Ticagrelor: An investigational oral antiplatelet treatment for reduction of major adverse cardiac events in patients with acute coronary syndrome

Acute coronary syndromes (ACS) are the leading cause of mortality and one of the main reasons for hospital admissions in the developed nations. Due to high rates of mortality and reinfarction, ACS represent a major public health concern. Platelets play a central role in atherothrombosis, the main pathologic substrate in ACS. Sufficient inhibition of platelet aggregation is therefore one of the key targets in the treatment of ACS. Blockade of the P2Y12 subtype of adenosine diphosphate (ADP) receptor on platelet cell membranes has been established as a key mechanism of platelet inhibition. Clopidogrel, an ADP receptor antagonist and a second-generation thienopyridine, has been demonstrated to be of clinical benefit in patients with ACS when added to aspirin. A delayed onset of action due to two-step conversion to the active metabolite, irreversible binding to P2Y12 receptors, and broad interindividual variability in levels of platelet response are the main limitations of clopidogrel. Prasugrel, a novel third-generation thienopyridine, provides faster and stronger inhibition of platelet aggregation than clopigodrel. However, like the active metabolite of clopidogrel, prasugrel binds irreversibly to the P2Y12 ADP receptor site, causing inhibition of platelet aggregation for the life of the platelet. Although in a randomized, double-blind trial prasugrel demonstrated superiority for multiple cardiovascular endpoints compared with standard-dose clopidogrel, it was also associated with an increased bleeding risk, including fatal bleeding. This review discusses the optimal antiplatelet regimens for management of patients with ACS, with special focus on ticagrelor, the first oral agent in a new chemical class of nonthienopyridine antiplatelet agents termed cyclopentyltriazolo-pyrimidines. Faster and greater platelet inhibition than clopidogrel, quick recovery of platelet function, and high efficacy regardless of clopidogrel response status, are the obvious advantages of ticagrelor as compared with thienopyridines. The prospective, randomized Platelet Inhibition and Patient Outcomes trial has established the clinical utility, enhanced efficacy, and similar safety of ticagrelor as compared with clopidogrel in a wide range of patients with ACS managed with contemporary antithrombotic therapies and invasive strategies when indicated. Dyspnea, ventricular pauses ≥3 seconds, and elevation of serum creatinine and uric acid are the most common known adverse effects associated with ticagrelor, and require further comprehensive assessment

Contrast-induced nephropathy in interventional cardiology

Development of contrast-induced nephropathy (CIN), ie, a rise in serum creatinine by either ≥0.5 mg/dL or by ≥25% from baseline within the first 2–3 days after contrast administration, is strongly associated with both increased inhospital and late morbidity and mortality after invasive cardiac procedures. The prevention of CIN is critical if long-term outcomes are to be optimized after percutaneous coronary intervention. The prevalence of CIN in patients receiving contrast varies markedly (from <1% to 50%), depending on the presence of well characterized risk factors, the most important of which are baseline chronic renal insufficiency and diabetes mellitus. Other risk factors include advanced age, anemia, left ventricular dysfunction, dehydration, hypotension, renal transplant, low serum albumin, concomitant use of nephrotoxins, and the volume of contrast agent. The pathophysiology of CIN is likely to be multifactorial, including direct cytotoxicity, apoptosis, disturbances in intrarenal hemodynamics, and immune mechanisms. Few strategies have been shown to be effective to prevent CIN beyond hydration, the goal of which is to establish brisk diuresis prior to contrast administration, and to avoid hypotension. New strategies of controlled hydration and diuresis are promising. Studies are mixed on whether prophylactic oral N-acetylcysteine reduces the incidence of CIN, although its use is generally recommended, given its low cost and favorable side effect profile. Agents which have been shown to be ineffective or harmful, or for which data supporting routine use do not exist, include fenoldopam, theophylline, dopamine, calcium channel blockers, prostaglandin E1, atrial natriuretic peptide, statins, and angiotensin-converting enzyme inhibitors

The Next Revolution: Percutaneous Aortic Valve Replacement

Aortic valve replacement (AVR) is a treatment of choice for patients with symptomatic severe aortic stenosis (AS). However, a significant proportion of these patients do not undergo surgical AVR due to high-risk features. Transcatheter aortic valve implantation (TAVI) has emerged as an alternative for patients with severe AS who are not candidates for open-heart surgery. Since the introduction of TAVI to the medical community in 2002, there has been an explosive growth in procedures. The balloon-expandable Edwards SAPIEN valve and the self-expanding CoreValve ReValving(TM) system contribute the largest patient experience with more than 10,000 patients treated with TAVI to date. Clinical outcomes have stabilized in experienced hands, with 30-day mortality less than 10%. Careful patient selection, growing operator experience, and an integrated multidisciplinary team approach contribute to notable improvement in outcomes. In the first randomized pivotal PARTNER trial, in patients with severe AS not suitable candidates for surgical AVR, TAVI compared with standard therapy, significantly improved survival and cardiac symptoms, but was associated with higher incidence of major strokes and major vascular events. The results of randomized comparison of TAVI with AVR among high-risk patients with AS for whom surgery is a viable option are eagerly awaited to provide further evidence on the applicability of TAVI in these patients