Polypill Strategy in Secondary Cardiovascular Prevention.

BACKGROUND: A polypill that includes key medications associated with improved outcomes (aspirin, angiotensin-converting-enzyme [ACE] inhibitor, and statin) has been proposed as a simple approach to the secondary prevention of cardiovascular death and complications after myocardial infarction. METHODS: In this phase 3, randomized, controlled clinical trial, we assigned patients with myocardial infarction within the previous 6 months to a polypill-based strategy or usual care. The polypill treatment consisted of aspirin (100 mg), ramipril (2.5, 5, or 10 mg), and atorvastatin (20 or 40 mg). The primary composite outcome was cardiovascular death, nonfatal type 1 myocardial infarction, nonfatal ischemic stroke, or urgent revascularization. The key secondary end point was a composite of cardiovascular death, nonfatal type 1 myocardial infarction, or nonfatal ischemic stroke. RESULTS: A total of 2499 patients underwent randomization and were followed for a median of 36 months. A primary-outcome event occurred in 118 of 1237 patients (9.5%) in the polypill group and in 156 of 1229 (12.7%) in the usual-care group (hazard ratio, 0.76; 95% confidence interval [CI], 0.60 to 0.96; P = 0.02). A key secondary-outcome event occurred in 101 patients (8.2%) in the polypill group and in 144 (11.7%) in the usual-care group (hazard ratio, 0.70; 95% CI, 0.54 to 0.90; P = 0.005). The results were consistent across prespecified subgroups. Medication adherence as reported by the patients was higher in the polypill group than in the usual-care group. Adverse events were similar between groups. CONCLUSIONS: Treatment with a polypill containing aspirin, ramipril, and atorvastatin within 6 months after myocardial infarction resulted in a significantly lower risk of major adverse cardiovascular events than usual care. (Funded by the European Union Horizon 2020; SECURE ClinicalTrials.gov number, NCT02596126; EudraCT number, 2015-002868-17.).

Incidence and risk of arterial and venous thrombotic events in Systemic Lupus Erythematosus patients: a population-based study.

OBJECTIVES: Current data on arterial and venous thrombotic events (ATE & VTE) and cardiovascular (CV) risk management in European systemic lupus erythematosus (SLE) population are limited. This study aimed to investigate the incidence and risk of thrombotic events and all-cause death in an Italian SLE cohort over the past decade, along with its pharmacotherapy. METHODS: Incident SLE cases between 2010 and 2019 were identified using administrative health databases of the Lombardy Region. The association between SLE and outcomes, compared with age- and sex-matched controls, was reported as incidence rate per 1000 person-years and as adjusted hazard ratios with 95% confidence intervals. RESULTS: Overall, 2133 SLE patients and 21 283 no-SLE individuals were included. A higher incidence rate of ATE (4.22 vs 2.26 1000 PY), VTE (1.85 vs 0.67 1000 PY,) and all-cause death (15.18 vs 6.22 1000 PY) was reported in SLE patients than in those without (p< 0.0001) as well as an increased risk of ATE (HR, 1.65; 95% CI, 1.20-2.26), VTE (HR, 2.25; 95% CI, 1.35-3.74), and all-cause death (HR, 1.81; 95% CI, 1.52-2.15). After SLE diagnoses, hydroxychloroquine and glucocorticoids were prescribed for at least 60% of patients. Additionally, a higher exposure to cardiovascular medications was also seen in SLE patients. CONCLUSION: Our findings confirmed higher risks of ATE, VTE and all-cause death in SLE patients. While increased CV medications use after SLE diagnoses suggests heightened awareness to CV risk profile, more attention is required to balance SLE disease activity with minimizing exposure to drugs associated with exacerbating CV risk.

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.

Diabetes mellitus duration and mortality in patients hospitalized with acute myocardial infarction.

