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.

Can ambulatory blood pressure measurements substitute assessment of subclinical cardiovascular damage?

OBJECTIVE: We have previously demonstrated that markers of subclinical organ damage (SOD) improve cardiovascular risk prediction in healthy individuals. We wanted to investigate whether this additive effect of SOD was due to inaccurate blood pressure (BP) measurement or whether ambulatory BP (AMBP) added further to risk prediction. METHODS: In a population cohort of 1385 Danish individuals free of cardiovascular disease and diabetes, we recorded traditional risk factors, AMBP and pulse wave velocity (PWV), urine albumin/creatinine ratio (UACR), left ventricular mass index (LVMI) and carotid atherosclerotic plaques at baseline. A composite cardiovascular endpoint (CEP) consisting of cardiovascular death and nonfatal myocardial infarction and stroke was recorded in national registries. RESULTS: During a median follow-up of 12.8 years, a total of 119 CEPs occurred. In categorical analysis, presence of SOD as well as masked hypertension increased sensitivity of Systemic Coronary Risk Estimation from 73.9 to 89.1% (P < 0.001) and reduced specificity from 60.1 to 41.8% (P < 0.001). In continuous analysis, logUACR [hazard ratio = 1.20 (95% confidence interval [CI] 1.05-1.38), P = 0.009], atherosclerotic plaques [hazard ratio = 1.82 (95% CI 1.21-2.74), P = 0.004] and 24-h SBP [hazard ratio = 1.34 (95% CI 1.12-1.60), P = 0.002] but not logPWV or LVMI predicted CEP in a model with adjustments for age, sex, conventional BP, total cholesterol and smoking. Compared with a risk model using only traditional risk factors, adding PWV, UACR, plaques, LVMI and 24-h SBP increased C-index significantly from 0.76 to 0.79% and produced a net reclassification improvement of 23.3% (P = 0.001). CONCLUSION: UACR and plaques predicted cardiovascular events independently of AMBP and improved risk prediction.

Impact of pressure recovery on echocardiographic assessment of asymptomatic aortic stenosis: a SEAS substudy.

OBJECTIVES: The aim of this analysis was to assess the diagnostic importance of pressure recovery in evaluation of aortic stenosis (AS) severity. BACKGROUND: Although pressure recovery has previously been demonstrated to be particularly important in assessment of AS severity in groups of patients with moderate AS or small aortic roots, it has never been evaluated in a large clinical patient cohort. METHODS: Data from 1,563 patients in the SEAS (Simvastatin and Ezetimibe in Aortic Stenosis) study was used. Inner aortic diameter was measured at annulus, sinus, sinotubular junction, and supracoronary level. Aortic valve area index (AVAI) was calculated by continuity equation and pressure recovery and pressure recovery adjusted AVAI (energy loss index [ELI]), by validated equations. Primarily, sinotubular junction diameter was used to calculate pressure recovery and ELI, but pressure recovery and ELI calculated at different aortic root levels were compared. Severe AS was identified as AVAI and ELI < or =0.6 cm(2)/m(2). Patients were grouped into tertiles of peak transaortic velocity. RESULTS: Pressure recovery increased with increasing peak transaortic velocity. Overestimation of AS severity by unadjusted AVAI was largest in the lowest tertile and if pressure recovery was assessed at the sinotubular junction. In multivariate analysis, a larger difference between AVAI and ELI was associated with lower peak transaortic velocity (beta = 0.35) independent of higher left ventricular ejection fraction (beta = -0.049), male sex (beta = -0.075), younger age (beta = 0.093), and smaller aortic sinus diameter (beta = 0.233) (multiple R(2) = 0.18, p < 0.001). Overall, 47.5% of patients classified as having severe AS by AVAI were reclassified to nonsevere AS when pressure recovery was taken into account. CONCLUSIONS: For accurate assessment of AS severity, pressure recovery adjustment of AVA must be routinely performed. Estimation of pressure recovery at the sinotubular junction is suggested.