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OBJECTIVE: Approximately 10% of patients with myocardial infarction (MI) have no obstructive coronary artery disease. The prognosis and role of intensified antiplatelet therapy in those patients were evaluated. METHODS: We analysed data from the Clopidogrel and Aspirin Optimal Dose Usage to Reduce Recurrent Events-Seventh Organisation to Assess Strategies in Ischaemic Symptoms trial randomising patients with ACS referred for early intervention to receive either double-dose (600 mg, day 1; 150 mg, days 2-7; then 75 mg/day) or standard-dose (300 mg, day 1; then 75 mg/day) clopidogrel. Outcomes in patients with myocardial infarction with non-obstructive coronary arteries (MINOCA) versus those with obstructive coronary artery disease (CAD) and their relation to standard-dose versus double-dose clopidogrel were evaluated. The primary outcome was cardiovascular (CV) death, MI or stroke at 30 days. RESULTS: We included 23 783 patients with MI and 1599 (6.7%) with MINOCA. Patients with MINOCA were younger, presented more frequently with non-ST-segment elevation MI and had fewer comorbidities. All-cause mortality (0.6% vs 2.3%, p=0.005), CV mortality (0.6% vs 2.2%, p=0.006), repeat MI (0.5% vs 2.3%, p=0.001) and major bleeding (0.6% vs 2.4%, p

Sacubitril-Valsartan in Acute Myocardial Infarction In a randomized trial, 5661 patients with acute myocardial infarction and a reduced left ventricular ejection fraction, pulmonary congestion, or both were assigned to receive either sacubitril-valsartan or ramipril. At a median of 22 months, there was no significant difference between the two groups in the incidence of death from cardiovascular causes or incident heart failure. Background In patients with symptomatic heart failure, sacubitril-valsartan has been found to reduce the risk of hospitalization and death from cardiovascular causes more effectively than an angiotensin-converting-enzyme inhibitor. Trials comparing the effects of these drugs in patients with acute myocardial infarction have been lacking. Methods We randomly assigned patients with myocardial infarction complicated by a reduced left ventricular ejection fraction, pulmonary congestion, or both to receive either sacubitril-valsartan (97 mg of sacubitril and 103 mg of valsartan twice daily) or ramipril (5 mg twice daily) in addition to recommended therapy. The primary outcome was death from cardiovascular causes or incident heart failure (outpatient symptomatic heart failure or heart failure leading to hospitalization), whichever occurred first. Results A total of 5661 patients underwent randomization; 2830 were assigned to receive sacubitril-valsartan and 2831 to receive ramipril. Over a median of 22 months, a primary-outcome event occurred in 338 patients (11.9%) in the sacubitril-valsartan group and in 373 patients (13.2%) in the ramipril group (hazard ratio, 0.90; 95% confidence interval [CI], 0.78 to 1.04; P=0.17). Death from cardiovascular causes or hospitalization for heart failure occurred in 308 patients (10.9%) in the sacubitril-valsartan group and in 335 patients (11.8%) in the ramipril group (hazard ratio, 0.91; 95% CI, 0.78 to 1.07); death from cardiovascular causes in 168 (5.9%) and 191 (6.7%), respectively (hazard ratio, 0.87; 95% CI, 0.71 to 1.08); and death from any cause in 213 (7.5%) and 242 (8.5%), respectively (hazard ratio, 0.88; 95% CI, 0.73 to 1.05). Treatment was discontinued because of an adverse event in 357 patients (12.6%) in the sacubitril-valsartan group and 379 patients (13.4%) in the ramipril group. Conclusions Sacubitril-valsartan was not associated with a significantly lower incidence of death from cardiovascular causes or incident heart failure than ramipril among patients with acute myocardial infarction. (Funded by Novartis; PARADISE-MI ClinicalTrials.gov number, .)

