缬沙坦联合苯磺酸氨氯地平治疗糖尿病合并高血压疗效观察

目的观察缬沙坦联合氨氯地平治疗糖尿病合并高血压的降压疗效及肾脏保护作用。方法108例糖尿病合并高血压患者随机分成观察组（55例）与对照组（53例）。对照组口服缬沙坦80-160mg／d,观察组口服缬沙坦80mg／d及苯磺酸氨氯地平5～10mg／d。两组均治疗12周。治疗前、后分别测量静息状态下的血压、尿白蛋白的排泄率（UAEa）、空腹血糖和血肌酐。结果观察组降压疗效及UAER明显优于对照组（P〈0．05）。结论缬沙坦联合苯磺酸氨氯地平治疗糖尿病合并高血压安全有效,且有明显的肾脏保护作用。     

缬沙坦治疗慢性心力衰竭合并肾功能不全效果观察

目的 探讨缬沙坦治疗慢性心力衰竭（CHF）合并轻中度肾功能不全患者的临床疗效.方法 将83例心功能Ⅲ～Ⅳ级并轻中度肾功能不全的CHF患者随机分成两组,对照组（43例）应用利尿剂、β受体阻滞剂、洋地黄等常规治疗;观察组（40例）在常规治疗基础上给予缬沙坦治疗.两组治疗前、治疗8周后,双向侧流免疫法测定血清N末端脑钠肽前体（NT-proBNP）;超声心动图测量左心室舒张末期内径（LVEDd）;计算左心室射血分数（LVEF）;乳胶颗粒增强免疫比浊法测量血清胱抑素C（Cys-C）;日立7600自动生化仪检测血清肌酐（Scr）;简化MDRD公式计算肾小球滤过率（GFR）.结果 两组治疗8周后,血清NT-proBNP、Cys-C、Scr水平均较治疗前降低,LVEF、GFR升高,P均＜0.05.观察组治疗后比对照组改善显著（P均＜0.05）.结论 缬沙坦能显著降低CHF合并轻中度肾功能不全患者的血清NT-proBNP、Cys-C水平,提高LVEF,改善GFR,提升治疗效果.     

氯沙坦及苯那普利治疗慢性肾功能不全合并高血压疗效比较

目的 探讨治疗慢性肾功能不全合并高血压的最佳药物。方法 将78例慢性肾功能不全患者随机分为氯沙坦组43例和苯那普利组35例,分别13服氯沙坦50mg／d和苯那普利10mg／d连续8周,观察用药前及用药后4、8周血压、尿蛋白、血尿素氮（BUN）、肌酐（Scr）、尿酸（uA）和钾的变化及咳嗽反应。结果 用药后两组血压、尿蛋白定量均明显下降,P〈0．01;治疗8周氯沙坦组BUN、Scr有所下降,苯那普利组Scr下降有显著意义（P〈0．05）,而仅氯沙坦组血尿酸减低（4周时P〈0．05;8周时P〈0．01）,苯那普利组发生咳嗽反应4例。结论 氯沙坦及苯那普利在控制血压、降低尿蛋白、改善肾功能等方面疗效相近;氯沙坦尚有可减低血尿酸水平、无咳嗽反应及用药耐受性更好等特点。     

半胱氨酸蛋白酶抑制物C在心力衰竭的临床意义

目的观察慢性心力衰竭患者血清半胱氨酸蛋白酶抑制物C的变化及其临床意义。方法心力衰竭60例．心功能正常对照患者30例，测定半胱氨酸蛋白酶抑制物C、血肌酐、血尿素氮、血尿酸浓度，与左心室射血分数、左心室舒张末内径进行相关分析，并随访半年。结果半胱氨酸蛋白酶抑制物C水平在血尿素氮、血肌酐、血尿酸正常的心力衰竭患者高于对照组（P〈O．01），与左心室射血分数呈负相关（r=--O．288，P〈O．05），与左心室舒张末内径呈正相关（r=O．561，P〈O．01）；在心力衰竭患者中，半胱氨酸蛋白酶抑制物C大于1mg／L病人因心力衰竭加重而再住院率明显高于半胱氨酸蛋白酶抑制物C不大于1mg／L病人（P=0．039）。结论无原发性肾脏病变的心力衰竭患者存在早期的肾功能异常，半胱氨酸蛋白酶抑制物C不但是反映心力衰竭患者早期肾功能损伤的敏感指标，而且也是心力衰竭患者预后的重要危险因素。     

