An evidence-based assessment of the NCEP Adult Treatment Panel II guidelines. National Cholesterol Education Program

CONTEXT: The Second Report of the National Cholesterol Education Program (NCEP) Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults (Adult Treatment Panel II) was issued without the benefit of multiple recently published large clinical trials. OBJECTIVE: To analyze the panel's guidelines for treatment of high cholesterol levels in the context of currently available clinical trial results. DATA SOURCES: MEDLINE was searched for all English-language clinical trial data from 1993 through February 1999 relating to the effects of cholesterol treatment on cardiovascular clinical outcomes. STUDY SELECTION: Studies that were selected for detailed review assessed the effects of cholesterol lowering on either coronary events, coronary mortality, stroke, and/or total mortality, preferably by randomized, double-blind, placebo-controlled design. Selection was by consensus of a general internist, a lipid clinic director, and a researcher in atherosclerotic plaque biology. A core of 37 of the 317 initially screened studies were selected and used as the primary means by which to assess the guidelines. DATA EXTRACTION: By consensus of the group, only prespecified end points of trials were included, unless post hoc analysis addressed issues not studied elsewhere. DATA SYNTHESIS: Recent clinical trial data mostly support the Adult Treatment Panel II guidelines for cholesterol management. While existing trials have validated the target low-density lipoprotein cholesterol (LDL-C) goals in the report, studies are lacking that address mortality benefit from reduction below these levels. Few lipid-lowering trials have treated patients with low high-density lipoprotein cholesterol and/or elevated triglyceride levels with LDL-C levels at or below treatment goals. CONCLUSIONS: Lipid-lowering therapy generally should be more aggressively applied to patients with diabetes and/or at the time of coronary heart disease (CHD) diagnosis. The evidence for statin use in secondary CHD prevention in postmenopausal women outweighs current evidence for use of estrogen replacement in this setting. Further studies are needed to address the effects of lipid modification in primary prevention of CHD in populations other than middle-aged men and to study markers of lipid metabolism other than LDL-C.     

他汀类药物预防脑卒中的meta分析

 【目的】 探讨他汀类药物对脑卒中的预防作用【方法】 通过检索国内外文献数据库,检索2002年1月至2010年1月已经发表关于他汀的临床随机对照试验,对其进行meta分析【结果】 共纳入随机对照试验16个,高危人群中,他汀组比对照组所有脑卒中发生率降低13%(95% CI 3% ~ 22%,P = 0.01),作分层处理,肾病血透及肾移植病人所有脑卒中发生率增加21%(95% CI 0% ~ 46%,P = 0.05),另一层为除外肾病血透和肾移植病人的高危人群,所有脑卒中发生率降低19%(95% CI 13% ~ 24%,P < 0.001),他汀组比对照组致死性卒中发生率降低16%(95% CI 0 ~ 30%,P = 0.05),出血性卒中发生率的RR值1.18(95% CI 0.92-1.50,P = 0.19),两组之间出血性卒中发生率的差别无统计学意义 【结论】 他汀类药物能降低脑卒中的发生率和死亡率,对脑出血没有预防作用,不会增加脑出血发生率?但肾病血透病人及肾移植病人.有脑出血病史的病人使用他汀要慎重     

The benefits of reducing cholesterol levels: the need to distinguish primary from secondary prevention. 1. A meta-analysis of cholesterol-lowering trials.

OBJECTIVE: To use meta-analysis to estimate the benefits of drug treatment to lower cholesterol levels in the primary and secondary prevention of coronary heart disease (CHD) events. DATA SOURCES: MEDLINE search from 1967 to 1990; bibliographies of review articles. STUDY SELECTION: Nine trials met the entry criteria: they were monofactorial, randomised and controlled. DATA EXTRACTION: Two independent, unblinded observers. DATA SYNTHESIS: The odds ratio (and 95% Cl) for death from CHD was 0.85 (0.64, 1.14) in primary prevention and 0.84 (0.75, 0.95) in secondary prevention studies when calculated by the method of Peto. The event rate in the secondary prevention studies was higher than that in the primary prevention studies, and the absolute risk reduction achieved by therapy in the former (3.2%) was much higher than that in the latter (0.1%). The number of subjects needing to be treated to prevent one death from CHD was 38 in secondary prevention and 675 in primary prevention. Results with the method of DerSimonian and Laird were similar. CONCLUSIONS: The benefits of cholesterol lowering to prevent death from CHD are substantially greater in the secondary prevention setting than in primary prevention.     

