Renin-Angiotensin-Aldosterone System Blockers and the Risk of Covid-19.

BACKGROUND: A potential association between the use of angiotensin-receptor blockers (ARBs) and angiotensin-converting-enzyme (ACE) inhibitors and the risk of coronavirus disease 2019 (Covid-19) has not been well studied. METHODS: We carried out a population-based case-control study in the Lombardy region of Italy. A total of 6272 case patients in whom infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) was confirmed between February 21 and March 11, 2020, were matched to 30,759 beneficiaries of the Regional Health Service (controls) according to sex, age, and municipality of residence. Information about the use of selected drugs and patients' clinical profiles was obtained from regional databases of health care use. Odds ratios and 95% confidence intervals for associations between drugs and infection, with adjustment for confounders, were estimated by means of logistic regression. RESULTS: Among both case patients and controls, the mean (±SD) age was 68±13 years, and 37% were women. The use of ACE inhibitors and ARBs was more common among case patients than among controls, as was the use of other antihypertensive and non-antihypertensive drugs, and case patients had a worse clinical profile. Use of ARBs or ACE inhibitors did not show any association with Covid-19 among case patients overall (adjusted odds ratio, 0.95 [95% confidence interval {CI}, 0.86 to 1.05] for ARBs and 0.96 [95% CI, 0.87 to 1.07] for ACE inhibitors) or among patients who had a severe or fatal course of the disease (adjusted odds ratio, 0.83 [95% CI, 0.63 to 1.10] for ARBs and 0.91 [95% CI, 0.69 to 1.21] for ACE inhibitors), and no association between these variables was found according to sex. CONCLUSIONS: In this large, population-based study, the use of ACE inhibitors and ARBs was more frequent among patients with Covid-19 than among controls because of their higher prevalence of cardiovascular disease. However, there was no evidence that ACE inhibitors or ARBs affected the risk of COVID-19.

Impact of chronic GLP-1 RA and SGLT-2I therapy on in-hospital outcome of diabetic patients with acute myocardial infarction.

BACKGROUND: Glucagon-like peptide-1 receptor agonists (GLP-1 RA) and sodium glucose cotransporter-2 inhibitors (SGLT-2i) demonstrated cardiovascular and renal protection. Whether their benefits occur also during hospitalization for acute myocardial infarction (AMI) in patients with diabetes mellitus (DM) is not known. We evaluated in-hospital outcomes of patients hospitalized with AMI according to their chronic use of GLP-1 RA and/or SGLT-2i. METHODS: Using the health administrative databases of Lombardy, patients hospitalized with AMI from 2010 to 2019 were included. They were stratified according to DM status, then grouped into three cohorts using a propensity score matching: non-DM patients; DM patients treated with GLP-1 RA and/or SGLT-2i; DM patients not treated with GLP-1 RA/SGLT-2i. The primary endpoint of the study was the composite of in-hospital mortality, acute heart failure, and acute kidney injury requiring renal replacement therapy. RESULTS: We identified 146,798 patients hospitalized with AMI (mean age 71 ± 13 years, 34% females, 47% STEMI; 26% with DM). After matching, 3,090 AMI patients (1030 in each group) were included in the analysis. Overall, the primary endpoint rate was 16% (n = 502) and progressively increased from non-DM patients to DM patients treated with and without GLP-1 RA/SGLT-2i (13%, 16%, and 20%, respectively; P < 0.0001). Compared with non-DM patients, DM patients with GLP-1 RA/SGLT-2i had a 30% higher risk of the primary endpoint, while those not treated with GLP-1 RA/SGLT-2i had a 60% higher risk (P < 0.0001). CONCLUSION: Chronic therapy with GLP-1 RA and/or SGLT-2i has a favorable impact on the clinical outcome of DM patients hospitalized with AMI.

Prognostic Impact of Percutaneous Coronary Intervention in Chronic Dialysis Patients with Acute Myocardial Infarction: Findings from the Lombardy Health Database.

