Publications of the Week (May 11, 2022)

2022-05-11

Nirmatrelvir in nonhospitalized adults at high risk of severe COVID-19

Hammond J, Leister-Tebbe H, Gardner A, et al; EPIC-HR Investigators. Oral Nirmatrelvir for High-Risk, Nonhospitalized Adults with Covid-19. N Engl J Med. 2022 Apr 14;386(15):1397-1408. doi: 10.1056/NEJMoa2118542. Epub 2022 Feb 16. PMID: 35172054; PMCID: PMC8908851.

Background: Nirmatrelvir, when combined with the pharmacologic enhancer ritonavir, is an oral antiviral drug that may limit disease progression and severity in patients with symptomatic coronavirus disease 2019 (COVID-19), with the potential to reduce hospitalizations.

Methods: This randomized controlled trial recruited symptomatic, unvaccinated, nonhospitalized adults at high risk of progression to severe COVID-19, who were allocated in a double-blind manner to receive an active drug (nirmatrelvir 300 mg plus ritonavir 100 mg) or placebo twice daily for 5 days. The main outcomes were COVID-19–related hospitalization, death from any cause, and safety over a 28-day period.

Results: There were 2246 patients studied: 1120 patients in the nirmatrelvir plus ritonavir group and 1126 in the placebo group. In the final analysis of 1379 patients, those taking nirmatrelvir plus ritonavir had an 88.9% lower relative risk of hospitalization or death (0.7% vs 6.5%, absolute difference of –5.81 percentage points; 95% CI, –7.78 to –3.84). There were 13 deaths, all occurring in the placebo group. The incidence of adverse events was similar in both groups (any adverse events, 22.6% vs 23.9%; serious adverse events 1.6% vs 6.6%). Dysgeusia (5.6% vs 0.3%) and diarrhea (3.1% vs 1.6%) occurred more frequently in the nirmatrelvir plus ritonavir than in the placebo group.

Conclusions: The authors concluded that in nonhospitalized, nonvaccinated patients with symptomatic COVID-19, treatment with nirmatrelvir plus ritonavir was effective, associated with an 89% reduction in disease progression leading to hospitalization or death, and appeared to be safe.

McMaster editors’ comment: Nirmatrelvir plus ritonavir (Paxlovid) should be considered in nonhospitalized, symptomatic COVID-19 patients with the following caveats: (1) it should be used in patients in whom the onset of symptoms occurred within 5 days and who have comorbidities—based on clinical judgement—that place them at increased risk of disease progression; (2) the reported results apply to nonvaccinated patients, and the absolute effect is likely smaller among those previously vaccinated; (3) the ritonavir component of Paxlovid is associated with multiple potential drug-drug interactions, including with selected anticoagulants, statins, and cardiac drugs (eg, beta-blockers, calcium channel blockers); in such patients, an individualized approach to management should be considered, which may include withholding an agent (eg, statin) or switching drugs (eg, rivaroxaban to edoxaban) for a 7-day period after initiation of Paxlovid.

See also

We would love to hear from you

Comments, mistakes, suggestions?

We use cookies to ensure you get the best browsing experience on our website. Refer to our Cookies Information and Privacy Policy for more details.