Study protocol for a multicentre, prospective cohort study of the association of angiotensin II type 1 receptor blockers on outcomes of coronavirus infection

IntroductionThe COVID-19 epidemic grows and there are clinical trials of antivirals. There is an opportunity to complement these trials with investigation of angiotensin II type 1 receptor blockers (ARBs) because an ARB (losartan) was effective in murine influenza pneumonia.Methods and analysisOur innovative design includes: ARBs; alignment with the WHO Ordinal Scale (primary endpoint) to align with other COVID-19 trials; joint longitudinal analysis; and predictive biomarkers (angiotensins I, 1–7, II and ACE1 and ACE2). Our hypothesis is: ARBs decrease the need for hospitalisation, severity (need for ventilation, vasopressors, extracorporeal membrane oxygenation or renal replacement therapy) or mortality of hospitalised COVID-19 infected adults. Our two-pronged multicentre pragmatic observational cohort study examines safety and effectiveness of ARBs in (1) hospitalised adult patients with COVID-19 and (2) out-patients already on or not on ARBs. The primary outcome will be evaluated by ordinal logistic regression and main secondary outcomes by both joint longitudinal modelling analyses. We will compare rates of hospitalisation of ARB-exposed versus not ARB-exposed patients. We will also determine whether continuing ARBs or not decreases the primary outcome. Based on published COVID-19 cohorts, assuming 15% of patients are ARB-exposed, a total sample size of 497 patients can detect a proportional OR of 0.5 (alpha=0.05, 80% power) comparing WHO scale of ARB-exposed versus non-ARB-exposed patients.Ethics and disseminationThis study has core institution approval (UBC Providence Healthcare Research Ethics Board) and site institution approvals (Health Research Ethics Board, University of Alberta; Comite d’etique de la recerche, CHU Sainte Justine (for McGill University and University of Sherbrook); Conjoint Health Research Ethics Board, University of Calgary; Queen’s University Health Sciences & Affiliated Hospitals Research Ethics Board; Research Ethics Board, Sunnybrook Health Sciences Centre; Veritas Independent Research Board (for Humber River Hospital); Mount Sinai Hospital Research Ethics Board; Unity Health Toronto Research Ethics Board, St. Michael’s Hospital). Results will be disseminated by peer-review publication and social media releases.Trial registration numberNCT04510623

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Problems in Coordinating and Accessing Primary Care for Attached and Unattached Patients Exacerbated During the COVID-19 Pandemic Year (the PUPPY Study): Protocol for a Longitudinal Mixed Methods Study (Preprint)

10.2196/preprints.29984 ◽

2021 ◽

Author(s):

Emily Gard Marshall ◽

Mylaine Breton ◽

Benoit Cossette ◽

Jennifer Isenor ◽

Maria Mathews ◽

...

Keyword(s):

Primary Care ◽

Mixed Methods ◽

Nova Scotia ◽

Research Ethics ◽

Health Research ◽

Health Sciences ◽

Mixed Methods Study ◽

Care Practice ◽

Research Ethics Board ◽

Unattached Patients

BACKGROUND The COVID-19 pandemic has significantly disrupted primary care in Canada, with many walk-in clinics and family practices initially closing or being perceived as inaccessible; pharmacies remaining open with restrictions on patient interactions; rapid uptake of virtual care; and reduced referrals for lab tests, diagnostics, and specialist care. OBJECTIVE The PUPPY Study (Problems in Coordinating and Accessing Primary Care for Attached and Unattached Patients Exacerbated During the COVID-19 Pandemic Year) seeks to understand the impact of the COVID-19 pandemic across the quadruple aims of primary care, with particular focus on the effects on patients without attachment to a regular provider and those with chronic health conditions. METHODS The PUPPY study builds on an existing research program exploring patients’ access and attachment to a primary care practice, pivoted to adapt to the emerging COVID-19 context. We intend to undertake a longitudinal mixed methods study to understand critical gaps in primary care access and coordination, as well as compare prepandemic and postpandemic data across 3 Canadian provinces (Quebec, Ontario, and Nova Scotia). Multiple data sources will be used such as a policy review; qualitative interviews with primary care policymakers, providers (ie, family physicians, nurse practitioners, and pharmacists), and patients (N=120); and medication prescriptions and health care billing data. RESULTS This study has received funding by the Canadian Institutes of Health Research COVID-19 Rapid Funding Opportunity Grant. Ethical approval to conduct this study was granted in Ontario (Queens Health Sciences & Affiliated Teaching Hospitals Research Ethics Board, file 6028052; Western University Health Sciences Research Ethics Board, project 116591; University of Toronto Health Sciences Research Ethics Board, protocol 40335) in November 2020, Québec (Centre intégré universitaire de santé et de services sociaux de l'Estrie, project 2020-3446) in December 2020, and Nova Scotia (Nova Scotia Health Research Ethics Board, file 1024979) in August 2020. CONCLUSIONS To our knowledge, this is the first study of its kind to explore the effects of the COVID-19 pandemic on primary care systems, with particular focus on the issues of patient’s attachment and access to primary care. Through a multistakeholder, cross-jurisdictional approach, the findings of the PUPPY study will inform the strengthening of primary care during and beyond the COVID-19 pandemic, as well as have implications for future policy and practice. INTERNATIONAL REGISTERED REPORT DERR1-10.2196/29984

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A Review of Angiotensin Receptor Blocker-based Therapies at all Levels of Cardiovascular Risk

European Cardiology Review ◽

10.15420/ecr.2011.7.4.254 ◽

2011 ◽

Vol 7 (4) ◽

pp. 254 ◽

Cited By ~ 1

Author(s):

Giuliano Tocci ◽

Lorenzo Castello ◽

Massimo Volpe ◽

◽

...

Keyword(s):

Angiotensin Ii ◽

Ventricular Hypertrophy ◽

Renin Angiotensin System ◽

Left Ventricular ◽

Clinical Settings ◽

Angiotensin Ii Receptor ◽

Angiotensin System ◽

Receptor Blockers ◽

Artery Disease

The renin–angiotensin system (RAS) has a key role in the maintenance of cardiovascular homeostasis, and water and electrolyte metabolism in healthy subjects, as well as in several diseases including hypertension, left ventricular hypertrophy and dysfunction, coronary artery disease, renal disease and congestive heart failure. These conditions are all characterised by abnormal production and activity of angiotensin II, which represents the final effector of the RAS. Over the last few decades, accumulating evidence has demonstrated that antihypertensive therapy based on angiotensin II receptor blockers (ARBs) has a major role in the selective antagonism of the main pathological activities of angiotensin II. Significant efforts have been made to demonstrate that blocking the angiotensin II receptor type 1 (AT1) subtype receptors through ARB-based therapy results in proven benefits in different clinical settings. In this review, we discuss the main benefits of antihypertensive strategies based on ARBs in terms of their efficacy, safety and tolerability.

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