Novel Trial Designs: Lessons Learned from Thrombus Aspiration During ST-Segment Elevation Myocardial Infarction in Scandinavia (TASTE) Trial.

In ST-elevation myocardial infarction (STEMI), thrombus material is often present in partial or total coronary occlusion of the coronary vessel. However, prior to the thrombus aspiration during ST-Segment Elevation Myocardial Infarction in Scandinavia (TASTE) trial, it remained unclear whether routine thrombus aspiration during percutaneous coronary intervention (PCI) treatment of STEMI would result in patients overall survival benefit. The TASTE trial was a multicenter, prospective, open-label, randomized, controlled clinical trial. In order to randomize patients to treatment and collect data, the infrastructure of a clinical population-based registry was used. Online data collection used the national comprehensive Swedish Coronary Angiography and Angioplasty Registry, a part of the SWEDEHEART registry. Monitoring and adjudication was done as part of the regular registry validation. There was no separate, dedicated monitoring or adjudication of endpoints. Included were 7244 patients with STEMI with chest pain and time of symptoms to hospital admission <24 h, in addition to new electrocardiographic ST-segment elevation or left bundle-branch block. Exclusion criteria were the need for emergency coronary artery bypass grafting. All-cause mortality at 30 days occurred in 2.8 % of the patients in the thrombus-aspiration group, as compared with 3.0 % in the PCI-only group (hazard ratio [HR] 0.94, 95 % confidence interval [CI] 0.72-1.22; p = 0.63). All-cause mortality at 1 year occurred in 5.3 % of the patients in the thrombus-aspiration group, as compared with 5.6 % in the PCI-only group (HR 0.94, 95 % CI 0.78-1.15; p = 0.57). No patients were lost to follow-up at 1 year. The incremental cost for trial execution was approximately US$300,000 or$50 per patient. Routine thrombus aspiration during PCI in patients with STEMI did not reduce the rate of all-cause mortality at 1 year. It is possible to design and conduct mega-trial at only small cost compared to a similar-sized conventional randomized clinical trial

Relation of lipid-lowering therapy to need for aortic valve replacement in patients with asymptomatic mild to moderate aortic stenosis

Abstract In this study, we aimed to determine if pretreatment low-density lipoprotein (LDL) levels and aortic stenosis (AS) severity alter the efficacy of lipid-lowering therapy on reducing aortic valve replacement (AVR). We used 1,687 patients with asymptomatic mild-to-moderate AS, who were randomly assigned (1:1) to 40/10 mg simvastatin/ezetimibe combination versus. placebo in the simvastatin and ezetimibe in aortic stenosis (SEAS) trial. Pretreatment LDL levels (&gt;4 mmol/L) and peak aortic jet velocity (3 m/s) were used to partition study participants into 4 groups, which were followed for a primary endpoint of AVR. Cox regression with tests for interaction was used to study the effect of randomized treatment in each subgroup. During a median follow-up of 4.3 years (IQR 4.2 to 4.7 years; total 7,396 patient-years of follow-up), 478 (28%) patients underwent AVR and 146 (9%) died. A significant risk dependency was detected between simvastatin/ezetimibe combination, LDL levels and mild versus moderate AS on rates of AVR (p = 0.01 for interaction). In stratified analyses, randomized treatment, therefore, reduced the rate of AVR in patients with LDL levels &gt;4 mmol and mild AS at baseline (HR 0.4; 95% CI: 0.2 to 0.9). There was no detectable effect of randomized treatment on the need for AVR in the 3 other participants subgroups. We conclude, that in a secondary analysis from a prospective randomized clinical trial, treatment with simvastatin/ezetimibe combination reduced the need for AVR in a subset of patients with mild AS and high pretreatment LDL levels (Unique identifier on clinicaltrials.gov: NCT00092677)