Anticoagulation and coronary artery disease – Results from the PLATO Trial.Patients with extensive coronary artery disease (CAD) have higher risk for future events and may derive more benefit from preventive treatment. Drs. Emmanouil S. Brilakis (VA North Texas Healthcare System and UT Southwestern Medical Center in Dallas, Texas, USA), Lars Wallentin (Dept of Medical Sciences and Uppsala Clinical Research Center, Uppsala, Sweden), and colleagues presented results from a substudy of the multicenter, randomized PLATelet Inhibition and Patient Outcomes (PLATO) Trial. The researchers compared the effects of treating CAD patients with ticagrelor, a platelet aggregation inhibitor, and clopidogrel, an oral, thienopyridine-class antiplatelet agent. Out of 15,388 patients with CAD 4,644 (30%) had extensive CAD (defined as three-vessel disease, left main disease, or prior coronary artery bypass graft surgery). Patients with extensive CAD had more high-risk characteristics at the beginning of the study’s inclusion and more events during follow-up. Ticagrelor, compared to clopidogrel, reduced the composite endpoint of cardiovascular death, myocardial infarction, and stroke in patients with extensive CAD [14.9% vs. 17.6%; hazard ratio (HR) 0.85 (0.73, 0.98)] similar to its reduction in those without extensive CAD [6.8% vs. 8.0%; HR 0.85 (0.74, 0.98), P-interaction=0.99]. Major bleeding was similar with ticagrelor vs. clopidogrel among patients without [7.3% vs. 6.4%; HR, 1.14 (0.98, 1.33)] and with [25.7% vs. 25.5%; HR, 1.02 (0.90, 1.15), P-interaction=0.23] extensive CAD. The study authors concluded that both, patients with and without extensive CAD, display a reduction of ischemic events by ticagrelor relative to clopidogrel with risk of bleeding similar to clopidogrel.
Anticoagulation and atrial fibrillation – Results from the ROCKET AF TrialAs previously reported, in the ROCKET-AF trial rivaroxaban, a factor Xainhibitor, was non-inferior to warfarin for the prevention of stroke and systemic embolic events and significantly reduced intracranial bleeding in patients with non-valvular atrial fibrillation (AF). Drs. Sean van Diepen and colleagues from the University of Alberta in Edmonton, Canada examined the efficacy and safety of rivaroxaban in heart failure (HF) patients. In a total of 9019 patient treatment related differences between patients with and without baseline HF were examined and the efficacy and safety of rivaroxaban and warfarin compared. The primary efficacy outcome was stroke or systemic embolism rate per 100 patient years by intention to treat. The safety outcomes were the rates of major or non-major clinically relevant (MNCR) bleeding and hemorrhagic stroke. The efficacy outcome in rivaroxaban and warfarin treated patients were similar in patients with HF (1.55 vs. 2.07) and without HF (1.94 vs. 2.28) (p =0.47 for interaction). In patients with HF, rivaroxaban was independently associated with a lower risk of the primary outcome (adjusted Hazard Ratio [adj HR] 0.74: 95% CI, 0.58 to 0.96; p=0.021). The risk of MNCR bleeding in HF patients was similar (adj HR 1.05, 95% CI 0.96 to 1.16, p=0.62); however, the incidence of hemorrhagic stroke was significantly lower with rivaroxaban (adj HR 0.38, 95% CI, 0.19 to 0.75, p=0.006). The authors conclude that treatment related outcomes were similar in patients with and without HF. Compared to warfarin, point estimates suggested a lower risk of stroke and systemic embolism and hemorrhagic stroke in rivaroxaban treated HF patients.
Risk of inducing diabetes by post-myocardial pharmacological treatment – Results from the NAVIGATOR TrialPrevious data suggests that beta-blockers, diuretics, and statins may increase the risk of new onset diabetes (NOD). Drs. LanShen and colleagues (Duke Clinical Research Institute, Duke University Medical Center in Durham, USA) examined to what degree use of these medications in patients with impaired glucose tolerance (IGT) and other CV risk factors is associated with NOD. Evaluating data from the Nateglinide and Valsartan in Impaired Glucose Tolerance Outcomes Research (NAVIGATOR) trial, the incidence diabetes among treatment-native patients at enrollment with diuretics (n=6343), beta-blockers (n=5637), statins (n=6143), and calcium channel blockers (CCBs) (n=6290) were examined. During a median 5 years of follow-up, diuretics, beta-blockers, statins, and CCBs were started in 1425 (22.5%), 993 (17.6 %), 1474 (24.0%), and 1274 (20.3%) of patients, respectively. After adjustment for time-varying confounders, reported prescription of diuretics and statins was associated with increased risk of NOD (HR [95% CI] 1.36 [1.16-1.59] and 1.30 [1.11-1.53], respectively). Beta-blocker treatment showed a trend towards increased risk of NOD (HR [95% CI] 1.2 [1.00-1.46]). No association was found between the use of CCB and NOD (HR [95% CI] 1.14 [0.94-1.38]). The authors conclude that among persons with IGT and other CV risk factors, diuretic and statin use was associated with an increased risk of NOD, while the use of beta-blockers was indeterminate.
Computational Fluid dynamics and Computed TomographyAortic valve insufficiency and atherosclerotic emboli have been described in patients with continuous flow left ventricular assist devices (cf-LVAD). Drs. ArjangRuhrparwar from our institution (Seniorconsultant surgeon and researcher from the Cardiac Surgery Department, University of Heidelberg, Germany) and colleagues described data established a novel method for analysis of flow dynamics and aortic wall shear stress (WSS) using computational fluid dynamics (CFD) from computer tomography (CT) studies. 5 patients with cf-LVAD and 2 patients with pulsatile flow (p) LVAD had a CT 9.9±9.2months after device implantation. Transient CFD simulations with turbulent models simulating LVAD flow waveforms for pulsatile cases were conducted. Flow pattern, dynamic pressure and wall shear stress (WSS) of the aorta were quantified. In cf- LVAD patients, outflow graft position (lateral or anterior) determined hemodynamics in the aorta. Based on this pilot data, the authors conclude that CFD of CT-scans enables analysis of pathologic aortic processes. Continuous vertical vortex formation in the aortic root may contribute to aortic insufficiency in patients with cf-LVAD support. Outflow graft position determines focal pressure on the aortic wall and shear off of aortic plaques. Further studies in larger patient populations are necessary.