半胱氨酸蛋白酶抑制物C在心力衰竭的临床意义

目的观察慢性心力衰竭患者血清半胱氨酸蛋白酶抑制物C的变化及其临床意义。方法心力衰竭60例．心功能正常对照患者30例，测定半胱氨酸蛋白酶抑制物C、血肌酐、血尿素氮、血尿酸浓度，与左心室射血分数、左心室舒张末内径进行相关分析，并随访半年。结果半胱氨酸蛋白酶抑制物C水平在血尿素氮、血肌酐、血尿酸正常的心力衰竭患者高于对照组（P〈O．01），与左心室射血分数呈负相关（r=--O．288，P〈O．05），与左心室舒张末内径呈正相关（r=O．561，P〈O．01）；在心力衰竭患者中，半胱氨酸蛋白酶抑制物C大于1mg／L病人因心力衰竭加重而再住院率明显高于半胱氨酸蛋白酶抑制物C不大于1mg／L病人（P=0．039）。结论无原发性肾脏病变的心力衰竭患者存在早期的肾功能异常，半胱氨酸蛋白酶抑制物C不但是反映心力衰竭患者早期肾功能损伤的敏感指标，而且也是心力衰竭患者预后的重要危险因素。     

不同剂量缬沙坦治疗高血压合并微量蛋白尿的分析

目的:观察不同剂量缬沙坦对高血压合并微量蛋白尿的逆转效果。方法:60例高血压病合并微量蛋白尿的病人,停服原用药1周再服用安慰剂1周后,随机均分为两组。第一组服用缬沙坦80mg／d;第二组服用缬沙坦160 mg／ d。疗程12周,监测血压每周1次,并记录出现的不良反应。第一组根据血压情况可加用氨氯地平2．5 mg／d。用药前、后测尿微量白蛋白、尿α1微球蛋白、血尿素氮、血肌酐、血尿酸、血常规和肝功能。结果:治疗12周后两组血压均下降,总有效率无显著差异。两组尿微量白蛋白和尿α1微球蛋白浓度均下降显著(P<0．01),缬沙坦160mg／d 组的比缬沙坦80mg／d组明显下降(P<0．01)。治疗后上述其他指标均无显著变化。结论:缬沙坦有明显降压作用及降低尿中微量白蛋白和尿α1微球蛋白水平作用。缬沙坦160 mg／d的疗效更明显优于缬沙坦80 mg／d组。     

硝苯地平缓释片治疗慢性肾功能不全合并高血压疗效评价

目的评价硝苯地平缓释片对慢性肾功能不全合并高血压的降压效果及安全性。方法将92例慢性肾功能不全合并高血压患者随机分成两组,治疗组给予硝苯地平缓释片10mg口服、2次／d,对照组予氯沙坦50mg口服、1次／d,疗程8周。观察两组治疗前后血压及肾功能的改善情况。结果两组治疗后血压均下降,治疗组总有效率显著高于对照组（P〈0．05）;两组治疗前后肾功能指标无明显变化。结论硝苯地平缓释片能有效控制慢性肾功能不全合并高血压,有一定的肾功能保护作用。     

缬沙坦对心室重塑及心功能影响的研究

目的对比血管紧张素Ⅱ(AngⅡ)受体拮抗剂缬沙坦和血管紧张素转换酶抑制剂(ACEI)洛汀新对心力衰竭患者心室重塑及心功能的影响，探讨缬沙坦逆转心室重塑、改善心功能的作用。方法心力衰竭患者100例，左室射血分数(LVEF)≤45％，心功能Ⅱ～Ⅳ级，随机分为对照组、缬沙坦组和洛汀新组。常规治疗基础上缬沙坦组加缬沙坦80mg／d，顿服；洛汀新组加洛汀新10mg／d，顿服，治疗16周，观察缬沙坦和洛汀新对心室重塑及心功能的影响。应用心脏彩超仪分别测定基线值、治疗后4周、16周左室结构及功能指标变化。结果经过16周治疗后，对照组临床症状、心功能分级、心室收缩功能及心室重塑指标略有改善，而缬沙坦组和洛汀新组均明显改善。结论AngⅡ受体拮抗剂缬沙坦能明显改善心力衰竭患者的心功能和逆转心室重塑。长期应用可改善衰竭心脏心肌细胞的生物学效应，这种有益的作用与ACEI类药物洛汀新相似。     

