bigbio/paramed · Datasets at Hugging Face

id stringlengths 1 5	document_id stringlengths 1 5	text_1 stringlengths 3 1.91k	text_2 stringlengths 5 1.83k	text_1_name stringclasses 1 value	text_2_name stringclasses 1 value
62001	62000	在上述研究中 , 基线收缩压都非常低 ( DIRECT 为 133 mmHg , 而 RASS 为 120mmHg11 ) .	in both of these studies , the baseline systolic blood pressure was quite low - 133 mm Hg in DIRECT @-@ Renal and 120 mm Hg in RASS.11	zh	en
62002	62001	而其余的研究 , 譬如心脏结局及预防评估 ( HOPE ) 18 , 替米沙坦治疗 ACEI 不耐受的心血管病患者的随机临床研究 ( Telmisartan Randomised Assessment Study in ACE Intolerant Subjects with Cardiovascular Disease , TRANSCEND , NCT00153101 ) 19 , 以及糖尿病和心血管疾病行动 : 百普乐 - 达美康对照评估研究 ( Action in Diabetes and Vascular Disease : Preterax and Diamicron - MR Controlled Evaluation study , ADVANCE , NCT00145925 ) 20 , 则已于之前报道了基线收缩压与微量白蛋白尿之间的正相关 .	other studies , such as the Heart Outcomes and Prevention Evaluation ( HOPE ) , 18 the Telmisartan Randomised Assessment Study in ACE Intolerant Subjects with Cardiovascular Disease ( TRANSCEND ; NCT00153101 ) , 19 and the Action in Diabetes and Vascular Disease : Preterax and Diamicron @-@ MR Controlled Evaluation study ( ADVANCE ; NCT00145925 ) , 20 had previously reported a positive relation between baseline systolic blood pressure and microalbuminuria .	zh	en
62003	62002	综上所述 , 基线血压愈高 , 则肾素 - 血管紧张素系统阻滞剂的潜在获益愈大 10 , 11 , 18 - 20 .	thus , overall , it appears that the higher the baseline blood pressure , the greater the potential benefit of an inhibitor of the renin @-@ angiotensin system.10,11,18 @-@ 20	zh	en
62004	62003	TRANSCEND 中同样观察到这个倾向 , 并且其有助于挑选无微量白蛋白尿的 2 型糖尿病患者作为 ARB 治疗的潜在候选者 .	this trend was also seen in TRANSCEND19 and may help to identify patients with type 2 diabetes and no microalbuminuria who might be potential candidates for ARB therapy .	zh	en
62005	62004	研究期间患者 GFR 的改变很小 , 奥美沙坦与估算 GFR 中微小但显著的下降相关 ( 约 4 mL / [ min · 1.73 m2 ] ) , 而使用非肾素 - 血管紧张素系统阻滞剂的患者 , 其 GFR 下降得更小 .	changes in the GFR were minimal over the course of the study ; olmesartan was associated with a slight but significant reduction in the estimated GFR ( about 4 ml per minute per 1.73 m2 ) , whereas an even smaller decrease in the estimated GFR was noted in patients treated with agents that do not block the renin @-@ angiotensin system .	zh	en
62006	62005	奥美沙坦及安慰剂组均确认了肾脏事件发生率 ( 定义为血肌酐水平的双倍增高或需要透析 ) 降低 .	it is reassuring that the rate of renal events ( defined as a doubling of the serum creatinine level or the need for dialysis ) was low and was identical in the olmesartan and placebo groups .	zh	en
62007	62006	在研究结束时未设置清除期 , 所以我们只能推测奥美沙坦组估算 GFR 值的下降及微量白蛋白尿发生率的降低是针对肾小球压力降低或潜在的器质性不良反应而产生的有利的血流动力学 ( 功能性 ) 反应 .	there was no washout period at the end of the study , so we can only speculate about whether the drop in the estimated GFR and the lower rate of microalbuminuria in the olmesartan group represent a favorable hemodynamic ( functional ) response to lower glomerular pressure or an adverse underlying structural change .	zh	en
62008	62007	近来的研究表明估算 GFR 值降低及微量白蛋白尿是独立的预后指标 14 , 15 , 21 .	recent studies suggest that a low estimated GFR and microalbuminuria are independent prognostic markers.14,15,21	zh	en
62009	62008	在一项荟萃分析里 21 , 估算 GFR < 60 mL / [ min · 1.73 m2 ] 预示了任意原因及心源性死亡 , 但在本试验中 , 没有发现估算 GFR75 ~ 104 mL / [ min · 1.73 m2 ] 与心血管疾病风险存在关联 .	in a meta @-@ analysis , 21 an estimated GFR below 60 ml per minute per 1.73 m2 was predictive of death from any cause and of death from cardiovascular causes , but as in the present trial , there was no relationship to the risk of cardiovascular disease when the estimated GFR was 75 to 104 ml per minute per 1.73 m2 .	zh	en
62010	62009	这提示 , 从长远来看在糖尿病患者中微量白蛋白尿发生率的改变比估算 GFR 的轻微下降显得更为重要 .	this supports the notion that in patients with diabetes , the observed change in the rate of microalbuminuria might in the long @-@ term be of greater importance than the small fall in the estimated GFR .	zh	en
62011	62010	本研究中的心血管及脑血管事件发生率低 ( 约 4% , 或 2.9 例 / 千人年 ) ; 与 BENEDICT 的情况相似 , 但低于 DIRECT - 2 ( 8.0 例 / 千人年 ) 10 , 11 , 并且与纳入了晚期肾疾病患者的研究血管紧张素 Ⅱ 拮抗剂洛沙坦减少非胰岛素依赖糖尿病终点研究 [ RENAAL ] 及厄贝沙坦糖尿病肾病研究 [ IDNT ] ) 那些相比 , 心脑血管事件发生率的下降更为明显 , 后述两项试验的心血管及脑血管意外发生率要高 19 倍或 60 例 / 千人年 8 , 9 .	the rates of cardiovascular and cerebrovascular events in the present study were low ( about 4 % , or 2.9 cases per 1000 person @-@ years ) ; they were similar to those in BENEDICT but lower than those in DIRECT @-@ 2 ( 8.0 cases per 1000 person years ) 10,11 and substantially lower than those in studies involving patients with more advanced renal disease , such as the Reduction of Endpoints in NIDDM with the Angiotensin II Antagonist Losartan ( RENAAL ) study and the Irbesartan Diabetes Nephropathy Trial ( IDNT ) , in which the rates were higher by a factor of approximately 20 , or 60 cases per 1000 person @-@ years.8,9	zh	en
62012	62011	尽管心血管事件发生率低 , 但奥美沙坦组中心源性死亡例数较安慰剂组多 ( 15 例对 3 例 , P = 0.01 ) .	despite the low rates of cardiovascular events , there were more deaths from cardiovascular causes in the olmesartan group than in the placebo group ( 15 vs. 3 , P = 0.01 ) .	zh	en
62013	62012	由于受影响的患者数量过少 , 难以解释此意外的发现 , 并且可能只是偶然 .	owing to the very small number of affected patients , it is difficult to interpret this unexpected finding , and it may simply be related to chance .	zh	en
62014	62013	尽管如此 , 由于其潜在的意义 , 我们对该发现进行了一些探索性分析 .	nevertheless , because of its potential significance , several exploratory analyses were performed .	zh	en
62015	62014	在奥美沙坦组中既往有冠心病的患者致死性心血管事件 ( 11 例对 VS 1 例 , P = 0.03 ) 较安慰剂组更为普遍 , 但在两组中既往无冠心病的患者中 , 其致死性心血管事件发生率是相似的 .	fatal cardiovascular events were more common in the olmesartan group than in the placebo group among patients with known preexisting coronary heart disease ( 11 events vs. 1 with placebo , P = 0.03 ) , but the rates were similar in the two groups among patients without preexisting coronary disease .	zh	en
62016	62015	此外 , 血压位于最低四分位数区间或随访期内血压下降幅度位于最高四分位数区间的既往冠心病患者发生致死性心血管事件更多 .	there was also a trend toward more fatal events in patients with preexisting coronary heart disease who were either in the lowest quartile of blood pressure or in the highest quartile of blood @-@ pressure reduction during follow @-@ up .	zh	en
62017	62016	由于 ROADMAP 及 ORIENT 的这些发现 , 美国食品药品管理局 ( FDA ) 正在重新审查现有数据 .	because of these findings in ROADMAP and ORIENT , the Food and Drug Administration is currently reviewing existing data .	zh	en
62018	62017	尽管如此 , 既往无冠心病的患者服用奥美沙坦并不会使非致死性心血管事件发生率上升 .	nevertheless , the rate of nonfatal cardiovascular events was not increased with olmesartan among patients without preexisting coronary heart disease .	zh	en
62019	62018	本研究的结果应与其他一些提示 ARB 具有心血管疾病有益作用的研究一起综合分析 22 , 23 .	the results of the current study must also be viewed in the context of the many other studies of renal and cardiovascular outcomes that have shown that ARBs have a beneficial effect on cardiovascular disease.22,23	zh	en
62020	62019	在长期单独使用替米沙坦及与雷米普利联合应用的全球终点试验 ( ONTARGET , NCT00153101 ) 24 与国际维拉帕米缓释片群多普利研究 ( INVEST , NCT00133692 ) 25 中 , 对于在接受 ACEI 或 ARB ( ONTARGET ) , 或者钙离子通道阻滞剂或 β 受体阻滞剂 ( INVEST ) 治疗期间收缩压低于 120 mmHg 且患有冠心病的患者 , 研究者观察到了心源性死亡率的上升 ; 因此 , 不良反应的发生与治疗后的血压关系 , 而不是所用药物的类型 , 似乎更为密切 .	in the Ongoing Telmisartan Alone and in Combination with Ramipril Global Endpoint Trial ( ONTARGET ; NCT00153101 ) 24 and the International Verapamil SR Trandolapril Study ( INVEST ; NCT00133692 ) , 25 an increase in the rate of death from cardiovascular causes was observed among patients with known coronary heart disease if the systolic blood pressure was below 120 mm Hg during the time the patient was receiving therapy with ACE inhibitors or ARBs ( in ONTARGET ) or calcium @-@ channel blockers or beta @-@ blockers ( in INVEST ) ; thus , any adverse effect appears to be related more closely to the achieved blood pressure than the class of drug that was used .	zh	en
62021	62020	对于潜在的过度治疗的考虑已反映在欧洲高血压学会指南中 , 该指南指出内科医师应避免心血管疾病患者降压过度 ( 即 < 120 / 70 mmHg ) 26 .	the concern about potential overtreatment is reflected in the guidelines published by the European Society of Hypertension , which state that physicians should avoid lowering blood pressure excessively ( i.e. , to values below 120 / 70 mm Hg ) in persons with underlying cardiovascular disease.26	zh	en
62022	62021	我们的研究存在一些局限性 .	our study has certain limitations .	zh	en
62023	62022	首先 , 我们不可能从一项短期预防性试验中得出微量白蛋白尿的改变能否影响长期的肾脏及心血管事件发生率的确定结论 .	first , it is not possible to draw definite conclusions from a short @-@ term prevention study about the way in which changes in microalbuminuria may affect the rates of renal and cardiovascular event rates in the long term .	zh	en
62024	62023	在研究过程本身 , 随访阶段时间过短 .	during the study itself , the follow @-@ up period was too short .	zh	en