Background: Patients on chronic dialysis are less likely to be treated with percutaneous coronary intervention (PCI) for acute myocardial infarction (AMI). This is due to the lack of evidence from randomized trials, concerns about possible PCI-related side effects, and multimorbidity. Therefore, routine use of PCI for treatment of dialysis patients with AMI remains an unresolved issue. Methods: We analyzed data of patients on chronic dialysis hospitalized with AMI from 2003 to 2018, by using the administrative Lombardy Health Database (Italy). Patients were grouped according to whether they underwent or not PCI during index hospitalization. The primary outcome was in-hospital mortality, 1-year mortality was the secondary endpoint. Results: During the study period, 265,048 patients were hospitalized with AMI. Of them, 3206 (1.2%) were on chronic dialysis (age 71 ± 11; 72% males). Among dialysis patients, 44% underwent PCI, while 54% underwent PCI among non-dialysis patients (p < 0.0001). Dialysis was an independent predictor of treatment with medical therapy only (OR 0.75 [95% CI 0.70-0.81]). In-hospital mortality in the dialysis cohort was 15%, significantly lower in patients treated with PCI than in those not treated with PCI (11% vs. 19%; p < 0.0001). One-year mortality was 47% and it was lower in PCI-treated patients (33% vs. 52%; p < 0.0001). The adjusted risk of the study endpoints was significantly lower in dialysis patients undergoing PCI: OR 0.62 (95% CI 0.50-0.76) for in-hospital mortality; HR 0.63 (95% CI 0.56-0.71) for 1-year mortality. Conclusions: This study showed that in AMI patients on chronic dialysis, PCI is associated with a significant in-hospital and 1-year survival benefit. Yet, they underwent PCI less frequently than patients with preserved renal function.

Risk of coronavirus disease 2019 hospitalization and mortality in rheumatic patients treated with hydroxychloroquine or other conventional disease-modifying anti-rheumatic drugs in Italy.

OBJECTIVES: To ascertain if the use of hydroxychloroquine(HCQ)/cloroquine(CLQ) and other conventional DMARDs (cDMARDs) and rheumatic diseases per se may be associated with COVID-19-related risk of hospitalization and mortality. METHODS: This case-control study nested within a cohort of cDMARD users was conducted in the Lombardy, Veneto, Tuscany and Lazio regions and Reggio Emilia province. Claims databases were linked to COVID-19 surveillance registries. The risk of COVID-19-related outcomes was estimated using a multivariate conditional logistic regression analysis comparing HCQ/CLQ vs MTX, vs other cDMARDs and vs non-use of these drugs. The presence of rheumatic diseases vs their absence in a non-nested population was investigated. RESULTS: A total of 1275 patients hospitalized due to COVID-19 were matched to 12 734 controls. Compared with recent use of MTX, no association between HCQ/CLQ monotherapy and COVID-19 hospitalization [odds ratio (OR) 0.83 (95% CI 0.69, 1.00)] or mortality [OR 1.19 (95% CI 0.85, 1.67)] was observed. A lower risk was found when comparing HCQ/CLQ use with the concomitant use of other cDMARDs and glucocorticoids. HCQ/CLQ was not associated with COVID-19 hospitalization as compared with non-use. An increased risk for recent use of either MTX monotherapy [OR 1.19 (95% CI 1.05, 1.34)] or other cDMARDs [OR 1.21 (95% CI 1.08, 1.36)] vs non-use was found. Rheumatic diseases were not associated with COVID-19-related outcomes. CONCLUSION: HCQ/CLQ use in rheumatic patients was not associated with a protective effect against COVID-19-related outcomes. The use of other cDMARDs was associated with an increased risk when compared with non-use and, if concomitantly used with glucocorticoids, also vs HCQ/CLQ, probably due to immunosuppressive action.

Non-stenotic fibro-calcific aortic valve as a predictor of myocardial infarction recurrence.