Primary Prevention of Acute Coronary Events With Lovastatin in Men and Women With Average Cholesterol Levels: Results of AFCAPS/TexCAPS

Context.— Although cholesterol-reducing treatment has been shown to reduce fatal and nonfatal coronary disease in patients with coronary heart disease (CHD), it is unknown whether benefit from the reduction of low-density lipoprotein cholesterol (LDL-C) in patients without CHD extends to individuals with average serum cholesterol levels, women, and older persons. Objective.— To compare lovastatin with placebo for prevention of the first acute major coronary event in men and women without clinically evident atherosclerotic cardiovascular disease with average total cholesterol (TC) and LDL-C levels and below-average high-density lipoprotein cholesterol (HDL-C) levels. Design.— A randomized, double-blind, placebo-controlled trial. Setting.— Outpatient clinics in Texas. Participants.— A total of 5608 men and 997 women with average TC and LDL-C and below-average HDL-C (as characterized by lipid percentiles for an age- and sex-matched cohort without cardiovascular disease from the National Health and Nutrition Examination Survey [NHANES] III). Mean (SD) TC level was 5.71 (0.54) mmol/L (221 [21] mg/dL) (51st percentile), mean (SD) LDL-C level was 3.89 (0.43) mmol/L (150 [17] mg/dL) (60th percentile), mean (SD) HDL-C level was 0.94 (0.14) mmol/L (36 [5] mg/dL) for men and 1.03 (0.14) mmol/L (40 [5] mg/dL) for women (25th and 16th percentiles, respectively), and median (SD) triglyceride levels were 1.78 (0.86) mmol/L (158 [76] mg/dL) (63rd percentile). Intervention.— Lovastatin (20-40 mg daily) or placebo in addition to a low–saturated fat, low-cholesterol diet. Main Outcome Measures.— First acute major coronary event defined as fatal or nonfatal myocardial infarction, unstable angina, or sudden cardiac death. Results.— After an average follow-up of 5.2 years, lovastatin reduced the incidence of first acute major coronary events (183 vs 116 first events; relative risk [RR], 0.63; 95% confidence interval [CI], 0.50-0.79; P<.001), myocardial infarction (95 vs 57 myocardial infarctions; RR, 0.60; 95% CI, 0.43-0.83; P=.002), unstable angina (87 vs 60 first unstable angina events; RR, 0.68; 95% CI, 0.49-0.95; P=.02), coronary revascularization procedures (157 vs 106 procedures; RR, 0.67; 95% CI, 0.52-0.85; P=.001), coronary events (215 vs 163 coronary events; RR, 0.75; 95% CI, 0.61-0.92; P=.006), and cardiovascular events (255 vs 194 cardiovascular events; RR, 0.75; 95% CI, 0.62-0.91; P=.003). Lovastatin (20-40 mg daily) reduced LDL-C by 25% to 2.96 mmol/L (115 mg/dL) and increased HDL-C by 6% to 1.02 mmol/L (39 mg/dL). There were no clinically relevant differences in safety parameters between treatment groups. Conclusions.— Lovastatin reduces the risk for the first acute major coronary event in men and women with average TC and LDL-C levels and below-average HDL-C levels. These findings support the inclusion of HDL-C in risk-factor assessment, confirm the benefit of LDL-C reduction to a target goal, and suggest the need for reassessment of the National Cholesterol Education Program guidelines regarding pharmacological intervention.      

