Statins and clinical outcomes with COVID-19: Meta-analyses of observational studies

Abstract

Aims People with cardiovascular disease or risk factors are at increased risk when exposed to SARS-CoV-2. Most are treated with statins, but the impact of these drugs on clinical outcomes of COVID-19 remains unclear. This report is therefore based on meta-analyses of retrospective observational studies aimed at investigating the impact of previous statin therapy in patients hospitalized for COVID-19. Methods In studies reporting on the clinical outcomes of COVID-19 in statin users vs non-users, two endpoints have been used—in-hospital death rates, and disease severity as assessed by admission to intensive care units (ICUs)—with a special focus on patients with diabetes. Results Regarding mortality, 13 studies were included in the meta-analysis for a total of 10,829 statin users (2517 deaths) and 31,893 non-users (7516 deaths): univariate analysis showed no statistically significant reduction in deaths (OR: 0.97, 95% CI: 0.92–1.03), although between-study heterogeneity was high (I² = 97%). As for disease severity, 11 studies were selected for a total of 3462 statin users (724 endpoints) and 10,560 non-users (1763 endpoints): here again, univariate analysis showed no reduction in severity (OR: 1.09, 95% CI: 0.99–1.22; I² = 93%). Collectively, in 10 studies using multivariable analysis adjusted for the more prevalent baseline risk factors among statin users, lower OR values were reported than with univariate analyses (0.73 ± 0.31 vs 1.44 ± 0.84, respectively; P = 0.0028; adjusted OR: P = 0.0237 vs non-users). Limited but conflicting findings were observed for diabetes patients. Conclusion Although no significant reductions in either in-hospital mortality or COVID-19 severity were reported among statin users compared with non-users after univariate comparisons, such reductions were observed after adjusting for confounding factors. These highly heterogeneous observational findings now require confirmation by ongoing randomized clinical trials.

Increased mortality risk associated with statins in the CORONADO study

“…Statin treatment has been shown to be beneficial in randomized controlled trials of particular patient groups, such as patients with diabetes, who are most at risk of COVID-19. In addition, the majority of analyses concerning mortality risk during COVID-19 have thus far indicated a beneficial or neutral effect of statin use [2]. Large studies from China [3] and the US [4,5], for example, indicated a 12-46% reduced mortality risk among statin users, including those with diabetes, and a UK-wide analysis of 2.9 million patients with T2D (mean age: 70 years) found that the risk of death due to COVID-19 was 28% lower among statin users [5].…”

Protecting older patients with cardiovascular diseases from COVID-19 complications using current medications

“…Statin treatment was associated with a significant 38% lower risk of death in type 2 diabetes, and nonsignificant 18% lower risk in type 1 diabetes. A meta-analysis of other serious complications (13 studies about death risk) has been recently published [ 59 ]. Patients in these studies have been usually upper middle-aged, average age being around 60 years.…”

“…Because observational studies of statins have not been unequivocal, confirmation from RCTs has been called for [ 59 ]. However, if a potential benefit of statin treatment is due to long term, ongoing use, then trials randomising patients during acute COVID-19 will not identify this benefit.…”

Hospital mortality in COVID-19 patients in Belgium treated with statins, ACE inhibitors and/or ARBs

“…Another study showed that outpatient statin treatment was associated with decreased COVID-19 mortality, although only 77% of outpatient-treated patients continued statin treatment after hospital admission [71]. If statins are withdrawn at the time of hospital admission, their beneficial effects are likely to be reduced [75, 76]. Thus, statin treatment should be continued (or started) after hospital admission [76, 77].…”

“…If statins are withdrawn at the time of hospital admission, their beneficial effects are likely to be reduced [75, 76]. Thus, statin treatment should be continued (or started) after hospital admission [76, 77]. Whether the same is true for ACEI and ARB treatment is uncertain [78, 79].…”