Vindication of HCQ

Let’s start with a quote from an op ed last month in the NY Daily News

Because of the medication’s politicization, and the pernicious tendency for dissenting perspectives to be silenced during the pandemic, data supporting hydroxychloroquine’s effectiveness have been almost inaudible. But a recent analysis pooling together results of randomized clinical trials testing hydroxychloroquine’s use in early COVID-19 infection should substantially raise the volume.

The hydroxychloroquine saga cannot be fully appreciated without first considering the unusual circumstances under which it arose. While the medical profession has always sustained debate over which treatments are best, the tenor of the hydroxychloroquine controversy is unique. Physicians who have advocated for its effectiveness have remained steadfast in their support of the medication, despite unsupportive clinical trials enrolling hospitalized patients, social media blackouts of their opinions, and a chorus of politicians and health officials telling them — and the country — that they’re not only wrong but reckless.

While physicians who hold marginalized or unpopular positions about treatments are often considered by peers to be motivated by profit or other self-serving interests, these physicians were unnoteworthy in that regard, and would largely have been considered “mainstream” prior to the pandemic. Their clinical experiences were dismissed as anecdotal, but consistently achieving patient outcomes that were markedly better than those reported around the country fueled their confidence and tenacity. The nation and the world may now benefit from their steadfastness.

Here’s a couple of papers which establish the life saving value in early hydroxychloroquine treatment. The first is the one referred to in the op-ed.

Randomized Controlled Trials of Early Ambulatory Hydroxychloroquine in the Prevention of COVID-19 Infection, Hospitalization, and Death: Meta-Analysis

Abstract

Objective–To determine if hydroxychloroquine (HCQ) reduces the incidence of new illness, hospitalization or death among outpatients at risk for or infected with SARS-CoV-2 (COVID-19). Design–Systematic review and meta-analysis of randomized clinical trials. Data sources–Search of MEDLINE, EMBASE, PubMed, medRxiv, PROSPERO, and the Cochrane Central Register of Controlled Trials. Also review of reference lists from recent meta-analyses. Study selection–Randomized clinical trials in which participants were treated with HCQ or placebo/standard-of-care for pre-exposure prophylaxis, post-exposure prophylaxis, or outpatient therapy for COVID-19. Methods–Two investigators independently extracted data on trial design and outcomes. Medication side effects and adverse reactions were also assessed. The primary outcome was COVID-19 hospitalization or death. When unavailable, new COVID-19 infection was used. We calculated random effects meta-analysis according to the method of DerSimonian and Laird. Heterogeneity between the studies was evaluated by calculation of Cochran Q and I2 parameters. An Egger funnel plot was drawn to investigate publication bias. We also calculated the fixed effects meta-analysis summary of the five studies. All calculations were done in Excel, and results were considered to be statistically significant at a two-sided threshold of P=.05. Results–Five randomized controlled clinical trials enrolling 5,577 patients were included. HCQ was associated with a 24% reduction in COVID-19 infection, hospitalization or death, P=.025 (RR, 0.76 [95% CI, 0.59 to 0.97]). No serious adverse cardiac events were reported. The most common side effects were gastrointestinal. Conclusion–Hydroxychloroquine use in outpatients reduces the incidence of the composite outcome of COVID-19 infection, hospitalization, and death. Serious adverse events were not reported and cardiac arrhythmia was rare. Systematic review registration–This review was not registered.

https://www.medrxiv.org/content/10.1101/2020.09.30.20204693v1

And

Pathophysiological Basis and Rationale for Early Outpatient Treatment of SARS-CoV-2 (COVID-19) Infection

Abstract

Approximately 9 months of the severe acute respiratory syndrome coronavius-2 (SARS-CoV-2 [COVID-19]) spreading across the globe has led to widespread COVID-19 acute hospitalizations and death. The rapidity and highly communicable nature of the SARS-CoV-2 outbreak has hampered the design and execution of definitive randomized, controlled trials of therapy outside of the clinic or hospital. In the absence of clinical trial results, physicians must use what has been learned about the pathophysiology of SARS-CoV-2 infection in determining early outpatient treatment of the illness with the aim of preventing hospitalization or death. This article outlines key pathophysiological principles that relate to the patient with early infection treated at home.

Therapeutic approaches based on these principles include 1) reduction of reinoculation, 2) combination antiviral therapy, 3) immunomodulation, 4) antiplatelet/antithrombotic therapy, and 5) administration of oxygen, monitoring, and telemedicine. Future randomized trials testing the principles and agents discussed will undoubtedly refine and clarify their individual roles; however, we emphasize the immediate need for management guidance in the setting of widespread hospital resource consumption, morbidity, and mortality.

https://www.amjmed.com/article/S0002-9343(20)30673-2/fulltext