Health outcomes associated with various antihypertensive therapies used as first-line agents: a network meta-analysis

CONTEXT: Establishing relative benefit or harm from specific antihypertensive agents is limited by the complex array of studies that compare treatments. Network meta-analysis combines direct and indirect evidence to better define risk or benefit. OBJECTIVE: To summarize the available clinical trial evidence concerning the safety and efficacy of various antihypertensive therapies used as first-line agents and evaluated in terms of major cardiovascular disease end points and all-cause mortality. DATA SOURCES AND STUDY SELECTION: We used previous meta-analyses, MEDLINE searches, and journal reviews from January 1995 through December 2002. We identified long-term randomized controlled trials that assessed major cardiovascular disease end points as an outcome. Eligible studies included both those with placebo-treated or untreated controls and those with actively treated controls. DATA EXTRACTION: Network meta-analysis was used to combine direct within-trial between-drug comparisons with indirect evidence from the other trials. The indirect comparisons, which preserve the within-trial randomized findings, were constructed from trials that had one treatment in common. DATA SYNTHESIS: Data were combined from 42 clinical trials that included 192 478 patients randomized to 7 major treatment strategies, including placebo. For all outcomes, low-dose diuretics were superior to placebo: coronary heart disease (CHD; RR, 0.79; 95% confidence interval [CI], 0.69-0.92); congestive heart failure (CHF; RR, 0.51; 95% CI, 0.42-0.62); stroke (RR, 0.71; 0.63-0.81); cardiovascular disease events (RR, 0.76; 95% CI, 0.69-0.83); cardiovascular disease mortality (RR, 0.81; 95% CI, 0.73-0.92); and total mortality (RR, 0.90; 95% CI, 0.84-0.96). None of the first-line treatment strategies-beta-blockers, angiotensin-converting enzyme (ACE) inhibitors, calcium channel blockers (CCBs), alpha-blockers, and angiotensin receptor blockers-was significantly better than low-dose diuretics for any outcome. Compared with CCBs, low-dose diuretics were associated with reduced risks of cardiovascular disease events (RR, 0.94; 95% CI, 0.89-1.00) and CHF (RR, 0.74; 95% CI, 0.67-0.81). Compared with ACE inhibitors, low-dose diuretics were associated with reduced risks of CHF (RR, 0.88; 95% CI, 0.80-0.96), cardiovascular disease events (RR, 0.94; 95% CI, 0.89-1.00), and stroke (RR, 0.86; 0.77-0.97). Compared with beta-blockers, low-dose diuretics were associated with a reduced risk of cardiovascular disease events (RR, 0.89; 95% CI, 0.80-0.98). Compared with alpha-blockers, low-dose diuretics were associated with reduced risks of CHF (RR, 0.51; 95% CI, 0.43-0.60) and cardiovascular disease events (RR, 0.84; 95% CI, 0.75-0.93). Blood pressure changes were similar between comparison treatments. CONCLUSIONS: Low-dose diuretics are the most effective first-line treatment for preventing the occurrence of cardiovascular disease morbidity and mortality. Clinical practice and treatment guidelines should reflect this evidence, and future trials should use low-dose diuretics as the standard for clinically useful comparisons.     