BACKGROUND: Cryptogenic strokes constitute 20 to 30% of ischemic strokes, and most cryptogenic strokes are considered to be embolic and of undetermined source. An earlier randomized trial showed that rivaroxaban is no more effective than aspirin in preventing recurrent stroke after a presumed embolic stroke from an undetermined source. Whether dabigatran would be effective in preventing recurrent strokes after this type of stroke was unclear. METHODS: We conducted a multicenter, randomized, double-blind trial of dabigatran at a dose of 150 mg or 110 mg twice daily as compared with aspirin at a dose of 100 mg once daily in patients who had had an embolic stroke of undetermined source. The primary outcome was recurrent stroke. The primary safety outcome was major bleeding. RESULTS: A total of 5390 patients were enrolled at 564 sites and were randomly assigned to receive dabigatran (2695 patients) or aspirin (2695 patients). During a median follow-up of 19 months, recurrent strokes occurred in 177 patients (6.6%) in the dabigatran group (4.1% per year) and in 207 patients (7.7%) in the aspirin group (4.8% per year) (hazard ratio, 0.85; 95% confidence interval [CI], 0.69 to 1.03; P = 0.10). Ischemic strokes occurred in 172 patients (4.0% per year) and 203 patients (4.7% per year), respectively (hazard ratio, 0.84; 95% CI, 0.68 to 1.03). Major bleeding occurred in 77 patients (1.7% per year) in the dabigatran group and in 64 patients (1.4% per year) in the aspirin group (hazard ratio, 1.19; 95% CI, 0.85 to 1.66). Clinically relevant nonmajor bleeding occurred in 70 patients (1.6% per year) and 41 patients (0.9% per year), respectively. CONCLUSIONS: In patients with a recent history of embolic stroke of undetermined source, dabigatran was not superior to aspirin in preventing recurrent stroke. The incidence of major bleeding was not greater in the dabigatran group than in the aspirin group, but there were more clinically relevant nonmajor bleeding events in the dabigatran group. (Funded by Boehringer Ingelheim; RE-SPECT ESUS ClinicalTrials.gov number, NCT02239120.).

A substantial proportion of patients with heart failure have preserved left ventricular ejection fraction (HF-PEF). Previous studies have reported mixed results whether survival is similar to those patients with heart failure and reduced EF (HF-REF). We compared survival in patients with HF-PEF with that in patients with HF-REF in a meta-analysis using individual patient data. Preserved EF was defined as an EF epsilon 50. The 31 studies included 41 972 patients: 10 347 with HF-PEF and 31 625 with HF-REF. Compared with patients with HF-REF, those with HF-PEF were older (mean age 71 vs. 66 years), were more often women (50 vs. 28), and have a history of hypertension (51 vs. 41). Ischaemic aetiology was less common (43 vs. 59) in patients with HF-PEF. There were 121 [95 confidence interval (CI): 117, 126] deaths per 1000 patient-years in those with HF-PEF and 141 (95 CI: 138, 144) deaths per 1000 patient-years in those with HF-REF. Patients with HF-PEF had lower mortality than those with HF-REF (adjusted for age, gender, aetiology, and history of hypertension, diabetes, and atrial fibrillation); hazard ratio 0.68 (95 CI: 0.64, 0.71). The risk of death did not increase notably until EF fell below 40. Patients with HF-PEF have a lower risk of death than patients with HF-REF, and this difference is seen regardless of age, gender, and aetiology of HF. However, absolute mortality is still high in patients with HF-PEF highlighting the need for a treatment to improve prognosis.

Aims A substantial proportion of patients with heart failure have preserved left ventricular ejection fraction (HF-PEF). Previous studies have reported mixed results whether survival is similar to those patients with heart failure and reduced EF (HF-REF). Methods and results We compared survival in patients with HF-PEF with that in patients with HF-REF in a meta-analysis using individual patient data. Preserved EF was defined as an EF ≥ 50%. The 31 studies included 41 972 patients: 10 347 with HF-PEF and 31 625 with HF-REF. Compared with patients with HF-REF, those with HF-PEF were older (mean age 71 vs. 66 years), were more often women (50 vs. 28%), and have a history of hypertension (51 vs. 41%). Ischaemic aetiology was less common (43 vs. 59%) in patients with HF-PEF. There were 121 [95% confidence interval (CI): 117, 126] deaths per 1000 patient-years in those with HF-PEF and 141 (95% CI: 138, 144) deaths per 1000 patient-years in those with HF-REF. Patients with HF-PEF had lower mortality than those with HF-REF (adjusted for age, gender, aetiology, and history of hypertension, diabetes, and atrial fibrillation); hazard ratio 0.68 (95% CI: 0.64, 0.71). The risk of death did not increase notably until EF fell below 40%. Conclusion Patients with HF-PEF have a lower risk of death than patients with HF-REF, and this difference is seen regardless of age, gender, and aetiology of HF. However, absolute mortality is still high in patients with HF-PEF highlighting the need for a treatment to improve prognosis.

