Elpida Kontsioti

and 4 more

AIM: To explore the level of agreement on drug-drug interaction (DDI) information listed in three major online drug information resources (DIRs) in terms of: (1) interacting drug pairs; (2) severity rating; (3) evidence rating and (4) clinical management recommendations. METHODS: We extracted DDI information from the British National Formulary (BNF), Thesaurus, and Micromedex. Following drug name normalisation, we estimated the overlap of the DIRs. We annotated clinical management recommendations either manually, where possible, or through application of a machine learning algorithm. RESULTS: The DIRs contained 51,481 (BNF), 38,037 (Thesaurus), and 65,446 (Micromedex) drug pairs involved in DDIs. The number of common DDIs across the three DIRs was 6,970 (13.54% of BNF, 18.32% of Thesaurus, and 10.65% of Micromedex). Micromedex and Thesaurus overall showed higher levels of similarity in their severity ratings, while the BNF agreed more with Micromedex on the critical severity ratings and with Thesaurus on the least significant ones. Evidence rating agreement between BNF and Micromedex was generally poor. Variation in clinical management recommendations was also identified, with some categories (i.e. Monitor and Adjust dose) showing higher levels of agreement compared to others (i.e. Use with caution, Wash-out, Modify administration). CONCLUSIONS: There is considerable variation in the DDIs included in the examined DIRs, together with variability in categorisation of severity and clinical advice given. DDIs labelled as critical are more likely to appear in multiple DIRs. Such variability in information could have deleterious consequences for patient safety, and there is a need for harmonisation and standardisation.

Innocent Asiimwe

and 5 more

Aims: To update our previously reported systematic review and meta-analysis of observational studies on cardiovascular drug exposure and COVID-19 clinical outcomes by focusing on newly published randomized controlled trials (RCTs). Methods: More than 500 databases were searched between 1-Nov-2020 and 2-Oct-2021 to identify RCTs that were published after our baseline review. One reviewer extracted data with other reviewers verifying the extracted data for accuracy and completeness. Results: After screening 22,414 records, we included 24 and 21 RCTs in the qualitative and quantitative syntheses, respectively. The most investigated drug classes were angiotensin-converting enzyme inhibitors (ACEIs)/angiotensin receptor blocker (ARBs) and anticoagulants, investigated by 10 and 11 studies respectively. In meta-analyses, ACEI/ARBs did not affect hospitalization length (mean difference/MD -0.42, 95% CI -1.83; 0.98 days, n=1183), COVID-19 severity (risk ratio/RR 0.90, 95% CI 0.71; 1.15, n=1661) and mortality (RR 0.92, 95% CI 0.58; 1.47, n=1646). Therapeutic anticoagulation also had no effect (hospitalization length MD -0.29, 95% CI -1.13 to 0.56 days, n=1449; severity RR 0.86, 95% CI 0.70;1.04, n=2696; and, mortality RR 0.93, 95% CI 0.77;1.13, n=5689). Other investigated drug classes were antiplatelets (aspirin, 2 trials), antithrombotics (sulodexide, 1 trial), calcium channel blockers (amlodipine, 1 trial) and lipid modifying drugs (atorvastatin, 1 trial). Conclusion: Moderate- to high-certainty RCT evidence suggests that cardiovascular drugs such as ACEIs/ARBs are not associated with poor COVID-19 outcomes, and should therefore not be discontinued. These cardiovascular drugs should also not be initiated to treat or prevent COVID-19 unless they are needed for an underlying currently approved therapeutic indication.

Innocent Asiimwe

and 5 more

Aims: To continually evaluate the role of cardiovascular drugs in COVID-19 clinical outcomes. Methods: Eligible publications were identified from >500 databases on 1-Nov-2020. One reviewer extracted data with 20% of the records independently extracted/evaluated by a second reviewer. Results: Of 52,735 screened records, 429 and 390 studies were included in the qualitative and quantitative syntheses, respectively. The most-reported drugs were angiotensin-converting enzyme inhibitors (ACEIs)/angiotensin receptor blockers (ARBs) with ACEI/ARB exposure having borderline association with positive COVID-19 status (OR 1.14, 95% CI 1.00–1.31). Among COVID-19 patients, unadjusted estimates showed that ACEI/ARB exposure was associated with hospitalization (OR 1.76, 1.34–2.32), disease severity (OR 1.41, 1.27–1.56) and all-cause mortality (OR 1.22, 1.12–1.33) but not hospitalization length (mean difference -0.27, -1.36; 0.82 days). After adjustment, ACEI/ARB exposure was not associated with positive COVID-19 status (OR 0.92, 0.71–1.19), hospitalization (OR 0.93, 0.70–1.24), disease severity (OR 1.05, 0.81–1.38), or all-cause mortality (OR 0.85, 0.71–1.01). Similarly, subgroup analyses involving only hypertensive patients revealed that ACEI/ARB exposure was not associated with positive COVID-19 status (OR 0.93, 0.79–1.09), hospitalization (OR 0.84, 0.58–1.22), hospitalization length (mean difference -0.14, -1.65; 1.36 days), disease severity (OR 0.92, 0.76–1.11) while it decreased the odds of dying (OR 0.76, 0.65–0.88). A similar trend was observed for other cardiovascular drugs. However, the validity of these findings is limited by a high level of heterogeneity and serious risk of bias. Conclusion: Cardiovascular drugs are not associated with poor COVID-19 outcomes in adjusted analyses. Patients should continue taking these drugs as prescribed.