最新科学论文表明:羟氯喹对心脏有保护作用,而不是有害

新闻简述:一篇8月20日发表于《新微生物和新感染》的综述文章表明,经检索大量经同行评审的科学文献,并未发现因使用羟氯喹和阿奇霉素而引起的心脏尖端扭转型室性心动过速或相关死亡的报道。相反,一致发现羟氯喹和阿奇霉素可显著降低心脏死亡率,并降低血栓形成、心律不齐和胆固醇。这否定了FDA和CDC警告的所谓“使用羟氯喹能导致致命性心脏尖端扭转型室性心动过速”的说法。此研究表明FDA和CDC限制使用羟氯喹治疗CCP病毒患者的决定缺乏科学依据。

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英汉对照全文点击下载PDF

翻译自: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7439006/pdf/main.pdf

Hydroxychloroquine Is Protective To The Heart, Not Harmful: 

A Systematic Review 

羟氯喹对心脏有保护作用,而不是有害:文献综述

Chadwick C. Prodromos MD 

查德威克·普罗德罗莫斯(医学博士)

Abstract 

摘要

Background: Hydroxychloroquine (HCQ) has been shown to be at least somewhat effective in  treating COVID 19 patients. Recently FDA and CDC warnings of fatal cardiac toxicity from Torsade de Pointes (TDP) arrhythmia from HCQ use have been made, notwithstanding the long safe HCQ use for lupus and rheumatoid arthritis. This has resulted in restricted access of HCQ for COVID 19 treatment. We hypothesized that HCQ and azithromycin have not been reported to cause significant acute cardiac arrhythmic mortality. 

背景:羟氯喹(HCQ)已被证明在治疗COVID 19病人方面至少在一定程度上是有效的。 FDA和CDC最近警告说使用HCQ导致致命性心脏尖端扭转型室性心动过速(TDP),却置 HCQ已长期的安全的被用于治疗狼疮和类风湿关节炎的事实于不顾。这举导致使用HCQ治疗COVID 19上受到限制。我们且认为尚未有因使用HCQ和阿奇霉素导致明显的急性心律失常死亡报告。

Methods: We performed a literature search for the effects of HCQ and azithromycin on the heart. 

方法:我们进行了文献搜索,探讨HCQ和阿奇霉素对心脏的影响。

Results: No Torsade de Pointes or related deaths were found to have been reported as a result of HCQ and azithromycin use in the peer reviewed literature. To the contrary HCQ/azithromycin were uniformly found to substantially reduce cardiac mortality and also to decrease thrombosis, arrhythmia and cholesterol in treated patients in recent peer reviewed studies and meeting presentations. 

结果:在同行评审的文献中,未发现因使用HCQ和阿奇霉素而引起的心脏尖端扭转型室性心动过速或相关死亡的报道。相反,在最近的同行评审研究和会议介绍中,一致发现HCQ /阿奇霉素可显着降低心脏死亡率,并降低血栓形成,心律不齐和胆固醇。

Conclusions: HCQ and azithromycin do not cause TDP cardiac mortality. HCQ decreases cardiac events. HCQ should not be restricted in use for COVID 19 patients because of fear of cardiac mortality. 

结论:HCQ和阿奇霉素不会引发TDP致死。 HCQ可减少心脏性事故。因此不应该以害怕导致心脏性死亡而限制使用HCQ治疗COVID 19患者。

Introduction 

介绍

Several clinical studies, now numbering thousands of patients, [1-4] have shown apparent substantial clinical benefit from the use of hydroxychloroquine (HCQ) in COVID 19 patients and have not reported adverse cardiac events. A number of meta-analyses [5-7] have also shown overall good results although with limited quality studies. Usage of HCQ would therefore be warranted for COVID 19 by physicians who were so inclined unless there were significant clinical risks to offset the apparent benefits. 

