Net clinical benefit of extended dual pathway inhibition according to baseline risk in patients with chronic coronary syndrome: a COMPASS substudy.

AIMS: Guidelines recommend extended dual pathway inhibition (DPI) with aspirin and rivaroxaban in patients with chronic coronary syndrome (CCS) at high ischaemic risk. The CHADS-P2A2RC score improves risk prediction and enables antithrombotic treatment allocation in these patients. This study evaluated the net clinical benefit of DPI treatment according to baseline risk as classified by the CHADS-P2A2RC score in patients with CCS included in the COMPASS (Cardiovascular Outcomes for People Using Anticoagulation Strategies) trial. METHODS AND RESULTS: COMPASS patients with CCS (n = 14 670), randomized to aspirin alone or DPI, were stratified according to cardiovascular risk using the CHADS-P2A2RC score. Endpoints were major adverse cardiovascular events (MACE), all-cause death, fatal/critical organ bleeding, and composite adverse events (MACE and bleeding). Net clinical benefit was the 30-month risk difference of MACE and bleeding. Thirty-month incidences of MACE [7.9% vs. 3.9%, hazard ratio (HR) 2.01, 95% confidence interval (CI) 1.83-2.18] and fatal/critical organ bleeding (1.2% vs. 0.8%, HR 1.49, 95% CI 1.06-1.92) were higher in high-risk (CHADS-P2A2RC ≥ 4) than in low/moderate-risk (CHADS-P2A2RC < 4) patients. DPI reduced MACE (low/moderate risk: HR 0.62, 95% CI 0.47-0.82; high risk: HR 0.82, 95% CI 0.68-0.99, P for interaction 0.09) and all-cause death (low/moderate risk: HR 0.65, 95% CI 0.46-0.91; high risk: HR 0.81, 95% CI 0.65-1.00, P for interaction 0.29), without substantially increasing fatal/critical organ bleeding (low/moderate risk: HR 1.35, 95% CI 0.72-2.53; high risk: HR 1.18, 95% CI 0.73-1.90, P for interaction 0.73). DPI provided net clinical benefit of similar magnitude in low/moderate-risk (-1.81%, 95% CI -3.00 to -0.62) and high-risk (-1.96%, 95% CI -3.60 to -0.33) CCS patients. CONCLUSION: As classified by the CHADS-P2A2RC score, low/moderate- and high-risk patients with CCS derived similar net clinical benefit and reduction in all-cause death from DPI treatment.

Non-HDL cholesterol and residual cardiovascular risk in statin-treated patients with and without diabetes: The Western Denmark Heart Registry.

AIMS: Assessment of residual cardiovascular risk in statin-treated patients with atherosclerotic cardiovascular disease (ASCVD) is pivotal for optimising secondary preventive therapies. This study investigates if non-high-density lipoprotein cholesterol (non-HDL-C) is associated with residual ASCVD risk in statin-treated ischemic heart disease (IHD) patients with and without diabetes. METHODS: Using the Western Denmark Heart Registry, we identified statin-treated patients with IHD examined by coronary angiography (CAG) from 2011-2020. Non-HDL-C was assessed within one year after CAG. Outcomes were ASCVD (myocardial infarction, ischemic stroke, and cardiovascular death) and all-cause death. Cox regression analyses obtained hazard ratios adjusted for age, sex, smoking, and hypertension. RESULTS: A total of 42,057 patients were included; 8,196 patients with diabetes and 33,861 without diabetes. During median 4.6 years of follow-up event rates per 1000 person-years of ASCVD were 28.8 (27.1-30.5) and 17.2 (16.5-17.8) among patients with and without diabetes. In patients with diabetes the adjusted hazard ratios (HR) of ASCVD as compared with non-HDL-C <25th percentile were 1.0 (0.9-1.2), 1.3 (1.1-1.6), and 1.6 (1.2-2.1) for patients in the 25th-74th, 75th-94th, and ≥95th percentile. In patients without diabetes corresponding adjusted HRs were 1.1 (0.9-1.1), 1.2 (1.1-1.4), and 1.7 (1.4-2.0). Results were consistent across sex, age, clinical presentation, and low-density lipoprotein cholesterol strata. CONCLUSIONS: In statin-treated IHD patients with and without diabetes non-HDL-C, especially above the 75th percentile, is associated with residual cardiovascular risk. These results have implications for secondary prevention targeting patients who may benefit most from intensified preventive therapy.

