Medications Associated with Lower Mortality in a SARS-CoV-2 Positive Cohort of 26,508 Veterans

BACKGROUND: Many severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) positive patients take commonly prescribed medications with properties which may affect mortality. OBJECTIVE: Assess if common medications postulated to affect clinical outcomes are associated with mortality in SARS-CoV-2 positive patients in the Veterans Health Administration (VHA). DESIGN: Observational national cohort analysis. PARTICIPANTS: Consecutive 26,508 SARS-CoV-2 positive Veterans (7% of 399,290 tested from March 1 to September 10, 2020) constitute the study cohort. MAIN MEASURES: The primary outcome was 30-day mortality from the first positive SARS-CoV-2 test date. In patients receiving medications or drug pairs within 2 weeks post-SARS-CoV-2 positive test, 30-day mortality was estimated as relative risk (RR) on the log-binomial scale or using multinomial models with and without adjusting for covariates. KEY RESULTS: The 26,508 SARS-CoV-2 positive patients were predominantly male (89%) and White (59%), and 82% were overweight/obese. Medications associated with decreased 30-day mortality risk included the following: metformin (aRR, 0.33; 95% CI, 0.25–0.43), colchicine, angiotensin-converting-enzyme inhibitors (ACEi), angiotensin II receptor blockers, statins, vitamin D, antihistamines, alpha-blockers, anti-androgens, and nonsteroidal anti-inflammatory drugs (aRR, 0.69; 95% CI, 0.61–0.78). The effect of co-prescribed medications on 30-day mortality risk revealed the lowest risk for combined statins and metformin (aRR, 0.21; 95% CI, 0.15–0.31), followed by ACEi and statins (aRR, 0.25; 95% CI, 0.18–0.35), ACEi and metformin (aRR, 0.26; 95% CI, 0.17–0.40), antihistamines and NSAIDs (aRR, 0.41; 95% CI, 0.32–0.52), and in men, combined alpha-blockers and anti-androgens (aRR, 0.51; 95% CI, 0.42–0.64). CONCLUSIONS: In this large national cohort, treatment of SARS-CoV-2 positive patients with individual or co-prescribed metformin and statins, ACEi and statins (or metformin) and other medications was associated with a markedly decreased 30-day mortality and can likely be continued safely. Clinical trials may assess their therapeutic benefit. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s11606-022-07701-3.