BACKGROUND: Diabetes mellitus (DM) is associated with an increased mortality risk in patients hospitalized with acute myocardial infarction (AMI); however, no studies have investigated the impact of the duration of DM on in-hospital mortality. In this study, we evaluated in-hospital mortality in AMI patients according to DM status and its duration. METHODS: Using health administrative databases of Lombardy, DM patients≥50 years hospitalized with AMI from 2010 to 2019 were included in the analysis and were stratified according to the duration of DM: <5, 5-10, and > 10 years. The primary endpoint was mortality during AMI hospitalization and the secondary endpoint was 1-year mortality in comparison with No-DM patients. Logistic and Cox regressions analyses were used to estimate odds ratios (ORs, CI 95%) and hazard ratios (HRs, CI 95%) for the outcomes, according to DM status and duration and AMI type (STEMI and NSTEMI). RESULTS: Our study cohort comprised 29,566 and 109,247 DM and No-DM patients, respectively. Adjusted ORs and HRs showed a significantly higher risk of in-hospital mortality (OR 1.50, 95% CI 1.43-1.58) and 1-year mortality (HR 1.51, 95% CI 1.46-1.55) in DM patients in comparison with those without. These risks increased progressively with the duration of DM, with the highest risk observed in patients with DM duration ≥ 10 years (OR 1.59, 95% CI 1.50-1.69 for in-hospital mortality and HR 1.59, 95% CI 1.53-1.64 for 1-year mortality). These findings were similar in STEMI and in NSTEMI patients. CONCLUSIONS: Our study demonstrates that the duration of DM parallels mortality risk in patients hospitalized with AMI, highlighting that DM duration should be considered as an important early prognostic risk factor in patients with AMI.

Effectiveness and safety of GLP-1 receptor agonists versus SGLT-2 inhibitors in type 2 diabetes: an Italian cohort study.

BACKGROUND: GLP-1 receptor agonists (GLP-1 RA) and SGLT-2 inhibitors (SGLT-2i) have shown to reduce the risk of major adverse cardiovascular events (MACE), death and worsening nephropathy when added to standard of care. However, these two dug classes differ in efficacy and safety. We compared the effectiveness and safety profile of GLP-1 RA and SGLT-2i in a large and unselected cohort of patients with type 2 diabetes resident in Lombardy from 2015 to 2020. METHODS: Using linkable administrative health databases, we included patients aged 50 years and older initiating GLP-1 RA or SGLT-2i. Clinical events were: death, hospital admission for myocardial infarction (MI), stroke, heart failure (HF), and renal disease as individual and composite outcomes (MACE-3: all cause-death, non-fatal MI, non-fatal stroke; MACE-4: MACE-3 plus unstable angina). Outcomes were evaluated separately in subjects with and without previous cardiovascular (CV) diseases. Treatments were compared using Cox proportional hazards regression model after Propensity Score Matching (PSM) in both intention-to-treat (ITT) and per protocol (PP) analyses. Serious adverse events were also evaluated. RESULTS: The analysis comprised 20,762 patients per cohort. The ITT analysis showed a significant risk reduction for non-fatal MI (HR 0.77; CI 95% 0.66-0.90), MACE-3 (HR 0.91; CI 95% 0.84-0.98), and MACE-4 (HR 0.92; CI 95% 0.86-0.99) in GLP-1RA compared with SGLT-2i users, while no difference was reported in the incidence of HF hospitalization and stroke between the two cohorts. Similar benefits were found in the subgroup of patients without previous CV diseases only. PP analysis largely confirmed the main results. The incidence of serious adverse events was low in both cohorts (< 1%). CONCLUSIONS: GLP-1RA showed to be equally safe and more effective than SGLT-2i in reducing the risk of MACE-3, MACE-4 and MI. This study adds to the growing body of real-world evidence addressing the specific clinical properties of GLP-1RA and SGLT-2i in everyday practice to tailor treatment to the individual patient.

Metformin use is associated with a decrease in the risk of hospitalization and mortality in COVID-19 patients with diabetes: A population-based study in Lombardy.

