Atorvastatin and statins in the treatment of heart failure

Heart failure (HF) affects approximately five million people in the US and survival at 5 years is only 50% despite advances in medical and device therapy. Statins are of novel therapy for these patients, which may be beneficial in both ischemic and non-ischemic HF. In addition to lipid-lowering and anti-atherosclerotic effects, statins demonstrate many non-lipid or pleiotropic effects that could be beneficial in HF. They may inhibit or reverse myocardial remodeling, inhibit inflammation in HF, improve endothelial function and restore autonomic nervous system balance. Numerous observational studies of HF cohorts have linked statin therapy with significantly improved survival. Small prospective clinical studies of atorvastatin and simvastatin in systolic HF are promising, documenting improved ventricular systolic function and decreased inflammatory biomarkers with statin therapy. Definitive recommendations regarding statin therapy in all HF must await the completion of large scale outcome trials of statins in non-ischemic HF.     

阿托伐他汀在慢性心力衰竭中的应用

目的观察阿托伐他汀在慢性心力衰竭（CHF）治疗中的作用与效果。方法选90例CHF患者,随机分成试验组（48例）和对照组（42例）。所有CHF患者均常规抗心衰治疗,试验组加用阿托伐他汀20mg/d,治疗6个月,对照组加用安慰剂。治疗前后行心脏彩色多普勒超声查左室射血分数（LVEF）、测量左室舒张末期内径（LVEDd）和左室收缩末期内径（LVESD）。结果试验组患者治疗后LVEF上升,LVEDd下降,治疗前后比较差异有非常显著性（P〈0.01）;LVESD下降,治疗前后比较有显著性差异（P〈0.05）。对照组LVEF、LVEDd、LVESD治疗前后比较差异无统计学意义（〈0.05）。结论CHF患者加用阿托伐他汀治疗后可改善心功能升高LVEF并降低LVEDd、LVESD。     

他汀类药物治疗慢性心力衰竭的疗效观察

目的：研究他汀类药物治疗慢性心力衰竭的疗效。方法选取万年县中医院2012年2月—2014年2月年收治的128例慢性心力衰竭患者,随机分为对照组和观察组,每组64例。对照组采用常规方法治疗,观察组采用他汀类药物治疗,比较两组患者的临床疗效以及心功能改善情况。结果治疗后观察组患者的心功能分级优于对照组,差异有统计学意义（ P<0.05）。观察组患者左心室射血分数高于对照组,6min步行试验距离长于对照组,差异有统计学意义（ P<0.05）。结论他汀类药物治疗慢性心力衰竭的疗效确切,可有效提高患者的心功能以及左心室射血分数。     

服用他汀类药物与慢性心力衰竭患者认知功能关系的研究

目的探讨他汀类药物治疗对慢性心衰患者认知功能的影响。方法入选70例NYHAⅡ～Ⅳ级、左室射血分数<45%的慢性心衰患者为观察对象。其中连续服用他汀类药物3个月的35例慢性心衰患者进入他汀组,35例未服用他汀类药物的慢性心衰患者进入对照组。使用简易智能量表(Mini-Mental State Examina-tion,MMSE)评估两组入选时及入选3个月后的认知功能情况。结果他汀组与对照组在筛选及3个月后随访时,MMSE评分差异无统计学意义(P=0.78,P=0.77);两组间随访前后认知功能障碍比率比较差异无统计学意义(P=0.75,P=0.38);两组内入选及随访认知功能障碍比率比较差异无统计学意义(P=0.74,P=0.57)。结论本研究未能发现他汀类药物可改善慢性心衰患者认知功能,提示短期服用他汀类药物不能改善慢性心衰患者认知功能。     

Teaching heart failure treatment guidelines and assessing heart failure therapy

Objectives

To determine the effectiveness of the heart failure screening form in teaching heart failure treatment guidelines and prompting students to evaluate patients'' medications to initiate patient education and provider intervention.

Design

Between 2002 and 2009, 123 students used the heart failure screeing form during an elective cardiology advanced pharmacy practice experience (APPE). A subset of 41 students were also assessed for change in heart failure knowledge and confidence pre- and post-APPE.

Assessment

A total of 1,114 heart failure patients were screened and assessed using the tool with a mean age of 71.9 ± 12.9 years. Of those, 535 (48%) patients met screening criteria and participated in heart failure education. From 2008 through 2009, there were 45 heart failure interventions with a 60% provider acceptance rate. Significant improvements were made in heart failure knowledge and in all areas of confidence at the end of the APPE for the 41 students assessed.

