OSLER-1 and OSLER-2 Clinical Trials
Evolocumab, a monoclonal antibody that inhibits pro-protein convertase subtilisin-kexin type 9 (PCSK9), significantly reduced low-density lipoprotein (LDL) cholesterol levels in short-term studies. The current aim was to obtain longer-term data using two extension studies. In two open-label, randomized trials, 4465 patients were enrolled to receive either evolocumab (140 mg every 2 weeks or 420 mg monthly) plus standard therapy or standard therapy alone. Data from the two trials were combined. Evolocumab reduced the level of LDL cholesterol by 61%, from a median of 120 mg per deciliter to 48 mg per deciliter (P<0.001). The drug was well tolerated, although neurocognitive events were reported more frequently in the evolocumab group. As to the discussion of a potentially harmful LDL reduction to very low levels, the risk of adverse events, including neurocognitive events, did not vary significantly according to the achieved level of LDL cholesterol. Cardiovascular events at one year were significantly reduced from 2.18% in the standard-therapy group to 0.95% in the evolocumab group.
New England Journal of Medicine 372:1500-1509.
The goal of this study was to compare the usefulness of coronary computed tomographic angiography with functional testing (exercise electrocardiography, nuclear stress testing, or stress echocardiography) in symptomatic patients (10,003) suggestive of coronary artery disease. The composite primary end point was death, myocardial infarction, hospitalization for unstable angina, or major procedural complication. In these subjects with suspected coronary artery disease who required noninvasive testing, a strategy of initial coronary computed tomographic angiography, as compared with functional testing, did not improve clinical outcomes over a median follow-up of 2 years. There were only minor differences regarding amount of following catheterizations and radiation exposure.
New England Journal of Medicine 2015. 372:1291-1300.
Remote ischemic preconditioning on clinical outcomes in 1600 patients undergoing coronary artery bypass graft with or without valve surgery. Patients were randomized in multiple centers to either true or sham remote ischemic conditioning (4 cycles of 5 min inflation to 200 mmHg and 5 min deflation of a blood pressure cuff placed on the upper arm, or sham 4 cycles of simulated inflations and deflations of the blood pressure cuff). There was no difference in the primary combined endpoint of cardiovascular death, non-fatal myocardial infarction, coronary revascularization and stroke at 1 year although hs-Trponin T levels were significantly reduced with remote ischemic conditioning.
PEGASUS-TIMI 54 Trial
This trial was designed to evaluate the benefits and safety of long-term dual antiplatelet therapy using ticagrelor beyond 1 year after a myocardial infarction. Ticagrelor is a P2Y12 receptor antagonist with established efficacy after an acute coronary syndrome. 21,162 patients who had suffered from myocardial infarction were treated with either 90 mg twice daily, or 60 mg twice daily ticagrelor, or placebo in addition to standard therapy. The primary efficacy composite end point of cardiovascular death, myocardial infarction or stroke was significantly and comparably reduced by both dosages of ticagrelor. However, rates of TIMI major bleeding were higher with ticagrelor 90 mg indicating that ticagrelor 60 mg twice daily may be the better option for a possible long-term dual antiplatelet therapy beyond 1 year after a myocardial infarction.
New England Journal of Medicine - 2015 Mar 14. Epub ahead of print.
AATAC-AF Heart Failure trial
This trial compared catheter ablation of persistent atrial fibrillation in patients with congestive heart failure compared to antiarrhythmic treatment with amiodarone. 203 patients with either a dual chamber implantable cardioverter defibrillator or cardiac resynchronization therapy device due accuracy in recognizing atrial fibrillation were enrolled. At 26 months, 70% of patients in the ablation arm compared with 34% in the amiodarone arm had freedom from recurrence of atrial fibrillation (P< 0.001) which was the primary end point. Moreover, catheter ablation was also significantly associated with reduced hospitalization rates (31% vs. 57%) and mortality (8% vs. 18%) compared with amiodarone treatment. A very interesting result, in terms of effects on ventricular function in patients with atrial fibrillation, is that subjects who were free from this arrhythmia had significant improvements in LV ejection fraction, exercise capacity, and quality of life.
This study reports on 355 patients with obesity (BMI≥27 kg/m2) and symptomatic paroxysmal or persistent atrial fibrillation that were offered to weight management (e.g. meal plans, very low-calorie meal replacement sachets, low and moderate intensity exercise/activity). The goal of this analysis was to evaluate the long-term impact of weight-loss on rhythm control in patients with atrial fibrillation. Long-term sustained weight-loss was associated with a dose-dependent and significant reduction of atrial fibrillation burden and maintenance of sinus rhythm. In conclusion, weight-loss and avoidance of weight-fluctuation constitute very attractive and important strategies for reducing atrial fibrillation independent of interventions and antiarrhythmic compounds.
Journal of the American College of Ccardiology - 2015. Epub ahead of print.
PRImary PCI in MULTIvessel disease: 627 patients presenting with an acute STEMI were randomized to either an infarct–related artery (IRA) PCI only or a FFR-guided complete revascularization approach, staged within the index hospitalization. The primary composite endpoint of all-cause mortality, nonfatal MI, and ischemia-driven revascularization was significantly reached by FFR-guided, staged, complete revascularization. However, this was driven by the need for future repeat revascularization of non-index lesions, but not by mortality or nonfatal MI rates.
This study evaluated the treatment with intramyocardial algisyl injection compared to standard therapy in individuals (78) with advanced heart failure. Algisyl is a permanent implant that consists of alginate hydrogel that is considered to ameliorate left ventricular wall stress. The results so far show that injection of algisyl-LVR in the myocardium is safe and feasible with significantly improved functional capacity, compared with optimal medical therapy through 6 months of follow-up in patients with advanced heart failure. The study will continue for 2 years of follow-up.