62025	62024	第二 , 两研究组的提前退出率均较高 ( 约 23% ) ; 然而 , 退出事件看来不会影响研究的总体结果 , 因为一项排除了这些患者的探索性分析并未影响主要终点 .	second , the rate of premature withdrawals in both study groups was high ( about 23 % in both groups ) ; however , it seems unlikely that withdrawals affected the overall findings of the study , since an exploratory analysis excluding these patients did not affect the primary end point .	zh	en
62026	62025	第三 , 尽管治疗组间血压的差异可能影响主要终点 , 并且基线血压高的患者获益更为显著 , 但研究中校正血压差异的分析并未消除奥美沙坦对主要终点的改善 .	third , although the differences in blood pressure between the treatment groups may have contributed to the primary outcome , and the benefit was greater in patients with higher baseline blood pressure , adjustment of the analysis for differences in blood pressure during the study did not eliminate the improvement in the primary end point that was seen with olmesartan .	zh	en
62027	62026	总之 , 这项试验表明即使在血压已经被有效控制在现行推荐标准范围的前提下 , 奥美沙坦依然能延迟 2 型糖尿病患者微量白蛋白尿的发生时间 .	in summary , this trial suggests that olmesartan increases the time to the onset of microalbuminuria in patients with type 2 diabetes , even when blood @-@ pressure control is excellent according to current recommendations .	zh	en
62028	62027	Dr . Haller reports receiving payment for board membership from Novartis , consulting fees from Bayer Schering Pharma and Daiichi Sankyo , lecture fees from Bayer Schering Pharma , Roche , and Menarini , payment for development of educational presentations from Daiichi Sankyo and Bayer Schering Pharma , and travel support from Amgen and Daiichi Sankyo ; Dr . Ito , consulting fees from Novartis Pharmaceuticals and Takeda Pharmaceutical , grant support paid to his institution , Tohoku University Graduate School of Medicine , from Banyu Pharmaceutical , Takeda Pharmaceutical , Astellas Pharma , Boehringer Ingelheim , Novartis Pharmaceuticals , Shionogi , and Dainippon Sumitomo Pharma , and lecture fees from Banyu Pharmaceutical , Takeda Pharmaceutical , Astellas Pharma , Boehringer Ingelheim , Novartis Pharmaceuticals , Shionogi , and Dainippon Sumitomo Pharma ; Dr . Izzo , consulting and lecture fees from Daiichi Sankyo ; Dr . Januszewicz , lecture fees from Boehringer Ingelheim , Novartis , Adamed , Bayer Healthcare , Sanofi - Aventis , Sandoz , Merck , and Krka ; Dr . Katayama , grant support from Daiichi Sankyo , Merck , Novartis , and Boehringer Ingelheim and lecture fees from Daiichi Sankyo , Merck , Novartis , and Astellas Pharma ; Dr . Menne , lecture fees from Berlin - Chemie , Novartis , and Daiichi Sankyo ; Dr . Mimran , payment for board membership and consulting fees from Daiichi Sankyo and Servier ; Dr . Ruilope , payment for board membership and consulting and lecture fees from Daiichi Sankyo ; Dr . Rump , consulting and lecture fees from Daiichi Sankyo ; Dr . Viberti , payment for board membership from GlaxoSmithKline , Novartis , and Pfizer and lecture fees from Guidotti and Malesci ; and Dr . Ritz , payment for board membership and lecture fees from Abbott and consulting fees from Hexal . No other Potential conflit of interest relevant to this article was reported .	Dr. Haller reports receiving payment for board membership from Novartis , consulting fees from Bayer Schering Pharma and Daiichi Sankyo , lecture fees from Bayer Schering Pharma , Roche , and Menarini , payment for development of educational presentations from Daiichi Sankyo and Bayer Schering Pharma , and travel support from Amgen and Daiichi Sankyo ; Dr. Ito , consulting fees from Novartis Pharmaceuticals and Takeda Pharmaceutical , grant support paid to his institution , Tohoku University Graduate School of Medicine , from Banyu Pharmaceutical , Takeda Pharmaceutical , Astellas Pharma , Boehringer Ingelheim , Novartis Pharmaceuticals , Shionogi , and Dainippon Sumitomo Pharma , and lecture fees from Banyu Pharmaceutical , Takeda Pharmaceutical , Astellas Pharma , Boehringer Ingelheim , Novartis Pharmaceuticals , Shionogi , and Dainippon Sumitomo Pharma ; Dr. Izzo , consulting and lecture fees from Daiichi Sankyo ; Dr. Januszewicz , lecture fees from Boehringer Ingelheim , Novartis , Adamed , Bayer Healthcare , Sanofi @-@ Aventis , Sandoz , Merck , and Krka ; Dr. Katayama , grant support from Daiichi Sankyo , Merck , Novartis , and Boehringer Ingelheim and lecture fees from Daiichi Sankyo , Merck , Novartis , and Astellas Pharma ; Dr. Menne , lecture fees from Berlin @-@ Chemie , Novartis , and Daiichi Sankyo ; Dr. Mimran , payment for board membership and consulting fees from Daiichi Sankyo and Servier ; Dr. Ruilope , payment for board membership and consulting and lecture fees from Daiichi Sankyo ; Dr. Rump , consulting and lecture fees from Daiichi Sankyo ; Dr. Viberti , payment for board membership from GlaxoSmithKline , Novartis , and Pfizer and lecture fees from Guidotti and Malesci ; and Dr. Ritz , payment for board membership and lecture fees from Abbott and consulting fees from Hexal .	zh	en
62029	62028	总结	summary	zh	en
62030	62029	过去的研究曾显示强化降糖增加晚期 2 型糖尿病患者死亡率及心血管疾病的高风险 .	intensive glucose lowering has previously been shown to increase mortality among persons with advanced type 2 diabetes and a high risk of cardiovascular disease .	zh	en
62031	62030	本文描述了平均为 3.7 年的强化降糖治疗在 5 年内的患者死亡率和主要心血管事件结局 .	this report describes the 5 @-@ year outcomes of a mean of 3.7 years of intensive glucose lowering on mortality and key cardiovascular events .	zh	en
62032	62031	我们将 2 型糖尿病和心血管疾病或者存在其他心血管危险因素的参与者随机分成强化治疗组 ( 目标为糖化血红蛋白水平低于 6.0% ) 或标准治疗组 ( 目标为糖化血红蛋白水平 7% ~ 7.9% ) .	we randomly assigned participants with type 2 diabetes and cardiovascular disease or additional cardiovascular risk factors to receive intensive therapy ( targeting a glycated hemoglobin level below 6.0 % ) or standard therapy ( targeting a level of 7 to 7.9 % ) .	zh	en
62033	62032	结束强化治疗时 , 由于强化治疗组死亡率较高 , 所有参与者的糖化血红蛋白目标值全部修改为 7% ~ 7.9% , 并随访至原计划的试验终点 .	after termination of the intensive therapy , due to higher mortality in the intensive @-@ therapy group , the target glycated hemoglobin level was 7 to 7.9 % for all participants , who were followed until the planned end of the trial .	zh	en
62034	62033	强化治疗终止后 , 强化治疗组的中位糖化血红蛋白水平从 6.4% 升至 7.2% , 降糖药物的使用情况 , 严重低血糖和其他不良事件的发生率在两组间大致相同 .	after the intensive intervention was terminated , the median glycated hemoglobin level in the intensive @-@ therapy group rose from 6.4 % to 7.2 % , and the use of glucose @-@ lowering medications and rates of severe hypoglycemia and other adverse events were similar in the two groups .	zh	en
62035	62034	与标准治疗相比 , 平均 3.7 年的旨在使糖化血红蛋白水平低于 6% 的强化降糖治疗减少了 5 年非致死性心肌梗死 , 但是增加了 5 年死亡率 .	as compared with standard therapy , the use of intensive therapy for 3.7 years to target a glycated hemoglobin level below 6 % reduced 5 @-@ year nonfatal myocardial infarctions but increased 5 @-@ year mortality .	zh	en
62036	62035	这样的治疗方法不能推荐用于晚期 2 型糖尿病的高危患者 ( 由美国国家心肺血液研究所 [ National Heart , Lung and Blood Institute ] 资助 ; ClinicalTrials . org , 注册号为 NCT00000620 ) .	such a strategy cannot be recommended for high @-@ risk patients with advanced type 2 diabetes . ( Funded by the National Heart , Lung and Blood Institute ; ClinicalTrials.gov number , NCT00000620 . )	zh	en
62037	62036	2 型糖尿病是心血管疾病与死亡相关的强有力而独立的危险因素 1 , 许多流行病学分析发现高血糖和这些结局之间存在渐进关系 2 - 5 .	type 2 diabetes mellitus is a strong , independent risk factor for cardiovascular disease and death , 1 and many epidemiologic analyses have identified a progressive relationship between hyperglycemia and these outcomes.2 @-@ 5	zh	en
62038	62037	因此 , 在随后的 17 个月的随访中 , 我们对强化治疗组的参与者采取了与标准对照组同样的治疗方案 .	therefore , we applied the approaches that were used in the standard control group to participants assigned to the intensive @-@ therapy group , for up to 17 months of additional follow @-@ up .	zh	en
62039	62038	本文报告了强化降糖治疗平均为期 3.7 年的患者随访 5 年的临床结果 .	we report the clinical outcomes at 5 years of follow @-@ up in response to a mean of 3.7 years of an intensive glycemia strategy .	zh	en
62040	62039	本试验的设计和主要研究成果过去已发表 6 , 7 .	the design and major results of the trial have been published previously.6,7	zh	en
62041	62040	参与者被随机分成两组 , 强化治疗组糖化血红蛋白目标值 < 6% , 而标准治疗组糖化血红蛋白目标值为 7% ~ 7.9% .	participants were randomly assigned to receive either intensive glucose @-@ lowering therapy targeting a glycated hemoglobin level of less than 6.0 % or standard glucose @-@ lowering therapy targeting a level of 7 to 7.9 % .	zh	en
62042	62041	所有患者均接受生活方式的咨询和管理糖尿病的辅导 .	all participants received counseling about lifestyle and education about the management of diabetes .	zh	en
62043	62042	强化治疗终止和结局评估	termination OF INTENSIVE REGIMEN AND ASSESSMENT OF OUTCOMES	zh	en
