Reed, Brent N.

The use of alemtuzumab for induction therapy in orthotopic heart transplantation remains controversial, despite its observed benefits in other transplant populations. This study aimed to evaluate whether alemtuzumab conferred a lower risk of rejection while reducing toxicities commonly attributed to standard immunosuppression in orthotopic heart transplantation. We included adult patients who underwent orthotopic heart transplantation and received induction therapy with alemtuzumab (n = 26) or standard immunosuppression (n = 26). The primary end point was freedom from grade ≥2 rejection at 12 months. Baseline characteristics were similar between the groups with the exception of poorer renal function in the alemtuzumab group ( P < .05). The primary end point of freedom from grade ≥2 rejection at 12 months was not different between alemtuzumab and standard therapy (76.9% vs 96.2%, P = .077), likely due to similarities in the rates of antibody-mediated rejection in the 2 groups. However, grade ≥2 acute cellular rejection was considerably lower with alemtuzumab (0% vs 19.2%, P = .02), as was acute cellular rejection of any severity (50% vs 7.7%, P = .004). Deterioration in renal function was significantly greater among patients receiving standard therapy as evidenced by decreases in glomerular filtration rate (−25.6 vs −9.2 mL/min, P = .032). No differences in hematologic or infectious complications were observed. In conclusion, alemtuzumab reduced several important rejection-related outcomes while ameliorating the toxicities associated with standard immunosuppression therapy, making it a promising agent for induction in orthotopic heart transplantation.

Nonsteroidal antiinflammatory drugs (NSAIDs) are used in the management of a variety of conditions, but their prevalence is likely underreported as a result of widespread availability and the perception that nonprescription therapies are unnecessary to report during medication history taking. However, NSAIDs are associated with a number of adverse effects, especially in patients with cardiovascular disease (CVD). Patients with CVD and comorbidities for which NSAIDs may provide symptomatic relief (e.g., osteoarthritis, rheumatoid arthritis) tend to be older, which places them at greater risk of harm. For these reasons, the use of NSAIDs in patients with CVD is a significant public health concern. An understanding of the risks associated with NSAIDs is critical for clinicians across practice settings. In this review, we detail the safety of NSAIDs in patients with CVD, provide recommendations on their use in specific disease states, and discuss therapeutic alternatives.

Atrial fibrillation ( AF ) is a cardiac arrhythmia associated with significant morbidity and mortality, affecting more than 3 million people in the United States and 1–2% of the population worldwide. Its estimated prevalence is expected to double within the next 50 years. During the past decade, there have been significant advances in the treatment of AF . Studies have demonstrated that a rate control strategy, with a target resting heart rate between 80 and 100 beats/minute, is recommended over rhythm control in the vast majority of patients. The CHA 2 DS 2 ≥ (congestive heart failure, hypertension, age ≥ 65 yrs, diabetes mellitus, stroke or transient ischemic attack, vascular disease, female gender) scoring system is a potentially useful stroke risk stratification tool that incorporates additional risk factors to the commonly used CHADS 2 (congestive heart failure, hypertension, age ≥ 75 years, diabetes mellitus, stroke transient ischemic attack) scoring tool. Similarly, a convenient scheme, termed HAS ‐ BLED (hypertension, abnormal renal/liver function, stroke, bleeding history or predisposition, labile international normalized ratio, elderly, drugs/alcohol concomitantly), to assess bleeding risk has emerged that may be useful in select patients. Furthermore, new antithrombotic strategies have been developed as potential alternatives to warfarin, including dual‐antiplatelet therapy with clopidogrel plus aspirin and the development of new oral anticoagulants such as dabigatran, rivaroxaban, and apixaban. Vernakalant has emerged as another potential option for pharmacologic conversion of AF , whereas recent trials have better defined the role of dronedarone in the maintenance of sinus rhythm. Finally, catheter ablation represents another alternative to manage AF , whereas upstream therapy with inhibitors of the renin‐angiotensin‐aldosterone system, statins, and polyunsaturated fatty acids could potentially prevent the occurrence of AF . Despite substantial progress in the management of AF , significant uncertainty surrounds the optimal treatment of this condition.