Discussion

The heart failure screening form is an effective tool to teach evidence-based medicine and to prompt students to initiate provider intervention and patient education. Its use is associated with significant increases in knowledge and confidence in heart failure medication therapy management in fourth-year pharmacy students.     

卡维地洛治疗慢性心力衰竭疗效观察

目的研究卡维地洛治疗慢性心力衰竭的疗效及其耐受剂量,用药的安全性。方法患者87例心功能分级(NYHA)Ⅱ级15例,Ⅲ级61例,Ⅳ级11例;LVEF<45%。随机分成两组,入选患者病情基本稳定无明显液体潴留,在常规应用血管紧张素转换酶抑制剂、利尿剂、洋地黄基础上,由小剂量开始服用卡维地洛3.125mg,2次/d。可耐受者每2～4周增加剂量,直至患者的最大耐受量。目标剂量为50mg/d。随访时间为6～18个月,以核素心肌显像观察左室功能和容积。结果经过6～18个月的观察和治疗,卡维地洛组临床症状和心功能明显改善,LVEF增加,由(23.31±6.0)%增至(43.53±4.6)%(P=0.0012)。左室收缩末期容积由(146.31±30.32)ml减至(69.56±14.27)ml(P=0.0026)。左室舒张末期容积减少由(189.97±29.9)ml减至(117.92±19.14)ml(P=0.0037)。卡维地洛组有53例(60.9%)耐受目标剂量(50mg/d),用药中无特殊不良反应。最常见的不良反应是头晕,未出现肝、肾功能损害及血脂、血糖、电解质和血象的变化。结论在心力衰竭标准治疗基础上应用卡维地洛,可以提高射血分数,缩小扩大的心室腔,改善心功能,改善心室重塑,用药安全、有效。     

Carvedilol in the treatment of chronic heart failure

Along with the angiotensin-converting enzyme inhibitors (ACEIs), the β-adrenergic receptor blockers have gradually emerged to be standard in the therapy of heart failure. Individual β-blockers that have been shown to reduce all-cause mortality in patients with heart failure include bisoprolol, metoprolol and carvedilol. Carvedilol distinguishes from the other β-blockers as being a non-selective ₁- and ₂-receptor blocker with ₁-receptor blockade effect and anti-oxidant properties. The drug does not have sympathomimetic activity and has vasodilatory effects attributable to its ₁-receptor blockade property. Experimental and clinical studies have confirmed carvedilol’s vasodilator, anti-oxidant and anti-apoptotic properties, which may contribute to its effect in reversing cardiac remodelling in animal models and patients with heart failure. These pharmacological properties render carvedilol a potentially useful agent in the treatment of patients with heart failure. Early studies of carvedilol in heart failure have reported beneficial haemodynamic effects but variable effects on exercise tolerance and clinical well being. The large-scale US Carvedilol Heart Failure Program and the Australian/New Zealand Heart Failure Collaborative Research Group reported beneficial effects of carvedilol on mortality, morbidity and clinical well being in patients with mild-to-moderate heart failure. The recently reported but yet unpublished preliminary results of the COPERNICUS study suggest that carvedilol improves mortality and morbidity in patients with advanced heart failure and severe symptoms. At this time, it is unclear whether the ancillary pharmacological properties of carvedilol can be translated to more superior clinical benefit compared to the other β-blockers. Preliminary studies examining surrogate end points suggest that carvedilol may improve left ventricular ejection fraction (LVEF) more than metoprolol. More conclusive information regarding their relative effects of clinical outcomes will await the completion of the COMET study, which compares the effect of metoprolol and carvedilol on mortality and morbidity, expected at the end of the year 2002.     

