Cardiac Safety Research Consortium (CSRC): Cardiovascular Safety and Adverse Event Case Report Forms.

Detection of off-target cardiovascular (CV) effects remains a significant challenge to drug development. Documentation of CV events in non-CV trials is often inadequate to interpret imbalances between treatment arms, which may lead to concerns about potential CV safety "signals." The Cardiac Safety Research Consortium (CSRC) public-private partnership has developed CV case report forms (CRFs) for adverse CV events, including death. These CRFs are intended to encourage collection, as near to the occurrence of an event as possible, of the minimum information necessary to assess, or possibly adjudicate, the event. A broad range of stakeholders (representing industry, academia, and regulatory authorities) developed these forms with the goal of balancing the collection of key information with the resources likely to be available. Use of these forms is optional, and sponsors may modify them. These forms have not undergone any type of "validation" process. The CSRC will continue to sponsor a working group to invite public comment and feedback on these forms.

Adjunctive use of the Rinspiration system for fluidic thrombectomy during primary angioplasty: the Rinspiration international registry.

BACKGROUND: Atherothrombotic embolization during primary percutaneous coronary intervention (PCI) induces microvascular obstruction and reduces myocardial tissue reperfusion. A variety of thrombectomy devices have been evaluated as an adjunct to primary PCI in patients with ST-elevation myocardial infarction (STEMI) to reduce distal embolization. Results have been inconsistent and difficult to predict. The aim of this study was to investigate the safety and efficacy of an innovative thrombectomy device, the Rinspiration System, which simultaneously "rinses" the vessel with turbulent flow and aspirates thrombus. METHODS: We prospectively enrolled 109 patients at six academic institutions in three countries referred for primary or rescue PCI for STEMI presenting within 12 hr of symptom onset. The primary endpoint was >or=50% ST-segment elevation resolution (STR) measured 60 min after PCI by continuous electrocardiographic recording, Secondary end points included STR > 70% at 60 min, final TIMI flow, myocardial blush score, and 30-day major adverse cardiac events (MACE). RESULTS: Mean symptom-to-PCI time was 4.7 +/- 2.7 hr. Rinspiration was successfully delivered in 98% of cases. Final TIMI three flow was achieved in 89% of patients and myocardial blush >or=2 in 78%. Rates of STR >or= 50% and >70% at 60 min were 97 and 80%, respectively. No device-related complications were observed. Thirty-day MACE rate was 4.6%. CONCLUSIONS: This international multicenter registry demonstrates that the adjunctive use of Rinspiration during primary PCI is safe and feasible. The excellent STR data compare favorably with results of previous trials using different devices for thrombus management, indicating a potential clinical benefit.

Impact of time to treatment on myocardial reperfusion and infarct size with primary percutaneous coronary intervention for acute myocardial infarction (from the EMERALD Trial).

The impact of time to treatment on outcomes after primary percutaneous coronary intervention (PCI) is controversial, and there are few data about time to treatment and infarct size. The EMERALD trial randomly assigned 501 high-risk patients with ST-elevation myocardial infarction undergoing primary PCI to stenting with or without GuardWire (Medtronic, Santa Rosa, California) distal protection. Infarct size using sestamibi imaging at 5 to 14 days and clinical outcomes were examined by time to treatment. There were no differences in outcomes between distal protection and control patients. Shorter time to reperfusion (<2 vs 2 to 3 vs >3 to 4 vs >4 hours) was associated with smaller infarct size (2% vs 9% vs 12% vs 11%, p=0.026), trends for better myocardial blush (p=0.08), and lower 6-month mortality rates (0% vs 0% vs 2.4% vs 5.3%, p=0.06). Incremental delays in reperfusion after 2 hours had little impact on infarct size. Shorter time to reperfusion impacted on infarct size in patients with anterior infarction (0% vs 17% vs 20.5% vs 30.5%, p=0.026), but not nonanterior infarction (3% vs 7% vs 7.5% vs 10%, p=0.23, p=0.022 for interaction). In conclusion, very early reperfusion with primary PCI is associated with smaller infarct size and has a much greater impact in anterior versus nonanterior infarction. Incremental delays in reperfusion after 2 hours have less effect on infarct size. These data have implications regarding the triage of patients for primary PCI.

Drug eluting stents and the critical path initiative: Evolving paradigms for safety evaluation.

Recent discussions between FDA and other stakeholders have focused on the benefits and risks associated with drug eluting stents (DES). A particular topic of focus is DES thrombosis, a rare, but serious, clinical event that may occur months to years after the initial implantation. FDA continues vigilant postmarket surveillance of DES currently on the market and is working with stent manufactures to ensure that new DES platforms in the development pipeline are safe and effective. FDA is also taking steps, under its Critical Path Initiative (CPI) [FDA. Innovation or Stagnation: Challenge and Opportunity on the Critical Path to New Medical Products, March 2004.http://www.fda.gov/oc/initiatives/criticalpath/whitepaper.html], to help address current and future DES safety issues. This article describes some of these activities.:

Initial experience with a novel coronary rinsing and thrombectomy system: "Rinspiration".

BACKGROUND: Intracoronary thrombus is often problematic during percutaneous coronary intervention. Rinspiration is a new thrombectomy catheter system designed to mechanically disrupt and remove intravascular thrombus. METHODS: Rinspiration thrombectomy was performed in 15 patients with angiographically visible thrombus in native coronary arteries (10 cases) and in saphenous grafts (5 cases). Indications included acute myocardial infarction in 11 patients and postinfarction ischemia in 4 patients. RESULTS: The Rinspiration system appeared relatively simple to use. There were no device-related complications. Thrombectomy resulted in an improvement in thrombus grade from 3.8 +/- 1.6 to 2.5 +/- 1.7 (p = 0.02), and TIMI flow from 1.5 +/- 1.3 to 2.2 +/- 1.0 (p = 0.047). Stenting further improved thrombus grade to 0.8 +/- 1.6 and TIMI flow to 2.6 +/- 0.8. At 30-day follow up all patients remained free of repeat revascularization and reinfarction; 1 patient died from hemorrhagic stroke. CONCLUSIONS: The Rinspiration system appears capable of safely removing intracoronary thrombus and warrants further evaluation.