数以千计的患者[1-4]的临床研究表明,在COVID 19的患者中使用羟氯喹(HCQ)具有明显的临床益处,并且尚未出现不良的心脏性事故报告。尽管优质的相关研究不多,但许多荟萃分析[5-7]都显示出总体良好的结果。因此,如果没有明显的临床风险可以抵消明显的益处,那么应该保证愿意使用HCQ的医生能将其用于治疗 COQID 19。

However, recently numerous warnings have been issued from the FDA [8], CDC [9], the American Heart Association [10] and elsewhere about potential fatal cardiac toxicity from Torsade de Pointes or other ventricular arrhythmias from HCQ use. These warnings state that such fatalities could occur secondary to the increase in QTc that is sometimes seen with the use of HCQ as well as azithromycin, which is often used in combination with HCQ. The FDA warning on reseased June 15th along with the revoking of it’s prior emergency use authorization states that “Additionally, in light of ongoing serious cardiac adverse events and other potential serious side effects, the known and potential benefits of chloroquine and hydroxychloroquine no longer outweigh the known and potential risks for the authorized use”[11]. However this warning does not reference any specific study, or comment on if any deaths have occurred.

但是,最近FDA [8]、CDC [9]、美国心脏协会[10]和其它机构已经发布了许多警告,这些警告涉及使用HCQ引起的心脏尖端扭转型室性心动过速或其它心律失常可能引起的致命性心脏毒性。这些警告指出,这种死亡可能是继QTc升高后引发的,HCQ和阿奇霉素(通常与HCQ并用)一起使用时有些时候会发生这种情况。 FDA在6月15日重新发布警告,并撤销了其先前颁布的紧急使用授权,并指出:“此外,鉴于持续的严重心脏不良事故和其它潜在的严重副作用,氯喹和羟氯喹已知和潜在益处不比已知和潜在的风险多,故不再授权使用(氯喹和羟氯喹)” [11]。但是,此警告没有引用任何特定的研究,也没有评论是导致了任何死亡。

These warnings however seemed odd to us since HCQ has been used in millions of lupus, and rheumatoid arthritis patients for more than fifty years with a general reputation for safety[12]. Practicing rheumatologists generally prescribe it without ordering a baseline EKG unless the patient has a history of cardiac disease. The 2019 hydroxychloroquine reccomendations for the European League against rheumatology (EULAR) only mention Journal Pre-proof screening for retinal toxicity in patients on hydroxychloroquine for extended periods of time[12]. Furthermore, azithromycin is also regularly prescribed without a baseline EKG and is not generally felt to be cardiotoxic to patients with an otherwise normal heart. 

然而,这些警告对我们来说似乎很奇怪,因为HCQ已在数以百万计的狼疮和类风湿性关节炎患者中使用了50多年,并且在安全性方面享有盛誉[12]。除非患者有心脏病史,否则风湿病医生通常不需要做基线心电图就能开处方。欧洲抗风湿病学联盟(EULAR)在2019年提出的羟氯喹建议仅提及期刊预检长期服用羟氯喹的患者的视网膜毒性[12]。此外,阿奇霉素也被视作常规处方药而无需看基线心电图,并且对心脏正常的患者来说不会产生心脏毒性。

These warnings have had the effect of restricting HCQ use to the hospital in some locales. This may not be consistent with good patient care since HCQ is known to be best applied earlier in the patient course before hospitalization. It has also resulted in some pharmacists, or entire pharmacy boards[13] refusing to fill HCQ prescriptions for COVID 19 thus restricting access to a potentially beneficial drug. Thus it would be of great benefit to know whether there is in fact significant cardiac risk from the use of HCQ. We hypothesized that the scientific literature would not show clinical evidence of increased cardiac mortality from HCQ or HCQ plus azithromycin from Torsade de Pointes: ie that the reported potential cardiac “risk”[9] of cardiac mortality would not be accompanied by reports of “actual” TDP or other QTc related cardiac mortality. 

