Impact of liver disease on oral anticoagulant prescription and major adverse events in patients with atrial fibrillation: analysis from a population-based cohort study.

AIMS: Data on the impact of liver disease (LD) in patients with atrial fibrillation (AF) and the role of oral anticoagulant (OAC) drugs for stroke prevention are limited. METHODS AND RESULTS: A retrospective observational population-based cohort study on the administrative health databases of Lombardy region Italy. All AF patients ≥40 years admitted to hospital from 2000 to 2018 were considered. Atrial fibrillation and LD diagnosis were established using ICD9-CM codes. Use of OAC was determined with Anatomical Therapeutic Chemical codes. Primary study outcomes were stroke, major bleeding, and all-cause death. Among 393 507 AF patients, 16 168 (4.1%) had concomitant LD. Liver disease AF patients were significantly less treated with OAC. Concomitant LD was associated with an increased risk in all the study outcomes [hazard ratio (HR): 1.18, 95% confidence interval (CI): 1.11-1.25 for stroke; HR: 1.57, 95% CI: 1.47-1.66 for major bleeding; HR: 1.41, 95% CI: 1.39-1.44 for all-cause death]. Use of OAC in patients with AF and LD resulted in a reduction in stroke (HR: 0.80, 95% CI: 0.70-0.92), major bleeding (HR: 0.86, 95% CI: 0.74-0.99), and all-cause death (HR: 0.77, 95% CI: 0.73-0.80), with similar results according to subgroups. A net clinical benefit (NCB) analysis suggested a positive benefit/risk ratio in using OAC in AF patients with LD (NCB: 0.408, 95% CI: 0.375-0.472). CONCLUSION: In AF patients, concomitant LD carries a significantly higher risk for all clinical outcomes. Use of OAC in AF patients with LD was associated with a significant favourable benefit/risk ratio, even in high-risk patient subgroups.

Sex-related differences in prevalence, treatment and outcomes in patients with atrial fibrillation.

To analyze sex-related differences about AF prevalence, use of OAC and outcomes focusing on the older age classes. We used administrative data of the Lombardy Region, describing period prevalence, use of OAC and outcomes from 2002 to 2014 for all patients diagnosed with AF. AF prevalence over the 2002-2014 period was higher in males than in females (2.7% vs. 2.1%, p < 0.001), increasing with age. From 2003 to 2014, not treated AF patients decreased mostly in males (from 40.3 to 33.7% with respect to 43.7-39.8% in females). Age-stratified adjusted logistic regression analysis found that females were more likely treated with OAC when < 65 years in 2003 (OR 1.51, 95% CI 1.35-1.69) and in 2014 (OR 1.32, 95% CI 1.13-1.53); contrariwise, were less likely treated with OAC when age ≥ 75 years, in 2003 (OR 0.92, 95% CI 0.86-0.98) and in 2014 (OR 0.77, 95% CI 0.72-0.81).Adjusted Cox regression analysis confirmed that female AF patients had a higher risk of stroke (HR 1.18, 95% CI 1.14-1.21) and a lower risk of major bleeding (HR 0.83, 95% CI 0.80-0.86), while, had a lower risk for all-cause death (HR 0.82, 95% CI 0.80-0.83). AF prevalence was higher in male than in female patients, while thromboembolic risk was higher in female. Older female patients were under-treated with OAC particularly in recent years. Over long-term follow-up, female had a higher risk of stroke and a lower risk of major bleeding and all-cause death.

Food and Drug Administration vs European Medicines Agency: Review times and clinical evidence on novel drugs at the time of approval.

The Food and Drug Administration (FDA) and European Medicines Agency (EMA) now have expedited review procedures for new drugs. We compared the review times of medicines licensed by the 2 agencies and explored differences in the evidence submitted. In 2015-2017 the FDA licensed 113 drugs, 66 of which reached Europe. The median review time was longer at the EMA than FDA and was shorter for drugs undergoing FDA-expedited programmes compared to the same drugs approved by the EMA through the standard procedure. We identified differences regarding the evidence submitted to the 2 regulators for 7 drugs. The greater use of expedited programmes by the FDA and administrative time at the European Commission mainly explain the later access of new drugs to the European market. The additional evidence submitted to the EMA is generally scant and limited to a few drugs.

Long-Term Outcomes of a Cohort of Hypertensive Subjects in Rural Ecuador.

