of fenoterol (400 mg) were administered, and in the IBF group, 160 mg of BI and 400 mg of fenoterol (four puffs). RESULTS: The patients did not differ from basal PEF (F = 36 ± 7% vs IBF = 35 ± 9% predicted) and basal FEV1 (F = 33 ± 9% vs IBF = 32 ± 9% predicted). Thirty-two patients of group F and 33 of group IBF were discharged from hospital after the inhalation treatment. The final FEV1 and PEF after inhalation treatments were F = 60 ± 13% vs IBF = 61 ± 11% e F = 74 ± 18% vs IBF = 77 ± 13% (NS). CONCLUSION: The addition of ipratropium bromide to fenoterol results in insignificant functional effect and without clinical impact in the treatment of acute asthma in adults