AIM: To compare the association of metformin use and coronavirus disease 2019 (COVID-19) outcomes in a cohort of 31 966 patients with diabetes in Lombardy. METHODS: We used a COVID-19 linkable administrative regional database to select patients with diabetes who were aged 40 years or older. They had at least two prescriptions of antidiabetic drugs in 2019 and a positive test for severe acute respiratory syndrome coronavirus-2 from 15 February 2020 to 15 March 2021. The association of metformin use and clinical outcomes was assessed by multivariable logistic regression analyses and after propensity score matching (PSM). Clinical outcomes were all-cause mortality, in-hospital mortality, hospitalization for COVID-19, and admission to an intensive care unit (ICU). RESULTS: In multivariable models, metformin use was associated with a significantly lower risk of total mortality (OR 0.70; 95% CI 0.66-0.75), in-hospital mortality (OR 0.68; 95% CI 0.63-0.73), hospitalization for COVID-19 (OR 0.86; 95% CI 0.81-0.91), and ICU admission (OR 0.81; 95% CI 0.69-0.94) compared with metformin non-users. Results were similar after PSM; metformin was associated with a significantly lower risk of total mortality (OR 0.79; 95% CI 0.73-0.86), in-hospital mortality (OR 0.74; 95% CI 0.67-0.81), and ICU admission (OR 0.77; 95% CI 0.63-0.95). CONCLUSIONS: In this large cohort, metformin use was associated with a protective effect in COVID-19 clinical outcomes, suggesting that it might be a potentially useful drug to prevent severe COVID-19 disease, although randomized controlled trials (RCTs) are needed to confirm this. While awaiting the results of RCTs, we suggest continuing prescribing metformin to COVID-19 patients with diabetes.

Lower risk of death and cardiovascular events in patients with diabetes initiating glucagon-like peptide-1 receptor agonists or sodium-glucose cotransporter-2 inhibitors: A real-world study in two Italian cohorts.

AIM: To examine the efficacy and safety of glucagon-like peptide-1 receptor agonists (GLP-1RAs) and sodium-glucose cotransporter-2 (SGLT2) inhibitors compared with other antihyperglycaemic agents (AHAs) in large and unselected populations of the Lombardy and Apulia regions in Italy. MATERIALS AND METHODS: An observational cohort study of first-time users of GLP-1RAs, SGLT2 inhibitors or other AHAs was conducted from 2010 to 2018. Death and cardiovascular (CV) events were evaluated using conditional Cox models in propensity-score-matched populations. Adjusted hazard ratios (HRs) with 95% confidence intervals (CIs) were calculated for each region and in a meta-analysis for pooled risks. RESULTS: After propensity-score matching, the Lombardy cohort included 18 716 and 11 683 patients and the Apulia cohort 9772 and 6046 patients for the GLP-1RA and SGLT2 inhibitor groups, respectively. Use of GLP-1RAs was associated with lower rates of death (HR 0.61, CI 0.56-0.65, Lombardy; HR 0.63, CI 0.55-0.71, Apulia), cerebrovascular disease and ischaemic stroke (HR 0.70, CI 0.63-0.79; HR 0.72, CI 0.60-0.87, Lombardy), peripheral vascular disease (HR 0.72, CI 0.64-0.82, Lombardy; HR 0.80, CI 0.67-0.98, Apulia), and lower limb complications (HR 0.67, CI 0.56-0.81, Lombardy; HR 0.69, CI 0.51-0.93, Apulia). Compared with other AHAs, SGLT2 inhibitor use decreased the risk of death (HR 0.47, CI 0.40-0.54, Lombardy; HR 0.43, CI 0.32-0.57, Apulia), cerebrovascular disease (HR 0.75, CI 0.61-0.91, Lombardy; HR 0.72, CI 0.54-0.96, Apulia), and heart failure (HR 0.56, CI 0.46-0.70, Lombardy; HR 0.57, CI 0.42-0.77, Apulia). In the pooled cohorts, a reduction in heart failure was also observed with GLP-1RAs (HR 0.89, 95% CI 0.82-0.97). Serious adverse events were quite low in frequency. CONCLUSION: Our findings from real-world practice confirm the favourable effect of GLP-1RAs and SGLT2 inhibitors on death and CV outcomes across both regions consistently. Thus, these drug classes should be preferentially considered in a broad type 2 diabetes population beyond those with CV disease.

Emergency department visits in older people: pattern of use, contributing factors, geographical differences and outcomes.

