Standard- vs High-Dose Clopidogrel Based on Platelet Function Testing After Percutaneous Coronary Intervention

　　基于血小板功能监测下冠状动脉介入治疗术后的标准剂量与高剂量氯吡格雷治疗对比JAMA. 2011;305(11):1097-1105. doi: 10.1001/jama.2011.290

　　Context High platelet reactivity while receiving clopidogrel has been linked to cardiovascular events after percutaneous coronary intervention (PCI), but a treatment strategy for this issue is not well defined.
　　背景：经皮冠状动脉介入（PCI）术后血小板反应性增高导致血栓往往会带来较为严重的心血管不良事件，但是针对其的治疗策略尚未被较好地确定。
　　Objective To evaluate the effect of high-dose compared with standard-dose clopidogrel in patients with high on-treatment platelet reactivity after PCI.
　　目的：通过对比高剂量的氯吡格雷和标准剂量的氯吡格雷，以评估其对于PCI术后血小板反应性增高患者的治疗效果。
　　Design, Setting, and Patients Randomized, double-blind, active-control trial (Gauging Responsiveness with A VerifyNow assay—Impact on Thrombosis And Safety [GRAVITAS]) of 2214 patients with high on-treatment reactivity 12 to 24 hours after PCI with drug-eluting stents at 83 centers in North America between July 2008 and April 2010.
　　设计：随机、双盲、主动控制试验（采用VerifyNow法作反应性放射计测，以判断对血栓及安全性的影响[GRAVITAS]）。这一随机试验包括了2214名治疗时（即在PCI之后12-24小时时所测量的）有着高血小板反应性的安装有药物洗脱支架的病人，这些病人是在2008年7月和2010年4月间在北美的83个治疗中心接受治疗的。
　　Interventions High-dose clopidogrel (600-mg initial dose, 150 mg daily thereafter) or standard-dose clopidogrel (no additional loading dose, 75 mg daily) for 6 months.
　　干预：高剂量氯吡格雷（初始剂量600 mg，此后每日150 mg）或标准剂量（无底药剂量，每日75 mg），给药时间6个月。
　　Main Outcome Measures The primary end point was the 6-month incidence of death from cardiovascular causes, nonfatal myocardial infarction, or stent thrombosis. The key safety end point was severe or moderate bleeding according to the Global Utilization of Streptokinase and t-PA for Occluded Coronary Arteries (GUSTO) definition. A key pharmacodynamic end point was the rate of persistently high on-treatment reactivity at 30 days.
　　主要测量结果：主要终点指标为非致命性心肌梗塞、支架血栓形成及心血管性死亡的6个月发生率；首要效力观察终点为基于“通用链激酶与t-PA针对冠脉闭塞 (GUSTO)”定义的中度或重度的出血；关键的药效学测量终点为30天内持续的高血小板反应率。
　　Results  At 6 months, the primary end point had occurred in 25 of 1109 patients (2.3%) receiving high-dose clopidogrel compared with 25 of 1105 patients (2.3%) receiving standard-dose clopidogrel (hazard ratio [HR], 1.01; 95% confidence interval [CI], 0.58-1.76; P=0.97). Severe or moderate bleeding was not increased with the high-dose regimen (15 [1.4%] vs 25 [2.3%], HR, 0.59; 95% CI, 0.31-1.11; P=0.10). Compared with standard-dose clopidogrel, high-dose clopidogrel provided a 22% (95% CI, 18%-26%) absolute reduction in the rate of high on-treatment reactivity at 30 days (62%; 95% CI,59%-65% vs 40%;95% CI,37%-43%;P<0.001).
　　结果：6个月时，在1109名接受高剂量氯吡格雷治疗策略的病人中，主要终点发生率为2.3%（25人），在1105名接受普通剂量氯吡格雷治疗策略的病人中，主要终点发生率同样为2.3%（25人），(hazard ratio [HR], 1.01; 95% confidence interval [CI], 0.58-1.76; P=0.97)。高剂量氯吡格雷组的中重度出血发生率并未增加(15 [1.4%] vs 25 [2.3%], HR, 0.59; 95% CI, 0.31-1.11; P=0.10)。较之标准剂量组，高剂量氯吡格雷组的30天内持续的高血小板反应率下降了22%(95% CI,18%-26%)。
　　Conclusions Among patients with high on-treatment reactivity after PCI with drug-eluting stents, the use of high-dose clopidogrel compared with standard-dose clopidogrel did not reduce the incidence of death from cardiovascular causes, nonfatal myocardial infarction, or stent thrombosis.
　　结论：在那些安置了药物洗脱支架的PCI之后有着高血小板反应性的病人中，与标准剂量相比，使用高剂量的氯吡格雷并不会使这些病人因心血管原因、非致命性心肌梗塞，或支架血栓形成等引起的死亡率降低。