这些警告已在某些地区限制了医院使用HCQ。这可能与良好的患者护理理念相悖,因为众所周知HCQ最好在患者住院之前更早的疗程中使用。这还导致一些药剂师或整个药房委员会[13]拒绝开具HCQ作为治疗COVID 19的处方药,从而限制了(患者)对潜在有效药的获取。因此,了解使用HCQ是否会产生明显的心脏风险将大有裨益。我们推断科学文献不会给出HCQ的使用或HCQ和阿奇霉素一起使用引发心脏尖端扭转型室性心动过速从而增加心脏死亡率的临床证据:即,报告所说的潜在心脏“风险”引发的心脏性死亡 [9]不会伴随产生关于TDP或其它与QTc相关的心脏死亡的实例报告。

Materials and Methods

资料和方法

We limited this study to HCQ and not chloroquine since chloroquine is more toxic than HCQ such that we do not believe chloroquine has a place in the treatment of COVID 19: particularly given the wide availability and low cost of HCQ. 

我们将这项研究限制在HCQ而不是氯喹上,因为氯喹比HCQ毒性更大,因此我们不认为氯喹在COVID 19的治疗中占有一席之地:特别是考虑到HCQ的广泛可用性和低成本。

We also excluded reports of HCQ cardiomyopathy. This is a rare condition that is only seen after many years, and usually decades, of use and thus is not relevant to the brief periods of time that HCQ is used to treat COVID 19. This cardiomyopathic damage is also not what is Journal Pre-proof referenced by agencies that warn of HCQ cardiotoxicity, which rather refers to QTc prolongation and the risk of Torsade de Pointes. 

我们还排除了HCQ心肌病的报道。这是一种罕见的疾病,仅在使用数年(通常是数十年)后才会出现,因此与使用HCQ短期治疗COVID 19无关。这种心肌病的损害也不是相关机构引用期刊预检关于HCQ心脏毒性的证据,这是指QTc延长和心脏尖端扭转型室性心动过速的风险。

We conducted a search of the Pubmed, Medline, Cochrane, Embase, and Google Scholar databases. Search terms included hydroxychloroquine and azithromycin and the following co-search terms: cardiac, heart, arrhythmia, ventricular arrhythmia, Torsade de Pointes, COVID 19, treatment for COVID 19, mortality and death. We identified relevant articles. We included only clinical series including case reports, prospective and retrospective cohort studies, and meta analyses. Due to the emerging nature of the COVID-19 pandemic we included pre-print papers in our analysis, including papers published on medRxiv (which are indexed in Google scholar). The last day of this search consultation was June 1st 2020. We identified 4 case reports [14, 15] of HCQ cardiomyopathy after long term use, which were excluded as explained above. The remaining papers were individually analyzed for evidence of cardiac morbidity and mortality.

我们在Pubmed、Medline、Cochrane、Embase和Google Scholar数据库里进行了搜索。搜索词包括羟氯喹和阿奇霉素,以及以下共同搜索词:心脏、心脏、心律不齐、室性心律失常、心脏尖端扭转型室性心动过速、COVID 19、COVID 19的治疗、死亡和死。我们确认了相关文章。我们仅包括临床系列,包括病例报告,前瞻性和回顾性队列研究以及荟萃分析。由于COVID-19大流行的新兴性质,我们在分析中包括了预印本论文,包括在medRxiv上发表的论文(已在Google学术搜索中进行索引)。这次搜索咨询的最后一天是2020年6月1日。我们排除了4例长期使用后HCQ心肌病的病例报告[14,15],原因如上所述。其余论文分别进行了分析,作为研究心脏发病率和死亡率的依据。

Results 

结果

Overall our literature search found that, except for a few Case reports of non-fatal adverse events, HCQ is actually consistently associated with a decreased incidence of cardiac adverse events and no cardiac mortality from Torsade de Pointes.   