AIMS: To assess the pattern of use of Emergency Departments (EDs), factors contributing to the visits, geographical distribution and outcomes in people aged 65 years or more living in the Italian Lombardy Region in 2012. METHODS: Based on an administrative database the study population was divided into groups according to the number of ED visits. A multinomial logistic regression model was performed to compare the characteristics of each group. The Getis-Ord's G statistic was used to evaluate the clusters of high and low visit prevalence odd ratios (OR) at district level. To estimate the severity of the disease leading to ED attendance, visits were stratified based on the level of emergency and outcome. RESULTS: About 2 million older people were included in the analyses: 78 % had no ED visit, 15 % only 1, 7 % 2 or more. Male sex, age 85 years or more, high number of drugs, ED visits and hospital admissions in the previous year and the location of an ED within 10 km from the patient's place were all factors associated with a higher risk to have more ED visits. Clusters of high and low prevalence of visits were found for occasional users. Overall, 83 % of ED visit with a low emergency triage code at admission had as visit outcome discharge at home. CONCLUSIONS: In older people several variables were associated with an increased risk to have a high number of ED visits. Most of the visits were done for non-urgent problems and significant geographic differences were observed for occasional users.

Epidemiologic Trends in Hospitalized Ischemic Stroke from 2002 to 2010: Results from a Large Italian Population-Based Study.

BACKGROUND: To describe the incidence of ischemic stroke, short-term mortality, recurrences, and prescription patterns. METHODS: Data from administrative health databases of the Lombardy Region from 2002 to 2010 (about 4 million people) were analyzed for stroke incidence and recurrence, mortality, and drug prescriptions after an ischemic stroke. RESULTS: A total of 43,352 patients with a first hospital admission for ischemic stroke were identified. During 8 years, stroke incidence decreased from 3.2 of 1000 to 2.4 of 1000 (P < .001) in people aged 65-74 years, from 7.1 of 1000 to 5.3 of 1000 (P < .001) at ages 75-84 years and from 11.9 of 1000 to 9.4 of 1000 (P < .001) at age 85 years or older. Stroke recurrences dropped by 30% (from 10.0% to 7.0%, P < .001) and 30-day mortality rate also decreased. Prescription trends showed linear increase in antiplatelets and lipid-lowering drugs, respectively, from 60.2% to 65.0% (P < .001) and from 19.1% to 34.6% (P < .001), whereas antihypertensive prescriptions did not change appreciably. Anticoagulant prescription increased in patients with atrial fibrillation, from 64.8% to 72.1% in the 65-74 years age group, (P = .004) and from 40.2% to 53.7% in the 75-84 years age group (P < .001); less than 20% of the 85 years or older age group were treated with anticoagulants (P < .0001). CONCLUSIONS: Stroke incidence, recurrence, and 30-day mortality decreased from 2002 to 2010 concomitant with an increase in prescriptions of secondary stroke prevention drugs.

Changes in prescribing patterns and clinical outcomes in elderly diabetic patients in 2000 and 2010: analysis of a large Italian population-based study.

PURPOSE: To describe prescribing patterns in elderly Italian diabetic patients of the Lombardy Region in 2000 and 2010 using an administrative database. Hospital admissions and mortality were also recorded and compared in the two index years. METHODS: Analyses were performed on the whole cohort of elderly diabetic patients and across age groups. Direct age standardization was done, with data from the Lombardy Region database for 2005 used as reference to compare diabetic populations in the two index years. Logistic regression models were used to analyze changes in hospital admissions and mortality and to calculate odds ratios. RESULTS: Using data retrieved from the Lombardy Region database we identified 176,384 and 283,982 elderly diabetic patients in 2000 and 2010, respectively. The overall rates of patients treated with antidiabetic drugs were 92.5% in 2000 and 97.0% in 2010. Between 2000 and 2010 the prescribing of glibenclamide declined by 30.0% (from 52.9 to 22.9%, p < 0.001) and that of biguanides rose by 17.4 % (from 47.5 to 64.8%, p < 0.001). In 2010 thiazolidinediones, dipeptidyl peptidase-4 inhibitors and incretin mimetic drugs were seldom prescribed. Drugs for cardiovascular prevention rose in all age classes from 2000 to 2010, and the rates of hospital admission overall fell from 32.0 to 26.8% (p < 0.001) during the same period, with the exception of those aged ≥85 years. Between 2000 and 2010 the mortality rate decreased in patients aged 65-74 years (from 3.4 to 2.9%, p < 0.0001) and rose significantly in those aged ≥85 years. CONCLUSIONS: The drug prescription profile of elderly diabetic patients changed from 2000 to 2010, with a tendency toward recommended drugs. These changes may possibly be linked to the decrease in both hospital admissions and mortality in the diabetic group aged 65-74 years.