Carvedilol in the treatment of chronic heart failure

Along with the angiotensin-converting enzyme inhibitors (ACEIs), the beta-adrenergic receptor blockers have gradually emerged to be standard in the therapy of heart failure. Individual beta-blockers that have been shown to reduce all-cause mortality in patients with heart failure include bisoprolol, metoprolol and carvedilol. Carvedilol distinguishes from the other beta-blockers as being a non-selective beta(1)- and beta(2)-receptor blocker with (1)-receptor blockade effect and anti-oxidant properties. The drug does not have sympathomimetic activity and has vasodilatory effects attributable to its (1)-receptor blockade property. Experimental and clinical studies have confirmed carvedilol's vasodilator, anti-oxidant and anti-apoptotic properties, which may contribute to its effect in reversing cardiac remodelling in animal models and patients with heart failure. These pharmacological properties render carvedilol a potentially useful agent in the treatment of patients with heart failure. Early studies of carvedilol in heart failure have reported beneficial haemodynamic effects but variable effects on exercise tolerance and clinical well being. The large-scale US Carvedilol Heart Failure Program and the Australian/New Zealand Heart Failure Collaborative Research Group reported beneficial effects of carvedilol on mortality, morbidity and clinical well being in patients with mild-to-moderate heart failure. The recently reported but yet unpublished preliminary results of the COPERNICUS study suggest that carvedilol improves mortality and morbidity in patients with advanced heart failure and severe symptoms. At this time, it is unclear whether the ancillary pharmacological properties of carvedilol can be translated to more superior clinical benefit compared to the other beta-blockers. Preliminary studies examining surrogate end points suggest that carvedilol may improve left ventricular ejection fraction (LVEF) more than metoprolol. More conclusive information regarding their relative effects of clinical outcomes will await the completion of the COMET study, which compares the effect of metoprolol and carvedilol on mortality and morbidity, expected at the end of the year 2002.     

阿托伐他汀联合曲美他嗪对冠心病心力衰竭临床治疗效果分析

目的:探讨阿托伐他汀与曲美他嗪联合治疗冠心病心力衰竭临床效果.方法:以冠心病心力衰竭患者为研究对象,随机分为对照组与观察组,对照组行常规治疗,观察组在此基础上行阿托伐他汀与曲美他嗪联合治疗,比较两组完成治疗后6min步行实验、心功能差异,并进行统计学分析.结果:对照组与观察组完成治疗后6min步行距离比较:321.6mvs390.7m,P=0.009;对照组患者左室舒张末期内径(LVEDD)和左室收缩末期内径(LVESD)显著高于观察组,P＜0.05,而在左室射血分数(LEVF)比较中则显著低于观察组,P＜0.05.结论:针对冠心病心力衰竭,采用阿托伐他汀与曲美他嗪联合治疗可以显著改善心功能,有较为肯定的临床治疗效果.     

急诊呼吸衰竭患者早期应用他汀类药物作用分析

目的:探讨急诊呼吸衰竭患者早期应用他汀类药物临床效果。方法:收集绍兴市中心医院收治急性呼吸衰竭患者106例,随机单盲取法分为2组各53例,所有患者均给予采用常规治疗,观察组在确诊后即刻给予阿伐他汀钙,对照组在病情稳定后给予阿伐他汀钙。观察两组治疗前后血气指标、肺功能及治疗效果。结果:观察组治疗后血气指标(p H、Pa O2)及肺功能指标(MMEF、FEV1、FEV1/FVC)较治疗前及对照组治疗后(P<0.05),血气指标中Pa CO2较治疗前及对照组治疗后低(P<0.05)。经24 h治疗,两组总有效率对比,无统计学差异(P>0.05)。两组治疗期间均未见肝肾功能损害及其它药物不良反应。结论:呼吸衰竭患者早期给予他汀类药物改善呼吸功能及血气指标作用明显。     

The role of statins in preventing the progression of congestive heart failure in patients with metabolic syndrome

Heart Failure (CHF) is a very important public health problem in the world and certainly one of the most common debilitating diseases and cause of mortality. Current knowledge underlines that incidence rates are also influenced by the coexisting pathologic conditions that accelerate the development of disease or increase its severity. Important scientific evidence is emerging to demonstrate a strong correlation between HF and the metabolic syndrome (MetS). Hypolipemia-inducing medication offers the opportunity to discuss the possible existence of pharmacological substances that in addition to their specific targets have several demonstrated pleiotropic effects that could be beneficial in HF. Although several trials investigated statins treatment effects on HF in general, some evidence exists about the role that these drugs can have in the progression of the disease in the specific category of HF patients affected by MetS. In this review the possible positive effects of the statins treatment in this specific subset of patients are discussed.     

心力衰竭治疗现状和展望

大量循证试验使近30年来心力衰竭的治疗取得了长足的进步。血管紧张素转换酶抑制药、血管紧张素Ⅱ受体1拮抗药、肾上腺素β受体阻滞药、醛固酮拮抗药和利尿药是目前心力衰竭治疗的重要药物。一些新的治疗方法正在研究中,钙离子敏感药、脑利钠多肽类似物、精氨酸加压素拮抗药、超滤和心脏再同步化治疗是目前研究较多的、新的心力衰竭的治疗方法。     

Nebivolol for the treatment of heart failure

Introduction: Heart failure (HF) is a common and disabling disease with a high prevalence in the elderly. Beta-blockers are among the mainstay therapies of HF because they antagonize the deleterious effects of the chronic activation of sympathetic nervous system. In large randomized clinical trials, bisoprolol, carvedilol and metoprolol reduced mortality and cardiovascular hospital admission and, hence, are included in current guidelines for HF treatment.

