Cost-effectiveness of prophylactic emicizumab versus prophylactic recombinant factor VIII in patients with moderate or mild hemophilia A without inhibitors in the United States.

Prophylactic emicizumab is cost-ineffective in adults with moderate or mild hemophilia A without inhibitors at current pricing. The price of prophylactic emicizumab would need to decrease by >35% to become cost-effective in this patient population.

Quality of primary health care in China: challenges and recommendations.

China has substantially increased financial investment and introduced favourable policies for strengthening its primary health care system with core responsibilities in preventing and managing chronic diseases such as hypertension and emerging infectious diseases such as coronavirus disease 2019 (COVID-19). However, widespread gaps in the quality of primary health care still exist. In this Review, we aim to identify the causes for this poor quality, and provide policy recommendations. System challenges include: the suboptimal education and training of primary health-care practitioners, a fee-for-service payment system that incentivises testing and treatments over prevention, fragmentation of clinical care and public health service, and insufficient continuity of care throughout the entire health-care system. The following recommendations merit consideration: (1) enhancement of the quality of training for primary health-care physicians, (2) establishment of performance accountability to incentivise high-quality and high-value care; (3) integration of clinical care with the basic public health services, and (4) strengthening of the coordination between primary health-care institutions and hospitals. Additionally, China should consider modernising its primary health-care system through the establishment of a learning health system built on digital data and innovative technologies.

ACC/AHA Special Report: Clinical Practice Guideline Implementation Strategies: A Summary of Systematic Reviews by the NHLBI Implementation Science Work Group: A Report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines.

BACKGROUND: In 2008, the National Heart, Lung, and Blood Institute convened an Implementation Science Work Group to assess evidence-based strategies for effectively implementing clinical practice guidelines. This was part of a larger effort to update existing clinical practice guidelines on cholesterol, blood pressure, and overweight/obesity. OBJECTIVES: Review evidence from the published implementation science literature and identify effective or promising strategies to enhance the adoption and implementation of clinical practice guidelines. METHODS: This systematic review was conducted on 4 critical questions, each focusing on the adoption and effectiveness of 4 intervention strategies: (1) reminders, (2) educational outreach visits, (3) audit and feedback, and (4) provider incentives. A scoping review of the Rx for Change database of systematic reviews was used to identify promising guideline implementation interventions aimed at providers. Inclusion and exclusion criteria were developed a priori for each question, and the published literature was initially searched up to 2012, and then updated with a supplemental search to 2015. Two independent reviewers screened the returned citations to identify relevant reviews and rated the quality of each included review. RESULTS: Audit and feedback and educational outreach visits were generally effective in improving both process of care (15 of 21 reviews and 12 of 13 reviews, respectively) and clinical outcomes (7 of 12 reviews and 3 of 5 reviews, respectively). Provider incentives showed mixed effectiveness for improving both process of care (3 of 4 reviews) and clinical outcomes (3 reviews equally distributed between generally effective, mixed, and generally ineffective). Reminders showed mixed effectiveness for improving process of care outcomes (27 reviews with 11 mixed and 3 generally ineffective results) and were generally ineffective for clinical outcomes (18 reviews with 6 mixed and 9 generally ineffective results). Educational outreach visits (2 of 2 reviews), reminders (3 of 4 reviews), and provider incentives (1 of 1 review) were generally effective for cost reduction. Educational outreach visits (1 of 1 review) and provider incentives (1 of 1 review) were also generally effective for cost-effectiveness outcomes. Barriers to clinician adoption or adherence to guidelines included time constraints (8 reviews/overviews); limited staffing resources (2 overviews); timing (5 reviews/overviews); clinician skepticism (5 reviews/overviews); clinician knowledge of guidelines (4 reviews/overviews); and higher age of the clinician (1 overview). Facilitating factors included guideline characteristics such as format, resources, and end-user involvement (6 reviews/overviews); involving stakeholders (5 reviews/overviews); leadership support (5 reviews/overviews); scope of implementation (5 reviews/overviews); organizational culture such as multidisciplinary teams and low-baseline adherence (9 reviews/overviews); and electronic guidelines systems (3 reviews). CONCLUSION: The strategies of audit and feedback and educational outreach visits were generally effective in improving both process of care and clinical outcomes. Reminders and provider incentives showed mixed effectiveness, or were generally ineffective. No general conclusion could be reached about cost effectiveness, because of limitations in the evidence. Important gaps exist in the evidence on effectiveness of implementation interventions, especially regarding clinical outcomes, cost effectiveness and contextual issues affecting successful implementation.

