Canagliflozin and Cardiovascular disease- results of the CANVAS trial.

Canagliflozin is a new novel oral antidiabetic agent belonging to the class of sodium-glucose co-transporter 2 (SGLT2) inhibitors, inhibiting glucose reabsorption in the proximal tubule, leading to increased urinary glucose excretion and subsequently to reduction in plasma glucose concentration, in individuals with hyperglycemia. Before the approval of canagliflozin by the Food and Drug Administration (FDA) in 2013, a pair-wise meta-analyses of trials involving canagliflozin did not differ from control in terms of all-cause mortality, cardiovascular death, myocardial infarction, and stroke. However, no large, randomized-controlled trials were available for comparison until the results of the CANVAS (Canagliflozin Cardiovascular Assessment Study) trial were published. The CANVAS Trial was designed to assess the cardiovascular safety and efficacy of canagliflozin. Recently, results of the completed CANVAS Trial were released which showed patients with type 2 diabetes and established cardiovascular disease or at high risk for cardiovascular events who were treated with canagliflozin had significantly lower rates of the primary cardiovascular outcome than patients assigned to placebo. All three components of the primary outcome - death from cardiovascular causes, nonfatal myocardial infarction, and nonfatal stroke - showed point estimates of effect that suggested benefit .These results may represent a significant additional therapeutic tool in the clinical prevention and management of cardiovascular mortality and morbidity. However, data on the long-term efficacy on the use of Canagliflozin is still incomplete and their use in patients with type 2 diabetes should be carefully considered.

Atrial fibrillation and heart failure- results of the CASTLE-AF trial.

Congestive Heart Failure (HF) and Atrial Fibrillation (AFIB) often coexist. Catheter ablation is a well-established option for symptomatic AFIB that is resistant to drug therapy in patients with otherwise normal cardiac function. This has been seen in various studies where catheter ablation was associated with positive outcomes in patients with HF. Recently, the study results from the Catheter Ablation versus Standard Conventional Therapy in Patients with Left Ventricular Dysfunction and Atrial Fibrillation (CASTLE-AF) trial were published. After a median follow-up of more than 3 years, patients getting catheter ablation for AFIB had significantly fewer hospital admissions as well as death from worsening HF. In addition, 63% of patients in the ablation group were in sinus rhythm, as compared with 22% of those in the medical-therapy group (P < 0.001). This trial may represent a significant additional therapeutic tool in the clinical prevention and management of cardiovascular mortality and morbidity. While catheter ablation does not eliminate the AFIB per se, it can limit the ventricular rate by eliminating triggers and altering electrophysiological connections in the heart in a similar fashion to rate control anti-arrhythmic drugs. Longer-duration normal sinus rhythm may improve outcomes by means of a number of mechanisms, including greater atrial emptying, all of which translate into improved cardiac output. A better understanding is needed as to why a decrease in density, but not complete elimination of atrial fibrillation, is sufficient for reverse remodelling. It is anticipated that the results of the CASTLE-AF trial will soon be implemented in international guidelines.

Canakinumab and cardiovascular outcomes: results of the CANTOS trial.

IL-1 cytokines are mainly responsible for controlling a series of pro-inflammatory reactions induced in response to pathogen mediated tissue injury. Among the IL-1 cytokine family, IL-1 ß results in upregulation of genes responsible for boosting immune system reactivity and inflammatory response. With growing pathophysiological relevance of IL-1ß in a myriad of disease pathogenesis, new biological drugs have been developed in recent years. One such drug, Canakinumab, targeting IL-1ß has been recently approved for clinical use. The recent results from the CANTOS (Canakinumab Anti-Inflammatory Thrombosis Outcome Study) trial are encouraging in this aspect. The results suggest that anti-inflammatory therapy using canakinumab at a dose of 150 mg every 3 months led to significantly lower recurrent cardiovascular events than the placebo drug. These results were independent of lipid-lowering effects of these drugs. If the results are widely applicable, the CANTOS trial would reaffirm the hypothesis of atherothrombosis due to inflammation, hence supporting the need for a cytokine-based therapy for the secondary prevention of cardiovascular diseases. Moreover, the potential benefits of the phenomenal reduction in the inflammatory cascade induced by canakinumab should be carefully balanced against its long-term safety profile which is yet unknown. However, the inflammatory hypothesis of atherothrombosis supports a cytokine-based therapy for the secondary prevention of cardiovascular disease. Furthermore, the potential benefits from the reduction in inflammatory markers induced by canakinumab should be carefully balanced against its unknown long-term safety profile.

Bioresorbable vascular scaffold versus metallic stent in percutaneous coronary intervention: results of the AIDA trial.

Drug-eluting stents have significantly improved the long-term outcomes of percutaneous coronary intervention (PCI) by decreasing the excessive growth of neointima. However, conventional stents have some limitations. PCI with a bioresorbable vascular scaffold (BVS) has emerged as an alternative since the presence of the prosthesis in the coronary artery is transient. A US Food and Drug Administration advisory panel of experts recommended approval of BVS based on the analysis of its risks and rewards in July 2016. In June 2017, the preliminary results of the Amsterdam Investigator-initiateD Absorb Strategy All-comers (AIDA) trial were released. This randomized controlled trial compared an everolimus-eluting BVS with an everolimus-eluting metallic stent in the context of routine clinical practice. The preliminary results revealed no significant difference in target-vessel failure when BVS was compared with metallic stenting. However, during the 2 years of follow-up, BVS was associated with a higher rate of device thrombosis. This is seen as an important development in the trial. There are some concerns regarding stent thrombosis and the restoration of real vessel functionality in the long term. For these reasons, for now, metallic stents remain the treatment of choice for PCI.