Local delivery of thrombolytics before thrombectomy in patients with ST-elevation myocardial infarction undergoing primary percutaneous coronary intervention — The DISSOLUTION randomized trial

Background: Ranolazine decreases the frequency of arrhythmias during the acute phases of ischemic heart disease (IHD), but it remains unknown if it has similar effects in the chronic phase of the disease. We performed a prospective, randomized, cross-over pilot trial to test the hypothesis that chronic treatment with ranolazine can reduce the incidence of documented arrhythmias and the related symptoms of palpitation in stable patients with IHD. Methods: We randomized 105 patients with stable IHD and symptoms of angina and palpitations already on therapy with betablockers and/or calcium antagonists to ranolazine (750 mg bid, N = 53) or placebo (N = 52) for 30 days (until T-1). After a washout period to avoid any carryover effect, cross-over was performed,and patients were switched to the other drug which was continued for 30 days (until T-2). All patients underwent symptomlimited exercise stress testing and 48-hour ECG Holter monitoring at T1 and T2. During the study period, patients were told to use a OmronN® portable ECG monitor HCG-801 device in case of symptoms of palpitations. Results: Ranolazine reduced the number of anginal episodes more commonly than placebo (5 ± 8 episodes/30 days vs. 21 ± 24 episodes/30 day, p = 0.001) and increased exercise durations at 1 mm ST-segment depression (514 ± 211 s vs. 402 ± 287 s, p = 0.025) and at onset of angina (614 ± 199 s vs. 519 ± 151 s, p = 0.007) at stress testing. These effects were coupled by significant decreases with ranolazine as compared with placebo treatment periods in the occurrence of frequent (N1000 beats) supraventricular arrhythmias (33% vs 52%, p = 0.01) and complex ventricular arrhythmias (17% vs 30%, p = 0.045). Complete resolution of symptoms of palpitations was significantly more common with ranolazine than placebo (31/53 vs 16/52 patients, p = 0.008). Also, portable ECG recordings showed that arrhythmias were less common during ranolazine vs. placebo, with significant decreases in number (7 ± 10 episodes/30 days vs. 23 ± 29 episodes/30 day, p = 0.001) and duration (10 ± 18 min/ 30 days vs. 19 ± 21 min/30 day, p = 0.021) of symptomatic arrhythmic episodes. No severe side effects were recorded during the trial period. Conclusion: The antianginal and antiischemic properties of ranolazine are paralleled by significant decreases in the occurrence of both arrhythmias and the related symptoms of palpitations in stable patients with IHD. (ClinicalTrials.gov identifier: NCT01495520)

Usefulness of Local Delivery of Thrombolytics Before Thrombectomy in Patients With ST-Segment Elevation Myocardial Infarction Undergoing Primary Percutaneous Coronary Intervention (the Delivery of Thrombolytics Before Thrombectomy in Patients With ST-Segment Elevation Myocardial Infarction Undergoing Primary Percutaneous Coronary Intervention [DISSOLUTION] Randomized Trial)

Thrombus aspiration during percutaneous coronary intervention can result in improved rates of normal epicardial flow and myocardial perfusion, but several unmet needs remain. The purpose of the Delivery of thrombolytIcs before thrombectomy in patientS with ST-segment elevatiOn myocardiaL infarction Undergoing primary percuTaneous coronary interventION (DISSOLUTION) trial was to evaluate the hypothesis that local delivery of thrombolytics can enhance the efficacy of thrombus aspiration in patients with ST-segment elevation myocardial infarction undergoing primary percutaneous coronary intervention. A total of 102 patients With ST-segment elevation myocardial infarction and angiographic evidence of massive thrombosis in the culprit artery were randomly assigned to receive a local, intrathrombus bolus of 200,000 U of urokinase (n = 51) or saline solution (n = 51) by way of an infusion microcatheter, followed by manual aspiration thrombectomy. The end points included the final Thrombolysis In Myocardial Infarction flow grade and frame count, myocardial blush grade, 60-minute ST-segment resolution >70%, and major adverse cardiac and cerebrovascular events, defined as the death, reinfarction, stroke, or clinically driven target vessel revascularization at 6 months. The use of intrathrombus urokinase was associated with a significantly higher incidence of Thrombolysis In Myocardial Infarction flow grade 3 (90% vs 66%, p = 0.008) and lower postpercutaneous coronary intervention Thrombolysis In Myocardial Infarction frame count (19 +/- 15 vs 25 +/- 17, p = 0.033). The postprocedural myocardial perfusion was significantly increased with the use of urokinase (myocardial blush grade 2 or 3, 68% vs 45%, p = 0.028), With more patients showing ST-segment resolution >70% (82% vs 55%, p = 0.006). At 6 months of follow-up, the patients treated with intrathrombus urokinase showed a better major adverse cardiac event-free survival (6% vs 21%; log-rank p = 0.044). In conclusion, local, intrathrombus delivery of thrombolytics before manual thrombectomy improved the postprocedural coronary flow and myocardial perfusion and the 6-month clinical outcomes. (C) 2013 Elsevier Inc. All rights reserved