Intravenous N-acetylcysteine in the prevention of contrast media-induced nephropathy.

OBJECTIVE: To define the clinical role of intravenous N-acetylcysteine for prophylaxis of contrast-induced nephropathy (CIN). DATA SOURCES: Randomized controlled clinical trials were identified using a search of MEDLINE (1990-September 2010) with the search terms acetylcysteine, N-acetylcysteine, NAC, intravenous, IV, nephropathy, nephrotoxic, radiocontrast, contrast, and media. The search was limited to studies published in English. Additional pertinent literature was retrieved by reviewing references of the articles obtained in the initial search. DATA SYNTHESIS: N-Acetylcysteine is a vasodilator and antioxidant that has been investigated for the prevention of CIN. In the majority of clinical trials, neither oral nor intravenous N-acetylcysteine has demonstrated clinical benefits at preventing CIN. The pharmacodynamic and pharmacokinetic profiles of intravenous N-acetylcysteine are significantly different from those of the oral product in that intravenous administration bypasses extensive first-pass metabolism. Studies have suggested that N-acetylcysteine directly affects serum creatinine levels in a way that is not associated with improvement of kidney function. Only intravenous N-acetylcysteine doses that were higher than the oral doses showed potential benefits, but they were associated with significant adverse events. Furthermore, the study populations were heterogeneous, including patients with various levels of kidney function and other risk factors, and the clinical definition of CIN was not well established. CONCLUSIONS: No conclusive evidence has shown that intravenous N-acetylcysteine is safe and effective in preventing CIN. Further clinical trials to define its role are warranted.

Ticagrelor: a novel oral antiplatelet agent.

OBJECTIVE: To review the pharmacology, clinical efficacy, and tolerability of ticagrelor and to discuss implications for use in the elderly. DATA SOURCE: A literature search was conducted in MEDLINE from 1966 to July 2010 using the MESH terms and key words AZD6140, ticagrelor, P2Y12 receptor antagonist. The search was limited to studies in English language with human subjects. STUDY SELECTION AND DATA EXTRACTION: Randomized controlled clinical trials were reviewed. References that were deemed relevant to pharmacodynamic/pharmacokinetic studies of P2Y12 antagonists and their historical background were also included. DATA SYNTHESIS: Ticagrelor is the first reversible oral P2Y12 antagonist currently undergoing Food and Drug Administration review for approval. The advantages of ticagrelor over clopidogrel are a more rapid onset of action, offset, and reversibility at the platelet P2Y12 receptor site. In the Study of Platelet Inhibition and Patient Outcomes trial, ticagrelor reduced the incidence of death as a result of cardiovascular causes, with no increase in major bleeding or bleeding related to coronary artery bypass graft (CABG) compared with clopidogrel. Subgroup analyses suggested that elderly patients may benefit more from ticagrelor than from clopidogrel. However, the increase in non-CABG-related bleeding and unique adverse events may limit ticagrelor's use in the elderly. CONCLUSION: The use of ticagrelor in the elderly should be determined on a case-by-case basis. More studies need to be conducted prior to establishing a role in therapy for the elderly.

Statin-associated incident diabetes: a literature review.

OBJECTIVE: To evaluate available evidence for incident diabetes associated with statin use and offer some practical management considerations. DATA SOURCES: A literature search was performed using MEDLINE from 2000 to October 2013. The following MESH terms and text key words alone or in combination were included: 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors, HMG-CoA reductase inhibitors, statins, incident diabetes, new-onset diabetes, insulin resistance, impaired insulin secretion, meta-analysis, cohort study, and observational study. STUDY SELECTION: Analyzed studies were published in English and investigated incident diabetes associated with statin use. DATA EXTRACTION: Author consensus determined study inclusion in this review, focusing on observational studies and meta-analyses. DATA SYNTHESIS: Since the report of incident diabetes associated with rosuvastatin, an unexpected finding in the Justification for the Use of Statins in Prevention: an Intervention Trial Evaluating Rosuvastatin, safety concerns with statins have emerged. Results of observational studies and meta-analyses show association of incident diabetes with statin use in patients with concomitant risk factors for diabetes. A pharmacodynamic mechanism has yet to be delineated, and individual statins may behave differently. Whether cardiovascular (CV) risk will increase with statin-associated incident diabetes remains unclear. CONCLUSION: Review of current, available clinical data suggest a possible association between statin use and incident diabetes in patients with underlying diabetes risk factors. Although study data may be insufficient to change the current practice paradigm, clinicians should vigilantly monitor for incident diabetes in patients on statins. Patients with a low risk of CV disease and high risk of diabetes should reconsider statin use and focus on lifestyle management.