ACEI or ARB and COVID-19 Severity and Mortality in US Veterans

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

Get a concise snapshot of the trial, including recruitment status, study phase, enrollment targets, and key timeline milestones.

Recruitment Status

COMPLETED

Total Enrollment

22213 participants

Study Classification

OBSERVATIONAL

Study Start Date

2020-01-19

Study Completion Date

2020-12-31

Brief Summary

Review the sponsor-provided synopsis that highlights what the study is about and why it is being conducted.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the virus responsible for COVID-19, enters type II pneumocytes using angiotensin-converting enzyme 2 (ACE2). It is unclear whether ACE inhibitors (ACEIs) and angiotensin receptor blockers (ARBs) increase, decrease, or have no significant effect on ACE2 expression or activity. Therefore, ACEI and ARB may be harmful, beneficial, or have no impact on Coronavirus Disease 2019 severity and mortality. The Specific Aims of this observational study are: (1) Among SARS-CoV-2-positive outpatients, compare all-cause hospitalization and mortality rates between: 1.1 Current users of a range of doses of ACEI/ARB- vs. non- ACEI/ARB-based regimens, and 1.2 Current users of a range of doses of ACEI- vs. ARB-based regimens, and (2) Among those hospitalized for COVID-19, compare all-cause mortality between: 2.1 Current users of a range of doses of ACEI/ARB- vs. non- ACEI/ARB-based regimens, and 2.2 Current users of a range of doses of ACEI- vs. ARB-based regimens.

Related Clinical Trials

Explore similar clinical trials based on study characteristics and research focus.

Elimination or Prolongation of ACE Inhibitors and ARB in Coronavirus Disease 2019

NCT04338009

COVID-19

COMPLETED NA

The Effect of RAAS Blockers on ACE2 Levels

NCT05418361

Renin-Angiotensin System

COMPLETED

Anti-Proteinuric Response to ACEI, ARB and Diuretics Combination.

NCT00200694

Heavy Proteinuria

TERMINATED PHASE4

Treatment of Angiotensin Peptide (1-7) for COVID-19

NCT04375124

COVID-19

COMPLETED NA

The Influence of Angiotensin Converting Enzyme Inhibitors and Angiotensin Receptor Blockers on Renal Function in Patients Undergoing Non-emergent Coronary Angiography

NCT01071642

Blood Pressure

COMPLETED NA

Detailed Description

Dive into the extended narrative that explains the scientific background, objectives, and procedures in greater depth.

The Coronavirus Disease 2019 (COVID-19) pandemic has killed \>129,000 Americans as of June 30, 2020. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the virus responsible for COVID-19, enters type II pneumocytes using angiotensin-converting enzyme 2 (ACE2). ACE inhibitors (ACEIs) and angiotensin receptor blockers (ARBs) may increase ACE2 expression. Theoretically, if ACEI/ARB use increases ACE2 expression in the lungs, ACEI/ARBs could promote SARS-CoV-2 entry into type II pneumocytes and worsen COVID-19 infection. In contrast, other evidence suggests that ACEI/ARBs may mitigate virus-induced inflammatory responses in the lungs by upregulating ACE2-mediated generation of the vasodilator and anti-inflammatory protein angiotensin-(1-7), thereby preventing tissue damage. Few data exist on the direction or magnitude of the association between ACEI/ARB use and COVID-19 severity, and whether these associations differ between ACEIs and ARBs. Because ACEI/ARBs are among the most commonly used prescription medications, it is critical to determine if ACEI/ARB users have a differential risk of more severe COVID-19 infection compared to non-users. The objective of this study is to reduce morbidity and mortality of the COVID-19 pandemic by generating timely evidence on the direction and magnitude of the association between ACEI/ARB use and COVID-19 severity and mortality.

Conditions

See the medical conditions and disease areas that this research is targeting or investigating.

Hypertension COVID

Study Design

Understand how the trial is structured, including allocation methods, masking strategies, primary purpose, and other design elements.

Observational Model Type

COHORT

Study Time Perspective

RETROSPECTIVE

Study Groups

Review each arm or cohort in the study, along with the interventions and objectives associated with them.