Prevalence and Predictors of Post-Acute COVID-19 Symptoms in Italian Primary Care Patients.

BACKGROUND: Despite all the progress in the management of acute COVID-19, it is still not clear why some people continue to experience symptoms after recovery. Using data from a self-administered online survey, we assessed the prevalence and predictors of post-acute COVID-19 in an unselected population followed by GPs. METHODS: Patients ≥18 years with a confirmed COVID-19 diagnosis were included. The survey collected information on demographics, risk factors, COVID-19 course and symptomatology. Fatigue and Quality of Life questionnaires were also administered. Descriptive statistics were used to describe patients' characteristics, stratified as acute and post-acute COVID-19. Logistic regression models were used to assess the association between clinical characteristics and post-acute COVID-19. RESULTS: A total of 1108 surveys were analyzed. Nearly 29% of patients reported post-acute COVID-19. The more persistent symptoms were fatigue, memory and concentration impairment. Adjusted Odds Ratio (OR) showed a significantly higher probability of post-acute COVID-19 for women compared to men (OR 1.9, 95% CI 1.4-2.5), for age >50 years than ≤50 years (OR 1.6, 95% CI 1.2-2.2), for BMI > 25 compared to BMI ≤ 25 (OR 1.6, 95% CI 1.1-2.1) and those with autoimmune diseases, compared to those without (OR 1.8 95% CI 1.1-2.9). In addition, a significant association was found with COVID-19 hospitalization, anxiety and allergies. We found that post-acute COVID-19 patients showed a higher fatigue and a worst quality of life. CONCLUSIONS: These findings suggest the need for tailored personalized strategies to improve the management of patients with post-acute COVID-19.

Proton Pump Inhibitor Use and the Risk of Cardiovascular Complications and Death in Older Adults with Diabetes: A Population-Based Cohort Study.

BACKGROUND: The unfavorable effect of proton pump inhibitors (PPIs) on cardiovascular (CV) outcomes and mortality was reported in the general population. We investigated the impact of PPIs on CV outcomes and total mortality in older people with diabetes mellitus (DM) for whom evidence is missing. METHODS: Using administrative health databases of the Lombardy Region, we analyzed the risk of myocardial infarction (MI), ischemic stroke and total mortality in individuals with DM (≥65 years of age) exposed to PPIs in 2015 and followed up to 2021. The outcomes were analyzed using a multivariable-adjusted Cox proportional hazards model to compute hazard ratios (HRs) with 95% confidence intervals (CIs). HRs between PPI users and non-users were also estimated in selected subgroups. A sensitivity analysis was also performed in a 1:1 propensity score matching population. RESULTS: A total of 284,068 patients were included in the analysis (49.4% PPI users, 50.6% non-PPI users). A higher prevalence of comorbidities and medications was reported in PPI users as compared with non-users. During a median follow-up of 6.7 years, the use of PPIs was associated with a higher risk for ischemic stroke (HR 1.14, 95% CI 95% 1.08-1.20), MI (HR 1.36, 95% CI 1.31-1.41) and total mortality (HR 1.24, 95% CI 1.22-1.26). These risks were higher in PPI users regardless of the PPI type. Among sexes, previous CV diseases, and insulin subgroups, the use of PPIs was correlated with a statistically significant increased risk of ischemic stroke in men, in individuals without a history of CV disease, and in those who were not treated with insulin. A significantly higher risk of MI was associated with PPIs for all subgroups, as well as for total mortality, with the exception of patients with a previous history of CV diseases. The sensitivity analysis confirmed the results of the unmatched cohort. CONCLUSIONS: Our findings confirmed an increased risk of CV events and all-cause mortality in a large population of older adults with DM exposed to PPIs. This could have an important impact on public health and costs for National Health Service, therefore a regular assessment of PPI appropriateness is recommended, particularly in this population.