62044	62043	招募分为 2 个阶段进行 , 分别是 2001 年 1 月至 6 月和 2003 年 2 月至 2005 年 10 月 .	recruitment occurred in two phases , from January to June 2001 and from February 2003 to October 2005 .	zh	en
62045	62044	2008 年 2 月 5 日 , 在平均治疗时间为 3.7 年后 , 参与者被通知将停止强化降糖治疗方案 .	on February 5 , 2008 , participants were informed of the decision to discontinue the intensive glucose @-@ lowering regimen , after a mean treatment period of 3.7 years .	zh	en
62046	62045	此后强化治疗组的参与者改为接受标准血糖治疗 , 糖化血红蛋白目标值由原来的低于 6% 修改为 7% ~ 7.9% .	participants in the intensive @-@ therapy group subsequently were switched to standard glycemic therapy , and their target glycated hemoglobin level of less than 6 % was changed to a target level of 7 to 7.9 % .	zh	en
62047	62046	由于参与者也接受调脂和降压的治疗 8 , 9 , 他们继续接受至少每 4 个月一次随访直到原计划的研究结束 ( 2009 年 6 月 ) .	since participants had also been assigned to receive treatment either to control lipid levels or to lower blood pressure , 8,9 they continued to be followed at least every 4 months until the originally planned end of the trial ( June 2009 ) .	zh	en
62048	62047	因此 , 中心委员会又继续搜集和裁定了临床结局以外 17 个月的数据 , 包括主要结局 ( 非致死性心肌梗死 , 非致死性卒中或心血管原因造成的死亡的复合事件 ) 和任何原因引起的死亡 ( 次要结局 ) , 该委员会成员对分组情况并不知情 .	thus , data on clinical outcomes , including the primary outcome ( a composite of nonfatal myocardial infarction , nonfatal stroke , or death from cardiovascular causes ) and death from any cause ( a secondary outcome ) , continued to be collected and adjudicated for an additional 17 months by a central committee whose members were unaware of study @-@ group assignments .	zh	en
62049	62048	干预效果	intervention EFFECTS	zh	en
62050	62049	本文报道了随后的 0.2 年 ( 即直到 2008 年 2 月 5 日 ) , 即至参与者被通知更改治疗方案时的干预效果 .	here we report the effect of the intervention during an additional 0.2 years ( i.e. , until February 5 , 2008 ) , which was when participants were informed of the change in approach .	zh	en
62051	62050	我们也报道了 2008 年 2 月 5 日之前的结果 , 即从 2007 年 12 月 10 日起没有被协调中心报道的结果 .	we also report on outcomes that occurred before February 5 , 2008 , that were not reported to the coordinating center as of December 10 , 2007 .	zh	en
62052	62051	因此 , 我们采用意向治疗分析报道平均 3.7 年的强化血糖干预加上随后平均 1.2 年的标准血糖治疗对心血管疾病的影响 .	therefore , we used intention @-@ to @-@ treat analyses to report on the effect of a mean of 3.7 years of an intensive glycemic intervention on cardiovascular disease , followed by a mean of 1.2 years of standard glycemic therapy .	zh	en
62053	62052	我们还报道了直至转变治疗方案时和至所有试验结束时血糖干预对于血压和血脂的影响的研究 .	also reported are the effects of the glycemic intervention until the transition date and until the end of the overall trial for both the blood @-@ pressure and lipid trials .	zh	en
62054	62053	对血脂和血压进行干预的治疗效果另做了报道 8 , 9 .	the treatment effects of the lipid and blood @-@ pressure interventions were reported separately.8,9	zh	en
62055	62054	所有的主要结局和次要结局均统一由 2 名对治疗分组情况不知情的裁定人员进行裁定 , 此外 , 由 2 位糖尿病专家 ( 他们对治疗分组不知情 ) 审定死亡是否由于低血糖造成 .	all primary and secondary outcomes were adjudicated centrally by two adjudicators who were unaware of treatment @-@ group assignments , and in addition , deaths were reviewed by two diabetes experts ( who were unaware of treatment @-@ group assignments ) to determine whether they were due to hypoglycemia .	zh	en
62056	62055	ACCORD 试验由美国国家心肺血液研究所 ( NHLBI ) 资助 , 试验方案 ( 可在 NEJM . org 上刊登的本文全文中获取 ) 由 NHLBI 审查小组并经各中心的伦理委员会批准 .	the ACCORD trial was sponsored by the National Heart , Lung , and Blood Institute ( NHLBI ) , and the protocol ( available with the full text of this article at NEJM.org ) was approved by an NHLBI review panel and by the ethics committee at each center .	zh	en
62057	62056	所有参与者都提供了书面知情同意书 .	all participants provided written informed consent .	zh	en
62058	62057	所有作者担保所报告数据的准确性和完整性 .	all authors vouch for the accuracy and completeness of the reported data .	zh	en
62059	62058	药品和器械的捐助者没有参与试验设计 , 数据收集或者稿件的准备 .	the donors of medications and devices had no role in the study design , data accrual and analysis , or manuscript preparation .	zh	en
62060	62059	协调中心使用 S - Plus 8.0 ( Insightful ) 或者 SAS 9.2 ( SAS Institute ) 软件进行所有的统计分析 .	all statistical analyses were conducted at the coordinating center with the use of S @-@ Plus software , version 8.0 ( Insightful ) , or SAS software , version 9.2 ( SAS Institute ) .	zh	en
62061	62060	参与者基线特征采用均数 , 标准差和百分数来描述 .	baseline characteristics of the participants were summarized with the use of means , standard deviations , and percentages .	zh	en
62062	62061	利用每月 ( 日历月 ) 糖化血红蛋白的中位水平展示由强化治疗转换为标准治疗的影响 .	median glycated hemoglobin levels were calculated monthly ( by calendar month ) to show the effect of the switch from intensive therapy to the standard approach .	zh	en
62063	62062	在由强化治疗转换为标准治疗前的最后一次随访与试验终止时参与者所用降糖药均被归纳分类 .	exposure to glucose @-@ lowering drugs was summarized as the number of participants who were prescribed a medication at the last visit before the transition date and at the trial termination .	zh	en
62064	62063	考虑随访数据的截尾 , 利用单位随访年的事件发生百分比描述主要安全性结局的发生率 .	the incidence of key safety outcomes was expressed as the percentage of events per follow @-@ up year , taking into account censoring of follow @-@ up data .	zh	en
62065	62064	利用 Kaplan - Meier 方法估计随访期间参与发生事件的百分比 .	Kaplan @-@ Meier estimates were used to calculate the percentage of participants who had an event during follow @-@ up .	zh	en
62066	62065	依据意向治疗原则 , Cox 比例风险回归分析被用于分析主要结局和次要结局 , 并通过这些模型得出的风险比和 95% 可信区间对于结局进行组间比较 .	primary and secondary outcomes were analyzed with the use of Cox proportional @-@ hazards regression analyses according to the intention @-@ to @-@ treat principle , and between @-@ group comparisons of the outcomes were performed with the use of hazard ratios and 95 % confidence intervals derived from these models .	zh	en
62067	62066	对于从随机分组到改变方案日 ( 2008 年 2 月 5 日 ) 及从随机分组直到最后一次随访 ( 2009 年 3 月 ~ 6 月 ) 的所有事件都经过上述分析 .	these analyses were performed for events occurring from randomization until the date of transition ( February 5 , 2008 ) and from randomization until the final visit ( between the beginning of March and the end of June 2009 ) .	zh	en
62068	62067	对于改变方案日之后的数据还进行了主要结局和任何原因导致的死亡的事后分析 .	an additional post hoc analysis was performed for the primary outcome and death from any cause with the use of data from the post @-@ transition phase only .	zh	en
62069	62068	对于强化治疗组和标准治疗组中没有最终随访数据的参与者 , 随访数据截尾至最后一次连续 4 个月随访的完成时刻 .	for analyses of outcomes , data from participants without final follow @-@ up data were censored as of the time of their last completed 4 @-@ month visit in both the intensive @-@ therapy and standard @-@ therapy groups .	zh	en
62070	62069	对于没有完成全部随访 , 且不确定是否已经死亡的美国参与者 , 其死亡数据截尾至最近能确定其存活的日期或者根据美国全国死亡索引 ( National Death Index ) 截尾至 2008 年 1 月 1 日 .	data on mortality for participants in the United States who were not followed for the full follow @-@ up period and who were not known to be deceased were censored as of the most recent date they were known to be alive or January 1 , 2008 , on the basis of the National Death Index .	zh	en
62071	62070	每 2 年用心电图诊断无症状性心肌梗死 , 梗死发生时间定为心电图显示新的心肌梗死时间和之前心电图时间的中点 .	silent myocardial infarctions were identified on the basis of electrocardiograms obtained every 2 years and were considered to have occurred at the midpoint of the dates between the electrocardiogram showing a new myocardial infarction and the previous electrocardiogram .	zh	en
62072	62071	主要结局的 Cox 模型包括治疗方案分组变量和以下分层变量 : 分配到血压或血脂实验组 ; 分配到强化干预血压实验组 ; 分配到贝特类干预的血脂实验组 ; 7 个临床中心网络 ; 之前是否存在心血管疾病 .	Cox models for the primary outcome contained a term representing study @-@ group assignments plus terms accounting for the following prespecified stratifying variables : assignment to the blood @-@ pressure trial or lipid trial ; assignment to the intensive blood @-@ pressure intervention in the blood @-@ pressure trial ; assignment to receive fibrate in the lipid trial ; the seven clinical center networks ; and the presence or absence of previous cardiovascular disease .	zh	en
62073	62072	对于所有的次要结局 , 因为预期事件的发生率会少于主要结局 , 在分析数据之前我们从模型中剔除了 7 个临床中心网络变量 .	for all secondary outcomes , an a priori decision was made to drop the clinical center networks from this model , because fewer events were expected than for the primary outcomes .	zh	en
62074	62073	除非另有说明 , 本研究的数据与安全监督委员会的监测报告中的名义 P 值未经多重检验的校正 .	unless otherwise indicated , nominal P values , unadjusted for the multiple tests performed for this report or for monitoring by the data and safety monitoring board , are reported .	zh	en
62075	62074	用 Kaplan - Meier 曲线和 Cox 回归模型对治疗方案变更之前没有发生主要结局或者变更当天仍存活的参与者 , 分析治疗方案分组对变更之后主要结局或者死亡的影响 .	the effect of the study @-@ group assignment on the primary outcome or mortality after the transition in participants who had not had a primary outcome and who were alive at the transition date was explored with the use of Kaplan @-@ Meier curves and Cox regression models .	zh	en
