With hydroxychloroquine Chloroquine, Existence Azithromycin Or ClarithromycinAccording to a major new international study, there is no benefit in treating COVID-10 patients and is instead associated with increased ventricular arrhythmias and mortality.
In the largest observational study of this type, which included nearly 100,000 people at 671 hospitals on six continents, researchers found results for 15,000 patients with COVID-19 combined with hydroxychloroquine and chloroquine alone or in combination with macrolides. , Compared to 80,000 control patients with COVID- 19 who do not receive these agents.
Treatment with either of these agents, alone or in combination, was associated with increased mortality during hospitalization: Mortality rates were greater than 16% in the treatment group to almost 24% compared to approximately 10% in patients in the control group. It was in the range of%.
Patients treated with hydroxychloroquine and macrolides have the highest incidence of serious arrhythmias, and even after considering demographic factors and comorbidities, this combination has a five-fold greater risk of developing serious arrhythmias. Found to be associated with an increase in excess of hospitalization.
“This real-world study is the largest ever and covers 100,000 patients. [with COVID-19] It’s spread across six continents, with only a few hints of benefits found, only risks, and the data is very simple, “said co-author of the study, head of the Heart Center of the University Hospital in Zurich, Switzerland. Said one Frank Ruschitzka doctor. theheart.org | Medscape Cardiology.
Research Published online May 22 Lancet.
“Inconclusive” evidence
The lack of an effective treatment for COVID-19 has led to the “diverting” of the antimalarial drug chloroquine and its analog hydroxychloroquine, which are used to treat autoimmune diseases. Based on anecdotal evidence or an open-label, randomized trial, “mostly inconclusive,” the authors write.
An additional drug used to treat COVID-19 is a second generation macrolide (azithromycin or clarithromycin) in combination with chloroquine or hydroxychloroquine, “despite limited evidence,” ventricular The authors say there is a risk of arrhythmia.
“Our main question is whether there are benefits associated with the use of combination regimens with hydroxychloroquine, chloroquine, or macrolides in the treatment of COVID-19, and, if not beneficial, harm. Lead author Mandeep R. Mehra, MD, MD, William Harvey Distinguished Chair in Advanced Cardiovascular Medicine at Brigham and Women’s Hospital in Boston, Massachusetts, theheart.org | Medscape Cardiology.
671 hospitals, including investigators hospitalized between December 20, 2019 and April 14, 2020, with confirmed COVID-19 infection (n = 96,032, mean age 53.8 years, 46.3% women) We used data from a multinational registry consisting of.
They also collected data on demographics, underlying comorbidities and medical history, and medications patients were taking at baseline.
Patients treated (n = 14,888) were divided into 4 groups: patients who received chloroquine alone (n = 1868), patients who received chloroquine with macrolide (n = 3783), and hydroxychloroquine alone. Patients who received (n = 3016) and patients who received hydroxychloroquine Macrolides (n = 6221).
The remaining patients (n = 81,144) who were not treated with these regimens were considered control groups.
Most patients (65.9%) come from North America, followed by Europe (17.39%), Asia (7.9%), Africa (4.6%), South America (3.7%), and Australia (0.6%). Most (66.9%) were white, followed by Asians (14.1%), blacks (9.4%), and Hispanics (6.2%).
Includes comorbidities and underlying disorders obesity, Hyperlipidemia, and High blood pressure It is about 30%.
Comorbidity and its underlying diseases
| Status | percent |
|---|---|
| Obesity (BMI ≥ 30 kg / m2) | 30.7 |
| hyperlipidaemia | 31.4 |
| High blood pressure | 26.9 |
| Diabetes | 13.8 |
| Chronic obstructive pulmonary disease | 3.3 |
| Underlying immunosuppressive state | 3.0 |
| Ex smoker | 17.2 |
| Current smoker | 9.9 |
| History of coronary artery disease | 12.6 |
| History of congestive heart failure | 2.5 |
| Arrhythmia history | 3.5 |
The researchers performed multiple analyzes to control confounding variables, including Cox proportional hazards regression and propensity score matching analysis.