Relevant to individuals, both with and without diabetes, who receive cholesterol-lowering therapy due to ischemic heart disease, having a high level of non-HDL cholesterol is associated with risk of heart attack, stroke, and death. In individuals with diabetes, having a high compared to a low non-HDL cholesterol level was associated with a 30-60% increased risk of heart attack, stroke, and death. For individuals without diabetes, the high non-HDL cholesterol level was linked to an increased risk by up to 70%.In clinical practice calculation of non-HDL cholesterol, from the standard lipid profile with no inconvenience to the patient, offers a possibility to identify patients who face a high risk of heart attack, stroke, and death. Patients with high levels of non-HDL cholesterol may benefit from optimized preventive therapy.

Absence of Coronary Artery Disease is a Strong Negative Predictor of Major Adverse Cardiovascular Events in Patients with Chronic Kidney Disease.

Purpose: To investigate the interplay between chronic kidney disease (CKD) and coronary artery disease (CAD) on the incidence of cardiovascular events in patients with suspected chronic coronary syndrome (CCS). Patients and Methods: Patients with suspected CCS who underwent first-time coronary angiography in Western Denmark between 2003 and 2016 were included in this cohort study. Moreover, an age- and sex-matched general population cohort was established. Patients were stratified according to estimated glomerular filtration rate (eGFR). Presence of CAD was defined as ≥1 obstructive stenosis or non-obstructive diffuse disease. Major adverse cardiovascular events (MACE) were defined as a composite of myocardial infarction, ischemic stroke, and cardiac death. Results: A total of 42,611 patients were included with a median follow-up of 7.3 years. Patients without and with CAD had MACE rates per 100 person-years that were 0.52 and 1.67 for eGFR ≥90 mL/min/1.73 m2, 0.68 and 2.09 for eGFR 60-89 mL/min/1.73 m2, 1.27 and 3.85 for eGFR 30-59 mL/min/1.73 m2, and 2.27 and 6.92 for eGFR <30 mL/min/1.73 m2. Comparing to eGFR ≥90 mL/min/1.73 m2, the adjusted incidence rate ratios for MACE were 1.29 (1.10-1.51) for eGFR 60-89 mL/min/1.73 m2, 1.86 (1.49-2.33) for eGFR 30-59 mL/min/1.73 m2, and 3.57 (1.92-6.67) for eGFR <30 mL/min/1.73 m2 in patients without CAD, and 1.11 (1.03-1.20), 1.71 (1.55-1.90), and 2.46 (1.96-3.09) in patients with CAD. The inverse relationship between kidney function and risk of MACE was confirmed when comparing patients with and without CAD to matched individuals in the general population. Conclusion: Absence of CAD is a strong negative predictor of major adverse cardiovascular events in patients with CKD.

Impact of Coronary Artery Disease in Women With Newly Diagnosed Heart Failure and Reduced Ejection Fraction.

BACKGROUND: The representation of women in heart failure studies has been inadequate, resulting in a knowledge gap regarding the prognostic impact of coronary artery disease (CAD) on all-cause mortality in women with newly diagnosed heart failure and reduced ejection fraction (HFrEF). OBJECTIVES: This study aims to assess the prognostic impact of CAD in women with HFrEF. METHODS: Using the Western Denmark Heart Registry, the authors identified 891 women and 2,403 men referred for first-time coronary angiography because of HFrEF. The authors stratified for presence of CAD, estimated 10-year all-cause mortality, and calculated crude and adjusted HRs (aHRs) with 95% CIs. RESULTS: The 10-year mortality was 60% in women with CAD and 27% in women without CAD; for men, the corresponding numbers were 54% and 36%. When adjusted for comorbidities, women without CAD had a lower relative 10-year mortality than men without CAD (aHR: 0.73; 95% CI: 0.58-0.91), whereas women with CAD had similar relative mortality as men with CAD (aHR: 1.00; 95% CI: 0.81-1.24) (Pinteraction = 0.037). Assessed by the number of coronary vessels with significant stenosis, CAD extent was associated with mortality for both women (P < 0.01) and men (P < 0.01). However, compared to those without CAD, the aHR was higher for women with any degree of CAD (aHR ranging from 1.61 [95% CI: 1.09-2.38] for diffuse CAD to 2.01 [95% CI: 1.19-3.40] for 3-vessel disease) than for men with 3-vessel disease (aHR: 1.51; 95% CI: 1.19-1.91). CONCLUSIONS: In patients with newly diagnosed HFrEF, the presence and extent of CAD has significantly greater prognostic impact among women than among men.

