A comprehensive comparative review of adenosine diphosphate receptor antagonists.

INTRODUCTION: Thrombosis risk necessitates dual antiplatelet therapy with aspirin and an adenosine diphosphate (ADP) receptor antagonist, in patients who have acute coronary syndrome. Current guidelines emphasize the critical role of dual antiplatelet therapy in both medical management and invasive strategy, especially in patients undergoing percutaneous coronary intervention. With the availability of multiple ADP-receptor antagonists, it is crucial to select the most appropriate agent for each patient. AREAS COVERED: The pertinent trials were identified through a MEDLINE search, in addition to a manual search from the articles retrieved. This review examines the differences between clopidogrel, prasugrel and ticagrelor in terms of their pharmacological/pharmacokinetic properties, clinical efficacy, drug interactions and safety parameters. EXPERT OPINION: Prasugrel and ticagrelor exhibit greater platelet inhibition and superior efficacy compared with clopidogrel, at the expense of higher bleeding risk. Prasugrel and ticagrelor should be preferred over clopidogrel in patients who are at a high risk of thrombotic events with low risk of bleeding. Additionally, these two agents may offer advantage over clopidogrel in those patients who might have risk for drug resistance due to CYP2C19 polymorphism. In selecting the ideal agent for patients, clinicians should tailor the antiplatelet regimen by considering individual risk factors and medication characteristics.

Daptomycin: evaluation of a high-dose treatment strategy.

With a decreasing pipeline of novel antibiotics and increasing antibacterial resistance, the need to optimise the current antibiotics in our armamentarium has become vitally important. Daptomycin is a novel lipopeptide antibiotic that exhibits concentration-dependent activity. Currently, the daptomycin dosage is 4 mg/kg/day for treatment of complicated skin and soft-tissue infections and 6 mg/kg/day for Staphylococcus aureus bloodstream infections, including those with right-sided endocarditis, however higher doses (>6 mg/kg/day) have been explored as a possible alternative. A comprehensive review of published data identified through a MEDLINE search of the literature from 1967-2011 and a manual search of references was performed with the primary objective of critically evaluating the safety and efficacy of high-dose daptomycin. Search results yielded two prospective trials, three retrospective reviews, case reports and in vitro simulation studies on high-dose daptomycin. To date, clinical trials, retrospective reviews, case reports and in vitro simulation models have documented the safety and tolerability of high-dose daptomycin, even when administered for a prolonged duration. Additionally, in vitro benefits observed include suppression of the emergence of daptomycin resistance and increased rapidity of bactericidal activity.

Role of combination therapy in the treatment of pulmonary arterial hypertension.

As a result of the multimechanistic pathology of pulmonary arterial hypertension (PAH), combination therapy is emerging as a potential treatment option. Recent guidelines from the American College of Chest Physicians and expert consensus from the American College of Cardiology Foundation and American Heart Association do not definitively support or disapprove of combination pharmacotherapy for the treatment of PAH. Published trials have investigated different combinations including endothelin receptor antagonists with prostanoids, prostanoids with phosphodiesterase inhibitors, and phosphodiesterase inhibitors with endothelin receptor antagonists. Pertinent trials on combination pharmacotherapy for PAH were identified through a MEDLINE search of literature from 1967-2009 in addition to a manual search of references from the articles retrieved. Search results identified 12 trials that evaluated combination therapy for PAH; some included an add-on agent for patients who failed treatment with monotherapy and others were placebo controlled. Even with the published data, the overall consensus is unclear. Well-designed, larger trials with validated end points are needed to further identify when to initiate combination therapy for the treatment of PAH. Meanwhile, perhaps the most appropriate situation for using combination pharmacotherapy may be in the setting of a lack of clinical improvement or deterioration.