Antidiabetic Drug Prescription Pattern in Hospitalized Older Patients with Diabetes.

OBJECTIVE: To describe the prescription pattern of antidiabetic and cardiovascular drugs in a cohort of hospitalized older patients with diabetes. METHODS: Patients with diabetes aged 65 years or older hospitalized in internal medicine and/or geriatric wards throughout Italy and enrolled in the REPOSI (REgistro POliterapuie SIMI-Società Italiana di Medicina Interna) registry from 2010 to 2019 and discharged alive were included. RESULTS: Among 1703 patients with diabetes, 1433 (84.2%) were on treatment with at least one antidiabetic drug at hospital admission, mainly prescribed as monotherapy with insulin (28.3%) or metformin (19.2%). The proportion of treated patients decreased at discharge (N = 1309, 76.9%), with a significant reduction over time. Among those prescribed, the proportion of those with insulin alone increased over time (p = 0.0066), while the proportion of those prescribed sulfonylureas decreased (p < 0.0001). Among patients receiving antidiabetic therapy at discharge, 1063 (81.2%) were also prescribed cardiovascular drugs, mainly with an antihypertensive drug alone or in combination (N = 777, 73.1%). CONCLUSION: The management of older patients with diabetes in a hospital setting is often sub-optimal, as shown by the increasing trend in insulin at discharge, even if an overall improvement has been highlighted by the prevalent decrease in sulfonylureas prescription.

Impact of first and second/third wave of COVID-19 pandemic on post-acute cardiovascular outcomes in Lombardy.

Background: COVID-19 has been associated with a higher risk of post-acute complications. Our aim was to analyze and compare post-acute cardiovascular complications of COVID-19 survivors of the first and second/third pandemic waves in Lombardy, in both hospitalized and non-hospitalized COVID-19 patients. Methods and results: We included adults aged ≥40 years infected during the first and second/third waves of COVID-19 pandemic. The follow-up initiated 30 days after COVID-19 diagnosis and continued up to 9 months. Hazard ratios (HRs) and 95% confidence intervals (CIs) of the post-acute cardiovascular outcomes were calculated against an inverse probability treatment weighted control group. Subgroup analysis were performed by age classes, sex, previous cardiovascular disease and stratified by COVID-19 hospitalization status to explore the impact of COVID-19 severity on outcomes. Compared to the control group, COVID-19 patients had an increased risk of hospitalization for any cardiovascular complications (HR 1st wave 1.53 95% CI: 1.38-1.69; HR 2nd/3rd wave 1.25 95% CI: 1.19-1.31) and for individual cardiovascular outcomes, although HRs were higher in COVID-19 group from the 1st pandemic wave. The results were confirmed in the subgroup analyses. Of note, the risk for any cardiovascular disease was also evident even among individuals who were not hospitalized during the acute phase of the infection. Conclusion: Our results provide evidence that COVID-19 is a risk factor for post-acute cardiovascular complications among different pandemic waves regardless of COVID-19 severity, age, sex and a history of cardiovascular diseases. Care strategies of people with COVID-19 should include cardiac monitoring.

Dipeptidyl Peptidase-4 Inhibitors, Glucagon-like Peptide-1 Receptor Agonists, and Sodium-Glucose Cotransporter-2 Inhibitors and COVID-19 Outcomes.

