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Background: Evidence is conflicting as to the efficacy of direct oral anticoagulation (DOAC) and vitamin K antagonist (VKA) for prevention of myocardial infarction (MI)., Objectives: This study aimed to investigate the risk of MI associated with the use of apixaban, dabigatran, rivaroxaban, and VKA in patients with atrial fibrillation., Methods: Patients with atrial fibrillation were identified using Danish health care registers and stratified by initial oral anticoagulant treatment. Standardized absolute 1-year risks were estimated based on Cox regression for hazard rates of MI hospitalizations and mortality. Reported were absolute risks separately for the oral anticoagulation treatments and standardized to the characteristics of the study population., Results: Of the 31,739 patients included (median age, 74 years; 47% females), the standardized 1-year risk of MI for VKA was 1.6% (95% confidence interval [CI]: 1.3 to 1.8), apixaban was 1.2% (95% CI: 0.9 to 1.4), dabigatran was 1.2% (95% CI: 1.0 to 1.5), and rivaroxaban was 1.1% (95% CI: 0.8 to 1.3). No significant risk differences were observed in the standardized 1-year risks of MI among the DOACs: dabigatran versus apixaban (0.04%; 95% CI: -0.3 to 0.4), rivaroxaban versus apixaban (0.1%; 95% CI: -0.4 to 0.3), and rivaroxaban versus dabigatran (-0.1%; 95% CI: -0.5 to 0.2). The risk differences for DOACs versus VKA were all significant: -0.4% (95% CI: -0.7 to -0.1) for apixaban, -0.4% (95% CI: -0.7 to -0.03) for dabigatran, and -0.5% (95% CI: -0.8 to -0.2) for rivaroxaban., Conclusions: No significant risk differences of MI were found in the direct comparisons of DOACs, and DOACs were all associated with a significant risk reduction of MI compared with VKA., (Copyright © 2018. Published by Elsevier Inc.)

Background: Dual anti-platelet treatment with clopidogrel and aspirin is indicated for most patients after myocardial infarction. We examined the risk/benefit relationship of dual anti-platelet treatment according to age in a nationwide cohort of 30,532 myocardial infarction patients without revascularization., Methods: Patients admitted with first-time myocardial infarction in 2002-2010, not undergoing revascularization, were identified from nationwide Danish registers. Dual anti-platelet treatment use was assessed by claimed prescriptions. Stratified into age groups, risk of bleeding, all-cause mortality and a combined endpoint of cardiovascular death, recurrent myocardial infarction and ischaemic stroke was analysed by Cox proportional-hazard models and tested in a propensity-score matched population., Results: A total of 21,302 users and 9230 non-users of dual anti-platelet treatment were included (mean age 67.02 (±13.8) years and 64.7% males). Use of dual anti-platelet treatment decreased with age: 80% (<60 years), 76% (60-69 years), 66% (70-79 years) and 52% (>79 years). We found a reduced risk of cardiovascular death, recurrent myocardial infarction and ischaemic stroke in users <60 years (Hazard ratio (HR) =0.69; 95% confidence interval (CI) 0.59-0.80), 60-69 years (HR=0.64; 95% CI 0.56-0.73), 70-79 years (HR=0.80; 95% CI 0.72-0.89) and >79 years (HR=0.92; 95% CI 0.84-1.01, NS). Risk of bleeding increased with dual anti-platelet treatment use in patients aged <60 years (HR=1.63; 95% CI 1.17-2.26), 60-69 years (HR=1.22; 95% CI 0.97-1.59, NS), 70-79 years (HR=1.42; 95% CI 1.17-1.72) and >79 years (HR=1.46; 95% CI 1.22-1.74). Similar tendencies in all four age groups were found in the propensity-matched population., Conclusion: Dual anti-platelet treatment use was less likely among elderly patients although similar effects regarding both risk and benefit were found in all age groups. Increased focus on initiating dual anti-platelet treatment in elderly, non-invasively treated myocardial infarction patients is warranted.