Areas covered: Nebivolol is a third-generation β-blocker with high selectivity for β1-adrenoceptors selectivity and vasodilating effects. It also shows antioxidant, antiproliferative and antithrombotic properties. Nebivolol is generally well tolerated. Typical β-blocker-related adverse events are same as that with placebo, except for bradycardia. In addition, it shows no negative effects on chronic obstructive pulmonary disease, erectile function, and glucose and lipid metabolism. The benefits of nebivolol for HF treatment have been evaluated in the SENIORS trial, where it reduced the composite endpoint of mortality and cardiovascular hospital admission.

Expert opinion: Nebivolol is a β-blocker with distinctive characteristics. Initiated at 1.25 mg and titrated up to 10 mg/day, it has shown safety and efficacy in one large outcome trial, when added to standard medical therapy, in elderly patients (≥ 70 years) affected by HF.     

Torasemide for the treatment of heart failure

Diuretics play an essential role in modern cardiovascular therapy, and are currently recommended for the treatment of congestive heart failure. Torasemide has been developed as a newer type of loop diuretic with a longer half-life, longer duration of action, and higher bioavailability compared to the most commonly used loop diuretic, furosemide. Torasemide also appears to have additional actions beyond the pure diuretic effect, such as anti-aldosterone effect and vasorelaxation effect. Studies have also investigated whether the superior pharmacokinetics and pharmacological activity of torasemide result in a favorable clinical outcome. Their results have indicated that, in comparison with furosemide, torasemide improves left ventricular function, reduces mortality as well as the frequency and duration of heart failure-related hospitalization, and improves quality of life, exercise tolerance and NYHA functional class in patients with congestive heart failure. Thus, torasemide appears to be a promising loop diuretic that contributes to a better management of patients with heart failure. Definitive clinical trials in a double-blind fashion are warranted.     

Nebivolol for the treatment of heart failure

INTRODUCTION: Heart failure (HF) is a common and disabling disease with a high prevalence in the elderly. Beta-blockers are among the mainstay therapies of HF because they antagonize the deleterious effects of the chronic activation of sympathetic nervous system. In large randomized clinical trials, bisoprolol, carvedilol and metoprolol reduced mortality and cardiovascular hospital admission and, hence, are included in current guidelines for HF treatment. AREAS COVERED: Nebivolol is a third-generation β-blocker with high selectivity for β1-adrenoceptors selectivity and vasodilating effects. It also shows antioxidant, antiproliferative and antithrombotic properties. Nebivolol is generally well tolerated. Typical β-blocker-related adverse events are same as that with placebo, except for bradycardia. In addition, it shows no negative effects on chronic obstructive pulmonary disease, erectile function, and glucose and lipid metabolism. The benefits of nebivolol for HF treatment have been evaluated in the SENIORS trial, where it reduced the composite endpoint of mortality and cardiovascular hospital admission. EXPERT OPINION: Nebivolol is a β-blocker with distinctive characteristics. Initiated at 1.25 mg and titrated up to 10 mg/day, it has shown safety and efficacy in one large outcome trial, when added to standard medical therapy, in elderly patients (≥ 70 years) affected by HF.     