PURPOSE: It has been reported that dipeptidyl peptidase-4 inhibitors (DPP-4i), glucagon-like peptide-1 receptor agonists (GLP-1 RA), and sodium-glucose cotransporter-2 inhibitors (SGLT-2i) have a role in modulation of inflammation associated with coronavirus disease 2019 (COVID-19). This study assessed the effect of these drug classes on COVID-19-related outcomes. METHODS: Using a COVID-19 linkable administrative database, we selected patients aged ≥40 years with at least 2 prescriptions of DPP-4i, GLP-1 RA, or SGLT-2i or any other antihyperglycemic drug and a diagnosis of COVID-19 from February 15, 2020, to March 15, 2021. Adjusted odds ratios (ORs) with 95% CIs were used to calculate the association between treatments and all-cause and in-hospital mortality and COVID-19-related hospitalization. A sensitivity analysis was performed by using inverse probability treatment weighting. FINDINGS: Overall, 32,853 subjects were included in the analysis. Multivariable models showed a reduction of the risk for COVID-19 outcomes for users of DPP-4i, GLP-1 RA, and SGLT-2i compared with nonusers, although statistical significance was reached only in DPP-4i users for total mortality (OR, 0.89; 95% CI, 0.82-0.97). The sensitivity analysis confirmed the main results reaching a significant reduction for hospital admission in GLP-1 RA users and in-hospital mortality in SGLT-2i users compared with nonusers. IMPLICATIONS: This study found a beneficial effect in the risk reduction of COVID-19 total mortality in DPP-4i users compared with nonusers. A positive trend was also observed in users of GLP-1 RA and SGLT-2i compared with nonusers. Randomized clinical trials are needed to confirm the effect of these drug classes as potential therapy for the treatment of COVID-19.

Prescribing trends of glucose-lowering drugs in older adults from 2010 to 2021: A population-based study of Northern Italy.

AIMS: To describe glucose-lowering drugs prescribing pattern in a large population of older diabetics from 2010 to 2021. METHODS: Using linkable administrative health databases, we included patients aged 65-90 years treated with glucose-lowering drugs. Prevalence rate of drugs was collected within each study year. A stratified analysis by gender, age and coexistence of cardiovascular disease (CVD) was conducted. RESULTS: A total of 251 737 and 308 372 patients were identified in 2010 and 2021, respectively. Use of metformin (68.4% to 76.6%), DPP-4i (1.6% to 18.4%), GLP-1-RA (0.4% to 10.2%), SGLT2i (0.6% to 11.1%) increased, while sulfonylureas (53.6% to 20.7%) and glinides (10.5% to 3.5%) decreased over time. Metformin, glitazones, GLP1-RA, SGLT2i and DPP4i (except for 2021) usage decreased with aging, in contrast to sulfonylureas, glinides and insulin. The coexistence of CVD was associated with a higher prescription of glinides, insulin, DPP-4i, GLP1-RA and SGLT2i, particularly in 2021. CONCLUSIONS: We found a significant increase in the prescriptions of GLP-1 RA and SGLT2i in older diabetics, mainly in those with CVD. However, drugs without CV benefits including sulfonylureas and DPP-4i continued to be highly prescribed in older patients. There is still room to improve the management in this population according to recommendations.

The Moli-sani risk score, a new algorithm for measuring the global impact of modifiable cardiovascular risk factors.

BACKGROUND: Cardiovascular (CV) disease is preventable through interventions targeting modifiable factors. Most algorithms based on modifiable CV risk factors (CV-rf) have been developed in US populations and do not account for the role of diet. We aimed to assess an algorithm based on modifiable CV-rf including diet, using data from an Italian population. METHODS: To derive the Moli-sani Risk Score (MRS), we used data on 16,656 men and women (age ≥ 35 y) from the population of the Moli-sani Study. The Risk-and-Prevention-Study, Italy (N = 8606) acted as external validation cohort and the Life's-Simple-7 score was used as benchmark. The MRS targeted at fatal or non-fatal CV events and included 9 common modifiable CV-rf. RESULTS: After 8.1 years (median) of follow-up, 816 events occurred in the derivation cohort. The MRS was calculated as a weighted sum of its 9 components, with weights reflecting the strength of the association. In comparison with individuals in the first, those in the fourth quartile of the score had hazard ratio (HR) for CV events equal to 3.18 (95%CI: 2.54-3.97). One more point in the score was associated with 7% (6%-8%) and 4% (3%-5%) higher hazard of events in the derivation and validation cohort, respectively. The MRS performed better than the Life's Simple-7 for discrimination. CONCLUSION: We propose the Moli-sani Risk Score, a validated, performing algorithm able to measure the combined impact that modifiable CV-rf have on CV risk. The score can be used to design preventive interventions, quantify the effectiveness of interventions, and compare different preventive strategies.