62076	62075	为了确定强化治疗组死亡率较高的因素 , 对包括基线特征 , 干预后糖化血红蛋白水平 , 糖化血红蛋白下降速率和低血糖事件进行了事后探索性分析 12 , 13 .	further post hoc exploratory analyses to identify factors associated with higher mortality in the intensive @-@ therapy group have examined baseline characteristics , 10 the achieved glycated hemoglobin level and the rapidity of its decline , 11 and hypoglycemic events.12,13	zh	en
62077	62076	参与者的基线特征此前已有报告 6 .	baseline characteristics of the participants have been reported previously.6	zh	en
62078	62077	表 1 所示是改变方案日之前及最后一次随访的特征数据 .	Table 1 shows these characteristics before the transition date and at the final visit .	zh	en
62079	62078	补充附录图 1 显示了 2 个研究组随访的完整性 .	Fig . 1 in the Supplementary Appendix ( available at NEJM.org ) shows the completeness of follow @-@ up in the two study groups .	zh	en
62080	62079	改变治疗方案之前强化治疗组和标准治疗组的平均糖化血红蛋白水平分别为 6.4% 和 7.5% .	median glycated hemoglobin levels before the transition date in the intensive @-@ therapy and standard @-@ therapy groups were 6.4 % and 7.5 % , respectively .	zh	en
62081	62080	改变方案日之后 , 我们放宽了特定适应证的治疗 ( 即使用较少的药物种类或及剂量 ) , 至少强化治疗组治疗放宽频率和标准治疗组相同 .	after the transition date , therapy was relaxed ( i.e. , fewer drugs or lower doses were used ) for a particular indication at least as often in the intensive @-@ therapy group as in the standard @-@ therapy group .	zh	en
62082	62081	例如在第一次改变方案后的随访 , 强化治疗组 94% 参与者出现治疗的放宽 , 标准治疗组为 64% .	for example , at the first post @-@ transition visit , relaxation of therapy was indicated in 94 % of participants in the intensive @-@ therapy group and 69 % of those in the standard @-@ therapy group .	zh	en
62083	62082	在最后一次随访时 , 血红蛋白水平的中位数强化治疗组为 7.2% , 标准治疗组为 7.6% ( 补充附录图 2 ) .	at the final visit , median glycated hemoglobin levels were 7.2 % in the intensive @-@ therapy group and 7.6 % in the standard @-@ therapy group ( Fig . 2 in the Supplementary Appendix ) .	zh	en
62084	62083	在最后的一次随访之前 , 接受二甲双胍 , 促胰岛素分泌剂 , 噻唑烷二酮类 , 胰岛素和胰岛素及口服药物联合治疗的参与者数量在两组中相似 ( 补充附录表 1 ) .	by the final visit , the numbers of participants who were receiving metformin , secretagogues , thiazolidinediones , insulin , and combination therapy with insulin and oral agents were similar in the two groups ( Table 1 in the Supplementary Appendix ) .	zh	en
62085	62084	改变治疗方案后 , 两组严重低血糖及其他不良事件的发生率相当 .	rates of severe hypoglycemia and other adverse events within the two groups were similar after the transition ( Table 2 in the Supplementary Appendix ) .	zh	en
62086	62085	图 1 显示了从随机分组开始到改变治疗方案时和随机分组开始到整个研究结束 , 以及改变方案日到研究终点的主要结局及由于各种原因导致的死亡的发生率 .	Figure 1 shows the incidence of the primary outcome and death from any cause from randomization until the time of transition , from randomization until the end of the whole study , and from the transition date until the termination of the trial .	zh	en
62087	62086	图 2 显示了强化降糖治疗从随机分组开始到强化治疗结束 , 以及到全部研究终止期间对于主要结局的影响 .	Figure 2 shows the effect of intensive glucose @-@ lowering therapy on all the major outcomes , from randomization until the end of the active treatment period and until the end of the study .	zh	en
62088	62087	强化治疗组对于主要结局的两个关键组分有不同的影响 .	the intensive therapy had different effects on two of the key components of this primary outcome .	zh	en
62089	62088	在改变治疗方案时 , 强化治疗组的非致死性心梗发生率低于标准治疗组 ( 1.08% 对 1.35% ; 风险比 , 0.79 ; 95% CI , 0.66 ~ 0.95 ; P = 0.01 ) , 但是由于心血管疾病所引起的死亡率不显著高于标准治疗组 ( 0.71% 对 0.55% ; 风险比 , 1.27 ; 95% CI , 0.99 ~ 1.63 ; P = 0.07 ) .	at the time of the transition , the rate of nonfatal myocardial infarction in the intensive @-@ therapy group was lower than that in the standard @-@ therapy group ( 1.08 % vs. 1.35 % ; hazard ratio , 0.79 ; 95 % CI , 0.66 to 0.95 ; P = 0.01 ) , but the rate of death from cardiovascular causes was nonsignificantly higher ( 0.71 % vs. 0.55 % ; hazard ratio , 1.27 % ; 95 % CI , 0.99 to 1.63 ; P = 0.07 ) .	zh	en
62090	62089	这些不同作用一直持续到研究的结束 , 强化治疗组非致死性心梗的发生率仍低于标准治疗组 ( 1.18 对 1.42 ; 风险比 , 0.82 ; 95% CI , 0.70 ~ 0.96 ; P = 0.01 ) , 而由于心血管疾病所引起的死亡率较高 ( 0.74 对 0.57 ; 风险比 , 1.29 ; 95% CI , 1.04 ~ 1.60 ; P = 0.02 ) .	these divergent effects were retained at the end of the study , with a rate of nonfatal myocardial infarction in the intensive @-@ therapy group that was lower than that in the standard @-@ therapy group ( 1.18 vs. 1.42 ; hazard ratio , 0.82 ; 95 % CI , 0.70 to 0.96 ; P = 0.01 ) and a rate of death from cardiovascular causes that was higher ( 0.74 vs. 0.57 ; hazard ratio , 1.29 ; 95 % CI , 1.04 to 1.60 ; P = 0.02 ) .	zh	en
62091	62090	最后 , 在改变治疗方案时 , 强化治疗组比标准治疗组任何原因导致的死亡率高出 21% ( 1.42 对 1.16 ; 95% CI , 1.02 ~ 1.44 ; 标称 P = 0.030 , 经数据与安全监察委员会就重复检验进行校正后 , P = 0.036 ) , 而在研究结束高出 19% ( 1.53 对 1.27 ; 95% CI , 1.03 ~ 1.38 ; P = 0.02 ) ( 图 1 , 图 2 ) .	finally , at the time of the transition , there was a 21 % higher rate of death from any cause in the intensive @-@ therapy group than in the standard @-@ therapy group ( 1.42 vs. 1.16 ; 95 % CI , 1.02 to 1.44 ; nominal P = 0.030 and P = 0.036 after adjustment for repeat testing by the data and safety monitoring board ) and a 19 % higher rate at the end of the study ( 1.53 vs. 1.27 ; 95 % CI , 1.03 to 1.38 ; P = 0.02 ) ( Figure 1 and Figure 2 ) .	zh	en
62092	62091	死亡原因列于表 2 .	the causes of death are listed in Table 2 .	zh	en
62093	62092	两组其他预先定义的心血管结局并无明显差异 .	there was no clear difference between study groups in any other predefined cardiovascular outcomes .	zh	en
62094	62093	表 3 列出了改变方案日后 2 个治疗组主要及次要结局的年发生率 , 图 1C 和 1F 显示了主要结局及由于任何原因导致死亡的相应的 Kaplan - Meier 曲线 .	Table 3 lists the annual incidence of the primary and secondary outcomes in the two treatment groups after the transition date , and Figure 1C and 1F show the corresponding Kaplan @-@ Meier curves for the primary outcome and death from any cause .	zh	en
62095	62094	改变治疗方案后与之前的主要结局的风险比 ( 改变之前比之后的风险比 , 0.95 ; 95% CI , 0.72 ~ 1.26 ; P = 0.72 ) 及任何原因导致死亡的风险比 ( 改变之前比之后的风险比 , 1.06 ; 95% CI , 0.76 ~ 1.46 ; P = 0.74 ) 无显著差异 .	hazard ratios in the post @-@ transition period were not significantly different from those in the pretransition period for either the primary outcome ( ratio of pretransition to post @-@ transition hazard ratios , 0.95 ; 95 % CI , 0.72 to 1.26 ; P = 0.72 ) or death from any cause ( ratio of pretransition to post @-@ transition hazard ratios , 1.06 ; 95 % CI , 0.76 to 1.46 ; P = 0.74 ) .	zh	en
62096	62095	基线糖化血红蛋白水平小于或等于 8% 与大于 8% 的参与者相比 , 强化治疗对于改变治疗方案前的主要结局的影响可能存在差异 ( 交互作用 , P = 0.03 ) ( 补充附录图 3 ) .	there was a possible difference in the effect of the intensive therapy on the pretransition primary outcome among participants with a baseline glycated hemoglobin level of 8 % or less as compared with those with a level of more than 8 % ( P = 0.03 for interaction ) ( Fig . 3 in the Supplementary Appendix ) .	zh	en
62097	62096	总共 4 , 733 名参与者被随机分配参加强化治疗或标准治疗来降低血压 , 5 , 518 名参与者随机分配到接受他汀类联合非诺贝特或安慰剂以控制低密度脂蛋白 .	a total of 4733 participants were randomly assigned to receive either intensive or standard therapy to lower their blood pressure , and 5518 participants were randomly assigned to a statin plus either fenofibrate or placebo for control of low @-@ density lipoprotein cholesterol .	zh	en
62098	62097	未发现降糖和降压对主要结局的发生存在交互作用 , 也未发现降糖和调脂对主要结局及任何原因引起的死亡存在交互作用 .	no significant interactions were noted between the glucose @-@ lowering study and the blood @-@ pressure study for the primary outcome , or between the glucose @-@ lowering study and the lipid study for either the primary outcome or death from any cause .	zh	en
62099	62098	然而 , 有证据显示强化降糖治疗和强化降压治疗在改变治疗方案前 ( 交互作用 , P = 0.03 ) 和研究结束时 ( 交互作用 , P = 0.05 ) 都对于任何原因导致的死亡存在交互作用 ( 补充附录图 4 ) .	however , there was evidence of an interaction between the intensive glucose @-@ lowering group and the intensive blood @-@ pressure @-@ lowering group with respect to death from any cause both before the transition ( P = 0.03 for interaction ) and at the end of the trial ( P = 0.05 for interaction ) ( Fig 4 in the Supplementary Appendix ) .	zh	en
62100	62099	在改变治疗方案前 , 这个交互作用的特征是强化降压组的参与者中强化降糖治疗组的死亡率略高于标准治疗组 ( 风险比 , 1.45 ; 95% CI , 1.00 ~ 2.12 ; P = 0.05 ) , 但在分配到标准降压治疗组的参与者中未发现此作用 ( 风险比 , 0.78 ; 95% CI , 0.52 ~ 1.18 ; P = 0.24 ) .	before the transition , this interaction was characterized by a marginally higher mortality rate in the intensive glucose @-@ lowering group than in the standard glucose @-@ lowering group among participants also assigned to the intensive blood @-@ pressure @-@ lowering group ( hazard ratio , 1.45 ; 95 % CI , 1.00 to 2.12 ; P = 0.05 ) but not among those also assigned to the standard blood @-@ pressure @-@ lowering group ( hazard ratio , 0.78 ; 95 % CI , 0.52 to 1.18 ; P = 0.24 ) .	zh	en

