Randomized Evaluation of TriGuard 3 Cerebral Embolic Protection After Transcatheter Aortic Valve Replacement: REFLECT II.

OBJECTIVES: The REFLECT II (Randomized Evaluation of TriGuard 3 Cerebral Embolic Protection After Transcatheter Aortic Valve Implantation) trial was designed to investigate the safety and efficacy of the TriGUARD 3 (TG3) cerebral embolic protection in patients undergoing transcatheter aortic valve replacement. BACKGROUND: Cerebral embolization occurs frequently following transcatheter aortic valve replacement and procedure-related ischemic stroke occurs in 2% to 6% of patients at 30 days. Whether cerebral protection with TriGuard 3 is safe and effective in reducing procedure-related cerebral injury is not known. METHODS: This prospective, multicenter, single-blind, 2:1 randomized (TG3 vs. no TG3) study was designed to enroll up to 345 patients. The primary 30-day safety endpoint (Valve Academic Research Consortium-2 defined) was compared with a performance goal (PG). The primary hierarchical composite efficacy endpoint (including death or stroke at 30 days, National Institutes of Health Stroke Scale score worsening in hospital, and cerebral ischemic lesions on diffusion-weighted magnetic resonance imaging at 2 to 5 days) was compared using the Finkelstein-Schoenfeld method. RESULTS: REFLECT II enrolled 220 of the planned 345 patients (63.8%), including 41 roll-in and 179 randomized patients (121 TG3 and 58 control subjects) at 18 US sites. The sponsor closed the study early after the U.S. Food and Drug Administration recommended enrollment suspension for unblinded safety data review. The trial met its primary safety endpoint compared with the PG (15.9% vs. 34.4% (p < 0.0001). The primary hierarchal efficacy endpoint at 30 days was not met (mean scores [higher is better]: -8.58 TG3 vs. 8.08 control; p = 0.857). A post hoc diffusion-weighted magnetic resonance imaging analysis of per-patient total lesion volume above incremental thresholds showed numeric reductions in total lesion volume >500 mm3 (-9.7%) and >1,000 mm3 (-44.5%) in the TG3 group, which were more pronounced among patients with full TG3 coverage: -51.1% (>500 mm3) and -82.9% (>1,000 mm3). CONCLUSIONS: The REFLECT II trial demonstrated that the TG3 was safe compared with a historical PG but did not meet its pre-specified primary superiority efficacy endpoint.

Does outpatient cardiac rehabilitation help patients with acute myocardial infarction quit smoking?

Outpatient cardiac rehabilitation (OCR) reinforces patients' efforts to quit smoking, but the association between participation in OCR and long-term smoking status after acute myocardial infarction (AMI) is unknown. We studied hospitalized smokers with confirmed AMI from two multicenter prospective registries (PREMIER, from January 1, 2003, to June 28, 2004, and TRIUMPH, from April 11, 2005, to December 31, 2008) to describe the association of OCR participation with smoking cessation. Eligible patients smoked at least 1 cigarette per day on average in the 30 days prior to enrollment and completed 12-month follow-up (N = 1307). Structured interviews were completed on subjects at baseline and during follow-up. OCR participation and abstinence from smoking within the prior 30-days (30-day point prevalence abstinence, PPA) were self-reported. We constructed a propensity model of OCR participation based on 22 baseline sociodemographic and clinical characteristics, and constructed hierarchical modified Poisson regression models of 30-day PPA at 12 months after matching on the propensity for OCR participation (with clinical site treated as a random effect). Seventy-four percent of subjects were referred to OCR at hospital discharge, but only 36% participated during follow-up. At 12-month follow-up, 30-day PPA was 57% in OCR participants, compared to 41% in matched OCR non-participants. Participation in OCR was a significant predictor of 30-day PPA at 12 months (adjusted RR 1.38, 95% CI 1.20-1.57). In conclusion, smokers who participated in OCR were significantly more likely to abstain from smoking 12 months after AMI hospitalization.