Thrombolytic therapy in patients requiring cardiopulmonary resuscitation

Cardiopulmonary resuscitation (CPR) is often considered a contraindication to thrombolytic therapy for acute myocardial infarction. Of 708 patients involved in the first 3 Thrombolysis and Angioplasty in Myocardial Infarction trials of lytic therapy for acute infarction, 59 patients required 10 minutes was an exclusion of the trials) or required CPR within 6 hours of treatment. The patients receiving CPR were similar to the remainder of the group with respect to baseline demographics. The indication for CPR was usually ventricular fibrillation (73%) or ventricular tachycardia (24%). The median duration of CPR was 1 minute, with twenty-fifth and seventy-fifth percentiles of 1 and 5 minutes, respectively. The median number of cardioversions/defibrillations performed was 2 (twenty-fifth and seventy-fifth percentiles of 1 and 3 minutes, respectively). Patients receiving CPR were more likely to have anterior infarctions (66 vs 39%), the left anterior descending artery as the infarct-related artery (63 vs 38%) and lower ejection fractions on the initial ventriculogram (46 +/- 11 vs 52 +/- 12%) than those not receiving CPR. Inhospital mortality was 12 vs 6% with most deaths due to pump failure (57%) or arrhythmia (29%) in the CPR group and pump failure (38%) or reinfarction (25%) in the non-CPR group. At 7 day follow-up the CPR group had a significant increase in ejection fraction (+5 +/- 9%) compared with no change in non-CPR group. There were no bleeding complications directly attributed to CPR. In particular, the decrease in hematocrit (median 11) and need for transfusion (37 vs 32%) were the same in both groups. In addition, the CPR group did not spend more days in the cardiac care unit or in hospital than the non-CPR group.In conclusion, patients who have received CPR for <10 minutes had no additional complications attributable to thrombolytic therapy (95% confidence interval 0 to 5%). Therefore, CPR, especially of short duration, should not be considered a contraindication to lytic treatment. In addition, our results suggest that patients requiring CPR during acute infarction constitute a high-risk subgroup which may particularly benefit from receiving thrombolytic therapy.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/29089/1/0000124.pd

Randomized Dose-Ranging Controlled Trial of AQ-13, a Candidate Antimalarial, and Chloroquine in Healthy Volunteers

OBJECTIVES: To determine: (1) the pharmacokinetics and safety of an investigational aminoquinoline active against multidrug–resistant malaria parasites (AQ-13), including its effects on the QT interval, and (2) whether it has pharmacokinetic and safety profiles similar to chloroquine (CQ) in humans. DESIGN: Phase I double-blind, randomized controlled trials to compare AQ-13 and CQ in healthy volunteers. Randomizations were performed at each step after completion of the previous dose. SETTING: Tulane–Louisiana State University–Charity Hospital General Clinical Research Center in New Orleans. PARTICIPANTS: 126 healthy adults 21–45 years of age. INTERVENTIONS: 10, 100, 300, 600, and 1,500 mg oral doses of CQ base in comparison with equivalent doses of AQ-13. OUTCOME MEASURES: Clinical and laboratory adverse events (AEs), pharmacokinetic parameters, and QT prolongation. RESULTS: No hematologic, hepatic, renal, or other organ toxicity was observed with AQ-13 or CQ at any dose tested. Headache, lightheadedness/dizziness, and gastrointestinal (GI) tract–related symptoms were the most common AEs. Although symptoms were more frequent with AQ-13, the numbers of volunteers who experienced symptoms with AQ-13 and CQ were similar (for AQ-13 and CQ, respectively: headache, 17/63 and 10/63, p = 0.2; lightheadedness/dizziness, 11/63 and 8/63, p = 0.6; GI symptoms, 14/63 and 13/63; p = 0.9). Both AQ-13 and CQ exhibited linear pharmacokinetics. However, AQ-13 was cleared more rapidly than CQ (respectively, median oral clearance 14.0–14.7 l/h versus 9.5–11.3 l/h; p ≤ 0.03). QTc prolongation was greater with CQ than AQ-13 (CQ: mean increase of 28 ms; 95% confidence interval [CI], 18 to 38 ms, versus AQ-13: mean increase of 10 ms; 95% CI, 2 to 17 ms; p = 0.01). There were no arrhythmias or other cardiac AEs with either AQ-13 or CQ. CONCLUSIONS: These studies revealed minimal differences in toxicity between AQ-13 and CQ, and similar linear pharmacokinetics

Lesion-directed administration of alteplase with intracoronary heparin in patients with unstable angina and coronary thrombus undergoing angioplasty

Percutaneous coronary revascularization in patients with unstable angina and coronary thrombus carries a high complication rate. A new strategy to reduce thrombus burden before revascularization was tested in a multicenter prospective trial. Patients with unstable angina and coronary thrombus (n = 45) received alteplase through an infusion catheter at the proximal aspect of the target lesion and concomitant intracoronary heparin via a standard guiding catheter. Angiography was performed before and after lesiondirected therapy and post-intervention. Systemic fibrinogen depletion and thrombin activation were not observed, while fibrinolysis was evident for ≥4 hr after treatment. Target lesion stenosis did not change significantly after lesion-directed therapy, but thrombus score was reduced, particularly among patients who had large thrombi (mean 2.2 vs. 1.6, P = 0.02). Revascularization was successful in 89% of patients. Median final stenosis was 30% and mean final thrombus score was 0.4. Complications included recurrent ischemia (11%), MI (7%), abrupt closure (7%), severe bleeding (4%), and repeat emergency angioplasty (2%). Patients with overt thrombus appeared to derive the most angiograpnic benefit from lesion-directed alteplase plus intracoronary heparin. Later revascularization was highly successful. This strategy may be a useful adjunct to percutaneous revascularization for patients with unstable angina and frank intracoronary thrombus. © 1996 Wiley-Liss, Inc.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/38222/1/1810370409_ftp.pd