(A-244) Drug-Drug Interactions between Nirmatrilvir-Ritonavir and Cardiovascular Agents: A Scoping Review

Background: While drug-drug interactions (DDIs) have been extensively evaluated for ritonavir, the potential DDIs of nirmatrelvir-ritonavir (NMVr), a widely used and guideline-based oral therapy for treatment of COVID-19, remain insufficiently characterized in term of clinical significance and epidemiological patterns. Given the frequent occurrence of DDIs between NMVr and cardiovascular medications, understanding these interactions is essential for optimize patient care, minimize adverse effects, and ensure the safety and efficacy of concomitant pharmacological treatments.

Objectives: To systematically review and synthesize existing evidence on DDIs between NMVr and cardiovascular drugs.

Methods: A comprehensive literature search was conducted following the PRISMA-ScR guideline from electronic databases, including PubMed, Embase, Web of Science, ScienceDirect (Elsevier), and Medline. Search terms included “Paxlovid,” “nirmatrelvir,” “ritonavir,” “DDI,” “drug-drug interaction,” “cardiovascular drug,” “antihypertensive,” “statin,” and “anticoagulant.” Eligible human observation studies or clinical trials reporting DDIs involving NMVr and cardiovascular drugs were included. Exclusion criteria encompassed non-English publications, pediatric populations studies, and case reports. Two independent reviewers screened titles, abstracts, and full texts with any discrepancies resolved by the third reviewer. Data extraction focused on participant’ demographics, clinical characteristics, prevalence and types of DDIs, implicated cardiovascular medications, and recommended management strategies.

Results: After screening 117 abstracts, six studies were included, comprising five observational studies and one clinical trial. Four studies assessed DDIs involving statins with reported prevalence ranging from 12% to 55%, and calcium channel blockers (CCBs) from 34% to 40%. Three studies focused on anticoagulants with prevalence between 20% to 30%. A single-center longitudinal study of 634 adult patients indicated that 54.8% of all NMVr-related DDIs involved cardiovascular drugs. Additionally, a U.S. national claims data study identified atorvastatin, simvastatin, and rosuvastatin as the most frequently implicated cardiovascular drugs. The most frequently recommended strategies for mitigating DDIs included temporarily discontinuing or dose adjustments of cardiovascular drugs based on pharmacokinetic properties.

Conclusions: The most frequently observed DDIs between NMVr and cardiovascular medications were with statins, followed by CCBs and anticoagulants. Further research is warranted to evaluate the safety and effectiveness of concomitant medication with NMV/r, particularly in patients with comorbidities.