1.1 Outpatient SARS-CoV-2 Positive, ACEI/ARB vs non-ACEI/ARB

Among Veterans with treated hypertension and without compelling indications who test positive for SARS-CoV-2, compare all-cause hospitalization and all-cause mortality rates between current users of a range of doses of ACEI/ARB- vs. non-ACEI/ARB-based regimens.

ACEI/ARB

Intervention Type DRUG

Veterans will be categorized as exposed to ACEI/ARB if they have one or more pharmacy fills for an oral ACEI or an ARB in the 90 days (± 14 days) prior to each Veteran's index date. Sacubitril/valsartan (Brand name: Entresto®) will be excluded from ARB exposures.

Non-ACEI/ARB

Intervention Type DRUG

Veterans will be categorized as exposed to a non-ACEI/ARB if they have one or more pharmacy fills for an oral non-ACEI or ARB medication in the 90 days (± 14 days) prior to each Veteran's index date and NO fills for an ACEI/ARB medication in the 90 days (± 14 days) prior to each Veteran's index date. Specific drug classes include: aldosterone receptor antagonist, beta-blocker, calcium channel blocker, centrally-acting drug, direct arterial vasodilator, direct renin inhibitor, thiazide diuretic, loop diuretic, and potassium sparing diuretic.

1.2 Outpatient SARS-CoV-2 Positive, ACEI vs. ARB

Among Veterans with treated hypertension who test positive for SARS-CoV-2, compare all-cause hospitalization and all-cause mortality rates between current users of a range of doses of ACEI- vs. ARB-based regimens.

ACEI

Intervention Type DRUG

Veterans will be categorized as exposed to an ACEI if they have one or more pharmacy fills for an oral ACEI in the 90 days (± 14 days) prior to each Veteran's index date and NO fills for an oral ARB in the 90 days (± 14 days) prior to each Veteran's index date.

ARB

Intervention Type DRUG

Veterans will be categorized as exposed to an ARB if they have one or more pharmacy fills for an oral ACEI in the 90 days (± 14 days) prior to each Veteran's index date and NO fills for an oral ACEI in the 90 days (± 14 days) prior to each Veteran's index date. Sacubitril/valsartan (Brand name: Entresto®) will be excluded from ARB exposures.

2.1 COVID-19 Hospitalized, ACEI/ARB vs non-ACEI/ARB

Among Veterans with treated hypertension and without compelling indications who are hospitalized for COVID-19, compare all-cause mortality rates between current users of a range of doses of ACEI/ARB- vs. non-ACEI/ARB-based regimens.

ACEI/ARB

Intervention Type DRUG

Veterans will be categorized as exposed to ACEI/ARB if they have one or more pharmacy fills for an oral ACEI or an ARB in the 90 days (± 14 days) prior to each Veteran's index date. Sacubitril/valsartan (Brand name: Entresto®) will be excluded from ARB exposures.

Non-ACEI/ARB

Intervention Type DRUG

Veterans will be categorized as exposed to a non-ACEI/ARB if they have one or more pharmacy fills for an oral non-ACEI or ARB medication in the 90 days (± 14 days) prior to each Veteran's index date and NO fills for an ACEI/ARB medication in the 90 days (± 14 days) prior to each Veteran's index date. Specific drug classes include: aldosterone receptor antagonist, beta-blocker, calcium channel blocker, centrally-acting drug, direct arterial vasodilator, direct renin inhibitor, thiazide diuretic, loop diuretic, and potassium sparing diuretic.

2.2 COVID-19 Hospitalized, ACEI vs. ARB

Among Veterans with treated hypertension who are hospitalized for COVID-19, compare all-cause mortality rates between current users of a range of doses of ACEI- vs. ARB-based regimens.

ACEI

Intervention Type DRUG

Veterans will be categorized as exposed to an ACEI if they have one or more pharmacy fills for an oral ACEI in the 90 days (± 14 days) prior to each Veteran's index date and NO fills for an oral ARB in the 90 days (± 14 days) prior to each Veteran's index date.

ARB

Intervention Type DRUG

Veterans will be categorized as exposed to an ARB if they have one or more pharmacy fills for an oral ACEI in the 90 days (± 14 days) prior to each Veteran's index date and NO fills for an oral ACEI in the 90 days (± 14 days) prior to each Veteran's index date. Sacubitril/valsartan (Brand name: Entresto®) will be excluded from ARB exposures.