他汀类药物治疗对延缓慢性肾脏病进展的荟萃分析

目的：评价他汀类药物治疗对非透析的慢性肾脏病患者肾脏病进展的影响。方法通过对电子数据库（时间截止2015年2月）的检索,筛选符合纳入标准的随机对照试验,采用随机效应模型合并相关肾脏病进展指标。结果共纳入28个研究,共包括45688例慢性肾脏病患者。Meta分析结果显示,与对照组相比,非透析的慢性肾脏病患者接受他汀类药物治疗不能减少终末期肾病的发生（RR=0.98,95%CI：0.91-1.05）,也不能降低肌酐翻倍风险（RR 1.43,95%CI 0.26 to 7.79）,但是可以降低肾小球滤过率下降≥25%的风险（RR=0.91,95%CI：0.83=0.99以及延缓肾小球滤过率下降（SMD=0.04,95%CI：0.02-0.07）。亚组分析显示,在中度慢性肾脏病患者中,他汀类药物治疗对治疗前后肾小球滤过率变化这一指标有疗效（SMD=0.09,95%CI：0.04=0.13）。阿托伐他汀（SMD=0.10,95%CI：0.03-0.17）及高强度降脂治疗（SMD=0.12,95%CI：0.02-0.21）对治疗前后肾小球滤过率变化这一指标有效。结论尽管他汀类药物对降低终末期肾病发及肌酐翻倍的发生率无明显效果,但可以延缓肾小球滤过率下降,其疗效与肾脏病分期、药物种类及降脂强度有关。     

Is elevated serum cholesterol level a risk factor for coronary heart disease in the elderly?

Since serum cholesterol is a major component in the causal pathway of atherosclerosis, a pathological process that usually progresses with age, we have evaluated reported findings of a diminished association between serum cholesterol level and coronary heart disease in the elderly. In the Honolulu (Hawaii) Heart Program, 1480 men aged 65 years and older and free of coronary heart disease were followed up for an average of 12 years. Incidence rates of coronary heart disease increased progressively from the lowest to the highest quartile of serum cholesterol level. The independent role of serum cholesterol level as a predictor of coronary heart disease risk was evaluated with other major risk factors using a Cox multivariate regression model. The upper-lower quartile relative risk for serum cholesterol level was 1.64 (95% confidence interval, 1.14 to 2.36). The relative risk for middle-aged men was also 1.64. The results suggest that serum cholesterol level is an independent predictor of coronary heart disease, even among men older than 65 years. Thus, an elevated serum cholesterol level in the elderly should be regarded, as in middle-aged men, to be an indicator for further evaluation of lipoprotein levels and possible intervention.     

中国2004—2010艾滋病母婴传播率及母婴阻断药物应用状况的系统评价

目的:了解我国2004-2010年艾滋病母婴传播及母婴阻断药物应用状况。方法：全面检索CBM和Pubmed等中英文数据库,检索时间均从建库到2013年5月。对纳入的文献采用参照AHRQ横断面研究评价标准和STROBE声明拟定的四条标准进行质量评价。并将样本量、监测地点和监测年份作为主要异质性来源进行meta回归分析。采用Comprehensive Meta-Analysis V2.0 software 进行meta分析。结果：共检索到文献2356篇,最终纳入51篇进行分析。2004-2010年我国艾滋病母婴传播率依次分别为12.90%（95% CI: 7.48 %- 21.36%）,16.35%（95% CI: 10.41%- 24.73%）,6.45%（95% CI: 3.73 %- 10.93%）,6.25%（95% CI: 2.39%- 15.36%）,5.56%（95% CI: 2.79 %- 10.76%）,3.10%（95% CI: 1.59 %- 5.97%）,2.29%（95% CI: 1.36 %- 3.83%）。2004-2010年,我国艾滋病孕产妇中阻断药物应用率依次分别为70.39%（95% CI: 24.42%-94.59%）,71.99%（95% CI: 61.49%-80.54%）,78.79%（95% CI: 70.19%-85.43%）,86.84%（95% CI: 79.24%-91.94%）,82.71%（95% CI: 76.62%-87.48%）,81.85%（95% CI: 75.55%-86.80%）,86.16%（95% CI: 53.20%-97.15%）。2005-2010年婴儿阻断药物应用率依次分别为80.72%（95%CI: 72.89%-86.70%）,81.84%（95% CI:71.55%-88.98%）,85.43%（95% CI:80.99%-88.97%）,89.75%（95% CI: 81.82%-94.45%）,92.39%（95% CI: 84.97%-96.31%）,90.34%（95% CI: 85.50%-93.68%）。 结论：近年来我国艾滋病母婴传播率呈下降趋势,孕产妇及婴儿阻断药物应用率都有所升高。