16-year follow-up of the Danish Acute Myocardial Infarction 2 (DANAMI-2) trial: primary percutaneous coronary intervention vs. fibrinolysis in ST-segment elevation myocardial infarction.

AIMS: The DANish Acute Myocardial Infarction 2 (DANAMI-2) trial found that interhospital transport to primary percutaneous coronary intervention (pPCI) was superior to fibrinolysis at the local hospital in patients with ST-segment elevation myocardial infarction (STEMI) at 30 days. The present study investigates the 16-year cardiovascular outcomes. METHODS AND RESULTS: We randomized 1572 STEMI patients to pPCI or fibrinolysis at 24 referral hospitals and 5 invasive centres in Denmark. Patients randomized to pPCI at referral hospitals were immediately transported to the nearest invasive centre. The main endpoint of the current study was a composite of death or rehospitalization for myocardial infarction (MI). Outcome information beyond 3 years was obtained through Danish health registries. After 16 years, pPCI-treated patients had a sustained lower rate of composite endpoint compared to patients treated with fibrinolysis in the overall cohort [58.7% vs. 62.3%; hazard ratio (HR) 0.86, 95% confidence interval (CI) 0.76-0.98], and among patients transported for pPCI (58.7% vs. 64.1%; HR 0.82, 95% CI 0.71-0.96). No difference in all-cause mortality was found, but cardiac mortality was reduced by an absolute of 4.4% in favour of pPCI (18.3% vs. 22.7%; HR 0.78, 95% CI 0.63-0.98). pPCI postponed a main event with 12.3 months in average compared to fibrinolysis (95% CI 5.0-19.5). CONCLUSION: The benefit of pPCI over fibrinolysis was maintained at 16-year follow-up. pPCI reduced the composite endpoint of death or rehospitalization for MI, reduced cardiac mortality, and delayed average time to a main event by approximately 1 year.

Diabetes Mellitus Is Associated With Increased Risk of Ischemic Stroke in Patients With and Without Coronary Artery Disease.

Background and Purpose- Diabetes mellitus (DM) and non-DM patients without coronary artery disease (CAD) have a similar low risk of myocardial infarction after coronary angiography. The risk of ischemic stroke in DM patients dependent on CAD status is less explored. We examined whether DM patients without CAD have a risk of ischemic stroke similar to that in patients with neither DM nor CAD. Methods- We conducted a cohort study of patients who underwent coronary angiography between 2004 and 2012 in Western Denmark. Patients diagnosed with previous ischemic stroke or transient ischemic attack were excluded. Patients were stratified according to the presence of DM and CAD. Follow-up started 30 days after coronary angiography. We computed event rates and adjusted incidence rate ratios using patients without DM or CAD as reference. We examined the trend between CAD extent and ischemic stroke in patients with DM. Results- A total of 81 909 patients were included. Median follow-up was 3.8 years. Patients with both DM and CAD were at the highest risk of ischemic stroke (1.32 events per 100 person-years; adjusted incidence rate ratio, 2.00 [95% CI, 1.72-2.32]). Patients with CAD alone (0.77 events per 100 person-years; adjusted incidence rate ratio, 1.27 [95% CI, 1.12-1.44]) or DM alone (0.95 events per 100 person-years; adjusted incidence rate ratio, 1.74 [95% CI, 1.42-2.15]) were at intermediate risk, whereas patients with neither DM nor CAD (0.52 events per 100 person-years) were at the lowest risk. Among patients with DM, extent of CAD was further predictive of risk (Ptrend<0.001). Conclusions- Not only CAD but also DM are associated with the risk of ischemic stroke after coronary angiography. Their combination further increases the risk of ischemic stroke depending on the extent of CAD.

Diabetes and Coronary Artery Disease as Risk Factors for Dementia.

AIM: Diabetes is associated with increased risk of dementia, but it is still debated to which degree this risk depends on the presence of atherosclerotic cardiovascular disease. We hypothesized that patients with diabetes and co-existing coronary artery disease (CAD), as a marker of systemic atherosclerotic cardiovascular disease, have substantially higher risk of developing dementia. METHODS: Patients ≥65 years, who underwent coronary angiography were stratified by diabetes and CAD. Outcomes were all-cause dementia, Alzheimer's dementia, and vascular dementia. We estimated adjusted hazard ratios (aHRs) using patients with neither diabetes nor CAD as a reference. RESULTS: A total of 103,859 patients were included. Of these, 23,189 (22%) had neither diabetes nor CAD, 3,876 (4%) had diabetes, 61,020 (59%) had CAD, and 15,774 (15%) had diabetes and CAD. During a median follow-up of 6.3 years, 5,592 (5.5%) patients were diagnosed with all-cause dementia. Patients with diabetes and CAD had the highest hazard rate of all-cause dementia (aHR 1.37, 95% CI 1.24-1.51), including Alzheimer's dementia (aHR 1.41, 95% CI 1.23-1.62) and vascular dementia (aHR 2.03, 95% CI 1.69-2.45). Patients with diabetes alone (aHR 1.14, 95% CI 0.97-1.33) or CAD alone (aHR 1.11, 95% CI 1.03-1.20) had a modestly increased rate of all-cause dementia. CONCLUSION: The combination of diabetes and CAD is associated with increased rate of dementia, in particular vascular dementia, suggesting that the diabetes-related risk of dementia is partly mediated through concomitant atherosclerotic cardiovascular disease. This underscores the importance of atherosclerotic cardiovascular disease prevention in diabetes patients to reduce cognitive decline.