卡维地洛治疗老年高血压合并多脏器功能损害临床观察

目的观察卡维地洛治疗老年高血压及合并有多脏器功能损害的疗效及安全性。方法对22例老年高血压患者合并冠心病、心力衰竭、糖尿病、肾功能不全、脑梗塞等多脏器损害患者经卡维地洛治疗8周后疗效的观察。结果卡维地洛治疗8周前后对收缩压、心率、左心室射血分数、左心室舒张末径、24小时尿微量白蛋白尿、血肌酐均明显下降并有显著差异（P〈0.05）。结论卡维地洛在治疗老年高血压合并多脏器损害患者安全、有效。尤其是对脉压差大的老年高血压患者更为适用。     

低蛋白饮食加α-酮酸对慢性肾功能衰竭甲状旁腺素的影响

目的 评价低蛋白饮食加α-酮酸(开同)治疗慢性肾功能不全合并继发性甲状旁腺亢进的疗效。方法 选择30例慢性肾功能不全合并继发性甲状旁腺亢进患者，肌酐200～100μmol／L，用低蛋白饮食加α-酮酸治疗3个月，每天蛋白质摄入量0．6g／kg，开同4～8片／d，观察生化指标：肌酐、尿素氮、全段甲状旁腺激素、血钙、血磷、碱性磷酸酶、HCO3^-等治疗前后的变化。结果 治疗第1个月患者的全段甲状旁腺激素、血磷等有所下降，治疗3个月时下降更显著。结论 低蛋白饮食加α-酮酸能有效治疗慢性肾功能不全合并继发性甲状旁腺功能亢进。     

慢性心力衰竭患者血浆基质金属蛋白酶水平及缬沙坦对其影响的研究

目的观察慢性心力衰竭患者血清基质金属蛋白酶水平的变化。方法选取慢性心力衰竭患者110例作为试验组,测定其血浆BNP和NO、MMP-2含量,同时经心超测量测定LVEDd和LVEF,进行MMPs与BNP,LVEDd和LVEF相关性分析。实验组经缬沙坦80mg/d治疗3周后,重复检测上述指标作治疗前后对比。此外选取心功能正常的健康体检者60例作为对照组。结果血清NO含量试验组明显低于对照组,试验组血清BNP和MMP-2浓度显著高于对照组,且MMP-2与BNP、左心室参数之间具有良好的相关性。实验组经3周缬沙坦治疗后,血清NO含量较治疗前明显升高,而血清BNP和MMP-2浓度显著降低。结论血清MMPs可能参与慢性心力衰竭的左心室重塑,缬沙坦改善慢性心力衰竭左心室重塑可能与其抑制MMPs有关。     

Optimal Therapeutic Strategy Using Sacubitril/Valsartan in a Patient with Systolic Heart Failure and Chronic Kidney Disease - An Initial Case Report in Japan

Sacubitril/valsartan has demonstrated its prognostic advantageousness over enalapril in patients with heart failure with a reduced ejection fraction. However, the optimal therapeutic strategy using sacubitril/valsartan in real-world practice, particularly among a Japanee cohort, remains uncertain. A 75-year-old man with systolic heart failure and chronic kidney disease was administered sacubitril/valsartan. Plasma B-type natriuretic peptide transiently increased, accompanied by an increase in the urine volume, which allowed us to terminate loop diuretics. The estimated glomerular filtration rate as well as heart failure symptom improved at the one-month follow-up. Sacubitril/valsartan might be a promising option to preserve the renal function and improve clinical outcomes when the dose of concomitant diuretics can be decreased, although further large-scale studies are warranted to validate our hypothesis.     