Importance: Antithrombotic treatment is indicated for use in patients after myocardial infarction (MI); however, concomitant use of nonsteroidal anti-inflammatory drugs (NSAIDs) could pose safety concerns., Objective: To examine the risk of bleeding and cardiovascular events among patients with prior MI taking antithrombotic drugs and for whom NSAID therapy was then prescribed., Design, Setting, and Participants: Using nationwide administrative registries in Denmark (2002-2011), we studied patients 30 years or older admitted with first-time MI and alive 30 days after discharge. Subsequent treatment with aspirin, clopidogrel, or oral anticoagulants and their combinations, as well as ongoing concomitant NSAID use, was determined., Exposures: Use of NSAIDs with ongoing antithrombotic treatment after first-time MI., Main Outcomes and Measures: Risk of bleeding (requiring hospitalization) or a composite cardiovascular outcome (cardiovascular death, nonfatal recurrent MI, and stroke) according to ongoing NSAID and antithrombotic therapy, calculated using adjusted time-dependent Cox regression models., Results: We included 61,971 patients (mean age, 67.7 [SD, 13.6] years; 63% men); of these, 34% filled at least 1 NSAID prescription. The number of deaths during a median follow-up of 3.5 years was 18,105 (29.2%). A total of 5288 bleeding events (8.5%) and 18,568 cardiovascular events (30.0%) occurred. The crude incidence rates of bleeding (events per 100 person-years) were 4.2 (95% CI, 3.8-4.6) with concomitant NSAID treatment and 2.2 (95% CI, 2.1-2.3) without NSAID treatment, whereas the rates of cardiovascular events were 11.2 (95% CI, 10.5-11.9) and 8.3 (95% CI, 8.2-8.4). The multivariate-adjusted Cox regression analysis found increased risk of bleeding with NSAID treatment compared with no NSAID treatment (hazard ratio, 2.02 [95% CI, 1.81-2.26]), and the cardiovascular risk was also increased (hazard ratio, 1.40 [95% CI, 1.30-1.49]). An increased risk of bleeding and cardiovascular events was evident with concomitant use of NSAIDs, regardless of antithrombotic treatment, types of NSAIDs, or duration of use., Conclusions and Relevance: Among patients receiving antithrombotic therapy after MI, the use of NSAIDs was associated with increased risk of bleeding and excess thrombotic events, even after short-term treatment. More research is needed to confirm these findings; however, physicians should exercise appropriate caution when prescribing NSAIDs for patients who have recently experienced MI.

Objectives: The purpose of this study was to investigate the risk of thrombosis and bleeding according to multiple antithrombotic treatment regimens in atrial fibrillation (AF) patients after myocardial infarction (MI) or percutaneous coronary intervention (PCI)., Background: The optimal antithrombotic treatment strategy is unresolved in patients with multiple indications., Methods: A total of 12,165 AF patients hospitalized with MI and/or undergoing PCI between 2001 and 2009 were identified by nationwide registries (60.7% male; mean age 75.6 years). Risk of MI/coronary death, ischemic stroke, and bleeding according to antithrombotic treatment regimen was estimated by Cox regression models., Results: Within 1 year, MI or coronary death, ischemic stroke, and bleeding events occurred in 2,255 patients (18.5%), 680 (5.6%), and 769 (6.3%), respectively. Relative to triple therapy (oral anticoagulation [OAC] plus aspirin plus clopidogrel), no increased risk of recurrent coronary events was seen for OAC plus clopidogrel (hazard ratio [HR]: 0.69, 95% confidence interval [CI]: 0.48 to 1.00), OAC plus aspirin (HR: 0.96, 95% CI: 0.77 to 1.19), or aspirin plus clopidogrel (HR: 1.17, 95% CI: 0.96 to 1.42), but aspirin plus clopidogrel was associated with a higher risk of ischemic stroke (HR: 1.50, 95% CI: 1.03 to 2.20). Also, OAC plus aspirin and aspirin plus clopidogrel were associated with a significant increased risk of all-cause death (HR: 1.52, 95% CI: 1.17 to 1.99 and HR: 1.60, 95% CI: 1.25 to 2.05, respectively). When compared to triple therapy, bleeding risk was