Vindication of Salmeterol-Fluticasone Single-inhaler Combination

SOURCE: Stempel DA, Raphiou IH, Kral KM, et al. Serious asthma events with fluticasone plus salmeterol versus fluticasone alone. N Engl J Med 2016;374:1822-1830.

Monotherapy with salmeterol or other long-acting beta agonists (LABA) is not recommended for asthma treatment, based on the observation in asthma clinical trials that salmeterol monotherapy is associated with increased mortality. Similarly, a meta-analysis of patients who received combination treatment with salmeterol and fluticasone provided in separate inhalers also showed higher asthma-related hospitalizations and death. However, it did not go unnoticed that just because patients received prescriptions for separate salmeterol and fluticasone inhalers does not guarantee that they actually used both devices, hence allowing for the possibility that some patients assigned dual treatment actually were only receiving LABA (or fluticasone) monotherapy.

To better address FDA concerns about LABA safety, researchers performed a randomized, double-blind trial comparing LABA + fluticasone (within the same inhalation device) to fluticasone monotherapy (n = 11,679). The primary endpoint was serious asthma-related events (death, intubation, hospitalization) over 26 weeks.

There was no difference in serious asthma-related events between LABA + fluticasone and fluticasone monotherapy. However, asthma exacerbations were 21% lower in the combination LABA + fluticasone treatment group.

The prescription of LABA monotherapy for asthma patients is still appropriate, but data are reassuring in regard to LABA + fluticasone therapy through which many patients enjoy symptom control and reduced exacerbations.


Considering Perioperative Statins in Cardiac Surgery

SOURCE: Zheng Z, Jayaram R, Jiang L, et al. Perioperative rosuvastatin in cardiac surgery. N Engl J Med 2016;374:1744-1753.

Based on favorable effect on surrogate markers such as C-reactive protein, as well as small clinical trials that suggested reduced incidence of perioperative atrial fibrillation and other complications, guidelines have endorsed administration of perioperative statin therapy. The Statin Therapy in Cardiac Surgery trial was designed to provide more definitive information.

Patients undergoing elective cardiac surgery (n = 1,922) were randomized to perioperative rosuvastatin 20 mg/d or placebo. The primary outcomes were atrial fibrillation and myocardial infarction within five days of surgery.

As has been previously demonstrated, rosuvastatin treatment reduced low-density lipoprotein levels and C-reactive protein. However, there was no difference in the incidence of atrial fibrillation or myocardial infarction.

Of concern, there was an increased risk for acute kidney injury in the rosuvastatin group; within the first 48 hours postoperatively, the frequency of acute injury of any severity was 24.7% in the rosuvastatin arm vs. 19.3% in the placebo arm. Fortunately, most of the acute kidney injury incurred was stage one (mild intensity).

Despite early data suggesting benefits of perioperative statin treatment, this larger data set fails to confirm benefit and indicates some potential harm.


Cocaine Use and Pyoderma Gangrenosum

SOURCE: Jeong HS, Layher H, Cao L, et al. Pyoderma gangrenosum (PG) associated with levamisole-adulterated cocaine: Clinical, serologic, and histopathologic findings in a cohort of patients. J Am Acad Dermatol 2016;74:892-898.

Clinicians should view photos of pyoderma gangrenosum. These images can be quite devastating and would likely add to the gravity of the information Jeong et al recently provided in a published report.

Pyoderma gangrenosum classically presents as a rapidly progressive, painful, suppurative cutaneous ulcer. The ulcer most commonly occurs on the legs but can appear anywhere on the body. Pyoderma gangrenosum is most commonly associated with malignancy and inflammatory disorders such as ulcerative colitis and rheumatoid arthritis.

In the United States, as much as 80% of cocaine is adulterated with levamisole, which is known to produce vasculitis. Jeong et al reported on eight consecutive patients presenting with pyoderma gangrenosum, each of whom had used cocaine. The biopsy pathology of cocaine/levamisole-induced pyoderma gangrenosum is indistinguishable from that associated with other disorders mentioned above. In addition to the other obvious concerns about cocaine use, add pyoderma gangrenosum to the list.