“In our observational studies, we could always have confounding, so we performed a consensus analysis based on propensity scores,” explains Ruschitzka.
There were no significant differences in demographics and distribution of comorbidities between groups.
As good as possible
“We found no benefit in any of the four treatment regimens for inpatients with COVID-19, but compared to controls, these patients had higher mortality and noticed severe ventricular arrhythmias. “Mehra reported.
Approximately 9.3% of patients in the control group died during hospitalization, compared with 16.4% of patients treated with chloroquine alone, 18.0% of patients treated with hydroxychloroquine alone, and chloroquine and macrolides. 22.2% of patients and 23.8% treated with hydroxychloroquine and macrolides.
After considering confounding variables, the researchers estimated that the risk of excess mortality due to the use of drug therapy ranged from 34% to 45%.
Patients treated with any of the four regimens sustain a more severe arrhythmia compared to the control group (0.35), with the greatest increase in the group treated with hydroxychloroquine and macrolide combination (8.1%) , Followed by chloroquine macrolide (6.5%), hydroxychloroquine alone (6.1%), chloroquine alone (4.3%).
“While the study was observable, the signal was robust, consistent across all regions of the world in diverse populations, and I was fairly relieved that the signal was not muted in some regions,” he said. Mehra commented.
“Two months ago, we were all wondering how to treat patients with COVID-19. [hydroxychloroquine] There was some anecdotal evidence, but now I have more than two months of experience and tried to provide science with some answers, “Ruschitzka said.
“There was no definite answer because this was not a randomized controlled trial, but the data provided by this [large, multinational] Real-world research is as good as it gets, and it’s the best data we have. ”
“Science speaks for itself”
Comments on research theheart.org | Medscape Cardiology, Dr. Christian Funk Brentano, MD, from the Hospital Petit Salpetriere in Paris, France and the University of Sorbonne, said the study was observable and therefore not as reliable as a randomized controlled trial, but “ still well documented. We used a number of people, and some sensitometric methods, all showing the same results. ”
Co-author of Funck-Brentano Accompanying editorial “There is currently no evidence that hydroxychloroquine and chloroquine work alone or in combination with macrolides, and there is evidence that they could harm and kill people,” he said.
Comments on research theheart.org | Medscape Cardiology, “ One observational study alone does not lead to a solid clinical recommendation, but doctors and public health officials can be aware of the findings, ” said Dr. David Holtgrave, Dean of Albany School of Public Health. I think of the peer-reviewed observational studies so far NIH COVID-19 Treatment Guidelines And FDA Statement on Drug Safety “While waiting for the results of randomized clinical trials of these agents for the treatment of COVID-19, about hydroxychloroquine to inform their decision-making,” Holtgrave, who was not involved in the study, said.
To his knowledge, “there are no published studies on the prophylactic use of these drugs to prevent COVID-19,” he added.
Mehra said that the basic principle of medical practice is “do no harm first” and “even in situations where we believe that a desperate illness requires desperate action, the responsible physician will take a step back and Need to ask if is doing any harm, we may say not, but I don’t think it would be wise to push something like this in the absence of good efficacy data. “
Ruschitzka added that those encouraging the use of these drugs should “review their decisions based on today’s data and let science tell itself”.
This study was supported by the William Harvey Distinguished Chair in Advanced Cardiovascular Medicine at Brigham and Women’s Hospital in Boston, Massachusetts, USA. Mehra reports personal rates from Abbott, Medtronic, Janssen, Mesoblast, Portola, Bayer, Baim Institute for Clinical Research, NuPulseCV, FineHeart, Leviticus, Roivant, and Triple Gene. Ruschitzka was paid for time spent as a committee member in clinical trials, advisory boards, other forms of consulting, and lectures and presentations. These payments were made directly to the University of Zurich and no personal payments were received in connection with these trials and other activities. Funk-Brentano, His co-author, and Holtgrave have not declared any relevant financial relationships.
Lancet.. Published May 22, 2020 Online. paper, comment
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