BACKGROUND: Patients with acute myocardial infarction (AMI) are at increased risk of recurrent cardiovascular events. Non-stenotic aortic valve fibro-calcific remodeling (AVSc), reflecting systemic damage, may serve as a new marker of risk. OBJECTIVES: To stratify subgroups of AMI patients with specific probabilities of recurrent AMI and to evaluate the importance of AVSc in this setting. METHODS: Consecutive AMI patients (n = 2530) were admitted at Centro Cardiologico Monzino (2010-2019) and followed up for 5 years. Patients were divided into study (n = 1070) and test (n = 966) cohorts. Topological data analysis (TDA) was used to stratify patient subgroups, while Kaplan-Meier and Cox regressions analyses were used to evaluate the significance of baseline characteristics. RESULTS: TDA identified 11 subgroups of AMI patients with specific baseline characteristics. Two subgroups showed the highest rate of reinfarction after 5 years from the indexed AMI with a combined hazard ratio (HR) of 3.8 (95%CI: 2.7-5.4) compared to the other subgroups. This was confirmed in the test cohort (HR = 3.1; 95%CI: 2.2-4.3). These two subgroups were mostly men, with hypertension and dyslipidemia, who exhibit higher prevalence of AVSc, higher levels of high-sensitive c-reactive protein and creatinine. In the year-by-year analysis, AVSc, adjusted for all confounders, showed an independent association with the increased risk of reinfarction (odds ratio of ∼2 at all time-points), in both the study and the test cohorts (all p < 0.01). CONCLUSIONS: AVSc is a crucial variable for identifying AMI patients at high risk of recurrent AMI and its presence should be considered when assessing the management of AMI patients. The inclusion of AVSc in risk stratification models may improve the accuracy of predicting the likelihood of recurrent AMI, leading to more personalized treatment decisions.

We wanted to understand the factors that make some acute myocardial infarction (AMI) patients more likely to experience recurrent infarction after leaving the hospital. Specifically, we asked whether a heart valve condition called non-stenotic aortic valve fibro-calcific remodeling (AVSc) could be a crucial factor. Our study used advanced data analysis techniques, including topological data analysis (TDA), to explore this question. We unveil that AVSc is indeed a significant predictor of recurrent infarction in AMI patients. Our findings suggest that the presence of aortic valve remodeling should be taken into account when assessing the risk of recurrent AMI and managing these patients.

Chronic anticoagulant treatment and risk of mortality in SARS-Cov2 patients: a large population-based study.

BACKGROUND: Hypercoagulability is often seen in COVID-19 patients and thromboembolic events appear frequent; antithrombotic treatment has been proposed therefore as part of standard treatment for COVID-19. Under these premises, prior-to-infection antithrombotic treatment may have a protective effect with respect to COVID-19 related thromboembolic events. Aim of the present work was to evaluate the impact of prior-to-infection anticoagulant or antiplatelet treatment on COVID-19 outcomes. METHODS: Beneficiaries of the Regional Health Service of the Lombardy region of Italy aged ≥40 years with a COVID-19 diagnosis made between February 21st and July 18th, 2020 were included in the present study. The impact on COVID-19 mortality of pre-existing and chronic therapy with anticoagulant drugs (vitamin-K antagonist or new oral anticoagulants) was evaluated. Analyses were repeated with antiplatelets drugs. RESULTS: Among 79,934 SARS-CoV-2 patients beneficiaries of the Regional Healthcare System of the Lombardy Region who received a diagnosis between February 21st and July 18th, 2020, chronic pre-existing anticoagulant assumption was present in 6.0% and antiplatelets in 12.7%. The overall unadjusted mortality rate was 20.6%, with male sex, age category and comorbidity burden being significantly associated to increased mortality risk. Anticoagulant chronic treatment was not associated with a reduction in mortality. Similar results were observed when repeating the analyses for pre-existing oral antiplatelet treatment. CONCLUSIONS: In a large population-based study evaluating more than 79,000 COVID-19 patients, pre-existing antithrombotic therapy was not associated to a benefit in terms of mortality. Further studies are needed to evaluate the role of antithrombotic therapy as standard treatment among COVID-19 patients.

Multiple Medication Adherence and Related Outcomes in Community-Dwelling Older People on Chronic Polypharmacy: A Retrospective Cohort Study on Administrative Claims Data.