Aims To determine whether changes in practice, over time, are associated with altered rates of major bleeding in acute coronary syndromes (ACS). Methods and results Patients from the Global Registry of Acute Coronary Events were enrolled between 2000 and 2007. The main outcome measures were frequency of major bleeding, including haemorrhagic stroke, over time, after adjustment for patient characteristics, and impact of major bleeding on death and myocardial infarction. Of the 50 947 patients, 2.3% sustained a major bleed; almost half of these presented with ST-elevation ACS (44%, 513). Despite changes in antithrombotic therapy (increasing use of low molecular weight heparin, P < 0.0001), thienopyridines ( P < 0.0001), and percutaneous coronary interventions ( P < 0.0001), frequency of major bleeding for all ACS patients decreased (2.6 to 1.8%; P < 0.0001). Most decline was seen in ST-elevation ACS (2.9 to 2.1%, P = 0.02). The overall decline remained after adjustment for patient characteristics and treatments ( P = 0.002, hazard ratio 0.94 per year, 95% confidence interval 0.91–0.98). Hospital characteristics were an independent predictor of bleeding ( P < 0.0001). Patients who experienced major bleeding were at increased risk of death within 30 days from admission, even after adjustment for baseline variables. Conclusion Despite increasing use of more intensive therapies, there was a decline in the rate of major bleeding associated with changes in clinical practice. However, individual hospital characteristics remain an important determinant of the frequency of major bleeding.

We performed a genome-wide association study on 1,292 individuals with abdominal aortic aneurysms (AAAs) and 30,503 controls from Iceland and The Netherlands, with a follow-up of top markers in up to 3,267 individuals with AAAs and 7,451 controls. The A allele of rs7025486 on 9q33 was found to associate with AAA, with an odds ratio (OR) of 1.21 and P = 4.6 x 10(-10). In tests for association with other vascular diseases, we found that rs7025486[A] is associated with early onset myocardial infarction (OR = 1.18, P = 3.1 x 10(-5)), peripheral arterial disease (OR = 1.14, P = 3.9 x 10(-5)) and pulmonary embolism (OR = 1.20, P = 0.00030), but not with intracranial aneurysm or ischemic stroke. No association was observed between rs7025486[A] and common risk factors for arterial and venous diseases-that is, smoking, lipid levels, obesity, type 2 diabetes and hypertension. Rs7025486 is located within DAB2IP, which encodes an inhibitor of cell growth and survival.

The incidence of thrombocytopenia after hospital admission, patient and treatment characteristics, and outcomes in patients enrolled in the prospective multinational GRACE were examined. Heparin (unfractionated or low molecular weight) and glycoprotein IIb/IIIa-inhibition can be associated with immune-mediated thrombocytopenia of clinical importance. The prevalence of thrombocytopenia in patients with acute coronary syndromes (ACSs) in general and specifically related to these therapies and associated outcomes have been studied little outside of clinical trials. Patients with an ACS were stratified into 4 groups of those with heparin-induced thrombocytopenia (HIT), those with glycoprotein IIb/IIIa-associated thrombocytopenia (GAT), those with other thrombocytopenia (not diagnosed as HIT or associated with glycoprotein inhibitors), and those with no thrombocytopenia. From June 2000 to September 2007, a total of 52,647 patients with an ACS and information for platelet count were enrolled in GRACE. Of these, 152 (0.3%) were reported to develop HIT, 324 (0.6%) developed GAT, and 368 (0.7%) developed other thrombocytopenia. Patients with HIT, GAT, or other thrombocytopenia were significantly more likely to die in the hospital versus those without these diseases (adjusted odds ratio [OR] 1.94, 95% confidence interval [CI] 1.07 to 3.53; adjusted OR 3.45, 95% CI 2.35 to 5.05; and adjusted OR 2.83, 95% CI 1.97 to 4.06, respectively). They were also more likely to experience major bleeding, (re)infarction, or stroke. In conclusion, in this large multinational registry, 1.6% of patients with ACS were reported to develop thrombocytopenia, with only 0.3% being HIT. Regardless of whether patients had clinically recognized HIT, GAT, or other thrombocytopenia, all 3 groups had significantly higher rates of major bleeding, recurrent infarction, stroke, and death.