62001

62000

在上述研究中 , 基线收缩压都非常低 ( DIRECT 为 133 mmHg , 而 RASS 为 120mmHg11 ) .

in both of these studies , the baseline systolic blood pressure was quite low - 133 mm Hg in DIRECT @-@ Renal and 120 mm Hg in RASS.11

zh

en

62002

62001

而其余的研究 , 譬如心脏结局及预防评估 ( HOPE ) 18 , 替米沙坦治疗 ACEI 不耐受的心血管病患者的随机临床研究 ( Telmisartan Randomised Assessment Study in ACE Intolerant Subjects with Cardiovascular Disease , TRANSCEND , NCT00153101 ) 19 , 以及糖尿病和心血管疾病行动 : 百普乐 - 达美康对照评估研究 ( Action in Diabetes and Vascular Disease : Preterax and Diamicron - MR Controlled Evaluation study , ADVANCE , NCT00145925 ) 20 , 则已于之前报道了基线收缩压与微量白蛋白尿之间的正相关 .

other studies , such as the Heart Outcomes and Prevention Evaluation ( HOPE ) , 18 the Telmisartan Randomised Assessment Study in ACE Intolerant Subjects with Cardiovascular Disease ( TRANSCEND ; NCT00153101 ) , 19 and the Action in Diabetes and Vascular Disease : Preterax and Diamicron @-@ MR Controlled Evaluation study ( ADVANCE ; NCT00145925 ) , 20 had previously reported a positive relation between baseline systolic blood pressure and microalbuminuria .

zh

en

62003

62002

综上所述 , 基线血压愈高 , 则肾素 - 血管紧张素系统阻滞剂的潜在获益愈大 10 , 11 , 18 - 20 .

thus , overall , it appears that the higher the baseline blood pressure , the greater the potential benefit of an inhibitor of the renin @-@ angiotensin system.10,11,18 @-@ 20

zh

en

62004

62003

TRANSCEND 中同样观察到这个倾向 , 并且其有助于挑选无微量白蛋白尿的 2 型糖尿病患者作为 ARB 治疗的潜在候选者 .

this trend was also seen in TRANSCEND19 and may help to identify patients with type 2 diabetes and no microalbuminuria who might be potential candidates for ARB therapy .

zh

en

62005

62004

研究期间患者 GFR 的改变很小 , 奥美沙坦与估算 GFR 中微小但显著的下降相关 ( 约 4 mL / [ min · 1.73 m2 ] ) , 而使用非肾素 - 血管紧张素系统阻滞剂的患者 , 其 GFR 下降得更小 .

changes in the GFR were minimal over the course of the study ; olmesartan was associated with a slight but significant reduction in the estimated GFR ( about 4 ml per minute per 1.73 m2 ) , whereas an even smaller decrease in the estimated GFR was noted in patients treated with agents that do not block the renin @-@ angiotensin system .

zh

en

62006

62005

奥美沙坦及安慰剂组均确认了肾脏事件发生率 ( 定义为血肌酐水平的双倍增高或需要透析 ) 降低 .

it is reassuring that the rate of renal events ( defined as a doubling of the serum creatinine level or the need for dialysis ) was low and was identical in the olmesartan and placebo groups .

zh

en

62007

62006

在研究结束时未设置清除期 , 所以我们只能推测奥美沙坦组估算 GFR 值的下降及微量白蛋白尿发生率的降低是针对肾小球压力降低或潜在的器质性不良反应而产生的有利的血流动力学 ( 功能性 ) 反应 .

there was no washout period at the end of the study , so we can only speculate about whether the drop in the estimated GFR and the lower rate of microalbuminuria in the olmesartan group represent a favorable hemodynamic ( functional ) response to lower glomerular pressure or an adverse underlying structural change .

zh

en

62008

62007

近来的研究表明估算 GFR 值降低及微量白蛋白尿是独立的预后指标 14 , 15 , 21 .

recent studies suggest that a low estimated GFR and microalbuminuria are independent prognostic markers.14,15,21

zh

en

62009

62008

在一项荟萃分析里 21 , 估算 GFR < 60 mL / [ min · 1.73 m2 ] 预示了任意原因及心源性死亡 , 但在本试验中 , 没有发现估算 GFR75 ~ 104 mL / [ min · 1.73 m2 ] 与心血管疾病风险存在关联 .

in a meta @-@ analysis , 21 an estimated GFR below 60 ml per minute per 1.73 m2 was predictive of death from any cause and of death from cardiovascular causes , but as in the present trial , there was no relationship to the risk of cardiovascular disease when the estimated GFR was 75 to 104 ml per minute per 1.73 m2 .

zh

en

62010

62009

这提示 , 从长远来看在糖尿病患者中微量白蛋白尿发生率的改变比估算 GFR 的轻微下降显得更为重要 .

this supports the notion that in patients with diabetes , the observed change in the rate of microalbuminuria might in the long @-@ term be of greater importance than the small fall in the estimated GFR .

zh

en

62011

62010

本研究中的心血管及脑血管事件发生率低 ( 约 4% , 或 2.9 例 / 千人年 ) ; 与 BENEDICT 的情况相似 , 但低于 DIRECT - 2 ( 8.0 例 / 千人年 ) 10 , 11 , 并且与纳入了晚期肾疾病患者的研究血管紧张素 Ⅱ 拮抗剂洛沙坦减少非胰岛素依赖糖尿病终点研究 [ RENAAL ] 及厄贝沙坦糖尿病肾病研究 [ IDNT ] ) 那些相比 , 心脑血管事件发生率的下降更为明显 , 后述两项试验的心血管及脑血管意外发生率要高 19 倍或 60 例 / 千人年 8 , 9 .

the rates of cardiovascular and cerebrovascular events in the present study were low ( about 4 % , or 2.9 cases per 1000 person @-@ years ) ; they were similar to those in BENEDICT but lower than those in DIRECT @-@ 2 ( 8.0 cases per 1000 person years ) 10,11 and substantially lower than those in studies involving patients with more advanced renal disease , such as the Reduction of Endpoints in NIDDM with the Angiotensin II Antagonist Losartan ( RENAAL ) study and the Irbesartan Diabetes Nephropathy Trial ( IDNT ) , in which the rates were higher by a factor of approximately 20 , or 60 cases per 1000 person @-@ years.8,9

zh

en

62012

62011

尽管心血管事件发生率低 , 但奥美沙坦组中心源性死亡例数较安慰剂组多 ( 15 例对 3 例 , P = 0.01 ) .

despite the low rates of cardiovascular events , there were more deaths from cardiovascular causes in the olmesartan group than in the placebo group ( 15 vs. 3 , P = 0.01 ) .

zh

en

62013

62012

由于受影响的患者数量过少 , 难以解释此意外的发现 , 并且可能只是偶然 .

owing to the very small number of affected patients , it is difficult to interpret this unexpected finding , and it may simply be related to chance .

zh

en

62014

62013

尽管如此 , 由于其潜在的意义 , 我们对该发现进行了一些探索性分析 .

nevertheless , because of its potential significance , several exploratory analyses were performed .

zh

en

62015

62014

在奥美沙坦组中既往有冠心病的患者致死性心血管事件 ( 11 例对 VS 1 例 , P = 0.03 ) 较安慰剂组更为普遍 , 但在两组中既往无冠心病的患者中 , 其致死性心血管事件发生率是相似的 .

fatal cardiovascular events were more common in the olmesartan group than in the placebo group among patients with known preexisting coronary heart disease ( 11 events vs. 1 with placebo , P = 0.03 ) , but the rates were similar in the two groups among patients without preexisting coronary disease .

zh

en

62016

62015

此外 , 血压位于最低四分位数区间或随访期内血压下降幅度位于最高四分位数区间的既往冠心病患者发生致死性心血管事件更多 .

there was also a trend toward more fatal events in patients with preexisting coronary heart disease who were either in the lowest quartile of blood pressure or in the highest quartile of blood @-@ pressure reduction during follow @-@ up .

zh

en

62017

62016

由于 ROADMAP 及 ORIENT 的这些发现 , 美国食品药品管理局 ( FDA ) 正在重新审查现有数据 .

because of these findings in ROADMAP and ORIENT , the Food and Drug Administration is currently reviewing existing data .

zh

en

62018

62017

尽管如此 , 既往无冠心病的患者服用奥美沙坦并不会使非致死性心血管事件发生率上升 .

nevertheless , the rate of nonfatal cardiovascular events was not increased with olmesartan among patients without preexisting coronary heart disease .

zh

en

62019

62018

本研究的结果应与其他一些提示 ARB 具有心血管疾病有益作用的研究一起综合分析 22 , 23 .

the results of the current study must also be viewed in the context of the many other studies of renal and cardiovascular outcomes that have shown that ARBs have a beneficial effect on cardiovascular disease.22,23

zh

en

62020

62019

在长期单独使用替米沙坦及与雷米普利联合应用的全球终点试验 ( ONTARGET , NCT00153101 ) 24 与国际维拉帕米缓释片群多普利研究 ( INVEST , NCT00133692 ) 25 中 , 对于在接受 ACEI 或 ARB ( ONTARGET ) , 或者钙离子通道阻滞剂或 β 受体阻滞剂 ( INVEST ) 治疗期间收缩压低于 120 mmHg 且患有冠心病的患者 , 研究者观察到了心源性死亡率的上升 ; 因此 , 不良反应的发生与治疗后的血压关系 , 而不是所用药物的类型 , 似乎更为密切 .

in the Ongoing Telmisartan Alone and in Combination with Ramipril Global Endpoint Trial ( ONTARGET ; NCT00153101 ) 24 and the International Verapamil SR Trandolapril Study ( INVEST ; NCT00133692 ) , 25 an increase in the rate of death from cardiovascular causes was observed among patients with known coronary heart disease if the systolic blood pressure was below 120 mm Hg during the time the patient was receiving therapy with ACE inhibitors or ARBs ( in ONTARGET ) or calcium @-@ channel blockers or beta @-@ blockers ( in INVEST ) ; thus , any adverse effect appears to be related more closely to the achieved blood pressure than the class of drug that was used .

zh

en

62021

62020

对于潜在的过度治疗的考虑已反映在欧洲高血压学会指南中 , 该指南指出内科医师应避免心血管疾病患者降压过度 ( 即 < 120 / 70 mmHg ) 26 .

the concern about potential overtreatment is reflected in the guidelines published by the European Society of Hypertension , which state that physicians should avoid lowering blood pressure excessively ( i.e. , to values below 120 / 70 mm Hg ) in persons with underlying cardiovascular disease.26

zh

en

62022

62021

我们的研究存在一些局限性 .

our study has certain limitations .

zh

en

62023

62022

首先 , 我们不可能从一项短期预防性试验中得出微量白蛋白尿的改变能否影响长期的肾脏及心血管事件发生率的确定结论 .