Mortality Trends After Primary Percutaneous Coronary Intervention for ST-Segment Elevation Myocardial Infarction.

BACKGROUND: Observational studies have reported that mortality rates after ST-segment elevation myocardial infarction (STEMI) have been stable since 2006 to 2010. OBJECTIVES: The aim of this study was to evaluate the temporal trends in 1-year, 30-day, and 31- to 365-day mortality after STEMI in Western Denmark where primary percutaneous coronary intervention (PCI) has been the national reperfusion strategy since 2003. METHODS: Using the Western Denmark Heart Registry, the study identified first-time PCI-treated patients undergoing primary PCI (pPCI) for STEMI from 2003 to 2018. Based on the year of pPCI, patients were divided into 4 time-interval groups and followed up for 1 year using the Danish national health registries. RESULTS: A total of 19,613 patients were included. Median age was 64 years, and 74% were male. One-year mortality decreased gradually from 10.8% in 2003-2006, 10.4% in 2007-2010, 9.1% in 2011-2014, to 7.7% in 2015-2018 (2015-2018 vs 2003-2006: adjusted HR [aHR]: 0.71; 95% CI: 0.62-0.82). The largest absolute mortality decline occurred in the 0- to 30-day period with a 2.3% reduction (aHR: 0.69; 95% CI: 0.59-0.82), and to a lesser extent in the 31- to 365-day period (risk reduction: 1.0%; aHR: 0.71; 95% CI: 0.56-0.90). CONCLUSIONS: In a high-income European country with a fully implemented pPCI strategy, 1-year mortality in pPCI-treated patients with STEMI decreased substantially between 2003 and 2018. Approximately three-quarters of the absolute mortality reduction occurred within the first 30 days after pPCI. These results indicate that optimization of early management of pPCI-treated patients with STEMI offers great opportunities for improving overall survival in contemporary clinical practice.

Sex Differences in 10-Year Outcomes After Percutaneous Coronary Intervention With Drug-Eluting Stents: Insights From the DECADE Cooperation.

BACKGROUND: Although some studies have investigated sex-related outcomes up to 5 years after percutaneous coronary intervention (PCI), analyses at longer follow-up (ie, to 10 years) in large cohorts treated exclusively with drug-eluting stent (DES) platforms are lacking. Therefore, this study aimed to define whether sex-related differences in long-term outcomes after PCI persist both in the DES era and at longer-term follow-up. METHODS: Individual data of patients treated with DES in 5 randomized controlled trials with 10-year follow-up were pooled. Patients were divided into 2 groups by sex. The analysis of individual participant data was performed using a 1-stage approach by entering a clustering effect by parent study in all univariable and multivariable models focusing on sex. The main outcomes of interest for this analysis included cardiovascular death, myocardial infarction, repeat revascularization, and definite stent thrombosis to 10 years after PCI. Survival was analyzed by the Kaplan-Meier method to estimate the time to first event, and differences between the 2 groups were tested with the log-rank test. Hazard ratios (HRs) and 95% CIs were calculated with a Cox proportional hazards model. Conventional multivariable analyses with adjustment for relevant variables were performed. RESULTS: Among 9700 patients undergoing PCI with DES implantation included in the present analysis, 2296 were women and 7404 were men. Through to 10 years, cardiovascular death occurred in 407 of the 2296 female patients and 1012 of the 7404 male patients (adjusted HR [HRadj], 0.94 [95% CI, 0.80-1.11]). Female sex was associated with a lower risk of repeat revascularization of the target lesion (HRadj, 0.80 [95% CI, 0.74-0.87]), target vessel (HRadj, 0.81 [95% CI, 0.76-0.87]), and nontarget vessels (HRadj, 0.69 [95% CI, 0.62-0.77]). Compared with male patients, female patients displayed an increased risk of myocardial infarction in the first 30 days after PCI with DES (HRadj, 1.65 [95% CI, 1.24-2.19]) but a comparable risk of myocardial infarction thereafter. The risk of definite stent thrombosis was not significantly different between female and male patients (HRadj, 1.14 [95% CI, 0.89-1.47]). CONCLUSIONS: Through to 10-year follow-up after PCI with DES, female patients are at increased risk of early myocardial infarction, receive fewer repeat revascularizations, and have no difference in cardiovascular mortality compared with male patients.