Poor medication adherence compromises treatment efficacy and adversely affects patients' clinical outcomes. This study aims to assess (1) multiple medication adherence to the most common drug classes chronically prescribed to older people, (2) the factors associated, and (3) the clinical outcomes. This retrospective cohort study included 122,655 community-dwelling patients aged 65-94 years old, newly exposed to chronic polypharmacy, and recorded in the Lombardy Region (northern Italy) administrative database from 2016 to 2018. Multiple medication adherence was assessed for drugs for diabetes, antithrombotics, antihypertensives, statins, and bisphosphonates, by calculating the daily polypharmacy possession ratio (DPPR). One-year mortality, nursing home, emergency department (ED), and hospital admission rates were calculated for 2019. The most prescribed drugs were antihypertensives (89.0%). The mean (std.dev) DPPR was 82.9% (15.6). Being female (OR = 0.85, 95%CI: 0.84-0.86), age ≥85 years (OR = 0.77, 95%CI: 0.76-0.79), and multimorbidity (≥4 diseases, OR = 0.88, 95%CI: 0.86-0.90) were associated with lower medication adherence. A higher DPPR was associated with clinical outcomes-in particular, improved survival (HR = 0.93 for 10/100-point increase, 95%CI: 0.92-0.94) and lower incidence in nursing home admissions (SDHR = 0.95, 95%CI: 0.93-0.97). Adherence to the most common chronic drugs co-prescribed to the older population was high. Better multiple medication adherence was associated with better clinical outcomes.

Is EuroSCORE II still a reliable predictor for cardiac surgery mortality in 2022? A retrospective study study.

OBJECTIVES: The European System for Cardiac Operation Risk Evaluation II (EuroSCORE II) is the most common tool used to evaluate the perioperative risk of mortality after cardiac surgery in Europe, and its use is currently recommended by the relevant guidelines. However, recently, its role has been questioned: Several papers have suggested that these algorithms may no longer be adequate for risk prediction due to an overestimation of adult cardiac surgical risk. Our goal was to validate the EuroSCORE II in the prediction of 30-day in-hospital mortality in patients undergoing open cardiac surgery in a high-volume hospital. METHODS: In this retrospective cohort study, we included all patients who underwent cardiac surgery from January 2016 to May 2022 within the departments of cardiac surgery of the Monzino Cardiology Centre in Milan, Italy. We evaluated the discrimination power of the EuroSCORE II by using the receiver operating characteristic curve and the corresponding area under the curve. We performed calibration plots to assess the concordance between the model's prediction and the observed outcomes. RESULTS: A total of 4,034 patients were included (mean age = 65.1 years; 68% males), of which 674 (16.7%) underwent isolated coronary artery bypass grafting. The EuroSCORE II showed a good discrimination power in predicting 30-day in-hospital mortality (area under the curve = 0.834). However, for interventions performed in an elective setting, very low values of the EuroSCORE II overestimated the observed mortality, whereas for interventions performed in an emergency setting, EuroSCORE II values above 10 extensively underestimated the observed mortality. CONCLUSIONS: Our study suggests that the EuroSCORE II seems not to be a reliable score in estimating the true risk of death, especially in high-risk patients.

Medication adherence in community-dwelling older people exposed to chronic polypharmacy.

BACKGROUND: To evaluate medication adherence and associated factors of seven of the most common drug classes prescribed to community-dwelling older people. METHODS: This is a retrospective cohort study on medication adherence in community-dwelling older people (65-94 years old) on chronic polypharmacy and recorded from 2013 to 2015 in the administrative database of the Lombardy region (Northern Italy). Adherence was assessed for diabetic drugs, antithrombotic agents, drugs acting on the renin-angiotensin system, statins, bisphosphonates, antidepressants and drugs for obstructive airway diseases by calculating the medication possession ratio (MPR). Patients were then divided in fully (MPR ≥80%), partially (40%≤MPR<80%) and poorly adherent (10%

Renin-Angiotensin-Aldosterone System Inhibitors and Risk of Death in Patients Hospitalised with COVID-19: A Retrospective Italian Cohort Study of 43,000 Patients.