first , it is not possible to draw definite conclusions from a short @-@ term prevention study about the way in which changes in microalbuminuria may affect the rates of renal and cardiovascular event rates in the long term .

zh

en

62024

62023

在研究过程本身 , 随访阶段时间过短 .

during the study itself , the follow @-@ up period was too short .

zh

en

62025

62024

第二 , 两研究组的提前退出率均较高 ( 约 23% ) ; 然而 , 退出事件看来不会影响研究的总体结果 , 因为一项排除了这些患者的探索性分析并未影响主要终点 .

second , the rate of premature withdrawals in both study groups was high ( about 23 % in both groups ) ; however , it seems unlikely that withdrawals affected the overall findings of the study , since an exploratory analysis excluding these patients did not affect the primary end point .

zh

en

62026

62025

第三 , 尽管治疗组间血压的差异可能影响主要终点 , 并且基线血压高的患者获益更为显著 , 但研究中校正血压差异的分析并未消除奥美沙坦对主要终点的改善 .

third , although the differences in blood pressure between the treatment groups may have contributed to the primary outcome , and the benefit was greater in patients with higher baseline blood pressure , adjustment of the analysis for differences in blood pressure during the study did not eliminate the improvement in the primary end point that was seen with olmesartan .

zh

en

62027

62026

总之 , 这项试验表明即使在血压已经被有效控制在现行推荐标准范围的前提下 , 奥美沙坦依然能延迟 2 型糖尿病患者微量白蛋白尿的发生时间 .

in summary , this trial suggests that olmesartan increases the time to the onset of microalbuminuria in patients with type 2 diabetes , even when blood @-@ pressure control is excellent according to current recommendations .

zh

en

62028

62027

Dr . Haller reports receiving payment for board membership from Novartis , consulting fees from Bayer Schering Pharma and Daiichi Sankyo , lecture fees from Bayer Schering Pharma , Roche , and Menarini , payment for development of educational presentations from Daiichi Sankyo and Bayer Schering Pharma , and travel support from Amgen and Daiichi Sankyo ; Dr . Ito , consulting fees from Novartis Pharmaceuticals and Takeda Pharmaceutical , grant support paid to his institution , Tohoku University Graduate School of Medicine , from Banyu Pharmaceutical , Takeda Pharmaceutical , Astellas Pharma , Boehringer Ingelheim , Novartis Pharmaceuticals , Shionogi , and Dainippon Sumitomo Pharma , and lecture fees from Banyu Pharmaceutical , Takeda Pharmaceutical , Astellas Pharma , Boehringer Ingelheim , Novartis Pharmaceuticals , Shionogi , and Dainippon Sumitomo Pharma ; Dr . Izzo , consulting and lecture fees from Daiichi Sankyo ; Dr . Januszewicz , lecture fees from Boehringer Ingelheim , Novartis , Adamed , Bayer Healthcare , Sanofi - Aventis , Sandoz , Merck , and Krka ; Dr . Katayama , grant support from Daiichi Sankyo , Merck , Novartis , and Boehringer Ingelheim and lecture fees from Daiichi Sankyo , Merck , Novartis , and Astellas Pharma ; Dr . Menne , lecture fees from Berlin - Chemie , Novartis , and Daiichi Sankyo ; Dr . Mimran , payment for board membership and consulting fees from Daiichi Sankyo and Servier ; Dr . Ruilope , payment for board membership and consulting and lecture fees from Daiichi Sankyo ; Dr . Rump , consulting and lecture fees from Daiichi Sankyo ; Dr . Viberti , payment for board membership from GlaxoSmithKline , Novartis , and Pfizer and lecture fees from Guidotti and Malesci ; and Dr . Ritz , payment for board membership and lecture fees from Abbott and consulting fees from Hexal . No other Potential conflit of interest relevant to this article was reported .

Dr. Haller reports receiving payment for board membership from Novartis , consulting fees from Bayer Schering Pharma and Daiichi Sankyo , lecture fees from Bayer Schering Pharma , Roche , and Menarini , payment for development of educational presentations from Daiichi Sankyo and Bayer Schering Pharma , and travel support from Amgen and Daiichi Sankyo ; Dr. Ito , consulting fees from Novartis Pharmaceuticals and Takeda Pharmaceutical , grant support paid to his institution , Tohoku University Graduate School of Medicine , from Banyu Pharmaceutical , Takeda Pharmaceutical , Astellas Pharma , Boehringer Ingelheim , Novartis Pharmaceuticals , Shionogi , and Dainippon Sumitomo Pharma , and lecture fees from Banyu Pharmaceutical , Takeda Pharmaceutical , Astellas Pharma , Boehringer Ingelheim , Novartis Pharmaceuticals , Shionogi , and Dainippon Sumitomo Pharma ; Dr. Izzo , consulting and lecture fees from Daiichi Sankyo ; Dr. Januszewicz , lecture fees from Boehringer Ingelheim , Novartis , Adamed , Bayer Healthcare , Sanofi @-@ Aventis , Sandoz , Merck , and Krka ; Dr. Katayama , grant support from Daiichi Sankyo , Merck , Novartis , and Boehringer Ingelheim and lecture fees from Daiichi Sankyo , Merck , Novartis , and Astellas Pharma ; Dr. Menne , lecture fees from Berlin @-@ Chemie , Novartis , and Daiichi Sankyo ; Dr. Mimran , payment for board membership and consulting fees from Daiichi Sankyo and Servier ; Dr. Ruilope , payment for board membership and consulting and lecture fees from Daiichi Sankyo ; Dr. Rump , consulting and lecture fees from Daiichi Sankyo ; Dr. Viberti , payment for board membership from GlaxoSmithKline , Novartis , and Pfizer and lecture fees from Guidotti and Malesci ; and Dr. Ritz , payment for board membership and lecture fees from Abbott and consulting fees from Hexal .

zh

en

62029

62028

总结

summary

zh

en

62030

62029

过去的研究曾显示强化降糖增加晚期 2 型糖尿病患者死亡率及心血管疾病的高风险 .

intensive glucose lowering has previously been shown to increase mortality among persons with advanced type 2 diabetes and a high risk of cardiovascular disease .

zh

en

62031

62030

本文描述了平均为 3.7 年的强化降糖治疗在 5 年内的患者死亡率和主要心血管事件结局 .

this report describes the 5 @-@ year outcomes of a mean of 3.7 years of intensive glucose lowering on mortality and key cardiovascular events .

zh

en

62032

62031

我们将 2 型糖尿病和心血管疾病或者存在其他心血管危险因素的参与者随机分成强化治疗组 ( 目标为糖化血红蛋白水平低于 6.0% ) 或标准治疗组 ( 目标为糖化血红蛋白水平 7% ~ 7.9% ) .

we randomly assigned participants with type 2 diabetes and cardiovascular disease or additional cardiovascular risk factors to receive intensive therapy ( targeting a glycated hemoglobin level below 6.0 % ) or standard therapy ( targeting a level of 7 to 7.9 % ) .

zh

en

62033

62032

结束强化治疗时 , 由于强化治疗组死亡率较高 , 所有参与者的糖化血红蛋白目标值全部修改为 7% ~ 7.9% , 并随访至原计划的试验终点 .

after termination of the intensive therapy , due to higher mortality in the intensive @-@ therapy group , the target glycated hemoglobin level was 7 to 7.9 % for all participants , who were followed until the planned end of the trial .

zh

en

62034

62033

强化治疗终止后 , 强化治疗组的中位糖化血红蛋白水平从 6.4% 升至 7.2% , 降糖药物的使用情况 , 严重低血糖和其他不良事件的发生率在两组间大致相同 .

after the intensive intervention was terminated , the median glycated hemoglobin level in the intensive @-@ therapy group rose from 6.4 % to 7.2 % , and the use of glucose @-@ lowering medications and rates of severe hypoglycemia and other adverse events were similar in the two groups .

zh

en

62035

62034

与标准治疗相比 , 平均 3.7 年的旨在使糖化血红蛋白水平低于 6% 的强化降糖治疗减少了 5 年非致死性心肌梗死 , 但是增加了 5 年死亡率 .

as compared with standard therapy , the use of intensive therapy for 3.7 years to target a glycated hemoglobin level below 6 % reduced 5 @-@ year nonfatal myocardial infarctions but increased 5 @-@ year mortality .

zh

en

62036

62035

这样的治疗方法不能推荐用于晚期 2 型糖尿病的高危患者 ( 由美国国家心肺血液研究所 [ National Heart , Lung and Blood Institute ] 资助 ; ClinicalTrials . org , 注册号为 NCT00000620 ) .

such a strategy cannot be recommended for high @-@ risk patients with advanced type 2 diabetes . ( Funded by the National Heart , Lung and Blood Institute ; ClinicalTrials.gov number , NCT00000620 . )

zh

en

62037

62036

2 型糖尿病是心血管疾病与死亡相关的强有力而独立的危险因素 1 , 许多流行病学分析发现高血糖和这些结局之间存在渐进关系 2 - 5 .

type 2 diabetes mellitus is a strong , independent risk factor for cardiovascular disease and death , 1 and many epidemiologic analyses have identified a progressive relationship between hyperglycemia and these outcomes.2 @-@ 5

zh

en

62038

62037

因此 , 在随后的 17 个月的随访中 , 我们对强化治疗组的参与者采取了与标准对照组同样的治疗方案 .

therefore , we applied the approaches that were used in the standard control group to participants assigned to the intensive @-@ therapy group , for up to 17 months of additional follow @-@ up .

zh

en

62039

62038

本文报告了强化降糖治疗平均为期 3.7 年的患者随访 5 年的临床结果 .

we report the clinical outcomes at 5 years of follow @-@ up in response to a mean of 3.7 years of an intensive glycemia strategy .

zh

en

62040

62039

本试验的设计和主要研究成果过去已发表 6 , 7 .

the design and major results of the trial have been published previously.6,7

zh

en

62041

62040

参与者被随机分成两组 , 强化治疗组糖化血红蛋白目标值 < 6% , 而标准治疗组糖化血红蛋白目标值为 7% ~ 7.9% .

participants were randomly assigned to receive either intensive glucose @-@ lowering therapy targeting a glycated hemoglobin level of less than 6.0 % or standard glucose @-@ lowering therapy targeting a level of 7 to 7.9 % .

zh

en

62042

62041

所有患者均接受生活方式的咨询和管理糖尿病的辅导 .

all participants received counseling about lifestyle and education about the management of diabetes .

zh

en

62043

62042

强化治疗终止和结局评估

termination OF INTENSIVE REGIMEN AND ASSESSMENT OF OUTCOMES

zh

en

62044

62043

招募分为 2 个阶段进行 , 分别是 2001 年 1 月至 6 月和 2003 年 2 月至 2005 年 10 月 .

recruitment occurred in two phases , from January to June 2001 and from February 2003 to October 2005 .

