Prospective meta-analysis protocol on randomised trials of renin-angiotensin system inhibitors in patients with COVID-19: an initiative of the International Society of Hypertension.

INTRODUCTION: Whether ACE inhibitors (ACEi) or angiotensin II receptor blocker (ARB) therapy should be continued, initiated or ceased in patients with COVID-19 is uncertain. Given the widespread use of ACEi/ARBs worldwide, guidance on the use of these drugs is urgently needed. This prospective meta-analysis aims to pool data from randomised controlled trials (RCTs) to assess the safety and efficacy of ACEi/ARB therapy in adults infected with SARS-CoV-2. METHODS AND ANALYSIS: RCTs will be eligible if they compare patients with COVID-19 randomised to ACEi/ARB continuation or commencement versuss no ACEi/ARB therapy; study duration ≥14 days; recruitment completed between March 2020 and May 2021. The primary outcome will be all-cause mortality at ≤30 days. Secondary outcomes will include mechanical ventilation, admission to intensive care or cardiovascular events at short-term follow-up (≤30 days) and all-cause mortality at longer-term follow-up (>1 month). Prespecified subgroup analyses will assess the effect of sex; age; comorbidities; smoking status; ethnicity; country of origin on all-cause mortality. A search of ClinicalTrials.gov has been performed, which will be followed by a formal search of trial registers, preprint servers, MEDLINE, EMBASE and Cochrane Central Register of Controlled Trials to identify RCTs that meet inclusion criteria. To date, a search of ClinicalTrials.gov identified 21 potentially eligible trials for this meta-analysis. We will request trial investigators/sponsors to contribute standardised grouped tabular outcome data. ETHICS AND DISSEMINATION: Ethics approval and informed consent will be the responsibility of the individual RCTs. Dissemination of results will occur by peer-reviewed publication. The results of our analysis can inform public health policy and clinical decision making regarding ACEi/ARB use in patients with COVID-19 on a global scale.

Low total cholesterol is associated with increased major adverse cardiovascular events in men aged ≥70 years not taking statins.

OBJECTIVE: Low levels of total cholesterol (TC) are associated with adverse outcomes in older populations. Whether this phenomenon is independent of statin use is unknown. We investigated the association between low TC levels and long-term major adverse cardiovascular events (MACE) in a prospective study of men aged ≥70 years without ischaemic heart disease (IHD) and whether this was influenced by statin use. METHODS: The CHAMP (Concord Health and Ageing in Men Project) cohort is a prospective cohort study of community-dwelling men aged ≥70 years. The relationship between TC and long-term MACE was analysed using Cox-regression modelling adjusted for comorbidities and stratified by statin use. RESULTS: The study cohort comprised 1289 men (mean (±SD) age, 77.0±5.5 years; mean follow-up, 6.4±2.7 years). Decreasing TC level was associated with increased comorbidity burden, frailty and MACE (linear trend p<0.001). In men not on statin therapy (n=731), each 1 mmol/L decrease in TC was associated with increased MACE (HR 1.27, 95% CI 1.10 to 1.45, p=0.001) and mortality (HR 1.22, 95% CI 1.03 to 1.44, p=0.02) adjusted for comorbidities. In contrast, low TC in men on statins (n=558) was not associated with MACE (HR 0.91, 95% CI 0.74 to 1.11) or mortality (HR 0.86, 95% CI 0.68 to 1.09). CONCLUSION: Low TC is associated with increased risk of MACE in older men without IHD who are not taking statin therapy but not in those on statins.