Microvascular disease increases the risk of lower limb amputation - A Western Danish cohort study.

BACKGROUND: Peripheral artery disease is the leading cause of nontraumatic lower limb amputation. Microvascular disease (MVD) increases the risk of lower limb amputation in patients with peripheral artery disease (PAD). We estimated the risk of lower limb amputation associated with MVD and PAD in a Danish cohort. METHODS: We included every resident without previous lower limb amputation in Western Denmark aged 50-75 years on 1 January 2012 and followed them for 7 years. Participants were stratified by MVD and PAD. We estimated adjusted hazard ratios of lower limb amputation using individuals with no MVD and no PAD as reference. We also provide a sex-specific analysis and estimated the population attributable fraction of the male sex. RESULTS: We included 933,597 individuals, of whom 16,741 had MVD only, 18,217 had PAD only and 1,827 had MVD and PAD. Both MVD only (adjusted hazard ratio 3.36, 95% CI 2.98-3.73) and PAD only (adjusted hazard ratio 7.32, 95% CI 6.62-8.08) increased the risk of lower limb amputation separately. Individuals with MVD and PAD had the highest risk of amputation (adjusted hazard ratio 12.27, 95% CI 10.43-14.80). Men had an increased absolute risk of amputation. The population attributable fraction associated with the male sex was 31%. CONCLUSIONS: Microvascular disease and PAD are independently associated with a threefold and sevenfold increase of amputation risk, respectively. Combined, they had an additive effect constituting a 12-fold amputation risk. The amputation risk was higher in men than women, and 3 in 10 amputations were attributed to the male sex.

Effectiveness and Safety of Ticagrelor Implementation in Patients with Acute Coronary Syndrome undergoing Percutaneous Coronary Intervention: A Cohort Study in Western Denmark.

BACKGROUND: Ticagrelor was introduced in Denmark in 2011 after randomised data showed its superiority over clopidogrel for patients with acute coronary syndrome (ACS). We assessed the effectiveness and safety of ticagrelor implementation in ACS patients undergoing percutaneous coronary intervention (PCI). METHODS: We identified PCI-treated ACS patients in Western Denmark who redeemed a P2Y12 inhibitor prescription within 14 days. Using Danish health registries, 1-year outcomes were compared before (2007-2010) and after (2012-2015) introduction of ticagrelor. Outcomes were MACE (death, myocardial infarction, and ischaemic stroke) and hospitalisation for bleeding. Inverse probability of treatment weights were used to estimate weighted incidence rate ratios (wIRRs). FINDINGS: We included 14,450 patients; 7,102 were treated in the earlier time period (99·9% clopidogrel) and 7,348 in the later time period (87·8% ticagrelor). Ticagrelor implementation was not associated with a clinically relevant difference in 1-year risk of MACE with 413 events in the ticagrelor period vs. 424 events in the clopidogrel period (cumulative incidence percentage [CIP] 5·6% vs. 6·0%; wIRR 1·06, 95% CI 0·92-1·22). The 1-year risk of bleeding was also similar between groups with 335 bleedings requiring hospitalisation in the ticagrelor period vs. 309 events in the clopidogrel period (CIP 4·6% vs. 4·4%; wIRR 1·05, 95% CI 0·89-1·23). Results were robust in patients above and below 70 years of age. INTERPRETATION: Implementation of ticagrelor was not associated with changes in risks of ischaemic or bleeding events in Danish PCI-treated ACS patients.

Statin but not aspirin treatment is associated with reduced cardiovascular risk in patients with diabetes without obstructive coronary artery disease: a cohort study from the Western Denmark Heart Registry.