总的来说,我们的文献检索发现,除了少数非致命性不良事件的病例报告外,实际上,HCQ一直与心脏不良事件的发生率降低有关,而且没有扭转型室性心动过速的心源性死亡情况。

Table 1. Literature Review Results on HCQ and Cardiac Events

表1. HCQ与心脏事件关系的文献回顾

文献  研究方式病人数HCQ剂量和疗程HCQ 用药持续时间协同用药病人的并发症/心脏病史 研究结果
Morgan 2006  [16] 报导病例200 mg每日两次三年 41岁女性,患有充血性心衰和左心室功能障碍。 同时患有系统性红斑狼疮和高血压。  肛门再造术后3年
QTc间隔延长
O’laug lin  2016  [17] 报导病例 1 每天200 mg  2 年50岁,女性,系统性红斑狼疮病史, 透析中的终末期肾病 及抗凝剂引起的心房颤动
QTc间隔延长
Chen  2006  [18] 报导病例每天200 mg 1 年每天15毫克强的松龙,每天200毫克的替奥菲林。67岁的老人,有系统性红斑狼疮、肝硬化和门静脉血栓形成、哮喘和老年病史。心肌梗死伴室间隔缺损QTc间隔延长导致 尖端扭转型室速
Asli  2020  [19] 报导病例400 mg  立即服用量, 然后 200 mg 每日两次3 天最初是阿莫西林-后来改成了克拉维酸60岁女性,有高血压病史,高脂血症,超重右束支阻滞和QTc间隔延长 
Erkan  2002  [20] 横断研究133名患者患有抗磷脂综合征NA 

NA 所有有抗磷脂症病史的患者发现服用阿司匹林或羟氯喹的抗磷脂抗体阳性患者血栓形成率较低
Izmirl y 2012 [21] 历史队列研究40名新生儿,其母亲均接受了HCQ。临产至少每日 200 mg 
至少在妊娠10周之前母亲以前生过心脏性新生狼疮患儿的新生儿,或母亲有抗SSA/Ro和/或SSB/LA抗体的新生儿母亲接受羟氯喹的婴儿患心脏新生儿狼疮的几率降低64%。
Petri  1994  [22] 纵向队列研究264名患者,125名患者使用羟氯喹研究中80%的患者都在接受泼尼松治疗所有系统性红斑狼疮的病人发现使用羟氯喹与降低血清胆固醇水平有关
Hung  [23] 基于人群的回顾式队列研究173人,在HCQ组> 180 天风湿性关节炎患者显示服用羟氯喹的类风湿性关节炎患者发生冠状动脉疾病的风险有所降低
Konig  2020  [24] 前瞻性队列研究812 患者 
所有系统性红斑狼疮的病人HCQ血液水平与任何血栓事件的风险成反比
Hooks  2020  [35] 回顾性队列研究819名患者接受  HCQ每日中位剂量400毫克中位时间1006天所有风湿病患者12例QTc超过500 ms的患者,平均患者治疗时QTc增加7.6 ms。 治疗时平均QTc为430.9 ms。
Chorin  2020  [36] 回顾性研究251 负荷剂量为400毫克,一天两次,然后200毫克,每天两次。
5 days



 

阿奇霉素每天500毫克,连续5天

23%的患者QTc>500毫秒,其中一名患者出现多形性室性心动过速(怀疑为尖端扭转型室速)
Liu  2018  [37] 系统回顾和元分析患者总数 19,679



羟氯喹或氯喹的使用与风湿病患者的心血管疾病风险降低30%有关。
Remp enault 2019  [38] 系统回顾和元分析12,245 HCQ  患者 NA NA NA NA 接受HCQ的类风湿关节炎患者表现出可改变的心血管疾病危险因素,包括改善:血脂情况、糖尿病发生率、糖化血红蛋白和减少心血管事件。
Matti eu 2018 [39]系统审查和元分析24,923 HCQ  患者NANANANA风湿病患者接受HCQ治疗后,心血管疾病风险状况较好,心血管事件较少。

Non-Fatal Cardiac Adverse Event Clinical Series 

非致命性心脏不良事件临床系列报导  

We found 1 case series [36] of 251 COVID 19 patients treated with HCQ and azithromycin. 23% developed extreme QTc prolongation. However, HCQ was discontinued in patients with QTc prolongation and no deaths occurred.  