The primary health-care system in China.

China has made remarkable progress in strengthening its primary health-care system. Nevertheless, the system still faces challenges in structural characteristics, incentives and policies, and quality of care, all of which diminish its preparedness to care for a fifth of the world's population, which is ageing and which has a growing prevalence of chronic non-communicable disease. These challenges include inadequate education and qualifications of its workforce, ageing and turnover of village doctors, fragmented health information technology systems, a paucity of digital data on everyday clinical practice, financial subsidies and incentives that do not encourage cost savings and good performance, insurance policies that hamper the efficiency of care delivery, an insufficient quality measurement and improvement system, and poor performance in the control of risk factors (such as hypertension and diabetes). As China deepens its health-care reform, it has the opportunity to build an integrated, cooperative primary health-care system, generating knowledge from practice that can support improvements, and bolstered by evidence-based performance indicators and incentives.

Achieving best outcomes for patients with cardiovascular disease in China by enhancing the quality of medical care and establishing a learning health-care system.

China has an immediate need to address the rapidly growing population with cardiovascular disease events and the increasing number of people living with this illness. Despite progress in increasing access to services, China faces the dual challenge of addressing gaps in quality of care and producing more evidence to support clinical practice. In this Review, we address opportunities to strengthen performance measurement, programmes to improve quality of care, and national capacity to produce high-impact knowledge for clinical practice. Moreover, we propose recommendations, with implications for other diseases, for how China can immediately make use of its Hospital Quality-Monitoring System and other existing national platforms to assess and improve performance of medical care, and to generate new knowledge to inform clinical decisions and national policies.

Community Level Association between Home Health and Nursing Home Performance on Quality and Hospital 30-day Readmissions for Medicare Patients.

We evaluated whether community-level home health agencies and nursing home performance is associated with community-level hospital 30-day all-cause risk-standardized readmission rates for Medicare patients used data from the Centers for Medicare & Medicaid Service from 2010 to 2012. Our final sample included 2,855 communities that covered 4,140 hospitals with 6,751,713 patients, 13,060 nursing homes with 1,250,648 residents, and 7,613 home health agencies providing services to 35,660 zipcodes. Based on a mixed effect model, we found that increasing nursing home performance by one star for all of its 4 measures and home health performance by 10 points for all of its 6 measures is associated with decreases of 0.25% (95% CI 0.17-0.34) and 0.60% (95% CI 0.33-0.83), respectively, in community-level risk-standardized readmission rates.

Improvements in the distribution of hospital performance for the care of patients with acute myocardial infarction, heart failure, and pneumonia, 2006-2011.

BACKGROUND: Medicare hospital core process measures have improved over time, but little is known about how the distribution of performance across hospitals has changed, particularly among the lowest performing hospitals. METHODS: We studied all US hospitals reporting performance measure data on process measures for acute myocardial infarction (AMI), heart failure (HF), and pneumonia (PN) to the Centers for Medicare & Medicaid Services from 2006 to 2011. We assessed changes in performance across hospital ranks, variability in the distribution of performance rates, and linear trends in the 10th percentile (lowest) of performance over time for both individual measures and a created composite measure for each condition. RESULTS: More than 4000 hospitals submitted measure data each year. There were marked improvements in hospital performance measures (median performance for composite measures: AMI: 96%-99%, HF: 85%-98%, PN: 83%-97%). A greater number of hospitals reached the 100% performance level over time for all individual and composite measures. For the composite measures, the 10th percentile significantly improved (AMI: 90%-98%, P<0.0001 for trend; HF: 70%-92%, P=0.0002; PN: 71%-92%, P=0.0003); the variation (90th percentile rate minus 10th percentile rate) decreased from 9% in 2006 to 2% in 2011 for AMI, 25%-8% for HF, and 20%-7% for PN. CONCLUSIONS: From 2006 to 2011, not only did the median performance improve but the distribution of performance narrowed. Focus needs to shift away from processes measures to new measures of quality.