Valsartan for the treatment of heart failure

Heart failure (HF) still has a discouraging prognosis. Therapeutic strategies aim to reduce mortality as well as slow the progression of the disease, improve symptoms and reduce the frequency of hospital admission. Activation of the renin-angiotensin-aldosterone system (RAAS) is a hallmark of several cardiocirculatory diseases, including HF. Drugs for evidence-based therapy of HF are angiotensin-converting enzyme inhibitors (ACEIs), beta-blockers and aldosterone antagonists. A promising alternative is a more complete action on the RAAS through selective blockade of the angiotensin type 1 (AT(1)) receptors, taking into account not only physiopathological issues but also pharmacological, experimental and clinical data. The effect of valsartan, an orally-active, selective antagonist of AT(1) receptors, on the outcome in patients with chronic and symptomatic HF was evaluated in a large-scale, international, placebo-controlled clinical study, the Valsartan in Heart Failure Trial (Val-HeFT). In this study, overall mortality was similar in the valsartan and placebo groups (19.7 and 19.4%, respectively). However, valsartan, in addition to recommended therapy of HF including an ACEI, significantly reduced the combined end point of mortality and morbidity, with a significant reduction in the risk of hospitalisation, paralleled by improvements in New York Heart Association (NYHA) functional class, signs and symptoms and quality of life. Valsartan also improved left ventricular anatomy and function and significantly reduced neurohormonal activation. These results were confirmed and extended by the CHARM trial, where the benefits of candesartan were proved not only in all 7599 patients with HF, but also in the 2548 given an ACEI, the 2028 not given an ACEI and in the 3023 patients with an ejection fraction of > 40%. In conclusion, the first choice for HF remains an ACEI with a beta-blocker, but two new options are emerging. In patients intolerant to ACEI, the combination of valsartan or candesartan with a beta-blocker is proposed, whereas an ACEI with either valsartan or candesartan can be considered in patients intolerant to or with contraindications to beta-blockers.     

Valsartan for the treatment of heart failure

Heart failure (HF) still has a discouraging prognosis. Therapeutic strategies aim to reduce mortality as well as slow the progression of the disease, improve symptoms and reduce the frequency of hospital admission. Activation of the renin-angiotensin-aldosterone system (RAAS) is a hallmark of several cardiocirculatory diseases, including HF. Drugs for evidence-based therapy of HF are angiotensin-coverting enzyme inhibitors (ACEIs), β-blockers and aldosterone antagonists. A promising alternative is a more complete action on the RAAS through selective blockade of the angiotensin type 1 (AT₁) receptors, taking into account not only physiopathological issues but also pharmacological, experimental and clinical data. The effect of valsartan, an orally-active, selective antagonist of AT₁ receptors, on the outcome in patients with chronic and symptomatic HF was evaluated in a large-scale, international, placebo-controlled clinical study, the Valsartan in Heart Failure Trial (Val-HeFT). In this study, overall mortality was similar in the valsartan and placebo groups (19.7 and 19.4%, respectively). However, valsartan, in addition to recommended therapy of HF including an ACEI, significantly reduced the combined end point of mortality and morbidity, with a significant reduction in the risk of hospitalisation, paralleled by improvements in New York Heart Association (NYHA) functional class, signs and symptoms and quality of life. Valsartan also improved left ventricular anatomy and function and significantly reduced neurohormonal activation. These results were confirmed and extended by the CHARM trial, where the benefits of candesartan were proved not only in all 7599 patients with HF, but also in the 2548 given an ACEI, the 2028 not given an ACEI and in the 3023 patients with an ejection fraction of > 40%. In conclusion, the first choice for HF remains an ACEI with a β-blocker, but two new options are emerging. In patients intolerant to ACEI, the combination of valsartan or candesartan with a β-blocker is proposed, whereas an ACEI with either valsartan or candesartan can be considered in patients intolerant to or with contraindications to β-blockers.     

Usefulness of pimobendan in the treatment of heart failure

The effects of the benzimidazole-pyridazinone pimobendan (UD-CG 115 BS) on systemic haemodynamics, myocardial performance and the distribution of cardiac output were studied in open-chest anaesthetized pigs. After intravenous bolus injections (0.1-0.5 mg X kg-1, n = 7) increases in heart rate (up to 37%), LVdP/dtmax (up to 54%) and decreases in systemic vascular resistance (up to 33%) and left ventricular filling pressure (up to 50%) were observed, while cardiac output was unchanged. Vasodilation occurred in nearly all regional vascular beds, but was most pronounced in the adrenals (200%), followed by stomach (150%), small intestines (130%), heart (125%) and brain (110%). O2-consumption was not affected in spite of the increases in heart rate and myocardial inotropy. To evaluate the direct effects on the myocardial, pimobendan was also infused (1-5 micrograms X kg-1 X min-1, n = 7) directly into the left anterior descending coronary artery. In addition to a marked vasodilation of the coronary bed (140%), also a lowering of the left ventricular filling pressure (up to 20%) and cardiac output (15%) was observed, but no changes in regional myocardial function, LVdP/dtmax and systemic vascular resistance occurred. Immediately after intracoronary bolus injections (1 mg X kg-1, n = 4), vasodilation of the coronary vessels was apparent, but myocardial contractility was not affected. This may explain that cyclic AMP content, determined in biopsies excised 30 s after injection, was unaltered. It may be concluded that pimobendan exerts actions on the cardiovascular system which may be useful in the treatment of heart failure.