我们发现1个病例系列[36],251例COVID 19患者接受HCQ和阿奇霉素治疗。23%出现极度QTc延长。但对QTc延长的患者停用HCQ,无死亡发生。

Cardiac Mortality from HCQ Induced TDP or Other Arrhythmia 

HCQ诱发的尖端扭转型室性心动过速或其它心律失常造成的心脏死亡

None reported:  We did not find any reports of a cardiac death from TDP or other arrhythmia from the use of HCQ. 

未报告:我们未发现使用HCQ后因TDP或其它心律失常导致心脏死亡的报告。 

Papers Showing a Decreased Incidence of Cardiac Events from the Use of HCQ 

显示使用HCQ可降低心脏事件发生率的论文

Eight papers showed a decreased incidence of cardiovascular disease (CVD) in patients taking HCQ.  Hung [23]in 2018 found a decrease in risk of coronary artery disease (CAD) in rheumatoid arthritis (RA) patients taking HCQ.   Liu [37]  found this protective effect of HCQ on 2018 found that CQ and HCQ lower CVD in rheumatic disease from their study results. Mathieu [39] also in 2018 found that RA patients using hydroxychloroquine had an improved cardiovascular risk profile when compared to other RA patients.  

八篇论文显示,服用HCQ的患者心血管疾病(CVD)的发生率降低。 Hung[23]在2018年发现服用HCQ的类风湿性关节炎(RA)患者发生冠状动脉疾病(CAD)的风险降低。  Liu[37]在2018年发现HCQ对2018年发现CQ和HCQ降低风湿病CVD的这种保护作用,从他们的研究结果来看。Mathieu[39]也在2018年发现,与其他RA患者相比,使用羟氯喹的RA患者的心血管风险状况有所改善。

Sharma [30] in 2016 found that hydroxychloroquine use was associated with a 72% decrease in the risk of incident CVD in RA patients.  Van Halm [29] in 2018 found that HCQ reduced cardiac events in RA patients. Yang [31] in 2019 found a decreased risk for coronary arter disease in SLE patients with high dosage use of HCQ for at least 318 days. Shapiro [32] in 2017 found decreased mortality with HCQ. In 514 RA patients – 241 HCQ, 273 control – the mortality rate for HCQ was 22.4%, vs 38.5% in control. 13.3% of HCQ patients using 400mg/day suffered cardiovascular events compared with 38.1% in the control group.  They concluded that HCQ use in RA patients was associated with decreased cardiovascular morbidity, especially in higher dosage HCQ patient of 400 mg per day. 

Sharma[30]在2016年发现,羟氯喹的使用与RA患者发生CVD的风险降低72%有关。Van Halm[29]在2018年发现,HCQ可降低RA患者的心脏事件。Yang[31]在2019年发现,系统性红斑狼疮患者大剂量使用HCQ至少318天,冠状动脉疾病风险降低。Shapiro[32]在2017年发现使用HCQ可降低死亡率。在514名RA患者中(241名HCQ,273名对照)HCQ的死亡率为22.4%,而对照的死亡率为38.5%。使用400mg/天的HCQ患者中,13.3%的患者发生心血管事件,而对照组为38.1%。 他们的结论是,RA患者使用HCQ与心血管发病率降低有关,尤其是每天400mg的高剂量HCQ患者。

Neonatal Cardiac Lupus 

新生儿红斑狼疮累及心脏

Izmirly [21] in 2013 showed the recurrence rate of cardiac-Neonatal Lupus in fetuses exposed to HCQ was 7.5% (3/40) compared to 21.2% (46/217) in the unexposed group (p=0.050). While there were no deaths in the exposed group, the overall case fatality rate of the cardiac-NL fetuses in the unexposed group was 22%.