AIMS: Patients with diabetes and no obstructive coronary artery disease (CAD) as assessed by coronary angiography (CAG) are frequently treated with aspirin and statins. We examined the effectiveness of aspirin and statin treatment on cardiovascular and bleeding incidence in patients with diabetes and absent obstructive CAD. METHODS AND RESULTS: The study included patients with diabetes and absent obstructive CAD as assessed by CAG from 2003 to 2016 in Western Denmark. We stratified patients by aspirin and statin treatment within 6 months after CAG in two separate analyses. Outcomes were MACE (major adverse cardiovascular events, a composite of myocardial infarction, ischaemic stroke, and death) and bleeding (aspirin only). To account for confounding, we used propensity score-based weights to estimate the inverse probability of treatment-weighted hazard ratios (HRIPTW). We included 4124 patients with diabetes but without CAD as assessed by CAG, among whom 2474 (60%) received aspirin and 2916 (71%) received statin treatment within 6 months following CAG. Median follow-up was 4.9 years. Aspirin did not reduce 10-year MACE [21.3% vs. 21.8%, HRIPTW 1.01, 95% confidence interval (CI) 0.82-1.25], all-cause death (HRIPTW 0.96, 95% CI 0.74-1.23), or bleeding (HRIPTW 0.95, 95% CI 0.73-1.23), compared to those not receiving aspirin treatment. Statin treatment reduced MACE (25% vs. 37%, HRIPTW 0.58, 95% CI 0.48-0.70) compared to those not receiving statin treatment. CONCLUSION: Among patients with diabetes and no obstructive CAD, aspirin neither reduced MACE nor increased bleeding. In contrast, statin treatment was associated with a major reduction in risk of MACE.

Thirteen-year trends in cardiovascular risk in men and women with chronic coronary syndrome.

AIMS: To examine combined and sex-specific temporal changes in risks of adverse cardiovascular events and coronary revascularization in patients with chronic coronary syndrome undergoing coronary angiography. METHODS AND RESULTS: We included all patients with stable angina pectoris and coronary artery disease examined by coronary angiography in Western Denmark from 2004 to 2016. Patients were stratified by examination year interval: 2004-2006, 2007-2009, 2010-2012, and 2013-2016. Outcomes were 2-year risk of myocardial infarction, ischaemic stroke, cardiac death, and all-cause death estimated by adjusted incidence rate ratios using patients examined in 2004-2006 as reference. A total of 29 471 patients were included, of whom 70% were men. The 2-year risk of myocardial infarction [2.8% vs. 1.9%, adjusted incidence rate ratio 0.65, 95% confidence interval (CI) 0.53-0.81], ischaemic stroke (1.8% vs. 1.1%, adjusted incidence rate ratio 0.48, 95% CI 0.37-0.64), cardiac death (2.1% vs. 0.9%, adjusted incidence rate ratio 0.38, 95% CI 0.29-0.51), and all-cause death (5.0% vs. 3.6%, adjusted incidence rate ratio 0.65, 95% CI 0.55-0.76) decreased from the first examination interval (2004-2006) to the last examination interval (2013-2016). Coronary revascularizations also decreased (percutaneous coronary intervention: 51.6% vs. 42.5%; coronary artery bypass grafting: 24.6% vs. 17.5%). Risk reductions were observed in both men and women, however, women had a lower absolute risk. CONCLUSION: The risk for adverse cardiovascular events decreased substantially in both men and women with chronic coronary syndrome from 2004 to 2016. These results most likely reflect the cumulative effect of improvements in the management of chronic coronary artery disease.

CHA2 DS2 -VASc impact on risk following percutaneous coronary intervention in atrial fibrillation.

AIMS: In 2010, the European Society of Cardiology Guidelines on atrial fibrillation (AF) introduced the CHA2 DS2 -VASc score to guide initiation of oral anticoagulation. In patients with AF undergoing percutaneous coronary intervention (PCI), triple therapy with oral anticoagulation and dual antiplatelet therapy was recommended to reduce ischaemic risk. We examined how the CHA2 DS2 -VASc score impacted oral anticoagulation use and risks of ischaemic and hospitalized bleeding events in patients with AF undergoing PCI. METHODS: We included 6,014 patients with AF undergoing first-time PCI in Western Denmark between 2003 and 2017. We divided patients into four groups based on year of PCI and estimated 1-year risks of major adverse cardiac events (MACE) and hospitalization for bleeding. RESULTS: The proportion of oral anticoagulation users was 48% in 2003-2006 and 49% in 2006-2010. Following the CHA2 DS2 -VASc score implementation, the proportion increased to 59% in 2011-2014 and 77% in 2015-2017. Using 2003-2006 as reference, risks of MACE were similar in 2007-2010 (adjusted relative risk [RRadj ] 0.99, 95% confidence interval [CI] 0.83-1.18) and 2011-2014 (RRadj 0.92, 95% CI 0.78-1.09), but declined by 23% in 2015-2017 (RRadj 0.77, 95% CI 0.65-0.92). Hospitalizations for bleeding did not increase despite wider use of triple therapy. CONCLUSION: Implementation of the CHA2 DS2 -VASc score in the 2010 European guidelines on AF was associated with an increased utilization of oral anticoagulation and triple therapy among AF patients undergoing PCI. These changes were associated with a gradual decline in the risk of MACE, while the risk of hospitalized bleeding remained unchanged.