Features of high quality discharge planning for patients following acute myocardial infarction.

BACKGROUND: Hospital discharge planning is required as a Medicare Condition of Participation (CoP), and is essential to the health and safety for all patients. However, there have been no studies examining specific hospital discharge processes, such as patient education and communication with primary care providers, in relation to hospital 30-day risk standardized mortality rates (RSMRs) for patients with acute myocardial infarction (AMI). OBJECTIVE: To identify hospital discharge processes that may be associated with better performance in hospital AMI care as measured by RSMR. DESIGN: We conducted a qualitative study of U.S. Hospitals, which were selected based on their RSMR reported by the Centers for Medicare & Medicaid Services (CMS) Hospital Compare website for the most recent data available (January 1, 2005 - December 31, 2007). We selected hospitals that ranked in the top 5 % and the bottom 5 % of RSMR for the two consecutive years. We focused on hospitals at the extreme ends of the range in RSMR, known as deviant case sampling. We excluded hospitals that did not have the ability to perform percutaneous coronary intervention in order to decrease the heterogeneity in our sample. PARTICIPANTS: Participants included key hospital clinical and administrative staff most involved in discharge planning for patients admitted with AMI. METHODS: We conducted 14 site visits and 57 in-depth interviews using a standard discussion guide. We employed a grounded theory approach and used the constant comparative method to generate recurrent and unifying themes. KEY RESULTS: We identified five broad discharge processes that distinguished higher and lower performing hospitals: 1) initiating discharge planning upon patient admission; 2) using multidisciplinary case management services; 3) ensuring that a follow-up plan is in place prior to discharge; 4) providing focused education sessions for both the patient and family; and 5) contacting the primary care physician regarding the patient's hospitalization and follow-up care plan. CONCLUSION: Comprehensive and more intense discharge processes that start on admission continue during the patient's hospital stay, and follow up with the primary care physician within 2 days post-discharge, may be critical in reducing hospital RSMR for patients with AMI.

In-Hospital Observation on Oral Diuretics After Treatment for Acute Decompensated Heart Failure: Evaluating the Utility.

BACKGROUND: Following treatment for acute decompensated heart failure, in-hospital observation on oral diuretics (OOD) is recommended, assuming it provides actionable information on discharge diuretic dosing and thus reduces readmissions. METHODS: In the Mechanisms of Diuretic Resistance (MDR) cohort, we analyzed in-hospital measures of diuretic response, provider's decisions, and diuretic response ≈30 days postdischarge. In a Yale multicenter cohort, we assessed if in-hospital OOD was associated with 30-day readmission risk. The main objective of this study was to evaluate the utility of in-hospital OOD. RESULTS: Of the 468 patients in the MDR cohort, 57% (N=265) underwent in-hospital OOD. During the OOD, weight change and net fluid balance correlated poorly with each other (r=0.36). Discharge diuretic dosing was similar between patients who had increased, stable, or decreased weight (decreased discharge dose from OOD dose in 77% versus 72% versus 70%, respectively), net fluid status (decreased discharge dose from OOD dose in 100% versus 69% versus 74%, respectively), and urine output (decreased discharge dose from OOD dose in 69% versus 79% versus 72%, respectively) during the 24-hour OOD period (P>0.27 for all). In participants returning at 30 days for formal quantification of outpatient diuretic response (n=98), outpatient and inpatient OOD natriuresis was poorly correlated (r=0.26). In the Yale multicenter cohort (n=18 454 hospitalizations), OOD occurred in 55% and was not associated with 30-day hospital readmission (hazard ratio, 0.98 [95% CI, 0.93-1.05]; P=0.51). CONCLUSIONS: In-hospital OOD did not provide actionable information on diuretic response, was not associated with outpatient dose selection, did not predict subsequent outpatient diuretic response, and was not associated with lower readmission rate. Additional research is needed to replicate these findings and understand if these resources could be better allocated elsewhere. REGISTRATION: URL: https://www. CLINICALTRIALS: gov; Unique identifier: NCT02546583.

