Cordarone Tablets may cause a clinical syndrome of cough and progressive dyspnea accompanied by functional, radiographic, gallium-scan, and pathological data consistent with pulmonary toxicity, the frequency of which varies from 2 to 7% in most published reports, but is as high as 10 to 17% in some reports. Therefore, when Cordarone therapy is initiated, a baseline chest X-ray and pulmonary-function tests, including diffusion capacity, should be performed. The patient should return for a history, physical exam, and chest X-ray every 3 to 6 months.
Noninferiority trials have serious inherent limitations , the main one being that (unlike in a superiority trial), given a finding of noninferiority, it is impossible to distinguish between true equivalence and poor execution or faulty pretrial a priori assumptions regarding expectations of benefit and event rates. In this particular trial, a 15% absolute difference in the primary outcome was arguably too large to use as a noninferiority threshold. That threshold implies acceptance of 1 additional COPD exacerbation for each 7 patients treated. If a superiority trial showed a week's extra steroids prevented 1 COPD exacerbation for 10 or even 20 patients treated (, a 5-10% noninferiority margin), I think many doctors and patients would endorse longer-course prednisone. This trial (as designed) would fail to detect that.
Results We identified 17 randomized trials (n = 2138) and 3 quasi-randomized trials (n = 246) that had acceptable methodological quality to pool in a meta-analysis. Twenty-eight-day mortality for treated vs control patients was 388/1099 (%) vs 400/1039 (%) in randomized trials (risk ratio [RR], ; 95% confidence interval [CI], -; P =.05; I 2 =53% by random-effects model) and 28/121 (%) vs 24/125 (%) in quasi-randomized trials (RR, , 95% CI, -; P = .83). In 12 trials investigating prolonged low-dose corticosteroid treatment, 28-day mortality for treated vs control patients was 236/629 (%) vs 264/599 (44%) (RR, ; 95% CI, -; P = .02). This treatment increased 28-day shock reversal (6 trials; 322/481 [%] vs 276/471 [%]; RR, ; 95% CI, -; P = .02; I 2 = 4%) and reduced intensive care unit length of stay by days (8 trials; 95% CI, – to –; P < .001; I 2 = 0%) without increasing the risk of gastroduodenal bleeding (13 trials; 65/800 [%] vs 56/764 [%]; P = .50; I 2 = 0%), superinfection (14 trials; 184/998 [%] vs 170/950 [%]; P = .92; I 2 = 8%), or neuromuscular weakness (3 trials; 4/407 [1%] vs 7/404 [%]; P = .58; I 2 = 30%). Corticosteroids increased the risk of hyperglycemia (9 trials; 363/703 [%] vs 308/670 [46%]; P < .001; I 2 = 0%) and hypernatremia (3 trials; 127/404 [%] vs 77/401 [%]; P < .001; I 2 = 0%).