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Unfractionated heparin and low-molecular-weight heparins are often used to treat acute coronary syndromes. In this study, the pentasaccharide fondaparinux was found to have efficacy equal to that of enoxaparin in terms of anti-ischemic benefits but was associated with substantially less bleeding and lower long-term morbidity and mortality. Fondaparinux was found to have efficacy equal to that of enoxaparin in terms of anti-ischemic benefits but was associated with substantially less bleeding and lower long-term morbidity and mortality. The combined use of anticoagulants, 1 antiplatelet agents, 2 – 4 and an invasive strategy 5 in high-risk patients with acute coronary syndromes reduces ischemic coronary events but also increases bleeding. Bleeding may increase the risk of death, 6 myocardial infarction, and stroke. Therefore, future therapies should either preserve or enhance benefits without increasing bleeding. Unfractionated heparin and low-molecular-weight heparins are commonly used in patients with acute coronary syndromes, but enoxaparin may be modestly superior to unfractionated heparin in reducing the risk of death or myocardial infarction. 7 Fondaparinux (Arixtra, GlaxoSmithKline), a synthetic pentasaccharide, selectively binds antithrombin and causes rapid and predictable inhibition of factor Xa. . . .

In this trial, patients with acute coronary syndromes undergoing an early invasive approach were randomly assigned to treatment with heparin or enoxaparin plus a glycoprotein IIb/IIIa inhibitor, bivalirudin plus a glycoprotein IIb/IIIa inhibitor, or bivalirudin alone. Rates of ischemic events at 30 days were similar for all three groups, whereas major bleeding was significantly reduced in the group receiving bivalirudin alone. The trial suggests that bivalirudin monotherapy may be similar in efficacy to standard therapy, although bivalirudin monotherapy is associated with a reduced risk of bleeding. Pretreatment with a thienopyridine seems to be necessary if bivalirudin monotherapy is used. This trial suggests that bivalirudin monotherapy may be similar in efficacy to standard therapy, although bivalirudin monotherapy is associated with a reduced risk of bleeding. More than 1.4 million persons are admitted to hospitals in the United States every year with acute coronary syndromes (e.g., unstable angina or myocardial infarction without ST-segment elevation). 1 An early invasive strategy for patients with moderate- or high-risk acute coronary syndromes, consisting of angiography followed by percutaneous coronary intervention (PCI), coronary-artery bypass grafting (CABG), or medical management, results in higher rates of event-free survival than does conservative care 2 and is recommended by the American Heart Association, the American College of Cardiology, and the European Society of Cardiology. 3 – 5 Aspirin, clopidogrel, a platelet glycoprotein IIb/IIIa inhibitor, and an antithrombotic agent (either . . .

This trial compared the efficacy of antiplatelet therapy with prasugrel or clopidogrel in patients with non–ST-segment elevation MI or unstable angina. Although prasugrel provides more intense platelet inhibition, clinical outcomes were similar with the two drugs. Clinical-practice guidelines for patients with acute coronary syndromes consisting of unstable angina or myocardial infarction without ST-segment elevation recommend a strategy of early invasive management (angiography within 48 to 72 hours with provisional revascularization) for patients at moderate to high risk. 1 , 2 However, analyses from clinical trials and national registries have shown that many such patients are treated medically without revascularization and that such patients have poorer long-term cardiovascular outcomes than those who undergo revascularization. 3 – 6 Even though patients with acute coronary syndromes who receive only medical therapy have an increased-risk profile, they have been underrepresented in large-scale, contemporary, randomized . . .

An early invasive strategy is better than a conservative strategy, especially for higher-risk patients. The syndrome of unstable angina and myocardial infarction without ST-segment elevation accounts for approximately 1.4 million hospital admissions annually in the United States and 2 million to 2.5 million worldwide. 1 Until fairly recently, initial treatment focused on medical stabilization through the use of antianginal and antithrombotic agents, including aspirin and unfractionated or low-molecular-weight heparin. 2 – 5 The next step is to decide whether to refer the patient for cardiac catheterization and revascularization, if appropriate (a routine invasive approach), or to follow a conservative strategy, in which cardiac procedures are performed only if the patient has spontaneous or provoked recurrent ischemia. There . . .

Non-ST elevation acute coronary syndromes are responsible for approximately 1 million admissions to U.S. hospitals and twice as many to European hospitals each year. Thus, they are among the most common serious illnesses in adults, and are associated with an in-hospital mortality of approximately 5%. The most common cause is rupture of an atherosclerotic coronary plaque, resulting in subtotal coronary occlusion. Diagnosis is based on the clinical picture of retrosternal chest pain, aided by electrocardiographic findings of ST segment deviations and biomarker abnormalities (elevation of troponin and natriuretic peptides) and cardiac imaging (myocardial scans showing perfusion defects). Treatment involves antiischemic agents (nitrates and β blockers), antiplatelet drugs (aspirin, P2Y(12), and glycoprotein IIb/IIIa receptor blockers), and anticoagulants (unfractionated and low-molecular-weight heparins). Patients should undergo risk stratification, and those with high-risk factors should undergo coronary arteriography promptly with the intent to carry out coronary revascularization. Those at low risk should continue to receive intensive antiischemic and antithrombotic therapy. At discharge, patients should receive intensive lipid-lowering therapy with high doses of a statin, as tolerated.