nonsignificantly lower for OAC plus clopidogrel (HR: 0.78, 95% CI: 0.55 to 1.12) and significantly lower for OAC plus aspirin and aspirin plus clopidogrel., Conclusions: In real-life AF patients with indication for multiple antithrombotic drugs after MI/PCI, OAC and clopidogrel was equal or better on both benefit and safety outcomes compared to triple therapy., (Copyright © 2013 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Aims: The benefit of extending clopidogrel treatment beyond the 12-month period recommended in current guidelines after myocardial infarction (MI) is debated. We analysed the risk of adverse cardiovascular outcomes after discontinuation of 12 months of clopidogrel treatment., Methods and Results: This Danish retrospective nationwide study included all patients treated with clopidogrel after discharge from a first-time MI during 2004-09. The risk of death or recurrent MI after the discontinuation of clopidogrel was studied by multivariable Poisson regression models. Patients treated with and without percutaneous coronary intervention (PCI) were analysed separately. The follow-up was 18 months. Of the 29,268 patients included, 3214 (11.0%) experienced death or recurrent MI. There were 9819 (33.6%) patients treated only medically and 19,449 (66.4%) patients treated with PCI. Twelve months after the index MI, for patients treated only medically, the risk of death or recurrent MI in the first 90-day period of clopidogrel discontinuation was 1.07 (0.65-1.76; P= 0.79) [adjusted incidence rate ratio (IRR) and 95% confidence interval] compared with the next 90-day period of discontinuation. For patients treated with PCI, the corresponding IRR was 1.59 (1.11-2.30; P= 0.013). The risk of recurrent MI yielded an IRR of 0.77 (0.36-1.67; P= 0.51) for patients treated only medically and 1.87 (1.11-3.15; P= 0.019) for PCI-treated patients., Conclusion: Discontinuation of clopidogrel 12 months after MI is associated with an increased risk of death or recurrent MI in the first 90 days of discontinuation compared with the next 90-day period of discontinuation for patients treated with PCI, but not for patients not treated with PCI.

Background: Uncertainty remains over optimal antithrombotic treatment of patients with atrial fibrillation presenting with myocardial infarction and/or undergoing percutaneous coronary intervention. We investigated the risk and time frame for bleeding following myocardial infarction/percutaneous coronary intervention in patients with atrial fibrillation according to antithrombotic treatment., Methods and Results: Patients with atrial fibrillation and admitted with myocardial infarction or for percutaneous coronary intervention between 2000 and 2009 (11 480 subjects, mean age 75.6 years [SD ±10.3], males 60.9%) were identified by individual level linkage of nationwide registries in Denmark. Fatal or nonfatal (requiring hospitalization) bleeding was determined according to antithrombotic treatment regimen: triple therapy (TT) with vitamin K antagonist (VKA)+aspirin+clopidogrel, VKA+antiplatelet, and dual antiplatelet therapy with aspirin+clopidogrel. We calculated crude incidence rates and adjusted hazard ratios by Cox regression models. Within 1 year, 728 bleeding events were recorded (6.3%); 79 were fatal (0.7%). Within 30 days, rates were 22.6, 20.3, and 14.3 bleeding events per 100 person-years for TT, VKA+antiplatelet, and dual antiplatelet therapy, respectively. Both early (within 90 days) and delayed (90-360 days) bleeding risk with TT exposure in relation to VKA+antiplatelet was increased; hazard ratio 1.47 (1.04;2.08) and 1.36 (0.95;1.95), respectively. No significant difference in thromboembolic risk was observed for TT versus VKA+antiplatelet; hazard ratio, 1.15 (0.95;1.40)., Conclusions: High risk of bleeding is immediately evident with TT after myocardial infarction/percutaneous coronary intervention in patients with atrial fibrillation. A continually elevated risk associated with TT indicates no safe therapeutic window, and TT should only be prescribed after thorough bleeding risk assessment of patients.