County-level variation in cardioprotective antihyperglycemic prescribing among medicare beneficiaries.

Background: Cardioprotective antihyperglycemic agents, SGLT2 inhibitors (SGLT2i) and GLP-1 receptor agonists (GLP1RA), improve outcomes of patients with type 2 diabetes, but adoption has been limited. Differences across individuals have been noted but area-level variation is unknown. Objectives: Given healthcare access and sociodemographic differences, we evaluated whether SGLT2i and GLP-1RA utilization varies across US counties. Methods: We linked 2019 Medicare Part D national prescription data with county-level demographic measures from the Agency for Health Quality and Research. We compared the number of beneficiaries receiving prescriptions for any cardioprotective antihyperglycemic to the number receiving metformin prescriptions across US counties. In multivariable linear regression with SGLT2i-to-metformin and GLP1RA-to-metformin prescriptions as outcomes, we evaluated county factors associated with use of cardioprotective agents while adjusting for sociodemographic measures, region, and cardiometabolic risk factor prevalence. Results: In 3066 US counties, there were a median 2,416 (IQR, 1681-3190) metformin-receiving beneficiaries per 100,000 population. A median 6.2% of beneficiaries receiving metformin received SGLT2i therapy, varying across counties (IQR, 3.4%-9.2%). A median 9.4% (IQR, 5.0%-13.0%) of beneficiaries receiving metformin received GLP-1RA. In adjusted analyses, higher percentage of Black population was associated with lower use at the county level of people on SGLT2i or GLP-1RA relative to metformin (a SD higher proportion of Black individuals with 0.4% [95% CI, -0.6% to -0.1%] and 0.5% [-0.8% to -0.2%] lower SGLT2i and GLP-1RA prescribing relative to metformin, respectively; P < 0.01). A higher median age of county residents, rural location, and lower prevalence of diabetes were associated with lower SGLT2i prescribing. Similarly, more advanced age of county residents, rural location, proportion of Hispanic individuals, and household income and lower education levels were associated with lower GLP-1RA prescribing. Prescribing was higher in the Northeast and lower in the West as compared with the Midwest for both classes. Conclusion: There was large variation by county in cardioprotective antihyperglycemic prescribing, with a pattern of lower use in Black-predominant and rural counties, highlighting the critical need to investigate equity in uptake of novel therapeutic agents.

Percutaneous Left Atrial Appendage Occlusion in Comparison to Non-Vitamin K Antagonist Oral Anticoagulant Among Patients With Atrial Fibrillation.

