Self-Reported Antihypertensive Medication Class and Temporal Relationship to Treatment Guidelines

The greater antihypertensive responses to initial therapy with calcium channel blockers (CCBs) or thiazide-type diuretics than renin-angiotensin system blockers as initial therapy in non-Hispanic Black (NHB) adults was recognized in the US High BP guidelines from 1988 to 2003. The 2014 Report from Panel Members Appointed to the Eighth Joint National Committee (2014 aJNC8 Report) and the 2017 American College of Cardiology/American Heart Association High Blood Pressure Guideline were the first to recommend CCBs or thiazide-type diuretics rather than renin-angiotensin system blockers as initial therapy in NHB. We assessed the temporal relationship of these recommendations on self-reported CCB or thiazide-type diuretics monotherapy by NHB and NHW adults with hypertension absent compelling indications for β-blockers or renin-angiotensin system blockers in National Health and Nutrition Examination Surveys 2015 to 2018 versus 2007 to 2012 (after versus before 2014 aJNC8 Report). CCB or thiazide-type diuretics monotherapy was unchanged in NHW adults (17.1% versus 18.1%, P =0.711) and insignificantly higher after 2014 among NHB adults (43.7% versus 38.2%, P =0.204), although CCB monotherapy increased (29.5% versus 21.0%, P =0.021) and renin-angiotensin system blocker monotherapy fell (44.5% versus 31.0%, P =0.008). Although evidence-based CCB monotherapy increased among NHB adults in 2015 to 2018, hypertension control declined as untreated hypertension and monotherapy increased. While a gap between recommended and actual monotherapy persists, evidence-based monotherapy appears insufficient to improve hypertension control in NHB adults, especially given evidence for worsening therapeutic inertia. Initiating treatment with single-pill combinations and timely therapeutic intensification when required to control hypertension are evidence-based, race-neutral options for improving hypertension control among NHB adults.

Non-employment and low educational level as risk factors for inequitable treatment and mortality in heart failure: a population-based cohort study of register data

Background The risk of heart failure is disproportionately high among the socioeconomically disadvantaged. Furthermore, socioeconomically deprived patients are at risk of inequitable access to heart failure treatment and poor outcomes. Non-employment as a risk factor in this respect has not previously been studied at the level of the individual. The aim of this register-based cohort study was to analyse equity in access to renin-angiotensin system blockers and mortality, by employment status and educational level. Methods The study population consisted of Swedish patients aged 20–64 years hospitalised for heart failure in July 2006–December 2010, without a heart failure hospitalisation within one year or more before index hospitalisation and without renin-angiotensin system blocker dispensation in the 6 months preceding index hospitalisation. Non-access to renin-angiotensin system blockers, measured as drug dispensations, was investigated by employment status and educational level through logistic regression. Cox regression models were used to obtain hazard ratios for all-cause death by educational level and employment status. Interaction analysis was used to test whether associations between access to treatment and mortality differed by employment status. Results Among the 3874 patients, 1239 (32%) were women. The median age was 57 years. Fifty-three percent were employed. The non-employed patients had more comorbidity and lower access (68%) to renin-angiotensin system blockers compared with the employed (82%). The adjusted odds ratio for non-access to renin-angiotensin system blockers among the non-employed was 1.76. Non-employment was associated with an adjusted hazard ratio of 1.76 for death. Low educational level was associated with a higher death risk. Mortality was highest among the non-employed without access to renin-angiotensin system blockers and the association between access to renin-angiotensin system blockers and survival was slightly weaker in this group. Conclusions Non-employment and low educational level were associated with elevated mortality in heart failure. Non-employment was a risk factor for lower access to evidence-based treatment, and among the non-employed access to treatment was associated with a slightly smaller risk reduction than among the employed. The results underscore that clinicians need to be aware of the importance of socioeconomic factors in heart failure care.