Aims: The impact of insulin secretagogues (ISs) on long-term major clinical outcomes in type 2 diabetes remains unclear. We examined mortality and cardiovascular risk associated with all available ISs compared with metformin in a nationwide study., Methods and Results: All Danish residents >20 years, initiating single-agent ISs or metformin between 1997 and 2006 were followed for up to 9 years (median 3.3 years) by individual-level linkage of nationwide registers. All-cause mortality, cardiovascular mortality, and the composite of myocardial infarction (MI), stroke, and cardiovascular mortality associated with individual ISs were investigated in patients with or without previous MI by multivariable Cox proportional-hazard analyses including propensity analyses. A total of 107 806 subjects were included, of whom 9607 had previous MI. Compared with metformin, glimepiride (hazard ratios and 95% confidence intervals): 1.32 (1.24-1.40), glibenclamide: 1.19 (1.11-1.28), glipizide: 1.27 (1.17-1.38), and tolbutamide: 1.28 (1.17-1.39) were associated with increased all-cause mortality in patients without previous MI. The corresponding results for patients with previous MI were as follows: glimepiride: 1.30 (1.11-1.44), glibenclamide: 1.47 (1.22-1.76), glipizide: 1.53 (1.23-1.89), and tolbutamide: 1.47 (1.17-1.84). Results for gliclazide [1.05 (0.94-1.16) and 0.90 (0.68-1.20)] and repaglinide and [0.97 (0.81-1.15) and 1.29 (0.86-1.94)] were not statistically different from metformin in both patients without and with previous MI, respectively. Results were similar for cardiovascular mortality and for the composite endpoint., Conclusion: Monotherapy with the most used ISs, including glimepiride, glibenclamide, glipizide, and tolbutamide, seems to be associated with increased mortality and cardiovascular risk compared with metformin. Gliclazide and repaglinide appear to be associated with a lower risk than other ISs.

What Is Already Known About This Subject: General use of hormone replacement therapy (HRT) dropped drastically after 2002 when pivotal randomized trials showed increased risk of coronary artery disease and other complications with HRT. HRT is not recommended for primary or secondary prevention of coronary heart disease and guidelines recommend discontinuation of HRT after myocardial infarction (MI). It is unknown whether women actually discontinue HRT after MI., What This Study Adds: Women who use HRT when they experience their MI generally continue using HRT. We found a remarkably low increase in discontinuation after 2002, in contrast to the general drop in use of HRT., Aim: To characterize the pattern of use and discontinuation of postmenopausal hormone replacement therapy (HRT) in women with myocardial infarction (MI) before and after 2002, where the general use of HRT dropped drastically subsequent to the results of the Women's Health Initiative trial., Methods: All Danish women aged ≥40 years hospitalized with MI in the period 1997 to 2005 and their use of HRT were identified by individual-level-linkage of nationwide registers of hospitalization and drug dispensing from pharmacies. Characteristics associated with HRT use at time of MI and subsequent HRT discontinuation were analysed by multivariable logistic regression., Results: In the study period, 34,778 women were discharged after MI. Of these, 3979 (11.4%) received HRT at the time of MI and their most used categories of HRT were vaginal oestrogen and oral oestrogen alone (46.6% and 28.7%, respectively). The percentage of women who continued HRT during the first year after discharge was 85.0% in the period 2000-2002 and had decreased to 79.6% in the period 2003-2005. Vaginal oestrogen use was associated with overall discontinuation of HRT (odds ratio [OR] 1.37, 95% confidence interval [CI] 1.10, 1.72), whereas use of oral oestrogen alone and use of oral cyclic combined oestrogen/progestogen were associated with change of HRT after MI (OR 2.33, 95% CI 1.10, 4.93 and OR 2.94, 95% CI 1.35, 6.39, respectively)., Conclusion: The majority of women experiencing an MI during ongoing HRT continued HRT after discharge and this pattern of HRT use did not change markedly after 2002., (© 2010 The Authors. British Journal of Clinical Pharmacology © 2010 The British Pharmacological Society.)