BACKGROUND: In contrast with the abundance of global epidemiological descriptive data on cardiovascular diseases and their risk factors, information on the outcomes of real populations prospectively followed up in their life and care settings is much rarer, especially in low-income countries. OBJECTIVES: This study sought to evaluate the feasibility and the overall results of a hypertension control program, based mainly on a network of community nonprofessional health promoters, in the poor rural region of Borbon (Ecuador). METHODS: This is a prospective cohort study describing the results of a program of hypertension diagnosis, treatment and follow-up from 2004 to 2015 in the area, carried out mainly by the health promoters. RESULTS: The number of hypertensive patients identified and followed over the years increased from 1,024 in 2004 to 1,733 in 2015. The percentage of patients with no visits during a year was reduced to <10%, whereas the proportion of hypertensive subjects attending all 4 scheduled annual checks approached and, in some years, exceeded 50%. From 2004 to 2015, the proportion of patients at high or very high cardiovascular risk progressively decreased from 26.6% in 2004 to 17.5% in 2015 (p for trend <0.01), whereas the proportion of hypertensive patients at low or very low risk increased from 30.4% in 2004 to 45.0% in 2015 (p for trend <0.01). CONCLUSIONS: In a poor, disadvantaged area, a strategy of control mainly based on the involvement and responsibility of community health promoters (with health professionals as supporters more than direct actors) can achieve adequate follow-up of the population of hypertensive patients and improve their global cardiovascular risk level.

Long-Term Relationship Between Atrial Fibrillation, Multimorbidity and Oral Anticoagulant Drug Use.

OBJECTIVES: To analyze the relationship between atrial fibrillation (AF) and Charlson comorbidity index (CCI) in a population-based cohort study over a long-term follow-up period, in relation to oral anticoagulant (OAC) prescriptions and outcomes. PATIENTS AND METHODS: We used data from the administrative health databases of Lombardy. All patients with AF and age 40 years and older and who were admitted to the hospital in 2002 were considered for analysis and followed up to 2014. AF diagnosis and CCI were established according to codes from the International Classification of Diseases, Ninth Revision. RESULTS: In 2002, 24,040 patients were admitted with a diagnosis of AF. CCI was higher in patients with AF than in those without AF (1.8±2.1 vs 0.2±0.9; P<.001). Over 12 years of follow-up, AF was associated with an increased risk of higher CCI (beta coefficient, 1.69; 95% CI, 1.67-1.70). In patients with AF, CCI was inversely associated with OAC prescription at baseline (P<.001) and at the end of the follow-up (P=.03). Patients with AF and a high CCI (≥4) had a higher cumulative incidence of stroke, major bleeding, and all-cause death (all P<.001), compared with those with low CCI (range, 0-3). Adjusted Cox regression analysis revealed that time-dependent continuous CCI was associated with an increased risk for stroke, major bleeding, and all-cause death (all P<.001). CONCLUSIONS: In hospitalized patients, AF is associated with an increase in CCI that is inversely associated with OAC prescriptions during follow-up. CCI is independently associated with an increased risk of stroke, major bleeding, and all-cause death.

Peripheral arterial disease: Changes in clinical outcomes and therapeutic strategies in two cohorts, from 2002 to 2008 and from 2008 to 2014. A population-based study.

Background The aim of our study was to evaluate whether treatments for peripheral artery disease changed in two different cohorts identified in 2002 and 2008, and whether this had an impact on mortality and major clinical outcomes after six years of follow-up. Methods Using administrative health databases of the largest region in Northern Italy, we identified patients admitted to hospital for peripheral artery disease in 2002 and 2008. Both cohorts were followed for six years. All cause death, acute coronary syndrome, stroke and major amputations, cardiovascular prevention drugs and revascularization procedures were collected. Incidence of events was plotted using adjusted cumulative incidence function estimates. The risk, for each outcome, was compared between 2002-2008 and 2008-2014 using a multivariable Fine and Gray's semiparametric proportional subdistribution hazards model. Results In 2002 and 2008, 2885 and 2848 patients were identified. Adjusting for age, sex, Charlson comorbidity index and severity of peripheral artery disease we observed a significant reduction (in 2008 vs. 2002) in the risk of acute coronary syndrome (28%), stroke (27%) and major amputation (17%). No change was observed in the risk of death. The percentages of patients with peripheral artery revascularizations, during the hospital stay, increased: 43.8% in 2002 vs. 49.0% in 2008, p < 0.001. From 2002 to 2008 there was a significant absolute increase in the prescription of lipid-lowering drugs (+18%), antiplatelets (+7.2%) and angiotensin-converting enzyme inhibitors/angiotensin receptor blockers (+11.8%), p < 0.001. Conclusions In six years of follow-up we observed a reduction in risk of major cardiovascular events in 2008-2014 in comparison with the 2002-2008 cohort. Increasing use of revascularization interventions and cardiovascular prevention drugs could have contributed to the better prognosis.