Izmirly[21]在2013年的研究显示,暴露于HCQ的胎儿心脏-新生儿狼疮的复发率为7.5%(3/40),而未暴露组为21.2%(46/217)(p=0.050)。而且暴露组没有死亡,但未暴露组中累及心脏新生儿狼疮胎儿的总死亡率为22%。 

Atrial Fibrillation 

房颤

Gupta  [33] in 2018 showed a 67% decreased risk of atrial fibrillation in patients taking HCQ.   

Gupta[33]在2018年的研究显示,服用HCQ的患者发生房颤的风险降低了67%。

Thrombosis  

血栓形成  

3 papers [20, 24, 25] showed a decreased incidence of thrombosis in patients taking HCQ.  Konig [24] in a 2019 study, presented at the American College of Rheumatology Annual Conference, found a lower incidence of thrombosis the higher the level of HCQ in the blood. 

三篇论文[20,24,25]显示服用HCQ的患者血栓发生率降低。 Konig[24]在2019年美国风湿病学学院年会上发表的一项研究中发现,血液中HCQ含量越高,血栓发生率越低。

Cholesterol and Lipid Profile 

胆固醇和血脂情况

Two papers [22, 26] showed lower cholesterol or lipid profile in patients taking HCQ. 

两篇论文[22,26]显示,服用HCQ的患者胆固醇或血脂较低。

Clinical Series Using HCQ in COVID 19 

COVID 19中使用HCQ的临床系列

A clinical series [2] of 1061 COVID 19 patients treated with HCQ and azithromycin had 8 deaths.   However, all of these deaths were caused by respiratory failure from COVID-19, and no patients showed Torsades de Pointes. They obtained a baseline EKG in all patients and discontinued HCQ when necessary.  They have now treated over 4000 patients with no cardiac mortality. 

一个临床系列[2],1061例COVID 19患者接受HCQ和阿奇霉素治疗,有8例死亡。  但这些死亡均由COVID-19引起的呼吸衰竭引起,没有患者出现躯体疾病。他们获得了所有患者的基线心电图,并在必要时停止使用HCQ。 目前他们已经治疗了4000多名患者,没有出现心脏死亡。

Azithromycin 

阿奇霉素

We found 5 reports of the cardiotoxicity of HCQ on COVID 19 patients. [27, 28, 34-36]. All papers described increased “risk” of TDP or related ventricular arrhythmia.  However, none of the 5 papers reported an actual HCQ-AZ death. A report by Farkas [40], explained that HCQ is actually an anti-arrhythmic drug and that it has never been shown to predispose to TDP.  Ohara further describes azithromycin has never been shown to cause TDP in a paper entitled, “Azithromycin Can Prolong QT Interval and 169 Suppress Ventricular Contraction, but Will Not Induce Torsade de Pointes” [41]. In addition, azithromycin has been shown to improve cardiac remodeling and decrease heart failure after myocardial infarction in animal models [42].

我们发现了5份关于HCQ对COVID 19患者心脏毒性的报告[27, 28, 34-36] 。所有论文都描述了TDP或相关室性心律失常的 “风险”增加。 然而,这5篇论文中没有一篇报导了实际的HCQ-AZ死亡。Farkas[40]的报告,解释了HCQ实际上是一种抗心律失常的药物,而且从未被证明会诱发尖端扭转型室性心动过速(TDP)。 Ohara在题为 《阿奇霉素能延长QT间期和169抑制心室收缩,但不会诱发TDP》[41]的论文中进一步介绍了阿奇霉素从未被证明会导致TDP。此外,在动物模型中,阿奇霉素还被证明可以改善心脏重塑,减少心肌梗死后的心力衰竭[42]。

Discussion 

讨论

The most important finding of this review is that evidence shows HCQ to be overall significantly cardioprotective, and apparently not cardiotoxic in short term use. This supports Journal Pre-proof our hypothesis that prudent use of HCQ would not cause significant mortality from Torsade de Pointes or related cardiac causes. This finding of cardioprotection, which was surprising to us, goes well beyond our hypothesis. Perhaps because many of the studies showing cardioprotection are relatively recent, the cardioprotective effect seems to be generally unknown to both the general population and the medical community. The cardio-protection includes a decrease in cardiac events, in thrombosis in general, in arrhythmia, in lipid profile and even in fetal disease. With HCQ generally beneficial to the heart in patients with rheumatic disease, there would be no reason to think that it would be cardiotoxic in COVID 19 patients, unless these patients were late in the disease course with established viral cardiac damage. Even then this would be only a theoretical risk because it is also possible that HCQ might be 188 protective of further damage in this circumstance.