INTRODUCTION: The epidemic due to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection has been spreading globally, raising increasing concerns. There are several controversial hypotheses on the potentially harmful or beneficial effects of antihypertensive drugs acting on the renin-angiotensin-aldosterone system (RAAS) in coronavirus disease 2019 (COVID-19). Furthermore, there is accumulating evidence, based on several observational studies, that angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin receptor blockers (ARBs) do not increase the risk of contracting SARS-CoV-2 infection. On the other hand, conflicting findings regarding the role of ACEIs/ARBs as prognosis modifiers in COVID-19 hospitalised patients have been reported. OBJECTIVE: The aim of this large-scale, retrospective cohort study was to investigate whether prior exposure to ACEIs and/or ARBs was associated with all-cause mortality among over 40,000 hospitalised COVID-19 patients compared with calcium channel blockers (CCBs), a potential therapeutic alternative. METHODS: This study was conducted using COVID-19 registries linked to claims databases from Lombardy, Veneto and Reggio Emilia (overall, 25% of Italian population). Overall, 42,926 patients hospitalised between 21 February and 21 April 2020 with a diagnosis of COVID-19 confirmed by real-time polymerase chain reaction tests were included in this study. All-cause mortality occurring in or out of hospital, as reported in the COVID-19 registry, was estimated. Using Cox models, adjusted hazard ratios (HRs) of all-cause mortality (along with 95% confidence intervals [CIs]) were estimated separately for ACEIs/ARBs and other antihypertensives versus CCBs and non-use. RESULTS: Overall, 11,205 in- and out-of-hospital deaths occurred over a median of 24 days of follow-up after hospital admission due to COVID-19. Compared with CCBs, adjusted analyses showed no difference in the risk of death among ACEI (HR 0.97, 95% CI 0.89-1.06) or ARB (HR 0.98, 95% CI 0.89-1.06) users. When non-use of antihypertensives was considered as a comparator, a modest statistically significant increase in mortality risk was observed for any antihypertensive use. However, when restricting to drugs with antihypertensive indications only, these marginal increases disappeared. Sensitivity and subgroup analyses confirmed our main findings. CONCLUSIONS: ACEI/ARB use is not associated with either an increased or decreased risk of all-cause mortality, compared with CCB use, in the largest cohort of hospitalised COVID-19 patients exposed to these drugs studied to date. The use of these drugs therefore does not affect the prognosis of COVID-19. This finding strengthens recommendations of international regulatory agencies about not withdrawing/switching ACEI/ARB treatments to modify COVID-19 prognosis.

A new population-based risk stratification tool was developed and validated for predicting mortality, hospital admissions, and health care costs.

OBJECTIVES: The aim of this study was to develop a new population-based risk stratification tool (Chronic Related Score [CReSc]) for predicting 5-year mortality and other outcomes. STUDY DESIGN AND SETTING: The score included 31 conditions selected from a list of 65 candidates whose weights were assigned according to the Cox model coefficients. The model was built from a sample of 5.4 million National Health Service (NHS) beneficiaries from the Italian Lombardy Region and applied to the remaining 2.7 million NHS beneficiaries. Predictive performance was assessed by discrimination and calibration. CReSc ability in predicting secondary endpoints (i.e., hospital admissions and health care costs) was investigated. Finally, the relationship between CReSc and income was considered. RESULTS: Among individuals aged 50-85 years, CReSc performance showed (1) an area under the receiver operating characteristic curve of 0.730, (2) an improved reclassification from 44% to 52% with respect to other scores, and (3) a remarkable calibration. A trend toward increasing rates of all the considered endpoints as CReSc increases was observed. Compared with individuals on low-intermediate income, NHS beneficiaries on high income showed better CReSc profile. CONCLUSION: We developed a risk stratification tool able to predict mortality, costs, and hospital admissions. The application of CReSc may generate clinically and operationally important effects.