1.
Cardiovascular drugs and COVID-19 clinical outcomes: a systematic review and meta-analysis of randomized controlled trials
Asiimwe IG, Pushpakom SP, Turner RM, Kolamunnage-Dona R, Jorgensen AL, Pirmohamed M
British journal of clinical pharmacology. 2022
Abstract
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.
2.
Immunomodulatory interventions for focal epilepsy syndromes
Walker L, Pirmohamed M, Marson AG
Cochrane Database of Systematic Reviews. 2013;6:CD009945.
Abstract
BACKGROUND Epilepsy is a common neurological disorder made particularly disabling in the 30% of patients who do not achieve freedom from seizures despite multiple trials of antiepileptic drugs (AEDs). Experimental and clinical evidence supports a role for inflammatory pathway activation in the pathogenesis of epilepsy which, if effectively targeted by immunomodulatory interventions, highlights a potentially novel therapeutic strategy. OBJECTIVES To evaluate the efficacy and tolerability of immunomodulatory interventions as additional therapy in focal epilepsy syndromes in adults. SEARCH METHODS We searched the Cochrane Epilepsy Group Specialised Register (2 August 2012), the Cochrane Central Register of Controlled Trials (CENTRAL, The Cochrane Library 2012, Issue 7), MEDLINE (Ovid, 1946 to July week 3, 2012), the World Health Organization's International Clinical Trials Registry (2 August 2012), ClinicalTrials.gov (2 August 2012) and the Current Controlled Trials International Standard Randomised Controlled Trial Number Register (2 August 2012). There were no language restrictions. We reviewed the bibliographies of retrieved studies to search for additional reports of relevant studies. SELECTION CRITERIA Randomised controlled trials of add-on immunomodulatory drug interventions for the treatment of focal epilepsy in adults (aged over 16 years). DATA COLLECTION AND ANALYSIS Three review authors independently assessed trial quality and extracted data. The primary outcomes were 50% or greater reduction in seizure frequency and seizure freedom; the secondary outcomes included serious and commonly occurring adverse effects, allergy, withdrawal and quality of life assessment. MAIN RESULTS We identified one study involving both children and adults (n=61) that assessed the effect of intravenous immunoglobulin (IVIG) as add-on therapy for the treatment of epilepsy. The authors found no significant difference between IVIG and placebo for the primary outcomes of seizure freedom or 50% or greater reduction in seizure frequency. The study reported a statistically significant effect for global blind assessment (rating scale involving multiple seizure-related parameters) in favour of IVIG. Secondary outcomes including adverse effects and allergies were not demonstrated. AUTHORS' CONCLUSIONS It is not possible to draw any conclusions about the role of immunomodulatory interventions in reducing seizure frequency or the safety of these agents in adults with epilepsy. Further randomised controlled trials are needed.