Background This study aimed to compare percutaneous left atrial appendage occlusion (LAAO) with non-vitamin K antagonist oral anticoagulants among patients with atrial fibrillation. Methods and Results Using a US administrative database, 562 850 patients with atrial fibrillation were identified, among whom 8397 were treated with LAAO and 554 453 were treated with non-vitamin K antagonist oral anticoagulants between March 13, 2015 and December 31, 2018. Propensity score overlap weighting was used to balance baseline characteristics. The primary outcome was a composite end point of ischemic stroke or systemic embolism, major bleeding, and all-cause mortality. The mean age was 76.4±7.6 years; 280 097 (49.8%) were female. Mean follow-up was 1.5±1.0 years. LAAO was associated with no significant difference in the risk of the primary composite end point (hazard ratio [HR], 0.93 [0.84-1.03]), or the secondary outcomes including ischemic stroke/systemic embolism (HR, 1.07 [0.81-1.41]), and intracranial bleeding (HR, 1.08 [0.72-1.61]). LAAO was associated with a higher risk of major bleeding (HR, 1.22 [1.05-1.42], P=0.01) and a lower risk of mortality (HR, 0.73 [0.64-0.84], P<0.001). The lower risk of mortality associated with LAAO was most pronounced in patients with a prior history of intracranial bleeding. Conclusions In comparison to non-vitamin K antagonist oral anticoagulants, LAAO was associated with no significant difference in the risk of the composite outcome and a lower risk of mortality, which suggests LAAO might be a reasonable option in select patients with atrial fibrillation. The observation of higher bleeding risk associated with LAAO highlights the need to optimize postprocedural antithrombotic regimens as well as systematic efforts to assess and address bleeding predispositions.

Efficacy and Safety Considerations With Dose-Reduced Direct Oral Anticoagulants: A Review.

Importance: Dose-reduced regimens of direct oral anticoagulants (DOACs) may be used for 2 main purposes: dose-adjusted treatment intended as full-intensity anticoagulation (eg, for stroke prevention in atrial fibrillation [AF] in patients requiring dose reduction) or low-intensity treatment (eg, extended-duration treatment of venous thromboembolism [VTE]). We reviewed randomized clinical trials (RCTs) to understand the scenarios in which dose-adjusted or low-intensity DOACs were tested and reviewed the labeled indications by regulatory authorities, using data from large registries to assess whether the use of dose-reduced DOACs in routine practice aligned with the findings of RCTs. Observations: Among 4191 screened publications, 35 RCTs that used dose-adjusted DOACs were identified for dabigatran, apixaban, rivaroxaban, and edoxaban. Of these 35 RCTs, 29 were related to stroke prevention in AF. Efficacy and safety results for dose-adjusted DOACs in large RCTs of AF were similar to those found for full-dose DOACs. To our knowledge, dabigatran, apixaban, and rivaroxaban have not been studied as dose-adjusted therapy for acute VTE treatment. Low-intensity DOACs were identified in 37 RCTs. Low-intensity DOACs may be used for extended-duration treatment of VTE (apixaban and rivaroxaban), primary prevention in orthopedic surgeries (dabigatran, apixaban, and rivaroxaban), primary prevention in ambulatory high-risk cancer patients (apixaban and rivaroxaban) or (postdischarge) high-risk medical patients (rivaroxaban), in stable atherosclerotic vascular disease, or after a recent revascularization for peripheral artery disease in conjunction with aspirin (rivaroxaban). Minor variations exist between regulatory authorities in different regions regarding criteria for dose adjustment of DOACs. Data from large registries indicated that dose-reduced DOACs were used occasionally with doses or for clinical scenarios different from those studied in RCTs or recommended by regulatory authorities. Conclusions and Relevance: Dose adjustment and low-intensity treatment are 2 different forms of dose-reduced DOACs. Dose adjustment is mostly relevant for AF and should be done based on the approved criteria. Dose adjustment of DOACs should not be used for acute VTE treatment in most cases. In contrast, low-intensity DOACs may be used for primary or secondary VTE prevention for studied and approved indications. Attention should be given to routine practice patterns to align the daily clinical practice with existing evidence of safety and efficacy.

Catheter-Directed Thrombolysis vs Anticoagulation in Patients With Acute Intermediate-High-risk Pulmonary Embolism: The CANARY Randomized Clinical Trial.