Dual antithrombotic treatment in chronic coronary syndrome: European Society of Cardiology criteria vs. CHADS-P2A2RC score.

AIMS: According to the 2019 European Society of Cardiology (ESC) guidelines on chronic coronary syndromes (CCS), adding a P2Y12 inhibitor or rivaroxaban to aspirin should be considered in high-risk patients. We estimated the proportion of patients eligible for treatment with the ESC criteria and examined if a recently validated risk score (CHADS-P2A2RC) could improve risk prediction. METHODS AND RESULTS: We included 61 338 CCS patients undergoing first-time coronary angiography in Western Denmark (2003-16) and classified them according to the ESC criteria and the CHADS-P2A2RC score. The ESC criteria identified 33.9% as high risk, 53.3% as moderate risk, and 12.8% as low risk. The CHADS-P2A2RC score identified 24.9% as high risk (≥4 points), 48.1% as moderate risk (2-3 points), and 27.0% as low risk (≤1 points). Major adverse cardiovascular events per 100 person-years were 4.8 [95% confidence interval (CI) 4.6-5.0] in patients considered high risk with both schemes, 2.1 (95% CI 2.0-2.2) in patients considered high risk with the ESC but low-to-moderate risk with the CHADS-P2A2RC criteria, 3.8 (95% CI 3.6-4.1) in patients considered low-to-moderate risk with the ESC but high risk with the CHADS-P2A2RC criteria, and 1.5 (95% CI 1.5-1.6) in patients considered low-to-moderate risk with both schemes. The CHADS-P2A2RC score enabled correct downward risk reclassification of 5161 patients (8%) without events, yielding an improved specificity of 9.7%, a loss of sensitivity of 4.4%, and an overall net reclassification index of 0.053. CONCLUSION: Based on the 2019 ESC guidelines, dual antithrombotic treatment should be considered in one-third of CCS patients. The CHADS-P2A2RC score improved risk classification and may particularly identify low-risk patients with limited benefit from treatment.

Cardiovascular risk in patients with and without diabetes presenting with chronic coronary syndrome in 2004-2016.

BACKGROUND: It was recently shown that new-onset diabetes patients without previous cardiovascular disease have experienced a markedly reduced risk of adverse cardiovascular events from 1996 to 2011. However, it remains unknown if similar improvements are present following the diagnosis of chronic coronary syndrome. The purpose of this study was to examine the change in cardiovascular risk among diabetes patients with chronic coronary syndrome from 2004 to 2016. METHODS: We included patients with documentation of coronary artery disease by coronary angiography between 2004 and 2016 in Western Denmark. Patients were stratified by year of index coronary angiography (2004-2006, 2007-2009, 2010-2012, and 2013-2016) and followed for two years. The main outcome was major adverse cardiovascular events (MACE) defined as myocardial infarction, ischemic stroke, or death. Analyses were performed separately in patients with and without diabetes. We estimated two-year risk of each outcome and adjusted incidence rate ratios (aIRR) using patients examined in 2004-2006 as reference. RESULTS: Among 5931 patients with diabetes, two-year MACE risks were 8.4% in 2004-2006, 8.5% in 2007-2009, and then decreased to 6.2% in 2010-2012 and 6.7% in 2013-2016 (2013-2016 vs 2004-2006: aIRR 0.70, 95% CI 0.53-0.93). In comparison, 23,540 patients without diabetes had event rates of 6.3%, 5.2%, 4.2%, and 3.9% for the study intervals (2013-2016 vs 2004-2006: aIRR 0.57, 95% CI 0.48-0.68). CONCLUSIONS: Between 2004 and 2016, the two-year relative risk of MACE decreased by 30% in patients with diabetes and chronic coronary syndrome, but slightly larger absolute and relative reductions were observed in patients without diabetes.

Risk of Myocardial Infarction and Death After Noncardiac Surgery Performed Within the First Year After Coronary Drug-Eluting Stent Implantation for Acute Coronary Syndrome or Stable Angina Pectoris.