Impact of Renin‐Angiotensin System Blockers on Mortality in Veterans Undergoing Cardiac Surgery

Background Renin‐angiotensin system blockers (RASBs) have well‐validated benefit in patients with hypertension, coronary artery disease, and left ventricular systolic dysfunction. Their use in the perioperative period, however, has been controversial, including in patients undergoing cardiac surgery, who often have a strong indication for their use. In the current study, we explore the impact of RASB use with 30‐day and 1‐year mortality after cardiac surgery. Methods and Results The Veterans Affairs Surgical Quality Improvement Program and Corporate Data Warehouse were data sources for this retrospective cohort study. A total of 37 197 veterans undergoing elective coronary artery bypass grafting and or valve repair or replacement over a 10‐year period met inclusion criteria and were stratified into 4 groups by preoperative exposure (preoperative exposure versus no preoperative exposure) and postoperative continuing exposure (current exposure versus no current exposure) to RASBs. After adjusting for all baseline covariates, the preoperative exposure/current exposure group had lower 30‐day and 1‐year mortality than the preoperative exposure/no current exposure (30‐day hazard ratio [HR], 0.25; 95% CI, 0.19–0.33 [ P <0.001] and 1‐year HR, 0.40; 95% CI, 0.33–0.48 [ P <0.001] or no preoperative exposure/no current exposure (30‐day HR, 0.44; 95% CI, 0.32–0.60 [ P <0.001] and 1‐year HR, 0.72; 95% CI, 0.62–0.84 [ P <0.001] groups. The no preoperative exposure/current exposure group had significantly lower 30‐day (HR, 0.31; 95% CI, 0.14–0.71 [ P =0.006]) and 1‐year (HR, 0.64; 95% CI, 0.53–0.77 [ P <0.001]) mortality than the no preoperative exposure/no current exposure group. Conclusions Continuation of preoperative RASBs and initiation before discharge is associated with decreased mortality in veterans undergoing cardiac surgery. Given these findings, continuation of preoperative RASBs or initiation in the early postoperative period should be considered in patients undergoing cardiac surgery.

Outcomes of Hospitalized COVID-19 Patients Receiving Renin Angiotensin System Blockers and Calcium Channel Blockers

<b><i>Introduction:</i></b> Use of certain antihypertensive medications has been an area of interest during the COVID-19 pandemic, and several hypotheses have been developed regarding the effects of renin-angiotensin system blockers as well as calcium channel blockers in those infected with COVID-19. We seek to determine the association between exposure to ACEI, ARB, and CCB and outcomes in those admitted to the hospital with COVID-19 infection. <b><i>Methods:</i></b> This retrospective cohort study included 841 adult patients hospitalized with COVID-19 infection at the University of Chicago Medical Center between March 25 and June 22, 2020. Out of these 841, 453 patients had a personal history of hypertension. For the first part, we evaluated primary outcomes of in-hospital mortality and ICU admission in hospitalized COVID-19 patients based on their exposure to particular medications regardless of a personal history of hypertension and compared them with those who were not on these medications. For the second part, we evaluated the aforementioned outcomes in 453 patients with a personal history of hypertension based on their medication exposure. Secondary outcomes of length of stay, readmission rate, and new-onset dialysis requirement were also compared across the study groups. <b><i>Results:</i></b> Out of 841 patients, 111 (13.19%) were on ACEI/ARB (median age: 66.1, SD 15.4; 52.25% females) and 730 (86.80%) were not on them (median age: 56.6, SD 20.3; 50.14% females), while 277 (32.93%) used CCB (median age: 64.6, SD 15.2; 57.04% females) and 564 (67.06%) did not use CCB (median age: 54.6, SD 21.2; 47.16% females). After adjusting for demographics and covariates, neither ACEI/ARB nor CCB exposure was associated with any effect on mortality, but ACEI/ARB exposure was associated with 42% reduction in risk of ICU admissions (OR 0.58, 95% CI [0.35, 0.95], <i>p</i> value 0.03). In addition, combined use of ACEI/ARB and CCB was associated with statistically significant (45%) reduction in ICU admission (OR 0.55, 95% CI [0.32, 0.94], <i>p</i> value 0.029). Out of 453 patients with a personal history of hypertension, 85 (18.76%) were taking ACEI/ARB (median age 65, SD 15.6; 56.47% females) and 368 (81.24%) were not on ACEI/ARB (median age 62.8, SD 16.4; 54.89% females), while 208 (45.92%) out of 453 were on CCB (median age 65; SD 14.8; 60.1% females) and 245 (54.08%) were not on CCB (median age 61.7, SD 17.3; 51.02% females). In the fully adjusted model in this group, ACEI use was associated with 71% reduction in in-house mortality (OR 0.29, 95% CI [0.09, 0.93], <i>p</i> value 0.03). <b><i>Discussion/Conclusion:</i></b> Among all hospitalized patients with COVID-19 infection, exposure to ACEI/ARB, as well as combined exposure to ACEI/ARB and CCB, were associated with reduced incidence of ICU admissions. In those admitted patients who had a personal history of hypertension, there was a trend towards reduced in-hospital mortality in those exposed to ACEI.