The purpose of this study is to evaluate hospital mortality and major bleeding rates among patients receiving low molecular weight heparin (LMWH), unfractionated heparin (UFH), or both, and to investigate whether concomitant glycoprotein (GP) IIb/IIIa antagonists and coronary intervention affect patterns of use and outcomes with different heparins.With widespread use of glycoprotein (GP) IIb/IIIa inhibitors and invasive treatments, patients with high-risk acute coronary syndrome (ACS) may have a greater bleeding risk and may not gain additional benefit from LMWHs. The purpose of this study is to evaluate hospital mortality and major bleeding rates among patients receiving LMWH, UFH, or both, and to investigate whether concomitant GP IIb/IIIa antagonists and coronary intervention affect patterns of use and outcomes with different heparins.Data were analyzed from 28,445 patients with ACS; 21,287 had non-ST-segment elevation myocardial infarction or unstable angina and received LMWH or UFH.Fifty-one percent of patients received LMWH, 32% UFH, and 17% both. The lowest inhospital mortality and bleeding rates occurred with LMWH (2.7% and 1.8% vs UFH, 4.1% and 2.7%; all P.0001). After multivariable analysis, LMWH was associated with lower inhospital mortality rates in patients not treated with GP IIb/IIIa antagonists, irrespective of whether they had a percutaneous coronary intervention (PCI) (odds ratio 0.77, 95% confidence interval 0.63-0.94 without PCI vs odds ratio 0.45, 95% confidence interval 0.21-0.98 with PCI). Excess bleeding occurred with PCI in LMWH-treated patients. Patients older than 75 years who received GP IIb/IIIa antagonists and any antithrombotic but not PCI had an increased risk of major bleeding (LMWH 14%, UFH 8.3%).In patients with non-ST-elevation ACS without GP IIb/IIIa antagonists, LMWH was associated with a lower mortality rate and more bleeding episodes in PCI-treated patients than UFH; no differences occurred with GP IIb/IIIa antagonists. Elderly patients managed medically with GP IIb/IIIa antagonists and either heparin had a very high major bleeding risk.

Background Revascularization rates vary substantially between countries in patients with acute ST-elevation myocardial infarction (STEMI). The impact of early revascularization on clinical outcomes in such patients remains uncertain. The ASSENT-2 fibrinolytic trial provides the opportunity to compare revascularization rates following STEMI in patients across 29 countries, and to explore the relationship between revascularization and clinical outcome. Methods Countries participating in ASSENT-2 were grouped into tertiles according to their in-hospital revascularization rates (39%). Baseline characteristics, medication and procedure use, and clinical outcomes of the 16 949 patients enrolled were compared. Multiple Cox regressions were used to assess the relationship between the tertiles and 30-day mortality, the primary endpoint of the ASSENT-2 trial. Multilevel logistic regression models were developed to validate and further extend the findings from the single-level analyses. Results Patients in highest tertile countries were younger, heavier, and more often diabetic or hypertensive. They were more likely to have had a previous myocardial infarction or revascularization procedure. Time to treatment and hospital length of stay were shorter in the highest tertile, and beta-blocker use was more frequent. Stroke rates were low and similar across termites, with no statistically significant difference in rates of intracranial haemorrhage. Recurrent ischaemia and reinfarction were less common in the highest tertile. Mortality rates at 30 days were tower for countries with the highest revascularization rates (5.1% vs 6.9% vs 6.5% for the lower two tertiles, P < 0.001). At 1 year, mortality remained significantly lower in the highest tertile countries (8.4% vs 10.6% vs 9.9%, P = 0.001). Following adjustment for baseline patient characteristics, Cox regression analysis confirmed an excess of 30-day and 1-year mortality in the lowest and intermediate tertiles compared to the highest tertile. The multilevel analyses validated these findings, and demonstrated that a country’s life expectancy and the hospital volume were inversely related to both 30-day and 1-year mortality. Conclusions The highest rate of in-hospital revascularization following fibrinolytic therapy for acute myocardial infarction in this international study was associated with a reduction in recurrent ischaemia, reinfarction, and improved survival at both 30 days and at 1 year. The optimal rates of revascularization in this setting remain to be determined. (C) 2003 Published by Elsevier Ltd on behalf of The European Society of Cardiology.