Objectives: To study differences in the clinical efficacy of various brands of beta-blocker in secondary prevention after a myocardial infarction (MI)., Methods: All patients hospitalized with a first MI between 1995 and 2002 who were still alive 30 days after discharge and had had at least one prescription for a beta-blocker filled were identified by individual-level linkage of nationwide registries of hospitalizations and drugs dispensed from pharmacies. A total of 32,259 MI patients were included in the study. Multivariable Cox proportional hazard models were used to analyze the risks of death and recurrent MI related to treatment with different beta-blockers., Results: The risks for death and recurrent MI were similar in patients using different beta-blockers, except that mortality from all causes among patients with a prescription for sotalol was higher. Subgroup analyses of high-risk patients with diabetes or congestive heart failure and of patients using comparable dosages of beta-blockers did not show effects on the risk of death or recurrent MI., Conclusion: Except for sotalol, the different types of beta-blocker had similar clinical efficacy in reducing mortality and the recurrence of MI. The equivalent efficacy remained when high-risk patients were analyzed separately., ((c) 2008 S. Karger AG, Basel.)

Background: Previous studies reveal major differences in the estimated cardiovascular risk in diabetes mellitus, including uncertainty about the risk in young patients. Therefore, large studies of well-defined populations are needed., Methods and Results: All residents in Denmark > or = 30 years of age were followed up for 5 years (1997 to 2002) by individual-level linkage of nationwide registers. Diabetes patients receiving glucose-lowering medications and nondiabetics with and without a prior myocardial infarction were compared. At baseline, 71 801 (2.2%) had diabetes mellitus and 79 575 (2.4%) had a prior myocardial infarction. Regardless of age, age-adjusted Cox proportional-hazard ratios for cardiovascular death were 2.42 (95% confidence interval [CI], 2.35 to 2.49) in men with diabetes mellitus without a prior myocardial infarction and 2.44 (95% CI, 2.39 to 2.49) in nondiabetic men with a prior myocardial infarction (P=0.60), with nondiabetics without a prior myocardial infarction as the reference. Results for women were 2.45 (95% CI, 2.38 to 2.51) and 2.62 (95% CI, 2.55 to 2.69) (P=0.001), respectively. For the composite of myocardial infarction, stroke, and cardiovascular death, the hazard ratios in men with diabetes only were 2.32 (95% CI, 2.27 to 2.38) and 2.48 (95% CI, 2.43 to 2.54) in those with a prior myocardial infarction only (P=0.001). Results for women were 2.48 (95% CI, 2.43 to 2.54) and 2.71 (95% CI, 2.65 to 2.78) (P=0.001), respectively. Risks were similar for both diabetes types. Analyses with adjustments for comorbidity, socioeconomic status, and prophylactic medical treatment showed similar results, and propensity score-based matched-pair analyses supported these findings., Conclusions: Patients requiring glucose-lowering therapy who were > or = 30 years of age exhibited a cardiovascular risk comparable to nondiabetics with a prior myocardial infarction, regardless of sex and diabetes type. Therefore, requirement for glucose-lowering therapy should prompt intensive prophylactic treatment for cardiovascular diseases.

