Long-term benefits and risks of frontline nilotinib vs imatinib for chronic myeloid leukemia in chronic phase: 5-year update of the randomized ENESTnd trial.

In the phase 3 Evaluating Nilotinib Efficacy and Safety in Clinical Trials-Newly Diagnosed Patients (ENESTnd) study, nilotinib resulted in earlier and higher response rates and a lower risk of progression to accelerated phase/blast crisis (AP/BC) than imatinib in patients with newly diagnosed chronic myeloid leukemia in chronic phase (CML-CP). Here, patients' long-term outcomes in ENESTnd are evaluated after a minimum follow-up of 5 years. By 5 years, more than half of all patients in each nilotinib arm (300 mg twice daily, 54%; 400 mg twice daily, 52%) achieved a molecular response 4.5 (MR(4.5); BCR-ABL⩽0.0032% on the International Scale) compared with 31% of patients in the imatinib arm. A benefit of nilotinib was observed across all Sokal risk groups. Overall, safety results remained consistent with those from previous reports. Numerically more cardiovascular events (CVEs) occurred in patients receiving nilotinib vs imatinib, and elevations in blood cholesterol and glucose levels were also more frequent with nilotinib. In contrast to the high mortality rate associated with CML progression, few deaths in any arm were associated with CVEs, infections or pulmonary diseases. These long-term results support the positive benefit-risk profile of frontline nilotinib 300 mg twice daily in patients with CML-CP.

CT scan findings in oesophagogastric perforation after out of hospital cardiopulmonary resuscitation.

Rupture of the oesophagus or stomach at the time of cardiopulmonary resuscitation can occur with accidental oesophageal intubation. The common site of rupture is the lesser curvature of the stomach, but can also occur at the oesophagogastric junction. The patient presented with a massive pneumoperitoneum after an out of hospital ventricular fibrillation arrest. CT scanning was helpful in making the diagnosis. In out of hospital resuscitation, current JRCALC (Joint Royal Colleges Ambulance Liaison Committee) recommendations may not avoid this complication.

Outcome of different reperfusion strategies in patients with former contraindications to thrombolytic therapy: a comparison of primary angioplasty and tissue plasminogen activator. Primary Angioplasty in Myocardial Infarction (PAMI) Investigators.

High-risk patients have been excluded from most thrombolytic trials because of concern over hemorrhagic complications or lack of efficacy. However, based on several recent studies suggesting that patients with relative thrombolytic contraindications may also benefit from reperfusion, recommendations have been made to broadly expand the eligibility criteria for thrombolytic therapy, despite higher absolute complication rates. Primary percutaneous transluminal coronary angioplasty (PTCA) may be an attractive alternative for patients presenting at appropriately equipped hospitals who would otherwise remain at high risk after thrombolytic therapy. In the Primary Angioplasty in Myocardial Infarction (PAMI) trial, 395 patients with acute myocardial infarction were randomized to tissue plasminogen activator (t-PA) or primary PTCA. Conditions were present in 151 patients (38%) which formerly would have contraindicated thrombolytic therapy (age > 70 yr, symptom duration > 4 hr, or prior bypass surgery). In-hospital mortality was 4.3-fold higher in patients with former thrombolytic contraindications compared to lytic-eligible patients (8.6% vs. 2.0%, P = .002). Lytic-eligible patients treated with t-PA and PTCA had similar in-hospital mortality (1.7% vs. 2.4%, P = NS). In contrast, both in-hospital (2.9% vs. 13.2%, P = .025) and 6-mo mortality (2.9% vs. 15.7%, P = .009) were significantly reduced in patients with former thrombolytic contraindications treated by primary PTCA compared to t-PA. By logistic regression analysis, treatment by PTCA rather than t-PA was the strongest predictor of survival in patients with former thrombolytic contraindications. We conclude that patients with conditions formerly contraindicating thrombolytic therapy constitute a high-risk group with significant morbidity and mortality after lytic reperfusion. Our data suggest that patients with former contraindications to thrombolytic therapy may benefit by preferential management with primary PTCA without antecedent thrombolysis.

A comparison of immediate angioplasty with thrombolytic therapy for acute myocardial infarction. The Primary Angioplasty in Myocardial Infarction Study Group.

BACKGROUND: The success of thrombolytic therapy for acute myocardial infarction is limited by bleeding complications, the impossibility of reperfusing all occluded coronary arteries, recurrent myocardial ischemia, and the relatively small number of patients who are appropriate candidates for this therapy. We hypothesized that these problems could be overcome by the use of immediate percutaneous transluminal coronary angioplasty (PTCA), without previous thrombolytic therapy. METHODS: At 12 clinical centers, 395 patients who presented within 12 hours of the onset of myocardial infarction were treated with intravenous heparin and aspirin and then randomly assigned to undergo immediate PTCA (without previous thrombolytic therapy, 195 patients) or to receive intravenous tissue plasminogen activator (t-PA, 200 patients) followed by conservative care. Radionuclide ventriculography was performed to assess ventricular function within 24 hours and at six weeks. RESULTS: Among the patients randomly assigned to PTCA, 90 percent underwent the procedure; the success rate was 97 percent, and no patient required emergency coronary-artery bypass surgery. The in-hospital mortality rates in the t-PA and PTCA groups were 6.5 and 2.6 percent, respectively (P = 0.06). In a post hoc analysis, the mortality rates in the subgroups classified as "not low risk" were 10.4 and 2.0 percent, respectively (P = 0.01). Reinfarction or death in the hospital occurred in 12.0 percent of the patients treated with t-PA and 5.1 percent of those treated with PTCA (P = 0.02). Intracranial bleeding occurred more frequently among patients who received t-PA than among those who underwent PTCA (2.0 vs. 0 percent, P = 0.05). The mean (+/- SD) ejection fractions at rest (53 +/- 13 vs. 53 +/- 13 percent) and during exercise (56 +/- 13 vs. 56 +/- 14 percent) were similar in the t-PA and PTCA groups at six weeks. By six months, reinfarction or death had occurred in 32 patients who received t-PA (16.8 percent) and 16 treated with PTCA (8.5 percent, P = 0.02). CONCLUSIONS: As compared with t-PA therapy for acute myocardial infarction, immediate PTCA reduced the combined occurrence of nonfatal reinfarction or death, was associated with a lower rate of intracranial hemorrhage, and resulted in similar left ventricular systolic function.

Acute myocardial infarction temporally related to cocaine use. Clinical, angiographic, and pathophysiologic observations.

Ischemic chest pain syndromes and myocardial infarction occurred within minutes to hours of cocaine use in nine persons ages 23 to 39 years. Five developed symptoms after taking cocaine intranasally; three, after intravenous use; and one, after smoking cocaine. Four were habitual users and five were recreational users; eight also smoked cigarettes heavily. Ischemic syndromes recurred in five who continued to use cocaine. Coronary arteriography showed an abnormal infarct-related vessel (more than 50% stenosis, total occlusion, or intraluminal thrombus) in seven patients. The noninfarct-related vessels were normal in eight patients. The left anterior descending coronary artery and the anteroapical left-ventricular wall were involved in all patients. After three patients had successful thrombolysis of the obstructed infarct-related vessel, angiography showed a normal underlying vessel.