zh

en

62045

62044

2008 年 2 月 5 日 , 在平均治疗时间为 3.7 年后 , 参与者被通知将停止强化降糖治疗方案 .

on February 5 , 2008 , participants were informed of the decision to discontinue the intensive glucose @-@ lowering regimen , after a mean treatment period of 3.7 years .

zh

en

62046

62045

此后强化治疗组的参与者改为接受标准血糖治疗 , 糖化血红蛋白目标值由原来的低于 6% 修改为 7% ~ 7.9% .

participants in the intensive @-@ therapy group subsequently were switched to standard glycemic therapy , and their target glycated hemoglobin level of less than 6 % was changed to a target level of 7 to 7.9 % .

zh

en

62047

62046

由于参与者也接受调脂和降压的治疗 8 , 9 , 他们继续接受至少每 4 个月一次随访直到原计划的研究结束 ( 2009 年 6 月 ) .

since participants had also been assigned to receive treatment either to control lipid levels or to lower blood pressure , 8,9 they continued to be followed at least every 4 months until the originally planned end of the trial ( June 2009 ) .

zh

en

62048

62047

因此 , 中心委员会又继续搜集和裁定了临床结局以外 17 个月的数据 , 包括主要结局 ( 非致死性心肌梗死 , 非致死性卒中或心血管原因造成的死亡的复合事件 ) 和任何原因引起的死亡 ( 次要结局 ) , 该委员会成员对分组情况并不知情 .

thus , data on clinical outcomes , including the primary outcome ( a composite of nonfatal myocardial infarction , nonfatal stroke , or death from cardiovascular causes ) and death from any cause ( a secondary outcome ) , continued to be collected and adjudicated for an additional 17 months by a central committee whose members were unaware of study @-@ group assignments .

zh

en

62049

62048

干预效果

intervention EFFECTS

zh

en

62050

62049

本文报道了随后的 0.2 年 ( 即直到 2008 年 2 月 5 日 ) , 即至参与者被通知更改治疗方案时的干预效果 .

here we report the effect of the intervention during an additional 0.2 years ( i.e. , until February 5 , 2008 ) , which was when participants were informed of the change in approach .

zh

en

62051

62050

我们也报道了 2008 年 2 月 5 日之前的结果 , 即从 2007 年 12 月 10 日起没有被协调中心报道的结果 .

we also report on outcomes that occurred before February 5 , 2008 , that were not reported to the coordinating center as of December 10 , 2007 .

zh

en

62052

62051

因此 , 我们采用意向治疗分析报道平均 3.7 年的强化血糖干预加上随后平均 1.2 年的标准血糖治疗对心血管疾病的影响 .

therefore , we used intention @-@ to @-@ treat analyses to report on the effect of a mean of 3.7 years of an intensive glycemic intervention on cardiovascular disease , followed by a mean of 1.2 years of standard glycemic therapy .

zh

en

62053

62052

我们还报道了直至转变治疗方案时和至所有试验结束时血糖干预对于血压和血脂的影响的研究 .

also reported are the effects of the glycemic intervention until the transition date and until the end of the overall trial for both the blood @-@ pressure and lipid trials .

zh

en

62054

62053

对血脂和血压进行干预的治疗效果另做了报道 8 , 9 .

the treatment effects of the lipid and blood @-@ pressure interventions were reported separately.8,9

zh

en

62055

62054

所有的主要结局和次要结局均统一由 2 名对治疗分组情况不知情的裁定人员进行裁定 , 此外 , 由 2 位糖尿病专家 ( 他们对治疗分组不知情 ) 审定死亡是否由于低血糖造成 .

all primary and secondary outcomes were adjudicated centrally by two adjudicators who were unaware of treatment @-@ group assignments , and in addition , deaths were reviewed by two diabetes experts ( who were unaware of treatment @-@ group assignments ) to determine whether they were due to hypoglycemia .

zh

en

62056

62055

ACCORD 试验由美国国家心肺血液研究所 ( NHLBI ) 资助 , 试验方案 ( 可在 NEJM . org 上刊登的本文全文中获取 ) 由 NHLBI 审查小组并经各中心的伦理委员会批准 .

the ACCORD trial was sponsored by the National Heart , Lung , and Blood Institute ( NHLBI ) , and the protocol ( available with the full text of this article at NEJM.org ) was approved by an NHLBI review panel and by the ethics committee at each center .

zh

en

62057

62056

所有参与者都提供了书面知情同意书 .

all participants provided written informed consent .

zh

en

62058

62057

所有作者担保所报告数据的准确性和完整性 .

all authors vouch for the accuracy and completeness of the reported data .

zh

en

62059

62058

药品和器械的捐助者没有参与试验设计 , 数据收集或者稿件的准备 .

the donors of medications and devices had no role in the study design , data accrual and analysis , or manuscript preparation .

zh

en

62060

62059

协调中心使用 S - Plus 8.0 ( Insightful ) 或者 SAS 9.2 ( SAS Institute ) 软件进行所有的统计分析 .

all statistical analyses were conducted at the coordinating center with the use of S @-@ Plus software , version 8.0 ( Insightful ) , or SAS software , version 9.2 ( SAS Institute ) .

zh

en

62061

62060

参与者基线特征采用均数 , 标准差和百分数来描述 .

baseline characteristics of the participants were summarized with the use of means , standard deviations , and percentages .

zh

en

62062

62061

利用每月 ( 日历月 ) 糖化血红蛋白的中位水平展示由强化治疗转换为标准治疗的影响 .

median glycated hemoglobin levels were calculated monthly ( by calendar month ) to show the effect of the switch from intensive therapy to the standard approach .

zh

en

62063

62062

在由强化治疗转换为标准治疗前的最后一次随访与试验终止时参与者所用降糖药均被归纳分类 .

exposure to glucose @-@ lowering drugs was summarized as the number of participants who were prescribed a medication at the last visit before the transition date and at the trial termination .

zh

en

62064

62063

考虑随访数据的截尾 , 利用单位随访年的事件发生百分比描述主要安全性结局的发生率 .

the incidence of key safety outcomes was expressed as the percentage of events per follow @-@ up year , taking into account censoring of follow @-@ up data .

zh

en

62065

62064

利用 Kaplan - Meier 方法估计随访期间参与发生事件的百分比 .

Kaplan @-@ Meier estimates were used to calculate the percentage of participants who had an event during follow @-@ up .

zh

en

62066

62065

依据意向治疗原则 , Cox 比例风险回归分析被用于分析主要结局和次要结局 , 并通过这些模型得出的风险比和 95% 可信区间对于结局进行组间比较 .

primary and secondary outcomes were analyzed with the use of Cox proportional @-@ hazards regression analyses according to the intention @-@ to @-@ treat principle , and between @-@ group comparisons of the outcomes were performed with the use of hazard ratios and 95 % confidence intervals derived from these models .

zh

en

62067

62066

对于从随机分组到改变方案日 ( 2008 年 2 月 5 日 ) 及从随机分组直到最后一次随访 ( 2009 年 3 月 ~ 6 月 ) 的所有事件都经过上述分析 .

these analyses were performed for events occurring from randomization until the date of transition ( February 5 , 2008 ) and from randomization until the final visit ( between the beginning of March and the end of June 2009 ) .

zh

en

62068

62067

对于改变方案日之后的数据还进行了主要结局和任何原因导致的死亡的事后分析 .

an additional post hoc analysis was performed for the primary outcome and death from any cause with the use of data from the post @-@ transition phase only .

zh

en

62069

62068

对于强化治疗组和标准治疗组中没有最终随访数据的参与者 , 随访数据截尾至最后一次连续 4 个月随访的完成时刻 .

for analyses of outcomes , data from participants without final follow @-@ up data were censored as of the time of their last completed 4 @-@ month visit in both the intensive @-@ therapy and standard @-@ therapy groups .

zh

en

62070

62069

对于没有完成全部随访 , 且不确定是否已经死亡的美国参与者 , 其死亡数据截尾至最近能确定其存活的日期或者根据美国全国死亡索引 ( National Death Index ) 截尾至 2008 年 1 月 1 日 .

data on mortality for participants in the United States who were not followed for the full follow @-@ up period and who were not known to be deceased were censored as of the most recent date they were known to be alive or January 1 , 2008 , on the basis of the National Death Index .

zh

en

62071

62070

每 2 年用心电图诊断无症状性心肌梗死 , 梗死发生时间定为心电图显示新的心肌梗死时间和之前心电图时间的中点 .

silent myocardial infarctions were identified on the basis of electrocardiograms obtained every 2 years and were considered to have occurred at the midpoint of the dates between the electrocardiogram showing a new myocardial infarction and the previous electrocardiogram .

zh

en

62072

62071

主要结局的 Cox 模型包括治疗方案分组变量和以下分层变量 : 分配到血压或血脂实验组 ; 分配到强化干预血压实验组 ; 分配到贝特类干预的血脂实验组 ; 7 个临床中心网络 ; 之前是否存在心血管疾病 .

Cox models for the primary outcome contained a term representing study @-@ group assignments plus terms accounting for the following prespecified stratifying variables : assignment to the blood @-@ pressure trial or lipid trial ; assignment to the intensive blood @-@ pressure intervention in the blood @-@ pressure trial ; assignment to receive fibrate in the lipid trial ; the seven clinical center networks ; and the presence or absence of previous cardiovascular disease .

zh

en

62073

62072

对于所有的次要结局 , 因为预期事件的发生率会少于主要结局 , 在分析数据之前我们从模型中剔除了 7 个临床中心网络变量 .

for all secondary outcomes , an a priori decision was made to drop the clinical center networks from this model , because fewer events were expected than for the primary outcomes .

zh

en

62074

62073

除非另有说明 , 本研究的数据与安全监督委员会的监测报告中的名义 P 值未经多重检验的校正 .

unless otherwise indicated , nominal P values , unadjusted for the multiple tests performed for this report or for monitoring by the data and safety monitoring board , are reported .

zh

en

62075

62074

用 Kaplan - Meier 曲线和 Cox 回归模型对治疗方案变更之前没有发生主要结局或者变更当天仍存活的参与者 , 分析治疗方案分组对变更之后主要结局或者死亡的影响 .

the effect of the study @-@ group assignment on the primary outcome or mortality after the transition in participants who had not had a primary outcome and who were alive at the transition date was explored with the use of Kaplan @-@ Meier curves and Cox regression models .

zh

en

62076

62075

为了确定强化治疗组死亡率较高的因素 , 对包括基线特征 , 干预后糖化血红蛋白水平 , 糖化血红蛋白下降速率和低血糖事件进行了事后探索性分析 12 , 13 .

further post hoc exploratory analyses to identify factors associated with higher mortality in the intensive @-@ therapy group have examined baseline characteristics , 10 the achieved glycated hemoglobin level and the rapidity of its decline , 11 and hypoglycemic events.12,13

zh

en

62077

62076

参与者的基线特征此前已有报告 6 .

baseline characteristics of the participants have been reported previously.6

zh

en

62078

62077

表 1 所示是改变方案日之前及最后一次随访的特征数据 .