Prevalence and management of diabetes in immigrants resident in the Lombardy Region: the importance of ethnicity and duration of stay.

AIMS: To describe the prevalence and management of diabetes among immigrants according to ethnic group and duration of stay, compared to Italian citizens. METHODS: Diabetic immigrant and Italian residents aged 20-69 years in the administrative database of the Lombardy Region. Immigrants were classified by region of origin and as long-term residents (LTR) and short-term residents (STR). Age- and sex-adjusted prevalence and indicators of diabetes management were calculated for immigrants by region of origin and by length of stay using Cox proportional models. RESULTS: In 2010 19,992 immigrants (mean age 49.1 ± 10.8, 53.7% males) and 195,049 Italians (mean age 58.7 ± 9.3, 61.1 males) with diabetes were identified. Immigrants had a higher adjusted diabetes prevalence than Italians (OR 1.48; 95% CI 1.45-1.50). STR received significantly fewer recommended cardiovascular drugs (antiplatelets, statins and ACE-inhibitors/ARBs) than Italians, although prescription was higher among LTR from some ethnic groups. Immigrants were less likely to be seen by a diabetologist and to do at least one HbA1c test per year. Although the recommended tests/visits were more often done for the LTR than the STR, in the majority of ethnic groups these indicators were still far from optimal. CONCLUSION: The prevalence and management of diabetes differ between immigrants and Italians, although some improvement can be seen among LTR.

Diabetes mellitus: a risk factor for seizures in the elderly-a population-based study.

AIMS: To evaluate the association between diabetes mellitus (DM) and risk of seizures in a well-defined elderly population. METHODS: The administrative databases of the Lombardy region (a 10 million population area in Northern Italy) were used to identify persons aged 65 years or older with DM (defined by prescription of antidiabetic drugs and/or through ICD-9 CM code and/or exemption code for diabetes) during the year 2002. Seizure-free DM subjects were followed until 2012 in search of individuals with incident seizures (identified through ICD-9 CM codes for epilepsy/seizures or ATC codes for antiepileptic drugs associated with the prescription of an electroencephalogram). To adjust for confounding, comorbidities having epileptogenic potential were also identified through the ICD-9 CM codes. RESULTS: The population at risk included 1,494,071 persons. Of these, 136,941 seizure-free patients had DM. At the end of follow-up, the cumulative time-dependent incidence of seizures was 3.0% in DM patients and 1.9% in No-diabetic individuals (hazard ratio, HR 1.47; 95% confidence interval, 1.41-1.53, adjusted for age classes, sex, comorbidities and number of hospital admission). The HR was unchanged in patients with no history of stroke. The cumulative incidence of seizures after DM increased with the number of hospital admissions. CONCLUSIONS: DM is an independent risk factor for seizures in elderly individuals. In diabetic patients, the risk of seizures increases with the number of comorbidities, supporting the role of vascular disease as a cause of seizures.

Risk of dementia and death in patients with atrial fibrillation: A competing risk analysis of a population-based cohort.

BACKGROUND: Previous studies have stated that atrial fibrillation (AF) is associated with a higher risk of dementia. However, none have examined the competition between death and incident dementia in patients with AF. We evaluated the risk of incident dementia in patients with AF in comparison to people without this arrhythmia, considering of the competing risk of death. METHODS: AF and non-AF cohorts were identified using the large administrative database of the Lombardy Region and followed for ten years. Patients with incident dementia were identified if they had an ICD 9 code referring to dementia at hospital discharge or a prescription for any anti-dementia drug. The association of AF with dementia or death was assessed with the multivariable Cox proportional-regression model, sensitivity analysis with a 1:1 propensity score matching and competing-risk analysis. RESULTS: In 2003 a total of 27,431 patients were hospitalized for AF in the Lombardy Region, while the cohort of non-AF counted 1,600,200 people. AF was associated with a higher risk of dementia (17%) and death (51%) at multivariable Cox analysis. These results were confirmed by the model fitted after propensity score matching. However, competing risk analysis found the association between AF and incident dementia was no longer significant (HR 0.99; 95% CI 0.94-1.04). CONCLUSIONS: In this real-world population the association between AF and dementia was no longer statistically significant when death was considered a competing risk.