Rationale and design of the CV-PREVITAL study: an Italian multiple cohort randomised controlled trial investigating innovative digital strategies in primary cardiovascular prevention.

INTRODUCTION: Prevention of cardiovascular disease (CVD) is of key importance in reducing morbidity, disability and mortality worldwide. Observational studies suggest that digital health interventions can be an effective strategy to reduce cardiovascular (CV) risk. However, evidence from large randomised clinical trials is lacking. METHODS AND ANALYSIS: The CV-PREVITAL study is a multicentre, prospective, randomised, controlled, open-label interventional trial designed to compare the effectiveness of an educational and motivational mobile health (mHealth) intervention versus usual care in reducing CV risk. The intervention aims at improving diet, physical activity, sleep quality, psycho-behavioural aspects, as well as promoting smoking cessation and adherence to pharmacological treatment for CV risk factors. The trial aims to enrol approximately 80 000 subjects without overt CVDs referring to general practitioners' offices, community pharmacies or clinics of Scientific Institute for Research, Hospitalization and Health Care (Italian acronym IRCCS) affiliated with the Italian Cardiology Network. All participants are evaluated at baseline and after 12 months to assess the effectiveness of the intervention on short-term endpoints, namely improvement in CV risk score and reduction of major CV risk factors. Beyond the funded life of the study, a long-term (7 years) follow-up is also planned to assess the effectiveness of the intervention on the incidence of major adverse CV events. A series of ancillary studies designed to evaluate the effect of the mHealth intervention on additional risk biomarkers are also performed. ETHICS AND DISSEMINATION: This study received ethics approval from the ethics committee of the coordinating centre (Monzino Cardiology Center; R1256/20-CCM 1319) and from all other relevant IRBs and ethics committees. Findings are disseminated through scientific meetings and peer-reviewed journals and via social media. Partners are informed about the study's course and findings through regular meetings. TRIAL REGISTRATION NUMBER: NCT05339841.

Insulin treatment in patients with diabetes mellitus and heart failure in the era of new antidiabetic medications.

BACKGROUND: Coexistent heart failure (HF) and diabetes mellitus (DM) are associated with marked morbidity and mortality. Optimizing treatment strategies can reduce the number and severity of events. Insulin is frequently used in these patients, but its benefit/risk ratio is still not clear, particularly since new antidiabetic drugs that reduce major adverse cardiac events (MACEs) and renal failure have recently come into use. Our aim is to compare the clinical effects of insulin in a real-world setting of first-time users, with sodium-glucose cotransporter-2 inhibitor (SGLT-2i), glucagon-like peptide-1 receptor agonist (GLP-1RA) and the other antihyperglycemic agents (other-AHAs). METHODS: We used the administrative databases of two Italian regions, during the years 2010-2018. Outcomes in whole and propensity-matched cohorts were examined using Cox models. A meta-analysis was also conducted combining the data from both regions. RESULTS: We identified 34 376 individuals ≥50 years old with DM and HF; 42.0% were aged >80 years and 46.7% were women. SGLT-2i and GLP-1RA significantly reduced MACE compared with insulin and particularly death from any cause (SGLT-2i, hazard ratio (95% CI) 0.29 (0.23 to 0.36); GLP-1RA, 0.482 (0.51 to 0.42)) and first hospitalization for HF (0.57 (0.40 to 0.81) and 0.67 (0.59 to 0.76)). CONCLUSIONS: In patients with DM and HF, SGLT-2i and GLP-1RA significantly reduced MACE compared with insulin, and particularly any cause of death and first hospitalization for HF. These groups of medications had high safety profiles compared with other-AHAs and particularly with insulin. The inadequate optimization of HF and DM cotreatment in the insulin cohort is noteworthy.