On July 10, the FDA approved the thienopyridine prasugrel for use in patients with unstable angina or myocardial infarction who undergo percutaneous coronary intervention. Dr. Deepak Bhatt discusses the associated risk of bleeding, the mechanism of action, and the use of this antiplatelet therapy in clinical practice. On July 10, 2009, after an 18-month review, the Food and Drug Administration (FDA) approved the thienopyridine prasugrel for use in patients with unstable angina or myocardial infarction who undergo percutaneous coronary intervention (PCI). The new drug is the latest addition to a class of agents that inhibit the platelet adenosine diphosphate (ADP) receptor, preventing initial platelet activation and consequent platelet aggregation — a mechanism that has represented a major advance in the treatment of atherothrombotic diseases. 1 Indeed, the use of the thienopyridine ticlopidine in combination with aspirin to inhibit platelet aggregation facilitated the widespread use of coronary-artery stenting. Because . . .

Patients with acute coronary syndromes (ACS; unstable angina and non–ST-segment elevation myocardial infarction) are at significant risk for death and myocardial infarction. Early angiography followed by revascularization is considered the treatment of choice for moderate- to high-risk patients with ACS. However, despite the integration of newer therapies including stents, glycoprotein IIb/IIIa inhibitors, and thienopyridines, the rate of adverse ischemic events still remains unacceptably high, and the intensive pharmacologic regimens used to stabilize the disrupted atherosclerotic plaque and support angioplasty and surgical revascularization procedures elicit a high rate of bleeding complications. Pilot trials suggest that the thrombin-specific anticoagulant bivalirudin may improve clinical outcomes in ACS. In the Acute Catheterization and Urgent Intervention Triage strategY (ACUITY) trial, 13,800 patients with moderate- to high-risk ACS are being prospectively randomly assigned at up to 600 centers to unfractionated heparin or enoxaparin + IIb/IIIa inhibition, versus bivalirudin + IIb/IIIa inhibition, versus bivalirudin + provisional IIb/IIIa inhibition. All patients undergo cardiac catheterization within 72 hours, followed by percutaneous or surgical revascularization when appropriate. In a second random assignment, patients assigned to receive IIb/IIIa inhibitors are subrandomized to upstream drug initiation, versus IIb/IIIa inhibitor administration during angioplasty only. The primary study end point is the composite of death, myocardial infarction, unplanned revascularization for ischemia, and major bleeding at 30 days. Clinical follow-up will continue for 1 year. The ACUITY trial is the largest study yet performed in patients with ACS undergoing an invasive strategy. In addition to evaluating the utility of bivalirudin in ACS, this study will also provide important guidance regarding the necessity for and timing of IIb/IIIa inhibitor administration.

Several countries affected by the COVID-19 pandemic have reported a substantial drop in the number of patients attending the emergency department with acute coronary syndromes and a reduced number of cardiac procedures. We aimed to understand the scale, nature, and duration of changes to admissions for different types of acute coronary syndrome in England and to evaluate whether in-hospital management of patients has been affected as a result of the COVID-19 pandemic. We analysed data on hospital admissions in England for types of acute coronary syndrome from Jan 1, 2019, to May 24, 2020, that were recorded in the Secondary Uses Service Admitted Patient Care database. Admissions were classified as ST-elevation myocardial infarction (STEMI), non-STEMI (NSTEMI), myocardial infarction of unknown type, or other acute coronary syndromes (including unstable angina). We identified revascularisation procedures undertaken during these admissions (ie, coronary angiography without percutaneous coronary intervention [PCI], PCI, and coronary artery bypass graft surgery). We calculated the numbers of weekly admissions and procedures undertaken; percentage reductions in weekly admissions and across subgroups were also calculated, with 95% CIs. Hospital admissions for acute coronary syndrome declined from mid-February, 2020, falling from a 2019 baseline rate of 3017 admissions per week to 1813 per week by the end of March, 2020, a reduction of 40% (95% CI 37–43). This decline was partly reversed during April and May, 2020, such that by the last week of May, 2020, there were 2522 admissions, representing a 16% (95% CI 13–20) reduction from baseline. During the period of declining admissions, there were reductions in the numbers of admissions for all types of acute coronary syndrome, including both STEMI and NSTEMI, but relative and absolute reductions were larger for NSTEMI, with 1267 admissions per week in 2019 and 733 per week by the end of March, 2020, a percent reduction of 42% (95% CI 38–46). In parallel, reductions were recorded in the number of PCI procedures for patients with both STEMI (438 PCI procedures per week in 2019 vs 346 by the end of March, 2020; percent reduction 21%, 95% CI 12–29) and NSTEMI (383 PCI procedures per week in 2019 vs 240 by the end of March, 2020; percent reduction 37%, 29–45). The median length of stay among patients with acute coronary syndrome fell from 4 days (IQR 2–9) in 2019 to 3 days (1–5) by the end of March, 2020. Compared with the weekly average in 2019, there was a substantial reduction in the weekly numbers of patients with acute coronary syndrome who were admitted to hospital in England by the end of March, 2020, which had been partly reversed by the end of May, 2020. The reduced number of admissions during this period is likely to have resulted in increases in out-of-hospital deaths and long-term complications of myocardial infarction and missed opportunities to offer secondary prevention treatment for patients with coronary heart disease. The full extent of the effect of COVID-19 on the management of patients with acute coronary syndrome will continue to be assessed by updating these analyses. UK Medical Research Council, British Heart Foundation, Public Health England, Health Data Research UK, and the National Institute for Health Research Oxford Biomedical Research Centre.