Importance: The optimal treatment of intermediate-high-risk pulmonary embolism (PE) remains unknown. Objective: To assess the effect of conventional catheter-directed thrombolysis (cCDT) plus anticoagulation vs anticoagulation monotherapy in improving echocardiographic measures of right ventricle (RV) to left ventricle (LV) ratio in acute intermediate-high-risk PE. Design, Setting, and Participants: The Catheter-Directed Thrombolysis vs Anticoagulation in Patients with Acute Intermediate-High-Risk Pulmonary Embolism (CANARY) trial was an open-label, randomized clinical trial of patients with intermediate-high-risk PE, conducted in 2 large cardiovascular centers in Tehran, Iran, between December 22, 2018, through February 2, 2020. Interventions: Patients were randomly assigned to cCDT (alteplase, 0.5 mg/catheter/h for 24 hours) plus heparin vs anticoagulation monotherapy. Main Outcomes and Measures: The proportion of patients with a 3-month echocardiographic RV/LV ratio greater than 0.9, assessed by a core laboratory, was the primary outcome. The proportion of patients with an RV/LV ratio greater than 0.9 at 72 hours after randomization and the 3-month all-cause mortality were among secondary outcomes. Major bleeding (Bleeding Academic Research Consortium type 3 or 5) was the main safety outcome. A clinical events committee, masked to the treatment assignment, adjudicated clinical outcomes. Results: The study was prematurely stopped due to the COVID-19 pandemic after recruiting 94 patients (mean [SD] age, 58.4 [2.5] years; 27 women [29%]), of whom 85 patients completed the 3-month echocardiographic follow-up. Overall, 2 of 46 patients (4.3%) in the cCDT group and 5 of 39 patients (12.8%) in the anticoagulation monotherapy group met the primary outcome (odds ratio [OR], 0.31; 95% CI, 0.06-1.69; P = .24). The median (IQR) 3-month RV/LV ratio was significantly lower with cCDT (0.7 [0.6-0.7]) than with anticoagulation (0.8 [0.7-0.9); P = .01). An RV/LV ratio greater than 0.9 at 72 hours after randomization was observed in fewer patients treated with cCDT (13 of 48 [27.0%]) than anticoagulation (24 of 46 [52.1%]; OR, 0.34; 95% CI, 0.14-0.80; P = .01). Fewer patients assigned to cCDT experienced a 3-month composite of death or RV/LV greater than 0.9 (2 of 48 [4.3%] vs 8 of 46 [17.3%]; OR, 0.20; 95% CI, 0.04-1.03; P = .048). One case of nonfatal major gastrointestinal bleeding occurred in the cCDT group. Conclusions and Relevance: This prematurely terminated randomized clinical trial of patients with intermediate-high-risk PE was hypothesis-generating for improvement in some efficacy outcomes and acceptable rate of major bleeding for cCDT compared with anticoagulation monotherapy and provided support for a definitive clinical outcomes trial. Trial Registration: ClinicalTrials.gov Identifier: NCT05172115.

Proceedings From a National Heart, Lung, and Blood Institute and the Centers for Disease Control and Prevention Workshop to Control Hypertension.

Hypertension treatment and control prevent more cardiovascular events than management of other modifiable risk factors. Although the age-adjusted proportion of US adults with controlled blood pressure (BP) defined as <140/90 mm Hg, improved from 31.8% in 1999-2000 to 48.5% in 2007-2008, it remained stable through 2013-2014 and declined to 43.7% in 2017-2018. To address the rapid decline in hypertension control, the National Heart, Lung, and Blood Institute and the Division for Heart Disease and Stroke Prevention of the Centers for Disease Control and Prevention convened a virtual workshop with multidisciplinary national experts. Also, the group sought to identify opportunities to reverse the adverse trend and further improve hypertension control. The workshop immediately preceded the Surgeon General's Call to Action to Control Hypertension, which recognized a stagnation in progress with hypertension control. The presentations and discussions included potential reasons for the decline and challenges in hypertension control, possible "big ideas," and multisector approaches that could reverse the current trend while addressing knowledge gaps and research priorities. The broad set of "big ideas" was comprised of various activities that may improve hypertension control, including: interventions to engage patients, promotion of self-measured BP monitoring with clinical support, supporting team-based care, implementing telehealth, enhancing community-clinical linkages, advancing precision population health, developing tailored public health messaging, simplifying hypertension treatment, using process and outcomes quality metrics to foster accountability and efficiency, improving access to high-quality health care, addressing social determinants of health, supporting cardiovascular public health and research, and lowering financial barriers to hypertension control.