This study aimed to examine the 30-day risk of myocardial infarction (MI) and death in patients who underwent noncardiac surgery within 1 year after coronary drug-eluting stent implantation for acute coronary syndrome (ACS) or stable angina pectoris (SAP) and to compare it with the risk in surgical patients without known coronary artery disease. Patients with drug-eluting stent implantation for ACS (n = 2,291) or SAP (n = 1,804) who underwent noncardiac surgery were compared with a cohort from the general population without known coronary artery disease matched on the surgical procedure, hospital contact type, gender, and age. In patients with ACS, the 30-day MI risk was markedly increased when surgery was performed within 1 month after stenting (10% vs 0.8%; adjusted odds ratio [ORadj] 20.1, 95% confidence interval [CI] 8.85 to 45.6), whereas mortality was comparable (10% vs 8%, ORadj 1.17, 95% CI 0.76 to 1.79). When surgery was performed between 1 and 12 months after stenting, the 30-day absolute risk for MI was low but higher than in the comparison cohort (0.6% vs 0.2%, ORadj 2.18, 95% CI 0.89 to 5.38), whereas the mortality risks were similar (2.0% vs 1.8%, ORadj 1.03, 95% CI 0.69 to 1.55). In patients with SAP, the 30-day MI risk was low but higher than in the comparison cohort (0.4% vs 0.2%, ORadj 1.90, 95% CI 0.70 to 5.14), whereas the mortality risks were similar (2.2% vs 2.1%, ORadj 0.91, 95% CI 0.61 to 1.37). In conclusion, patients with ACS and SAP who underwent surgery between 1 and 12 months after stent implantation had a risk for MI and death that was similar to the risk observed in surgical patients without coronary artery disease.

Ten-year cardiovascular risk in diabetes patients without obstructive coronary artery disease: a retrospective Western Denmark cohort study.

BACKGROUND: Diabetes patients without obstructive coronary artery disease as assessed by coronary angiography have a low risk of myocardial infarction, but their myocardial infarction risk may still be higher than the general population. We examined the 10-year risks of myocardial infarction, ischemic stroke, and death in diabetes patients without obstructive coronary artery disease according to coronary angiography, compared to risks in a matched general population cohort. METHODS: We included all diabetes patients without obstructive coronary artery disease examined by coronary angiography from 2003 to 2016 in Western Denmark. Patients were matched by age and sex with a cohort from the Western Denmark general population without a previous myocardial infarction or coronary revascularization. Outcomes were myocardial infarction, ischemic stroke, and death. Ten-year cumulative incidences were computed. Adjusted hazard ratios (HR) then were computed using stratified Cox regression with the general population as reference. RESULTS: We identified 5734 diabetes patients without obstructive coronary artery disease and 28,670 matched individuals from the general population. Median follow-up was 7 years. Diabetes patients without obstructive coronary artery disease had an almost similar 10-year risk of myocardial infarction (3.2% vs 2.9%, adjusted HR 0.93, 95% CI 0.72-1.20) compared to the general population, but had an increased risk of ischemic stroke (5.2% vs 2.2%, adjusted HR 1.87, 95% CI 1.47-2.38) and death (29.6% vs 17.8%, adjusted HR 1.24, 95% CI 1.13-1.36). CONCLUSIONS: Patients with diabetes and no obstructive coronary artery disease have a 10-year risk of myocardial infarction that is similar to that found in the general population. However, they still remain at increased risk of ischemic stroke and death.

Peripheral artery disease, lower limb revascularization, and amputation in diabetes patients with and without coronary artery disease: a cohort study from the Western Denmark Heart Registry.