Renin–angiotensin system blockers, risk of SARS-CoV-2 infection and outcomes from CoViD-19: systematic review and meta-analysis

Aims This meta-analysis provides summary odds ratio (OR) estimates for associations between treatment with (vs. without) renin–angiotensin system blockers and risk of severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) infection and coronavirus disease 2019 (CoViD-19) severity (including case-fatality) in patients with hypertension, and in all patients (irrespective of hypertension). Methods and results PubMed, EMBASE, Web of Science, Google Scholar, medRxiv, and SSRN were searched (2 May 2020 to 12 August 2020) for non-randomized observational CoViD-19 studies. Event/patient numbers were extracted, comparing angiotensin-converting enzyme (ACE) inhibitor/angiotensin-receptor blocker (ARB) treatment (and each separately), to treatment with neither drug, for the outcomes: (i) likelihood of SARS-CoV-2 infection; (ii) CoViD-19 severity [including hospitalization, intensive therapy unit (ITU), ventilation]; (iii) case-fatality. The risk of bias was assessed (ROBINS-I). Random-effects meta-analysis estimates were pooled. Eighty-six studies including 459 755 patients (103 317 with hypertension), were analysed. In patients with hypertension, ACE inhibitor or ARB treatment was not associated with a greater likelihood of SARS-CoV-2 infection in 60 141 patients (OR 1.06, 95% CI 0.99–1.14), hospitalization in 5925 patients (OR 0.90, 0.62–1.31), ITU in 7218 patients (OR 1.06, 0.73–1.56), ventilation (or ITU/ventilation/death) in 13 163 patients (OR 0.91, 0.72–1.15) or case-fatality in 18 735 patients with 2893 deaths (OR 0.75, 0.61–0.92). Conclusion Angiotensin-converting enzyme inhibitors and ARBs appear safe in the context of SARS-CoV-2 infection and should not be discontinued. PROSPERO registration number CRD42020186996.

Renin-angiotensin system blockers and mortality in COVID-19: a territory-wide study from Hong Kong

AimsRenin–angiotensin system blockers such as angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin receptor blockers (ARBs) may increase the risk of adverse outcomes in COVID-19. In this study, the relationships between ACEI/ARB use and COVID-19 related mortality were examined.MethodsConsecutive patients diagnosed with COVID-19 by RT-PCR at the Hong Kong Hospital Authority between 1st January and 28th July 2020 were included.ResultsThis study included 2774 patients. The mortality rate of the COVID-19 positive group was 1.5% (n=42). Those who died had a higher median age (82.3[76.5-89.5] vs. 42.9[28.2-59.5] years old; P<0.0001), more likely to have baseline comorbidities of cardiovascular disease, diabetes mellitus, hypertension, and chronic kidney disease (P<0.0001). They were more frequently prescribed ACEI/ARBs at baseline, and steroids, lopinavir/ritonavir, ribavirin and hydroxychloroquine during admission (P<0.0001). They also had a higher white cell count, higher neutrophil count, lower platelet count, prolonged prothrombin time and activated partial thromboplastin time, higher D-dimer, troponin, lactate dehydrogenase, creatinine, alanine transaminase, aspartate transaminase and alkaline phosphatase (P<0.0001). Multivariate Cox regression showed that age, cardiovascular disease, renal disease, diabetes mellitus, the use of ACEIs/ARBs and diuretics, and various laboratory tests remained significant predictors of mortality.ConclusionsWe report that an association between ACEIs/ARBs with COVID-19 related mortality even after adjusting for cardiovascular and other comorbidities, as well as medication use. Patients with greater comorbidity burden and laboratory markers reflecting deranged clotting, renal and liver function, and increased tissue inflammation, and ACEI/ARB use have a higher mortality risk.Key PointsWe report that an association between ACEIs/ARBs with COVID-19 related mortality even after adjusting for cardiovascular and other comorbidities, as well as medication use.Patients with greater comorbidity burden and laboratory markers reflecting deranged clotting, renal and liver function, and increased tissue inflammation, and ACEI/ARB use have a higher mortality risk.