血清胱抑素C与慢性心力衰竭的关系及临床意义

目的 探讨血清胱抑素C与慢性心力衰竭的关系及对心衰程度的评估价值。方法 入选住院心衰患者及年龄、性别匹配的对照组各64例,完成病史采集、超声心动图检查,测血压、心率,检测肾功能指标、血清胱抑素C及N末端B型脑钠肽前体浓度(NT-proBNP, pg/ml)。结果 （1）心衰组中血压、心率、肾功能指标、左房室结构参数、NT-proBNP及血清胱抑素C均较对照组显著升高（P<0.0001）,而射血分数明显较对照组下降（P<0.0001）;（2）心衰组Pearson相关分析显示,血清胱抑素C与年龄、尿素氮、肌酐、尿酸、左房内径、左室舒张末内径及NT-proBNP呈显著正相关（P<0.05）,而与射血分数呈显著负相关（P<0.0001）;（3）心衰组多元逐步回归分析示,血清胱抑素C为NT-proBNP、左房内径、左室舒张末内径及射血分数的独立影响因素（P<0.0001）;（4）心衰组受试者工作特征曲线 （Receiver operating characteristic curve, ROC曲线）显示血清胱抑素C及肌酐对中重度临床心衰症状的诊断准确性分别为0.844和0.672,当血清胱抑素C> 0.89mg/L或肌酐>86.7μmol/L时,就有可能伴有较重的临床症状。结论 血清胱抑素C与心衰患者心功能和心脏结构密切相关,并且是比血清肌酐更为可靠的评估心衰程度的临床指标。     

Use of angiotensin-converting enzyme inhibitors in patients with heart failure and renal insufficiency: how concerned should we be by the rise in serum creatinine?

PURPOSE: To determine the association between the early rise in serum creatinine levels associated with the use of angiotensin-converting enzyme (ACE) inhibitors or angiotensin receptor blockers (ARBs) and the long-term renoprotective properties of these drugs in patients with chronic renal insufficiency. BACKGROUND: Large-scale clinical trials have demonstrated survival benefits of ACE inhibitors in patients with heart failure. In patients with renal insufficiency, whether associated with diabetes mellitus or not, use of ACE inhibitors is associated with slowing in the progression of renal disease. In fact, patients who have the most advanced renal insufficiency at baseline are the ones who show the maximum slowing of the disease progression, but these patients are also more likely to show an early rise in serum creatinine levels after ACE inhibitor therapy. There is evidence that patients with renal insufficiency often do not receive ACE inhibitors. There is also evidence that patients with heart failure are not receiving this life-saving drug or are receiving it at dosages lower than that used in the clinical trials. One of the main reasons for this underutilization of ACE inhibitors in patients with heart failure is the underlying renal insufficiency or the rise in serum creatinine level after initiation of therapy with an ACE inhibitor. METHODS: The authors reviewed 12 randomized clinical trials of ACE inhibitor or ARB therapy in patients with preexisting chronic renal insufficiency, with or without diabetes mellitus or heart failure. Studies were included for review if they met the following criteria: subjects were randomized to receive ACE inhibitor; subjects were followed up for a minimum of 2 years; and most of the subjects had baseline chronic renal insufficiency (>or=25% loss of renal function), irrespective of cause. Of the 12 studies that met these criteria, six were multicenter double-blind placebo-controlled studies. The other six were smaller randomized studies. The studies had a mean +/- standard deviation follow-up of 3.2 +/- 0.3 years. One thousand one hundred two patients were randomized to receive ACE inhibitors or ARBs. Of these, 705 (64%) had data on renal function at baseline (within 6 months of the start) and at the end of the study. The authors examined the changes in serum creatinine levels or glomerular filtration rates (GFR) in patients who were randomized to receive ACE inhibitors. The authors also assessed the blood pressures achieved in the trials. RESULTS: Patients with preexisting chronic renal insufficiency who achieved their blood pressure control goals were likely to demonstrate an early rise in serum creatinine levels, approximately 25% above the baseline (approximately 1.7 mg/dL) after initiation of ACE inhibitor or ARB therapy. This rise in serum creatinine was more acute (by approximately 15% from the baseline) during the first 2 weeks of therapy and was more gradual (additional approximately 10%) during the third and fourth weeks of therapy (Figure 1). The serum creatinine level was likely to stabilize after about 4 weeks, provided patients had a normal salt and fluid intake. In addition, patients who did not show a rise in serum creatinine level during the first 2 to 4 weeks of therapy, were less likely to experience one after that period, unless they were dehydrated from use of diuretics or gastroenteritis or had used a nonsteroidal antiinflammatory drug (NSAID). In spite of this early rise in serum creatinine in patients with chronic renal insufficiency (a serum creatinine level of >or=124 micromol/L or >or=1.4 mg/dL) who were randomized to receive an ACE inhibitor, these patients receiving the drug showed a 55% to 75% lower risk of worsening renal function than those with normal renal function receiving the drug. The rate of risk reduction was inversely related to the severity of renal impairment at baseline, but data were limited on the benefit of ACE inhibitors in patients with more advanced renal insufficiency (GFR <30 mL/min). The authors noted that those aged 65 and older were likely to have much lower GFRs for given levels of serum creatinine than younger patients and were therefore likely to have advanced renal insufficiency at serum creatinine levels as low as 2 mg/dL (vs 4 mg/dL for younger patients). Patients with normal renal function were likely to show a much smaller rise in serum creatinine level (approximately 10% above the baseline of 0.9 mg/dL), mostly occurring during the first week after initiation of therapy, with subsequent stabilization, whereas patients with normal renal function suffering from heart failure, volume depletion, or bilateral renal artery stenosis experienced a significant rise (approximately 225% above baseline) in serum creatinine level, much higher in magnitude and rate than that experienced by those with renal insufficiency (Figure 1). Serum creatinine levels in these patients sharply increased (by approximately 75% above baseline) in the 2 weeks after the initiation of therapy with an ACE inhibitor, followed by an even sharper increase (another approximately 150%) during the subsequent 2 weeks. Patients with chronic renal insufficiency (serum creatinine>1.5 mg/dL) who received therapy with ACE inhibitors had about a five times higher risk of developing hyperkalemia than those with normal renal function, whereas presence of heart failure increased the risk of hyperkalemia by about three times over those without heart failure. Concomitant use of diuretics was associated with an approximately 60% reduction in risk of hyperkalemia. CONCLUSION: The authors conclude that, in patients with renal insufficiency (serum creatinine>1.4 mg/dL) treated with ACE inhibitors, there is a strong association between early (within the first 2 months) and moderate (not exceeding 30% over baseline) rise in serum creatinine and slowing of the renal disease progression in the long run. The authors recommend that ACE inhibitor therapy should not be discontinued unless serum creatinine level rise above 30% over baseline during the first 2 months after initiation of therapy or hyperkalemia (serum potassium level >or=5.6 mmol/L) develops.     