本综述最重要的发现是,有证据表明HCQ总体上具有显著的心脏保护作用,而且在短期使用中显然没有心脏毒性。这支持了我们在 Journal Pre-proo 《期刊预审》论文中的假设,即,谨慎使用HCQ不会导致因药物引起的心律不整(Torsade de Pointes)或相关心脏病的重大死亡。心脏保护的这一发现,让我们很惊讶,远远超出了我们的假设。也许是因为很多关于心脏保护的研究都是相对较新的,而心脏保护作用对于一般人群和医学界来说似乎都是未知的。心脏保护包括减少心脏疾病、一般血栓形成、心律不齐、血脂检测以及胎儿疾病。由于HCQ通常对风湿病患者的心脏有益,所以没有理由认为它使COVID19患者的心脏中毒,除非这些是心脏病晚期患者,伴有确诊的病毒性心脏损伤。即使那样,这也只是一种理论上的风险,因为在这种情况下,HCQ也有可能防止进一步的损害。

The second major finding of this study is that we were unable to find any reports of TDP death from HCQ induced TDP in the peer reviewed literature. This suggests that, in fact, no actual significant risk of TDP exists if HCQ is used prudently in accordance with established guidelines. In this regard, the protocol used by Didier Raoult’s group [2] is instructive. They obtain a baseline EKG and serum electrolyte analysis before beginning HCQ. The EKG is repeated 48 hours after the start of treatment and HCQ is discontinued when the corrected QT interval is >500ms. Using this common sense protocol, they have now treated over 4000 patients without a single cardiac mortality. TDP may occasionally occur in association with HCQ use. But based on our finding of not a single mortality being reported in the peer reviewed literature, we believe that the frequency of HCQ associated TDP is extremely low and the incidence of subsequent TDP induced mortality caused by HCQ is rare if it exists at all.  Anecdotally the Department of Health and Human Services Pharmacovigilance Memorandum [43] which publishes self-reported adverse events from providers and patients reported 4 cases of TDP with 1 mortality from their entire database. The report is not peer reviewed. There is no way to verify the report itself, causality or whether appropriate procedures were followed. But at worst this would still represent only a single TDP mortality despite very widespread HCQ COVID-19 use.

本研究的第二个主要发现是,在同行评审的文献中,我们没有发现任何心律不整(TDP)是因为使用HCQ引起的 TDP 死亡的报道。这表明,实际上,如果按照既定的指南谨慎使用HCQ,就不存在出现TDP的重大风险。在这方面,迪迪埃·拉乌特(Didier Raoult)的[2]组所使用的方案是有指导意义的。他们在开始服用HCQ前进行基线心电图和血清电解质分析。治疗开始48小时后重复心电图检测,当QT间期为>500ms时,停止服用HCQ。使用这一常识性方案,他们现在已经治疗了4000多名患者,无一例心脏死亡。TDP偶尔会在使用HCQ时发生。但是,基于我们在同行评议的文献中没有发现任何有关死亡个案的报告,由此我们认为与HCQ相关的TDP的发生频率极低,而由HCQ引起的TDP的死亡率即使存在,也是非常罕见。据传闻,《卫生和公众服务部药物警戒备忘录》[43],发布了来自一些个人和患者的自我报告的不良案例,在这些案例的数据库中有4例 TDP 患者,其中1例死亡。这些报告未经同行评议,因此无法证实报告本身,其因果关系,或是否遵循了适当的程序等。但,实时是最坏的结果,也只显示有一例死亡,而且是在HCQ被非常广泛地用来治疗COVID-19患者的前提下。

The cardio-protective properties of HCQ should not be surprising. Cardiac events, including thrombosis are caused in part by inflammation[44]. HCQ is an anti-inflammatory drug[45]. Furthermore, its separately described anti-thrombotic properties[46] would also be expected to be cardio-protective.

