Recent Research

Statin use and pneumonia, helmet for ventilation in ARDS, and more.

Helmet for ventilation provides benefits in ARDS, but aspirin does not, studies find

Delivering noninvasive ventilation (NIV) by helmet helped patients with acute respiratory distress syndrome (ARDS), while aspirin treatment did not, according to 2 recent studies.

The first study included 83 medical ICU patients with ARDS who had received NIV delivered by face mask for at least 8 hours. Their median age was 59 years and median Acute Physiology and Chronic Health Evaluation II score was 26. They were randomized to either continue NIV by face mask or switch to a transparent hood that covers the entire head and has a rubber collar neck seal.

The trial was stopped early because the helmet met predefined criteria for efficacy. Helmeted patients had significantly lower intubation rates (18.2% vs. 61.5%; P<0.001) and more ventilator-free days (28 vs. 12.5; P<0.001) than patients with face masks. Mortality was also lower with the helmets (34.1% vs. 56.4%; absolute difference, −22.3% [95% CI, −43.3% to −1.4%]; P=0.02). Each group had 3 cases of interface-related skin ulcers (nose ulcers in the face mask group and neck ulcers in the helmet group).

The results are likely due to higher positive end-expiratory pressure and fresh gas flow with the helmet, the study authors speculated. They cautioned that the helmet is a “relatively novel approach to NIV” which could lead to carbon dioxide rebreathing and patient-ventilator dyssynchrony. In addition, clinicians would need to be trained in use of the helmet. The authors called for multicenter studies to replicate the study's findings. An accompanying editorial added comparison of the helmet to high-flow nasal cannula to the questions for future study, along with “clarification of appropriate eligibility criteria, optimal ventilator settings, and potential mechanisms of effect.”

The other study looked at patients believed to be at risk for ARDS on presentation to the ED. Four hundred patients were randomized to receive either placebo or aspirin at 325-mg loading dose followed by 81 mg/d until hospital day 7, discharge, or death. The primary outcome was development of ARDS within a week, and secondary outcomes included ventilator-free days, length of stay, 28-day and 1-year mortality, and change in serum biomarkers associated with ARDS.

The study's final analysis includes 390 patients and none of the studied outcomes were significantly different between aspirin and placebo patients. Limitations of the study include a lower-than-expected ARDS rate and the possibility that the dose of aspirin was too low, but still the results did not support continuation to a larger trial of aspirin for ARDS prevention, the authors concluded. An accompanying editorial noted that the study provided “many important lessons about the design and conduct of clinical trials of ARDS prevention.”

Both studies were presented at the American Thoracic Society International Conference and published with the editorial in the June 14 JAMA.

Endovascular therapy works best within 150 minutes of symptoms

Faster treatment significantly improved functional outcomes among stroke patients receiving endovascular therapy, a recent analysis found.

Researchers used data from the SWIFT PRIME study, a global multicenter trial comparing intravenous tissue plasminogen activator (tPA) treatment of acute ischemic stroke with tPA plus an endovascular mechanical thrombectomy device. The study was conducted from December 2012 to November 2014 and included 196 patients. Results of the new analysis were published in the June Radiology.

Patients who received reperfusion within 150 minutes of symptom onset had a 91% estimated probability of being functionally independent 90 days after discharge. That rate decreased by 10% over the next hour and by 20% with every subsequent hour, the analysis showed. Researchers calculated that every 6-minute delay from symptom onset to treatment was associated with 1 to 1.5 fewer functionally independent patients per 100 treated.

Average time from ED arrival to arterial access was 90 minutes in study patients, and time to reperfusion was 129 minutes. The data also showed that being transferred from a referring facility was associated with significantly longer time from symptom onset to groin puncture (275 minutes vs. 179.5 minutes). The authors noted that the speed with which patients were treated in SWIFT PRIME could be partially responsible for the significantly better outcomes found in this trial than in some similar previous ones.

Providing rapid care to transferred patients poses a number of challenges, including triage, consent and treatment at the referral center, and coordinating transport with tPA infusion, the authors noted. Potential solutions include training emergency medical services staff to recognize appropriate patients and take them directly to centers that offer endovascular therapy. The authors also called for improvements to “patient triage and transport at referring facilities, efficient imaging paradigms and consent processes, and procedural times in patients with difficult anatomy,” noting that “aggressive time metrics and frequent feedback likely played a key role” in the success of SWIFT PRIME. The study was funded by the endovascular device manufacturer, Covidien (now joined with Medtronic).