Comprehensive Comparative Effectiveness and Safety of First-Line ß-Blocker Monotherapy in Hypertensive Patients: A Large-Scale Multicenter Observational Study.

[Figure: see text].

Renin-angiotensin system blockers and susceptibility to COVID-19: an international, open science, cohort analysis.

BACKGROUND: Angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin receptor blockers (ARBs) have been postulated to affect susceptibility to COVID-19. Observational studies so far have lacked rigorous ascertainment adjustment and international generalisability. We aimed to determine whether use of ACEIs or ARBs is associated with an increased susceptibility to COVID-19 in patients with hypertension. METHODS: In this international, open science, cohort analysis, we used electronic health records from Spain (Information Systems for Research in Primary Care [SIDIAP]) and the USA (Columbia University Irving Medical Center data warehouse [CUIMC] and Department of Veterans Affairs Observational Medical Outcomes Partnership [VA-OMOP]) to identify patients aged 18 years or older with at least one prescription for ACEIs and ARBs (target cohort) or calcium channel blockers (CCBs) and thiazide or thiazide-like diuretics (THZs; comparator cohort) between Nov 1, 2019, and Jan 31, 2020. Users were defined separately as receiving either monotherapy with these four drug classes, or monotherapy or combination therapy (combination use) with other antihypertensive medications. We assessed four outcomes: COVID-19 diagnosis; hospital admission with COVID-19; hospital admission with pneumonia; and hospital admission with pneumonia, acute respiratory distress syndrome, acute kidney injury, or sepsis. We built large-scale propensity score methods derived through a data-driven approach and negative control experiments across ten pairwise comparisons, with results meta-analysed to generate 1280 study effects. For each study effect, we did negative control outcome experiments using a possible 123 controls identified through a data-rich algorithm. This process used a set of predefined baseline patient characteristics to provide the most accurate prediction of treatment and balance among patient cohorts across characteristics. The study is registered with the EU Post-Authorisation Studies register, EUPAS35296. FINDINGS: Among 1 355 349 antihypertensive users (363 785 ACEI or ARB monotherapy users, 248 915 CCB or THZ monotherapy users, 711 799 ACEI or ARB combination users, and 473 076 CCB or THZ combination users) included in analyses, no association was observed between COVID-19 diagnosis and exposure to ACEI or ARB monotherapy versus CCB or THZ monotherapy (calibrated hazard ratio [HR] 0·98, 95% CI 0·84-1·14) or combination use exposure (1·01, 0·90-1·15). ACEIs alone similarly showed no relative risk difference when compared with CCB or THZ monotherapy (HR 0·91, 95% CI 0·68-1·21; with heterogeneity of >40%) or combination use (0·95, 0·83-1·07). Directly comparing ACEIs with ARBs demonstrated a moderately lower risk with ACEIs, which was significant with combination use (HR 0·88, 95% CI 0·79-0·99) and non-significant for monotherapy (0·85, 0·69-1·05). We observed no significant difference between drug classes for risk of hospital admission with COVID-19, hospital admission with pneumonia, or hospital admission with pneumonia, acute respiratory distress syndrome, acute kidney injury, or sepsis across all comparisons. INTERPRETATION: No clinically significant increased risk of COVID-19 diagnosis or hospital admission-related outcomes associated with ACEI or ARB use was observed, suggesting users should not discontinue or change their treatment to decrease their risk of COVID-19. FUNDING: Wellcome Trust, UK National Institute for Health Research, US National Institutes of Health, US Department of Veterans Affairs, Janssen Research & Development, IQVIA, South Korean Ministry of Health and Welfare Republic, Australian National Health and Medical Research Council, and European Health Data and Evidence Network.