A new study has found that the addition of the cholesterol-lowering drug atorvastatin or the blood pressure medication telmisartan to the standard COVID-19 treatment of lopinavir/ritonavir did not improve virological or clinical outcomes in patients with mild to moderate COVID-19 infection. This is a significant finding, as previous observational studies had suggested that statins and angiotensin II receptor blockers (ARBs) like telmisartan could have beneficial effects on COVID-19 severity and mortality. The researchers conducted a randomized controlled trial in Côte d’Ivoire to evaluate the impact of these drugs on SARS-CoV-2 viral load and clinical outcomes. The results, published in the journal Scientific Reports, provide important insights into the role of these commonly used medications in the management of COVID-19.
Investigating Potential COVID-19 Treatments
The COVID-19 pandemic has prompted researchers to explore a wide range of existing drugs for their potential to treat the disease. Among the promising candidates were statins, a class of medications commonly used to lower cholesterol, and angiotensin II receptor blockers (ARBs), which are used to manage high blood pressure. Observational studies had suggested that these drugs could have beneficial effects on COVID-19 outcomes, potentially by modulating the body’s inflammatory response or interfering with the SARS-CoV-2 virus’s ability to enter cells.
Randomized Trial in Côte d’Ivoire
To further investigate the potential of statins and ARBs in COVID-19 treatment, a team of researchers conducted a randomized controlled trial in Côte d’Ivoire. The study, known as INTENSE-COV, enrolled 294 adults with mild to moderate COVID-19 infection. Patients were randomly assigned to one of three treatment groups: the standard COVID-19 treatment of lopinavir/ritonavir (LPVr) alone, LPVr plus the ARB telmisartan, or LPVr plus the statin atorvastatin.
The primary endpoint of the study was a composite measure of “viro-inflammatory success,” defined as a combination of a high cycle threshold (Ct) value in the SARS-CoV-2 RT-PCR test, indicating a low viral load, and a normal C-reactive protein (CRP) level, which is a marker of inflammation. The researchers also tracked clinical outcomes, such as the time to resolution of COVID-19 symptoms and the need for hospitalization.
No Significant Improvements with Telmisartan or Atorvastatin
The results of the INTENSE-COV trial were disappointing. The researchers found no significant differences in the primary endpoint of viro-inflammatory success at day 11 between the three treatment groups. Approximately 46% of patients in the LPVr-only group achieved this outcome, compared to 43% in the LPVr plus telmisartan group and 43% in the LPVr plus atorvastatin group.
Similarly, the researchers found no significant differences in the time to resolution of COVID-19 symptoms or the need for hospitalization between the three groups. The addition of telmisartan or atorvastatin to the standard LPVr treatment did not improve virological or clinical outcomes in this patient population.
Table 1 Baseline characteristics, ANRS COV01 INTENSE-COV.
Implications and Future Research
The findings of the INTENSE-COV trial are in contrast with the results of many observational studies that had suggested a potential benefit of statins and ARBs in COVID-19. The researchers propose that the positive associations observed in those studies may have been due to “heavy indication bias,” meaning that the samples were not truly comparable.
This randomized controlled trial provides strong evidence that the addition of telmisartan or atorvastatin to the standard COVID-19 treatment does not improve outcomes in patients with mild to moderate disease. These results align with those of other recent randomized trials that have also failed to find a benefit of statins in COVID-19 patients.
Fig. 2
While the findings are disappointing, they are an important contribution to the scientific understanding of COVID-19 treatment. The researchers note that the study was limited by the exclusion of severe COVID-19 cases and the relatively low level of inflammation in the study population. Future research may explore the potential benefits of these medications in patients with more severe disease or higher levels of inflammation.
Broader Implications and Lessons Learned
The INTENSE-COV trial highlights the importance of well-designed randomized controlled trials in evaluating the efficacy of potential COVID-19 treatments. While observational studies can provide valuable insights, they are prone to biases that can lead to misleading conclusions. The rigorous methodology of the INTENSE-COV trial, with its randomized design and clearly defined endpoints, provides a more reliable assessment of the clinical utility of statins and ARBs in COVID-19 management.
This study also underscores the need for a comprehensive, evidence-based approach to the development of COVID-19 therapies. While the initial enthusiasm for repurposed drugs was understandable, the INTENSE-COV trial serves as a reminder that not all promising leads will ultimately pan out. As the scientific community continues to explore new treatment options, the lessons learned from this study will help guide future research and ensure that valuable resources are directed towards the most promising avenues.
Author credit: This article is based on research by Fabrice Bonnet, Adama Doumbia, Vanessa Machault, Frederic Nogbou Ello, Pantxika Bellecave, Corine Bernice Akpovo, Baba Toumany Sidibe, Laura Fernandez, Antoine Kouamé, Edgard Adjogoua, Mireille Dosso, Serge Niangoran, Valérie Journot, Serge Paul Eholié.
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