Adverse Events After Initiating Angiotensin-Converting Enzyme Inhibitor/Angiotensin II Receptor Blocker Therapy in Individuals with Heart Failure and Multimorbidity

BackgroundCurrent clinical practice guidelines recommend routine kidney function and serum potassium testing within 30 days of initiating angiotensin-converting enzyme inhibitor (ACEI) or angiotensin II receptor blocker (ARB) therapy. However, evidence is lacking on whether routine follow-up testing reduces therapy-related adverse events in adults with heart failure and if multimorbidity influences the association between laboratory testing and these adverse events.MethodsWe conducted a retrospective cohort study among adults with heart failure from 4 US integrated health care delivery systems. Multimorbidity was defined using counts of chronic conditions. Patients with outpatient serum creatinine and potassium tests in the 30 days after starting ACEI or ARB therapy were matched 1:1 to patients without follow-up tests. We evaluated the association of follow-up testing with 30-day all-cause mortality and hospitalization with acute kidney injury or hyperkalemia using Cox regression.ResultsWe identified 3629 matched adults with heart failure initiating ACEI or ARB therapy between January 1, 2005, and December 31, 2012. Follow-up testing was not significantly associated with 30-day all-cause mortality (adjusted hazard ratio [aHR] 0.45, 95% confidence interval [CI] 0.14; 1.39) and hospitalization with hyperkalemia (aHR 0.73, 95% CI, 0.33; 1.61). However, follow-up testing was significantly associated with hospitalization with acute kidney injury (aHR, 1.40, 95% CI, 1.01; 1.94). Interaction between multimorbidity burden and follow-up testing was not statistically significant in any of the outcome models examined.ConclusionsRoutine laboratory monitoring after ACEI or ARB therapy initiation was not associated with risk of 30-day all-cause mortality or hospitalization with hyperkalemia across the spectrum of multimorbidity burden in a cohort of patients with heart failure.     