Interventions

Learn about the drugs, procedures, or behavioral strategies being tested and how they are applied within this trial.

ACEI/ARB

Veterans will be categorized as exposed to ACEI/ARB if they have one or more pharmacy fills for an oral ACEI or an ARB in the 90 days (± 14 days) prior to each Veteran's index date. Sacubitril/valsartan (Brand name: Entresto®) will be excluded from ARB exposures.

Intervention Type DRUG

Non-ACEI/ARB

Veterans will be categorized as exposed to a non-ACEI/ARB if they have one or more pharmacy fills for an oral non-ACEI or ARB medication in the 90 days (± 14 days) prior to each Veteran's index date and NO fills for an ACEI/ARB medication in the 90 days (± 14 days) prior to each Veteran's index date. Specific drug classes include: aldosterone receptor antagonist, beta-blocker, calcium channel blocker, centrally-acting drug, direct arterial vasodilator, direct renin inhibitor, thiazide diuretic, loop diuretic, and potassium sparing diuretic.

Intervention Type DRUG

ACEI

Veterans will be categorized as exposed to an ACEI if they have one or more pharmacy fills for an oral ACEI in the 90 days (± 14 days) prior to each Veteran's index date and NO fills for an oral ARB in the 90 days (± 14 days) prior to each Veteran's index date.

Intervention Type DRUG

ARB

Veterans will be categorized as exposed to an ARB if they have one or more pharmacy fills for an oral ACEI in the 90 days (± 14 days) prior to each Veteran's index date and NO fills for an oral ACEI in the 90 days (± 14 days) prior to each Veteran's index date. Sacubitril/valsartan (Brand name: Entresto®) will be excluded from ARB exposures.

Intervention Type DRUG

Other Intervention Names

Discover alternative or legacy names that may be used to describe the listed interventions across different sources.

benazepril captopril enalapril fosinopril lisinopril moexipril perindopril quinapril ramipril trandolapril azilsartan candesartan eprosartan irbesartan losartan olmesartan telmisartan valsartan doxazosin prazosin terazosin acebutolol nebivolol atenolol betaxolol bisoprolol metoprolol pindolol penbutolol carvedilol labetalol nadolol propranolol timolol amlodipine felodipine isradipine nifedipine nicardipine nisoldipine diltiazem verapamil clonidine guanfacine guanabenz methyldopa reserpine hydralazine minoxidil aliskiren spironolactone eplerenone bumetanide furosemide ethacrynic acid torsemide amiloride triamterene bendroflumethiazide chlorothiazide chlorthalidone hydrochlorothiazide indapamide metolazone benazepril captopril enalapril fosinopril lisinopril moexipril perindopril quinapril ramipril trandolapril azilsartan candesartan eprosartan irbesartan losartan olmesartan telmisartan valsartan

Eligibility Criteria

Check the participation requirements, including inclusion and exclusion rules, age limits, and whether healthy volunteers are accepted.

Inclusion Criteria

* Positive SARS-CoV-2 test in the outpatient setting (Aim 1) or hospitalized for COVID-19 (Aim 2)
* Meet continuous enrollment criteria (≥1 inpatient or any outpatient encounter in each of the two, six-month periods during the 365 days prior to the index date)
* Do not have data inconsistencies (test patients, not Veterans, multiple death dates in data, or not alive on index date)
* Diagnosed with hypertension at any point prior to the index date
* Had at least one prescription dispensed for an antihypertensive medication in the 90 days prior to the index date

Exclusion Criteria

* Aim 1.1 and 2.1 (ACEI/ARB vs. non-ACEI/ARB comparison): diagnosed with a compelling indication for ACEI/ARB at any point prior to the index date (i.e., diabetes, stroke, chronic kidney disease, heart failure with reduced ejection fraction, or coronary heart disease)
* Aim 1.2 and 2.2 (ACE vs. ARB comparison): prescription fills for both an ACEI and an ARB in the 90 days prior to the index date; no prescription fill for an ACEI or an ARB in the 90 days prior to the index date

Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No