We used national Danish healthcare registries to follow 103,859 patients examined by coronary angiography for up to 10 years to estimate the risk of dementia associated with diabetes and/or coronary artery disease. We found that diabetes and coronary artery disease are, separately, only modest risk factors of dementia. However, diabetes and coronary artery disease in combination were associated with highest risk of dementia, in particular vascular dementia. Out results suggests that the risk of dementia associated with diabetes is partly mediated through the presence atherosclerotic cardiovascular disease, which underscores the importance of atherosclerotic cardiovascular disease prevention in diabetes patients to reduce the risk of cognitive decline.

Antithrombotic treatment beyond 1 year after percutaneous coronary intervention in patients with atrial fibrillation.

AIMS: Beyond 1 year after percutaneous coronary intervention (PCI), guidelines recommend anticoagulant monotherapy in patients with atrial fibrillation (AF) rather than dual therapy with an anticoagulant and an antiplatelet drug. The risks and benefits of this strategy, however, remain uncertain. We examined hospitalization for bleeding and ischaemic risk beyond 1 year after PCI in patients with AF treated with monotherapy vs. dual therapy. Furthermore, among patients treated with monotherapy, we compared direct oral anticoagulant (DOAC) therapy and vitamin K antagonist (VKA) therapy. METHODS AND RESULTS: We included all patients with AF undergoing first-time PCI between 2003 and 2017 from the Western Denmark Heart Registry and followed them for up to 4 years. Follow-up started 15 months after PCI to enable assessment of medical treatment after 12 months. Using a Cox regression model, we computed weighted hazard ratios (HRw) of hospitalization for bleeding and major adverse cardiac events (MACEs). Analyses comparing monotherapy vs. dual therapy included 3331 patients, and analyses comparing DOAC vs. VKA monotherapy included 1275 patients. Risks of hospitalization for bleeding [HRw 0.90, 95% confidence interval (CI) 0.75-1.09] and MACE (HRw 1.04, 95% CI 0.90-1.19) were similar with monotherapy and dual therapy. Similarly, risks of hospitalization for bleeding (HRw 1.27, 95% CI 0.84-1.92) and MACE (HRw 1.15, 95% CI 0.87-1.50) were equal with DOAC and VKA monotherapy. CONCLUSION: Our results support long-term OAC monotherapy beyond 1 year after PCI in patients with atrial fibrillation and suggest that DOAC monotherapy is as safe and effective as VKA monotherapy.

Twenty-Year Temporal Trends in Risk of Ischemic Stroke in Incident Type 2 Diabetes: A Danish Population-Based Cohort Study.

OBJECTIVE: We examined temporal trends in risk of first-time ischemic stroke in patients with incident type 2 diabetes mellitus (T2DM) and no prior atherosclerotic cardiovascular disease (ASCVD). RESEARCH DESIGN AND METHODS: Using nationwide health registries, we identified all patients with incident T2DM without a prior hospital diagnosis of ASCVD from 1996 to 2015 in Denmark. Patients were assigned to 5-year periods based on the date of T2DM diagnosis and were followed for 5 years. Each patient was matched by sex and age with up to three individuals from the general population. Temporal trends in ischemic stroke were examined using Cox regression to compute hazard ratios (HRs). Temporal use of prophylactic cardiovascular medications was also assessed. RESULTS: The study comprised 288,825 patients with incident T2DM and 782,232 general population individuals. From 1996-2000 to 2011-2015, the 5-year risk of first-time ischemic stroke was approximately halved in the T2DM cohort (5.2% vs. 2.7%; sex- and age-adjusted HR 0.52 [95% CI 0.49-0.55]). Patients diagnosed in 2011-2015 had increased risk of ischemic stroke compared with individuals in the general population; however, the risk difference narrowed over time (5.2% vs. 2.9% in 1996-1999 [difference 2.3%]; 2.7% vs. 2.0% in 2011-2015 [difference 0.7%]). Use of prophylactic cardiovascular medications increased markedly during the overall study period, especially use of statins (from 5% to 50%) and multiple antihypertensive drugs (from 18% to 33%). CONCLUSIONS: From 1996 to 2015, the 5-year risk of first-time ischemic stroke was approximately halved in patients with incident T2DM and no prior ASCVD, coinciding with markedly increased use of prophylactic cardiovascular medications.

Diabetes is not a risk factor for myocardial infarction in patients without coronary artery disease: A study from the Western Denmark Heart Registry.

BACKGROUND: Diabetes is considered a risk factor for myocardial infarction. However, we have previously found that diabetes was not a short-term risk factor for myocardial infarction in the absence of obstructive coronary artery disease. METHODS: We conducted a cohort study of patients undergoing coronary angiography from 2003 to 2012 and followed them by cross-linking Danish health registries. Patients were stratified according to coronary artery disease and diabetes. Endpoints included myocardial infarction, cardiac death, all-cause death and coronary revascularization. RESULTS: 86,202 patients were included in total (diabetes: n = 12,652). Median follow-up was 8.8 years. Using patients with neither coronary artery disease nor diabetes as reference (cumulative myocardial infarction incidence 2.6%), the risk of myocardial infarction was low and not substantially increased for patients with diabetes alone (3.2%; hazard ratio 1.202, 95% confidence interval 0.996-1.451), was increased for patients with coronary artery disease alone (9.3%; hazard ratio 2.75, 95% confidence interval 2.52-3.01) and was highest for patients with both coronary artery disease and diabetes (12.3%; hazard ratio 3.79, 95% confidence interval 3.43-4.20). Similar associations were observed for cardiac death and coronary revascularization. CONCLUSION: Diabetes patients without coronary artery disease by coronary angiography have a low risk of myocardial infarction, not substantially increased compared to patients with neither coronary artery disease nor diabetes. In the presence of coronary artery disease, however, diabetes increases the risk of myocardial infarction.