INTRODUCTION: Patients with diabetes have increased risk of lower limb revascularization and amputation due to higher risk of peripheral artery disease (PAD) and peripheral neuropathy. The additive effect of coronary artery disease (CAD) is less clear. We examined the risk of PAD, lower limb revascularization, and amputation in diabetes and non-diabetes patients with and without CAD in patients examined by coronary angiography (CAG). RESEARCH DESIGN AND METHODS: We included all patients undergoing CAG between 2003 and 2016 in Western Denmark. Patients with previous CAD, PAD, lower limb revascularization, or amputation were excluded. Patients were stratified by diabetes and CAD status and followed for a maximum of 10 years. Outcomes were PAD, lower limb revascularization, and amputation. We estimated 10-year cumulative incidences and adjusted HRs (aHRs) using patients neither diabetes nor CAD as reference. RESULTS: A total of 118 787 patients were included, of whom 41 878 (35%) had neither diabetes nor CAD, 5735 (5%) had diabetes alone, 59 427 (50%) had CAD alone, and 11 747 (10%) had both diabetes and CAD. Median follow-up was 6.9 years. Diabetes patients without CAD had higher risk of PAD (3.5%, aHR 1.73, 95% CI 1.51 to 1.97), lower limb revascularization (1.6%, aHR 1.55, 95% CI 1.16 to 2.05), and lower limb amputation (2.4%, aHR 5.51, 95% CI 4.09 to 7.43) compared with patients with neither diabetes nor CAD. CAD was associated with 2.5-fold and 1.8-fold higher risk of PAD and amputation, respectively, among patients without diabetes, and associated with 3.9-fold and 9.5-fold higher risk of PAD and lower limb amputation among patients with diabetes. CONCLUSIONS: Despite absence of obstructive CAD, patients with diabetes remained at higher risk of PAD, lower limb revascularization, and lower limb amputation. Diabetes was more strongly associated with amputation than CAD, but CAD exacerbated the risks of PAD, revascularization, and amputation in patients with diabetes.

Insulin-treated versus noninsulin-treated diabetes and risk of ischemic stroke in patients with atrial fibrillation.

BACKGROUND: Diabetes mellitus (DM) and atrial fibrillation (AF) are known risk factors for ischemic stroke. Recent data, however, suggest that only insulin-treated DM is a risk factor for ischemic stroke among AF patients. OBJECTIVES: To evaluate the risk of stroke in patients with insulin and noninsulin treated DM. METHODS: We included AF patients undergoing coronary angiography in Western Denmark between 2003 and 2016. Patients were categorized as 1) insulin treated DM, 2) noninsulin treated DM, or 3) nonDM patients. The main outcome was ischemic stroke >30 days after CAG. RESULTS: AF patients (n = 21,223) were included, of whom 17,181 (81%) did not have DM, 2890 (14%) had noninsulin-treated DM and 1152 (5%) had insulin-treated DM. Median follow-up was 5.3 years. Ischemic stroke rates were 0.83 per 100 person-years for nonDM, 1.19 for noninsulin-treated DM and 1.40 for insulin-treated DM. Insulin-treated DM (adjusted hazard ratio (HRadj) 1.48, 95% CI 1.15-1.91) and noninsulin-treated DM patients (HRadj 1.30, 95% CI 1.09-1.54) had higher risks of ischemic stroke than nonDM patients. There was no difference between insulin-treated DM and noninsulin-treated DM (HRadj 1.09, 95% CI 0.82-1.46). Stratification by coronary artery disease yielded comparable risk estimates. CONCLUSION: In patients with AF, DM increases the risk of ischemic stroke, regardless of treatment.

Impact of rheumatoid arthritis on major cardiovascular events in patients with and without coronary artery disease.

INTRODUCTION: Rheumatoid arthritis (RA) is a risk factor for cardiovascular disease. The clinical consequences of coincident RA and coronary artery disease (CAD) are unknown. OBJECTIVE: We aimed to estimate the impact of RA on the risk of adverse cardiovascular events in patients with and without CAD. METHODS: A population-based cohort of patients registered in the Western Denmark Heart Registry, who underwent coronary angiography (CAG) between 2003 and 2016, was stratified according to the presence of RA and CAD. Endpoints were myocardial infarction (MI), major adverse cardiovascular events (MACE; MI, ischaemic stroke and cardiac death) and all-cause mortality. RESULTS: A total of 125 331 patients were included (RA: n=1732). Median follow-up was 5.2 years. Using patients with neither RA nor CAD as reference (cumulative MI incidence 2.7%), the 10-year risk of MI was increased for patients with RA alone (3.8%; adjusted incidence rate ratio (IRRadj) 1.63, 95% CI 1.04 to 2.54), for patients with CAD alone (9.9%; IRRadj 3.35, 95% CI 3.10 to 3.62), and highest for patients with both RA and CAD (12.2%; IRRadj 4.53, 95% CI 3.66 to 5.59). Similar associations were observed for MACE an all-cause mortality. CONCLUSIONS: In patients undergoing CAG, RA is significantly associated with the 10-year risk of MI, MACE and all-cause mortality regardless of the presence of CAD. However, patients with RA and CAD carry the largest risk, while the additive risk of RA in patients without CAD is minor. Among patients with RA, risk stratification by presence or absence of documented CAD may allow for screening and personalised treatment strategies.