对HCQ具有的心脏保护特性的功能,人们不应感到惊奇。心脏疾病包括血栓形成,部分是由炎症引起的[44]。HCQ是一种抗炎药[45]。此外,它本身具有的抗血栓特性[46],也被认为具有心脏保护作用。

Limitations of this study include the possibility that cardiac deaths have occurred but not been reported. However, even if a small number of TDP deaths have occurred, it would not change the finding that HCQ is overall safe and generally beneficial for the heart.

这项研究的局限性包括可能有些是已经发生了的心脏死亡案例但还未被报道的情况。然而,即使发生了少量TDP死亡案例,也不会改变HCQ总体上是安全的而且一般来说对心脏也是有益的这一发现。

In fact, the finding of an anti-thrombotic effect, an anti-arrhythmic effect, and a reduction in CVD events raises the possibility that HCQ should be considered in well controlled clinical trials as a treatment for COVID 19 patients who have sustained cardiac damage as a possible mitigant of these effects.

事实上,这项关于抗血栓作用、抗心律不齐作用、减少心血管疾病的发现,提高了在临床试验中应该考虑将HCQ用于治疗COVID 19病人的这种可能性,以此作为减轻对持续性心脏损伤的可能性并起到緩和的作用。

Conclusions 

结论

HCQ is apparently not dangerous to the heart and indeed is cardioprotective. It results in a lower incidence of cardiac events as well as lower levels of arrhythmia, cholesterol, and thrombosis. No TDP deaths from HCQ have apparently been reported in the peer reviewed Journal Pre-proof literature. The potential risk of fatal arrhythmia, e.g. TDP, from HCQ, appears to be essentially a theoretical risk only. It appears to occur very rarely if ever in clinical practice if HCQ is used according to standard treatment protocols. Azithromycin used in combination with HCQ also appears to be safe, does not appear to cause TDP mortality, and is also apparently cardioprotective. Due to its ability to decrease CVD events, decrease arrhythmia, decrease thrombosis and decrease cholesterol, HCQ should be considered as an agent for study to potentially treat patients who have developed cardiac damage from COVID 19.

HCQ显然对心脏没有危险,而且确实具有心脏保护作用。它可以降低心脏疾病的发生率,降低心律失常、胆固醇和血栓形成的水平。在同行评审的《期刊预审》中,显然没有由HCQ引起的TDP死亡的报道。致命心律失常的潜在风险,例如HCQ引起的TDP,似乎基本上只是一种理论上的风险。如果按照标准治疗方案使用HCQ,即使在临床实践中也很少发生。 阿奇霉素与HCQ并用似乎是安全的,似乎不会引起TDP死亡,并且显然具有心脏保护作用。 由于HCQ具有减少心脏病、减少心律不齐、减少血栓形成和降低胆固醇的能力,因此应被认为是潜在的治疗因COVID 19引起心脏损害的患者的研究药物。

参考文献(见英文原文)

阅读英文原文

翻译:【 一花一世界 】【Naomi (文花开) 】【 奔腾的长江 】校对&编辑:【Michelle】

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Seven
5 月 之前

希望能发起全球临床医生交流平台……

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joop12345
5 月 之前

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文喜
6 月 之前

这个结论非常鼓舞人心❗绝对是既打脸为医药集团站台的昧着良心的医生,又打脸这些医务人员背后的医药集团和政治集团‼️🦅🦅🦅

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Himalaya Rose Garden Team

“but those who hope in the Lord will renew their strength. They will soar on wings like eagles; they will run and not grow weary, they will walk and not be faint” 【Isaiah 40:31】 8月 24日