Objectives: To study differences in the clinical efficacy of various brands of β-blocker in secondary prevention after a myocardial infarction (MI). Methods: All patients hospitalized with a first MI between 1995 and 2002 who were still alive 30 days after discharge and had had at least one prescription for a β-blocker filled were identified by individual-level linkage of nationwide registries of hospitalizations and drugs dispensed from pharmacies. A total of 32,259 MI patients were included in the study. Multivariable Cox proportional hazard models were used to analyze the risks of death and recurrent MI related to treatment with different β-blockers. Results: The risks for death and recurrent MI were similar in patients using different β-blockers, except that mortality from all causes among patients with a prescription for sotalol was higher. Subgroup analyses of high-risk patients with diabetes or congestive heart failure and of patients using comparable dosages of β-blockers did not show effects on the risk of death or recurrent MI. Conclusion: Except for sotalol, the different types of β-blocker had similar clinical efficacy in reducing mortality and the recurrence of MI. The equivalent efficacy remained when high-risk patients were analyzed separately. Copyright © 2008 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Background--The optimal long-term antithrombotic treatment of patients with coexisting atrial fibrillation and stable coronary artery disease is unresolved, and commonly, a single antiplatelet agent is added to oral anticoagulation. We investigated the effectiveness and safety of adding antiplatelet therapy to vitamin K antagonist (VKA) in atrial fibrillation patents with stable coronary artery disease. Methods and Results--Atrial fibrillation patients with stable coronary artery disease (defined as 12 months from an acute coronary event) between 2002 and 2011 were identified. The subsequent risk of cardiovascular events and serious bleeding events (those that required hospitalization) was examined with adjusted Cox regression models according to ongoing antithrombotic therapy. A total of 8700 patients were included (mean age, 74.2 years; 38% women). During a mean follow-up of 3.3 years, crude incidence rates were 7.2, 3.8, and 4.0 events per 100 person-years for myocardial infarction/coronary death, thromboembolism, and serious bleeding, respectively. Relative to VKA monotherapy, the risk of myocardial infarction/coronary death was similar for VKA plus aspirin (hazard ratio, 1.12 [95% confidence interval, 0.94-1.34]) and VKA plus clopidogrel (hazard ratio, 1.53 [95% confidence interval, 0.93-2.52]). The risk of thromboembolism was comparable in all regimens that included VKA, whereas the risk of bleeding increased when aspirin (hazard ratio, 1.50 [95% confidence interval, 1.23-1.82]) or clopidogrel (hazard ratio, 1.84 [95% confidence interval, 1.11-3.06]) was added to VKA. Conclusions--In atrial fibrillation patients with stable coronary artery disease, the addition of antiplatelet therapy to VKA therapy is not associated with a reduction in risk of recurrent coronary events or thromboembolism, whereas risk of bleeding is increased significantly. The common practice of adding antiplatelet therapy to oral VKA anticoagulation in patients with atrial fibrillation and stable coronary artery disease warrants reassessment. [ABSTRACT FROM AUTHOR]

Abstract: Background: Vascular disease (including myocardial infarction and peripheral artery disease) has been proposed as a less well-validated risk factor for stroke in patients with atrial fibrillation. We investigated whether vascular disease is an independent risk factor of stroke/thromboembolism in atrial fibrillation and whether adding vascular disease improves Congestive heart failure, Hypertension, Age 75 years, Diabetes, previous Stroke (CHADS2) risk stratification. Methods: By using nationwide Danish registers, we identified all patients discharged with atrial fibrillation and not treated with vitamin K antagonist or heparin between 1997 and 2008. The rate of stroke/thromboembolism in patients with atrial fibrillation with and without vascular disease was determined, and the risk associated with vascular disease was estimated in Cox regression analyses. The value of adding vascular disease to the CHADS2 score was evaluated by Net Reclassification Improvement and Integrated Discrimination Improvement. Results: We included 87,202 patients with non-valvular atrial fibrillation; of these, 15,212 (17.4%) had vascular disease, 11,750 (77.2%) had myocardial infarction, 2503 (16.5%) had peripheral artery disease, and 959 (6.3%) had both. In patients with a CHADS2 score=0, the rate of stroke/thromboembolism at 1-year follow-up was 2.31 (1.63-3.26) and 1.52 (1.34-1.73) per 100 person-years in patients with and without vascular disease, respectively. Vascular disease increased the risk of stroke/thromboembolism in both univariate (hazard ratio [HR] 1.26; confidence interval [CI], 1.18-1.35) and multivariate (HR, 1.12; CI, 1.05-1.21) analyses. The risk of stroke/thromboembolism associated with peripheral artery disease alone (HR, 1.93; CI, 1.70-2.19) was greater than the risk with myocardial infarction alone (HR, 1.12; CI, 1.04-1.21), and vascular disease significantly improved the predictive ability of the CHADS2 score (Net Reclassification Improvement 0.032, P<.001). Conclusions: Vascular disease is an independent predictor of stroke/thromboembolism in atrial fibrillation and improves the predictive ability of the CHADS2 score. [Copyright &y& Elsevier]