In combination with LABA, LAMA may beat corticosteroid for COPD

Indacaterol–glycopyrronium may be more effective than salmeterol–fluticasone in preventing COPD exacerbations in patients who've had an exacerbation during the previous year, an industry-funded study found.

Researchers conducted a 52-week, randomized, double-blind, double-dummy, noninferiority trial (FLAME) among patients enrolled at 356 centers in 43 countries. Patients had COPD with a history of at least 1 exacerbation during the previous year. A 1-week screening period was followed by a 4-week run-in period, during which all patients were treated with inhaled tiotropium at a dose of 18 μg once daily.

After the run-in period, tiotropium was discontinued, and the patients were randomly assigned, in a 1:1 ratio, to receive by inhalation either the long-acting beta-agonist (LABA) indacaterol (110 μg) plus the long-acting muscarinic antagonist (LAMA) glycopyrronium (50 μg) once daily (n=1,680 patients) or the LABA salmeterol (50 μg) plus the inhaled glucocorticoid fluticasone (500 μg) twice daily (n=1,682).

The primary outcome was the annual rate of all COPD exacerbations. Also, because recent studies have suggested that LABA plus inhaled glucocorticoid regimens are more beneficial in reducing COPD exacerbations in patients with elevated eosinophils, researchers prospectively reviewed this relationship. Drug manufacturer Novartis developed the study protocol, funded the trial and its analyses, performed trial monitoring and reporting, provided oversight, and verified key results of the statistician. Results were published in the June 9 New England Journal of Medicine.

Indacaterol–glycopyrronium showed not only noninferiority but also superiority to salmeterol–fluticasone in reducing the annual rate of all COPD exacerbations, the study reported. The rate was 11% lower in the indacaterol–glycopyrronium group than in the salmeterol–fluticasone group (3.59 vs. 4.03; rate ratio [RR], 0.89; 95% CI, 0.83 to 0.96; P=0.003). The indacaterol–glycopyrronium group also had a longer time to the first exacerbation (71 days [95% CI, 60 to 82] vs. 51 days [95% CI, 46 to 57]; HR, 0.84 [95% CI, 0.78 to 0.91]). This represented a 16% lower risk (P<0.001). The annual rate of moderate or severe exacerbations was lower in the indacaterol–glycopyrronium group (0.98 vs. 1.19; RR, 0.83; 95% CI, 0.75 to 0.91; P<0.001). The time to the first moderate or severe exacerbation was also longer with indacaterol–glycopyrronium (HR, 0.78; 95% CI, 0.70 to 0.86; P<0.001), as was the time to the first severe exacerbation (HR, 0.81; 95% CI, 0.66 to 1.00; P=0.046).

The effect of indacaterol–glycopyrronium versus salmeterol–fluticasone on the rate of COPD exacerbations was independent of the baseline blood eosinophil count. Adverse event rates and deaths were similar in the 2 groups. The incidence of pneumonia was 3.2% in the indacaterol–glycopyrronium group and 4.8% in the salmeterol–fluticasone group (P=0.02).

Study authors noted that the trial was powered for a noninferiority analysis, but the LABA–LAMA regimen showed consistent superiority to the LABA–inhaled glucocorticoid regimen for all outcomes related to exacerbations, lung function, and health on a subsequent superiority analysis. “The consistent exacerbation outcomes have major implications for COPD management, especially among patients with a history of exacerbation,” they wrote. “Confirmation of these findings with the use of other combinations of long-acting bronchodilators would provide additional evidence to support the first-line use of a LABA–LAMA regimen in this patient population. However, we cannot exclude the possibility that some patients may benefit from the addition of inhaled glucocorticoids.”

The study and an accompanying editorial noted that the combination of 2 bronchodilators, such as a LABA and a LAMA, would be expected to produce more robust effects on lung function than would a LABA–inhaled glucocorticoid regimen among patients with symptomatic nonexacerbating COPD, and that physicians should continue to use guidelines to determine the appropriate regimen for the various phenotypes of COPD. The editorialist wrote “does the FLAME trial provide sufficient data to support the use of a LABA–LAMA regimen over the use of a LABA–inhaled glucocorticoid regimen in patients in GOLD group C or D (i.e., high-risk patients) who have a history of exacerbations? The FLAME trial seems to indicate that the answer is yes.” He added that more trials are needed.