Table 1 shows these characteristics before the transition date and at the final visit .

zh

en

62079

62078

补充附录图 1 显示了 2 个研究组随访的完整性 .

Fig . 1 in the Supplementary Appendix ( available at NEJM.org ) shows the completeness of follow @-@ up in the two study groups .

zh

en

62080

62079

改变治疗方案之前强化治疗组和标准治疗组的平均糖化血红蛋白水平分别为 6.4% 和 7.5% .

median glycated hemoglobin levels before the transition date in the intensive @-@ therapy and standard @-@ therapy groups were 6.4 % and 7.5 % , respectively .

zh

en

62081

62080

改变方案日之后 , 我们放宽了特定适应证的治疗 ( 即使用较少的药物种类或及剂量 ) , 至少强化治疗组治疗放宽频率和标准治疗组相同 .

after the transition date , therapy was relaxed ( i.e. , fewer drugs or lower doses were used ) for a particular indication at least as often in the intensive @-@ therapy group as in the standard @-@ therapy group .

zh

en

62082

62081

例如在第一次改变方案后的随访 , 强化治疗组 94% 参与者出现治疗的放宽 , 标准治疗组为 64% .

for example , at the first post @-@ transition visit , relaxation of therapy was indicated in 94 % of participants in the intensive @-@ therapy group and 69 % of those in the standard @-@ therapy group .

zh

en

62083

62082

在最后一次随访时 , 血红蛋白水平的中位数强化治疗组为 7.2% , 标准治疗组为 7.6% ( 补充附录图 2 ) .

at the final visit , median glycated hemoglobin levels were 7.2 % in the intensive @-@ therapy group and 7.6 % in the standard @-@ therapy group ( Fig . 2 in the Supplementary Appendix ) .

zh

en

62084

62083

在最后的一次随访之前 , 接受二甲双胍 , 促胰岛素分泌剂 , 噻唑烷二酮类 , 胰岛素和胰岛素及口服药物联合治疗的参与者数量在两组中相似 ( 补充附录表 1 ) .

by the final visit , the numbers of participants who were receiving metformin , secretagogues , thiazolidinediones , insulin , and combination therapy with insulin and oral agents were similar in the two groups ( Table 1 in the Supplementary Appendix ) .

zh

en

62085

62084

改变治疗方案后 , 两组严重低血糖及其他不良事件的发生率相当 .

rates of severe hypoglycemia and other adverse events within the two groups were similar after the transition ( Table 2 in the Supplementary Appendix ) .

zh

en

62086

62085

图 1 显示了从随机分组开始到改变治疗方案时和随机分组开始到整个研究结束 , 以及改变方案日到研究终点的主要结局及由于各种原因导致的死亡的发生率 .

Figure 1 shows the incidence of the primary outcome and death from any cause from randomization until the time of transition , from randomization until the end of the whole study , and from the transition date until the termination of the trial .

zh

en

62087

62086

图 2 显示了强化降糖治疗从随机分组开始到强化治疗结束 , 以及到全部研究终止期间对于主要结局的影响 .

Figure 2 shows the effect of intensive glucose @-@ lowering therapy on all the major outcomes , from randomization until the end of the active treatment period and until the end of the study .

zh

en

62088

62087

强化治疗组对于主要结局的两个关键组分有不同的影响 .

the intensive therapy had different effects on two of the key components of this primary outcome .

zh

en

62089

62088

在改变治疗方案时 , 强化治疗组的非致死性心梗发生率低于标准治疗组 ( 1.08% 对 1.35% ; 风险比 , 0.79 ; 95% CI , 0.66 ~ 0.95 ; P = 0.01 ) , 但是由于心血管疾病所引起的死亡率不显著高于标准治疗组 ( 0.71% 对 0.55% ; 风险比 , 1.27 ; 95% CI , 0.99 ~ 1.63 ; P = 0.07 ) .

at the time of the transition , the rate of nonfatal myocardial infarction in the intensive @-@ therapy group was lower than that in the standard @-@ therapy group ( 1.08 % vs. 1.35 % ; hazard ratio , 0.79 ; 95 % CI , 0.66 to 0.95 ; P = 0.01 ) , but the rate of death from cardiovascular causes was nonsignificantly higher ( 0.71 % vs. 0.55 % ; hazard ratio , 1.27 % ; 95 % CI , 0.99 to 1.63 ; P = 0.07 ) .

zh

en

62090

62089

这些不同作用一直持续到研究的结束 , 强化治疗组非致死性心梗的发生率仍低于标准治疗组 ( 1.18 对 1.42 ; 风险比 , 0.82 ; 95% CI , 0.70 ~ 0.96 ; P = 0.01 ) , 而由于心血管疾病所引起的死亡率较高 ( 0.74 对 0.57 ; 风险比 , 1.29 ; 95% CI , 1.04 ~ 1.60 ; P = 0.02 ) .

these divergent effects were retained at the end of the study , with a rate of nonfatal myocardial infarction in the intensive @-@ therapy group that was lower than that in the standard @-@ therapy group ( 1.18 vs. 1.42 ; hazard ratio , 0.82 ; 95 % CI , 0.70 to 0.96 ; P = 0.01 ) and a rate of death from cardiovascular causes that was higher ( 0.74 vs. 0.57 ; hazard ratio , 1.29 ; 95 % CI , 1.04 to 1.60 ; P = 0.02 ) .

zh

en

62091

62090

最后 , 在改变治疗方案时 , 强化治疗组比标准治疗组任何原因导致的死亡率高出 21% ( 1.42 对 1.16 ; 95% CI , 1.02 ~ 1.44 ; 标称 P = 0.030 , 经数据与安全监察委员会就重复检验进行校正后 , P = 0.036 ) , 而在研究结束高出 19% ( 1.53 对 1.27 ; 95% CI , 1.03 ~ 1.38 ; P = 0.02 ) ( 图 1 , 图 2 ) .

finally , at the time of the transition , there was a 21 % higher rate of death from any cause in the intensive @-@ therapy group than in the standard @-@ therapy group ( 1.42 vs. 1.16 ; 95 % CI , 1.02 to 1.44 ; nominal P = 0.030 and P = 0.036 after adjustment for repeat testing by the data and safety monitoring board ) and a 19 % higher rate at the end of the study ( 1.53 vs. 1.27 ; 95 % CI , 1.03 to 1.38 ; P = 0.02 ) ( Figure 1 and Figure 2 ) .

zh

en

62092

62091

死亡原因列于表 2 .

the causes of death are listed in Table 2 .

zh

en

62093

62092

两组其他预先定义的心血管结局并无明显差异 .

there was no clear difference between study groups in any other predefined cardiovascular outcomes .

zh

en

62094

62093

表 3 列出了改变方案日后 2 个治疗组主要及次要结局的年发生率 , 图 1C 和 1F 显示了主要结局及由于任何原因导致死亡的相应的 Kaplan - Meier 曲线 .

Table 3 lists the annual incidence of the primary and secondary outcomes in the two treatment groups after the transition date , and Figure 1C and 1F show the corresponding Kaplan @-@ Meier curves for the primary outcome and death from any cause .

zh

en

62095

62094

改变治疗方案后与之前的主要结局的风险比 ( 改变之前比之后的风险比 , 0.95 ; 95% CI , 0.72 ~ 1.26 ; P = 0.72 ) 及任何原因导致死亡的风险比 ( 改变之前比之后的风险比 , 1.06 ; 95% CI , 0.76 ~ 1.46 ; P = 0.74 ) 无显著差异 .

hazard ratios in the post @-@ transition period were not significantly different from those in the pretransition period for either the primary outcome ( ratio of pretransition to post @-@ transition hazard ratios , 0.95 ; 95 % CI , 0.72 to 1.26 ; P = 0.72 ) or death from any cause ( ratio of pretransition to post @-@ transition hazard ratios , 1.06 ; 95 % CI , 0.76 to 1.46 ; P = 0.74 ) .

zh

en

62096

62095

基线糖化血红蛋白水平小于或等于 8% 与大于 8% 的参与者相比 , 强化治疗对于改变治疗方案前的主要结局的影响可能存在差异 ( 交互作用 , P = 0.03 ) ( 补充附录图 3 ) .

there was a possible difference in the effect of the intensive therapy on the pretransition primary outcome among participants with a baseline glycated hemoglobin level of 8 % or less as compared with those with a level of more than 8 % ( P = 0.03 for interaction ) ( Fig . 3 in the Supplementary Appendix ) .

zh

en

62097

62096

总共 4 , 733 名参与者被随机分配参加强化治疗或标准治疗来降低血压 , 5 , 518 名参与者随机分配到接受他汀类联合非诺贝特或安慰剂以控制低密度脂蛋白 .

a total of 4733 participants were randomly assigned to receive either intensive or standard therapy to lower their blood pressure , and 5518 participants were randomly assigned to a statin plus either fenofibrate or placebo for control of low @-@ density lipoprotein cholesterol .

zh

en

62098

62097

未发现降糖和降压对主要结局的发生存在交互作用 , 也未发现降糖和调脂对主要结局及任何原因引起的死亡存在交互作用 .

no significant interactions were noted between the glucose @-@ lowering study and the blood @-@ pressure study for the primary outcome , or between the glucose @-@ lowering study and the lipid study for either the primary outcome or death from any cause .

zh

en

62099

62098

然而 , 有证据显示强化降糖治疗和强化降压治疗在改变治疗方案前 ( 交互作用 , P = 0.03 ) 和研究结束时 ( 交互作用 , P = 0.05 ) 都对于任何原因导致的死亡存在交互作用 ( 补充附录图 4 ) .

however , there was evidence of an interaction between the intensive glucose @-@ lowering group and the intensive blood @-@ pressure @-@ lowering group with respect to death from any cause both before the transition ( P = 0.03 for interaction ) and at the end of the trial ( P = 0.05 for interaction ) ( Fig 4 in the Supplementary Appendix ) .

zh

en

62100

62099

在改变治疗方案前 , 这个交互作用的特征是强化降压组的参与者中强化降糖治疗组的死亡率略高于标准治疗组 ( 风险比 , 1.45 ; 95% CI , 1.00 ~ 2.12 ; P = 0.05 ) , 但在分配到标准降压治疗组的参与者中未发现此作用 ( 风险比 , 0.78 ; 95% CI , 0.52 ~ 1.18 ; P = 0.24 ) .

before the transition , this interaction was characterized by a marginally higher mortality rate in the intensive glucose @-@ lowering group than in the standard glucose @-@ lowering group among participants also assigned to the intensive blood @-@ pressure @-@ lowering group ( hazard ratio , 1.45 ; 95 % CI , 1.00 to 2.12 ; P = 0.05 ) but not among those also assigned to the standard blood @-@ pressure @-@ lowering group ( hazard ratio , 0.78 ; 95 % CI , 0.52 to 1.18 ; P = 0.24 ) .

zh

en