Sacubitril/Valsartan: The Newest Addition to the Toolbox for Guideline-Directed Medical Therapy of Heart Failure

Sacubitril/valsartan combines a neprilysin inhibitor with an angiotensin receptor blocker. As an inhibitor of neprilysin, an enzyme that degrades biologically active natriuretic peptides, this first-in-class therapy increases levels of circulating natriuretic peptides, resulting in natriuretic, diuretic, and vasodilatory effects. In patients with chronic New York Heart Association class II-IV heart failure with reduced ejection fraction, the PARADIGM-HF trial demonstrated that sacubitril/valsartan significantly reduced the primary endpoint of cardiovascular mortality and heart failure hospitalization, compared with enalapril. The rate of all-cause mortality was also significantly reduced. Subsequently, the American College of Cardiology/American Heart Association/Heart Failure Society of America recently updated guideline recommendations for Stage C patients with heart failure with reduced ejection fraction to recommend angiotensin-converting enzyme inhibitors, angiotensin receptor blockers, or sacubitril/valsartan in conjunction with other evidence-based therapies to reduce morbidity and mortality. Several analyses have suggested the cost-effectiveness of this new therapy. To ensure tolerability, initiating the lower dosage form of sacubitril/valsartan is warranted in patients with severe renal impairment, moderate hepatic impairment, and low blood pressure, and close monitoring is warranted in such patients. A 36-hour washout period is recommended when switching patients from an angiotensin-converting enzyme inhibitor to sacubitril/valsartan. Similarly, sacubitril/valsartan is contraindicated in patients receiving concomitant angiotensin-converting enzyme inhibitor or angiotensin receptor blocker and those with a history of angioedema.     

Management of Heart Failure Patient with CKD

CKD is common in patients with heart failure, associated with high mortality and morbidity, which is even higher in people undergoing long-term dialysis. Despite increasing use of evidence-based drug and device therapy in patients with heart failure in the general population, patients with CKD have not benefitted. This review discusses prevalence and evidence of kidney replacement, device, and drug therapies for heart failure in CKD. Evidence for treatment with β-blockers, angiotensin-converting enzyme inhibitors, angiotensin receptor blockers, angiotensin receptor neprilysin inhibitors, and sodium-glucose cotransporter inhibitors in mild-to-moderate CKD has emerged from general population studies in patients with heart failure with reduced ejection fraction (HFrEF). β-Blockers have been shown to improve outcomes in patients with HFrEF in all stages of CKD, including patients on dialysis. However, studies of HFrEF selected patients with creatinine <2.5 mg/dl for ACE inhibitors, <3.0 mg/dl for angiotensin-receptor blockers, and <2.5 mg/dl for mineralocorticoid receptor antagonists, excluding patients with severe CKD. Angiotensin receptor neprilysin inhibitor therapy was successfully used in randomized trials in patients with eGFR as low as 20 ml/min per 1.73 m². Hence, the benefits of renin-angiotensin-aldosterone axis inhibitor therapy in patients with mild-to-moderate CKD have been demonstrated, yet such therapy is not used in all suitable patients because of fear of hyperkalemia and worsening kidney function. Sodium-glucose cotransporter inhibitor therapy improved mortality and hospitalization in patients with HFrEF and CKD stages 3 and 4 (eGFR>20 ml/min per 1.73 m²). High-dose and combination diuretic therapy, often necessary, may be complicated with worsening kidney function and electrolyte imbalances, but has been used successfully in patients with CKD stages 3 and 4. Intravenous iron improved symptoms in patients with heart failure and CKD stage 3; and high-dose iron reduced heart failure hospitalizations by 44% in patients on dialysis. Cardiac resynchronization therapy reduced death and hospitalizations in patients with heart failure and CKD stage 3. Peritoneal dialysis in patients with symptomatic fluid overload improved symptoms and prevented hospital admissions. Evidence suggests that combined cardiology-nephrology clinics may help improve management of patients with HFrEF and CKD. A multidisciplinary approach may be necessary for implementation of evidence-based therapy.     