The multicentre, randomised Benestent-II study investigated a strategy of implantation of a heparincoated Palmar-Schatz stent plus antiplatelet drugs compared with the use of balloon angioplasty in selected patients with stable or stabilised unstable angina, with one or more de-novo lesions, less than 18 mm long, in vessels of diameter 3 mm or more. 827 patients were randomly assigned stent implantation (414 patients) or standard balloon angioplasty (413 patients). The primary clinical endpoint was event-free survival at 6 months, including death, myocardial infarction, and the need for revascularisation. The secondary endpoints were the restenosis rate at 6 months and the cost-effectiveness at 12 months. There was also one-to-one subrandomisation to either clinical and angiographic follow-up or clinical follow-up alone. Analyses were by intention to treat. Four patients (one stent group, three angioplasty group) were excluded from analysis since no lesion was found. At 6 months, a primary clinical endpoint had occurred in 53 (12·8%) of 413 patients in the stent group and 79 (19·3%) of 410 in the angioplasty group (p=0·013). This significant difference in clinical outcome was maintained at 12 months. In the subgroup assigned angiographic follow-up, the mean minimum lumen diameter was greater in the stent group than in the balloon-angioplasty group, (1·89 [SD 0·65] vs 1·66 [0·57] mm, p=0·0002), which corresponds to restenosis rates (diameter stenosis ≥50%) of 16% and 31% (p=0·0008). In the group assigned clinical follow-up alone, event-free survival rate at 12 months was higher in the stent group than the balloon-angioplasty group (0·89 vs 0·79, p=0·004) at a cost of an additional 2085 Dutch guilders (US$1020) per patient. Over 12-month follow-up, a strategy of elective stenting with heparin-coated stents is more effective but also more costly than balloon angioplasty.

Non-ST-elevation myocardial infarction (NSTEMI) and unstable angina pectoris are frequent causes of hospital admission in the elderly. However, clinical trials targeting this population are scarce, and these patients are less likely to receive treatment according to guidelines. We aimed to investigate whether this population would benefit from an early invasive strategy versus a conservative strategy. In this open-label randomised controlled multicentre trial, patients aged 80 years or older with NSTEMI or unstable angina admitted to 16 hospitals in the South-East Health Region of Norway were randomly assigned to an invasive strategy (including early coronary angiography with immediate assessment for percutaneous coronary intervention, coronary artery bypass graft, and optimum medical treatment) or to a conservative strategy (optimum medical treatment alone). A permuted block randomisation was generated by the Centre for Biostatistics and Epidemiology with stratification on the inclusion hospitals in opaque concealed envelopes, and sealed envelopes with consecutive inclusion numbers were made. The primary outcome was a composite of myocardial infarction, need for urgent revascularisation, stroke, and death and was assessed between Dec 10, 2010, and Nov 18, 2014. An intention-to-treat analysis was used. This study is registered with ClinicalTrials.gov, number NCT01255540. During a median follow-up of 1·53 years of participants recruited between Dec 10, 2010, and Feb 21, 2014, the primary outcome occurred in 93 (40·6%) of 229 patients assigned to the invasive group and 140 (61·4%) of 228 patients assigned to the conservative group (hazard ratio [HR] 0·53 [95% CI 0·41–0·69], p=0·0001). Five patients dropped out of the invasive group and one from the conservative group. HRs for the four components of the primary composite endpoint were 0·52 (0·35–0·76; p=0·0010) for myocardial infarction, 0·19 (0·07–0·52; p=0·0010) for the need for urgent revascularisation, 0·60 (0·25–1·46; p=0·2650) for stroke, and 0·89 (0·62–1·28; p=0·5340) for death from any cause. The invasive group had four (1·7%) major and 23 (10·0%) minor bleeding complications whereas the conservative group had four (1·8%) major and 16 (7·0%) minor bleeding complications. In patients aged 80 years or more with NSTEMI or unstable angina, an invasive strategy is superior to a conservative strategy in the reduction of composite events. Efficacy of the invasive strategy was diluted with increasing age (after adjustment for creatinine and effect modification). The two strategies did not differ in terms of bleeding complications. Norwegian Health Association (ExtraStiftelsen) and Inger and John Fredriksen Heart Foundation.