　　Serum Levels of Phosphorus, Parathyroid Hormone, and Calcium and Risks of Death and Cardiovascular Disease in Individuals With Chronic Kidney Disease

　　慢性肾病患者血清磷、甲状旁腺激素、钙水平及心血管疾病死亡风险

　　JAMA. 2011;305(11):1119-1127. doi: 10.1001/jama.2011.308

　　Context Clinical practice guidelines on the management of mineral and bone disorders due to chronic kidney disease recommend specific treatment target levels for serum phosphorus, parathyroid hormone, and calcium. 
　　背景：对于由慢性肾病导致的矿物和骨代谢紊乱的治疗，临床指南中建议针对血清磷、甲状旁腺激素以及血清钙进行个体化特异疗法。
　　Objective To assess the quality of evidence for the association between levels of serum phosphorus, parathyroid hormone, and calcium and risks of death, cardiovascular mortality, and nonfatal cardiovascular events in individuals with chronic kidney disease. 
　　目的：通过循证评估慢性肾病患者的血清磷、血清钙和甲状旁腺激素与非致命性心血管事件、心血管病死亡率之间的关联。
　　Data Sources The databases of MEDLINE (1948 to December 2010) and EMBASE (1947 to December 2010) were searched without language restriction. Hand searches also were conducted of the reference lists of primary studies, review articles, and clinical guidelines along with full-text review of any citation that appeared relevant. 
　　数据源：检索1948 年至2010年 12月的MEDLINE数据库及1947年至2010年12月的EMBASE（二者均无语言限制）。并手动检索其主要研究结果、综述、临床指南，以及与之相关的引文中所出现的参考文献。
　　Study Selection Of 8380 citations identified in the original search, 47 cohort studies (n=327644 patients) met the inclusion criteria.
 文献选择：在原始检索后经鉴定的8380篇文献中，47类研究（涉及327644位病人）符合入选标准。
　　Data Extraction The characteristics of study design, participants, exposures, and covariates together with the outcomes of all-cause mortality, cardiovascular mortality, and nonfatal cardiovascular events at different levels of serum phosphorus, parathyroid hormone, and calcium were analyzed within studies. Data were summarized across studies (when possible) using random-effects meta-regression. 
　　数据提取：将试验设计、参与者、暴露水平、协同变量的特性，与不同水平组血清磷、甲状旁腺激素以及血清钙的全死因死亡率、心血管死亡率、非致命性心血管事件进行随机效应meta-回归分析。
　　Data Synthesis The risk of death increased 18% for every 1-mg/dL increase in serum phosphorus (relative risk [RR], 1.18 [95% confidence interval {CI}, 1.12-1.25]). There was no significant association between all-cause mortality and serum level of parathyroid hormone (RR per 100-pg/mL increase, 1.01 [95% CI, 1.00-1.02]) or serum level of calcium (RR per 1-mg/dL increase, 1.08 [95% CI, 1.00-1.16]). Data for the association between serum level of phosphorus, parathyroid hormone, and calcium and cardiovascular death were each available in only 1 adequately adjusted cohort study. Lack of adjustment for confounding variables was not a major limitation of the available studies. 
　　数据综合：血清磷每增加1mg/dL，死亡发生率增加18%（relative risk [RR], 1.18 [95% confidence interval {CI}, 1.12-1.25]）。甲状旁腺激素的增加（RR per 100-pg/mL increase, 1.01 [95% CI, 1.00-1.02]）或血清钙的增加（RR per 1-mg/dL increase, 1.08 [95% CI, 1.00-1.16]）与全死因死亡率之间没有显著的联系。血清磷水平、甲状旁腺激素和血清钙与心血管死亡率之间联系的数据，仅在一个进行充分调整的队列研究中有所体现，但缺乏对多变量混杂设计的调节并不是其主要的限制。
　　Conclusions The evidentiary basis for a strong, consistent, and independent association between serum levels of calcium and parathyroid hormone and the risk of death and cardiovascular events in chronic kidney disease is poor. There appears to be an association between higher serum levels of phosphorus and mortality in this population. 
　　结论：并无有力的证据支持血清钙或甲状旁腺素与慢性肾病患者的死亡率及心血管事件发生率之间的关系，但血清的高磷状态则与之不无关系。