Sleep Outcomes From AWAKE-HF: A Randomized Clinical Trial of Sacubitril/Valsartan vs Enalapril in Patients With Heart Failure and Reduced Ejection Fraction

BackgroundHeart failure and sleep-disordered breathing have been increasingly recognized as co-occurring conditions. Their bidirectional relationship warrants investigation into whether heart failure therapy improves sleep and sleep-disordered breathing. We sought to explore the effect of treatment with sacubitril/valsartan on sleep-related endpoints from the AWAKE-HF study.Methods and ResultsAWAKE-HF was a randomized, double-blind study conducted in 23 centers in the United States. Study participants with heart failure with reduced rejection fraction and New York Heart Association class II or III symptoms were randomly assigned to receive treatment with either sacubitril/valsartan or enalapril. All endpoints were assessed at baseline and after 8 weeks of treatment. Portable sleep-monitoring equipment was used to measure the apnea-hypopnea index, including obstructive and central events. Total sleep time, wake after sleep onset and sleep efficiency were exploratory measures assessed using wrist actigraphy.The results were as follows140 patients received treatment in the double-blind phase (sacubitril/valsartan, n = 70; enalapril, n = 70). At baseline, 39% and 40% of patients randomly assigned to receive sacubitril/valsartan or enalapril, respectively, presented with undiagnosed, untreated, moderate-to-severe sleep-disordered breathing (≥ 15 events/h), and nearly all had obstructive sleep apnea. After 8 weeks of treatment, the mean 4% apnea-hypopnea index changed minimally from 16.3/h to 15.2/h in the sacubitril/valsartan group and from 16.8/h to 17.6/h in the enalapril group. Mean total sleep time was long at baseline and decreased only slightly in both treatment groups at week 8 (–14 and –11 minutes for sacubitril/valsartan and enalapril, respectively), with small changes in wake after sleep onset and sleep efficiency in both groups.ConclusionsIn a cohort of patients with heart failure with reduced rejection fraction who met prescribing guidelines for sacubitril/valsartan, one-third had undiagnosed moderate-to-severe obstructive sleep apnea. The addition of sacubitril/valsartan therapy did not significantly improve sleep-disordered breathing or sleep duration or efficiency. Patients who meet indications for treatment with sacubitril/valsartan should be evaluated for sleep-disordered breathing.     

沙库巴曲缬沙坦在心血管疾病中应用研究进展

近年来,多项研究表明沙库巴曲缬沙坦治疗射血分数降低的心力衰竭(HFrEF)效果优于传统药物血管紧张素转换酶抑制剂(ACEI)/血管紧张素Ⅱ受体阻滞剂(ARB)。2019年欧洲心脏病学会专家共识会议报告指出,沙库巴曲缬沙坦可作为新发HFrEF或失代偿性心力衰竭〔左心室射血分数(LVEF)<40%〕住院或门诊患者的起始治疗方案。本文综述沙库巴曲缬沙坦在多种心血管疾病如HFrEF、射血分数中间值的心力衰竭、射血分数保留的心力衰竭、急性失代偿性心力衰竭、急性心肌梗死、高血压、慢性肾脏病、糖尿病、儿童心力衰竭中的研究进展,并分析其安全性和不良反应,同时指出未来研究方向。     

小剂量苯那普利和缬沙坦联合治老年早期糖尿病肾病

目的前瞻性研究小剂量苯那普利和缬沙坦联合治疗老年早期糖尿病肾病的疗效及合理性。方法120例老年2型糖尿病并早期糖尿病肾病患者随机分为联合治疗组（苯那普利5mg／d＋缬沙坦80mg／d）、苯那普利组（苯那普利10mg／d）和缬沙坦组（缬沙坦80mg／d）各40例，观察期24周。治疗前后检测平均动脉压、尿白蛋白排泄率、内生肌酐清除率、血清肌酐、血清尿素氨、空腹及餐后2h血糖、糖化血红蛋白、血清钾及血脂。结果3组治疗前后血压、血糖、血脂、血清钾差异无显著性，但治疗后尿白蛋白排泄率均较治疗前明显下降（P〈0.05）。各组间比较，联合治疗组尿白蛋白排泄率下降最明显（P〈0．05），缬沙坦组与苯那普利组比较差异无显著性（P〉0．05）。结论小剂量苯那普利和缬沙坦联合治疗老年早期糖尿病肾病疗效显著，安全合理，其肾脏保护作用独立于降血压作用。