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Correction
March 25, 2009

Incorrect Data in: Inhaled Anticholinergics and Risk of Major Adverse Cardiovascular Events in Patients With Chronic Obstructive Pulmonary Disease: A Systematic Review and Meta-analysis

JAMA. 2009;301(12):1227-1230. doi:10.1001/jama.2009.290

Incorrect Data: In the Review entitled “Inhaled Anticholinergics and Risk of Major Adverse Cardiovascular Events in Patients With Chronic Obstructive Pulmonary Disease: A Systematic Review and Meta-analysis” published in the September 24, 2008, issue of JAMA (2008;300[12]:1439-1450), incorrect data appear.

On page 1439, in the abstract, the Data Synthesis section should read “After a detailed screening of 103 articles, 17 trials enrolling 13 645 patients were analyzed. Follow-up duration ranged from 6 weeks to 5 years. Cardiovascular death, MI, or stroke occurred in 134 of 6984 patients (1.9%) receiving inhaled anticholinergics and 83 of 6661 patients (1.2%) receiving control therapy (RR, 1.60 [95% confidence interval {CI}, 1.22-2.10]; P < .001, I2 = 0%). Among individual components of the primary end point, inhaled anticholinergics significantly increased the risk of MI (RR, 1.52 [95% CI, 1.04-2.22]; P = .03, I2 = 0%) and cardiovascular death (RR, 1.92 [95% CI, 1.23-3.00]; P = .004, I2 = 0%) without a statistically significant increase in the risk of stroke (RR, 1.46 [95% CI, 0.81-2.62]; P = .20, I2 = 0%). All-cause mortality was reported in 146 of the patients treated with inhaled anticholinergics (2.2%) and 108 of the control patients (1.7%) (RR, 1.29 [95% CI, 1.00-1.65]; P = .05, I2 = 0%). A sensitivity analysis restricted to 5 long-term trials (>6 months) confirmed the significantly increased risk of cardiovascular death, MI, or stroke (2.9% of patients treated with anticholinergics vs 1.8% of the control patients; RR, 1.73 [95% CI, 1.27-2.35]; P < .001, I2 = 0%).

On page 1441, the following text should be added at the end of column 1 after the citation for Table 1 and in column 2 after the citations for Table 2 and Table 3, “(Casaburi et al19 and Brusasco et al24 reported trial findings that had already been published without acknowledging the respective earlier publications by Casaburi et al23 and Donohue et al25).” Also on page 1441, column 2, in the first full paragraph, the first 3 sentences should be “The trials included 13 645 participants, in which 6984 received inhaled anticholinergics and 6661 received control therapy. Under the heading “Primary Outcome,” the first sentence should be “Inhaled anticholinergics significantly increased the risk of cardiovascular death, MI, or stroke (1.9% vs 1.2% for control; RR, 1.60 [95% CI, 1.22-2.10]; P < .001) in a meta-analysis of 17 trials involving 13 645 patients (Figure 2).4,19-22,24,26-34” In the next paragraph, the first 3 sentences should be “Among individual components of the primary outcome, inhaled anticholinergics significantly increased the risk of MI (1.2% vs 0.8% for control; RR, 1.52 [95% CI, 1.04-2.22]; P = .03) in a meta-analysis of 11 trials involving 10 553 patients.4,19-22,24,26,28,31-33 Inhaled anticholinergics also significantly increased the risk of cardiovascular death (0.9% vs 0.5% for control; RR, 1.92 [95% CI, 1.23-3.00]; P = .004) in a meta-analysis of 12 trials involving 11 283 patients.4,19-21,24,27,29-31,33 Under the heading “Secondary Outcome,” the 2 sentences should be “Inhaled anticholinergics did not significantly increase the risk of all-cause mortality (2.2% vs 1.7% for control; RR, 1.29 [95% CI, 1.00-1.65]; P = .05) in a meta-analysis of 17 trials involving 12 931 patients.4,19-22,24,26-34 There was evidence of low statistical heterogeneity among the included trials (I2 = 0%) (Table 4).”

On page 1443, in column 1, the first sentence in the first full paragraph should be “Inhaled anticholinergics significantly increased the risk of cardiovascular death, MI, and stroke in a sensitivity analysis limited to the 5 long-term trials (>6 months) involving 7222 patients (2.9% vs 1.8% for control; RR, 1.73 [95% CI, 1.27-2.35]; P < .001) (Figure 3).4,19-22” The third sentence in this paragraph should be “The significantly increased risk of cardiovascular death, MI, and stroke was demonstrated even when we separately analyzed inhaled tiotropium vs control therapy (RR, 2.09 [95% CI, 1.20-3.63]; P = .009),19-22 and inhaled ipratropium vs control therapy (RR, 1.57 [95% CI, 1.08-2.28]; P = .02)4 in the long-term trials.” The next sentence should be “Although, there was no statistically significant increase in the risk of cardiovascular death, MI, and stroke in a sensitivity analysis of the 12 short-term trials (<26 weeks) involving 6423 patients (0.7% for anticholinergics vs 0.6% for control; RR, 1.23 [95% CI, 0.69-2.20]; P = .48), the direction of the drug effect was similar to that of the long-term trials (Figure 4).24,26-34

On page 1446, in Table 3, under the heading “Long-Term (>6 mo-5 y),” under “Chan et al,22 2007c,” the value for the “All-Cause Mortality” column in the row for “Tiotropium,” should be “15” instead of “17.” In the next row for “Placebo,” the value for the “Total No. of Participants” column should be “305” instead of “350.” The corrected Figure 2, Figure 3, and Figure 4 and Table 4 appear herein.

Figure 2. Meta-analysis of Randomized Controlled Trials of Inhaled Anticholinergics vs Control for Major Adverse Cardiovascular Outcomes Composite
Figure 2. Meta-analysis of Randomized Controlled Trials of Inhaled Anticholinergics vs Control for Major Adverse Cardiovascular Outcomes Composite

Cardiovascular outcomes composite indicates cardiovascular death, myocardial infarction, and stroke. Size of the data markers indicates weight of the study. CI indicates confidence interval.

Figure 3. Meta-analysis of Short-term Randomized Controlled Trials of Inhaled Anticholinergics vs Control for Major Adverse Cardiovascular Outcomes Composite
Figure 3. Meta-analysis of Short-term Randomized Controlled Trials of Inhaled Anticholinergics vs Control for Major Adverse Cardiovascular Outcomes Composite

Cardiovascular outcomes composite indicates cardiovascular death, myocardial infarction, and stroke. Long-term indicates longer than 6 months to 5 years. Size of the data markers indicates weight of the study. CI indicates confidence interval.

Figure 4. Meta-analysis of Short-term Randomized Controlled Trials of Inhaled Anticholinergics vs Control for Major Adverse Cardiovascular Outcomes Composite
Figure 4. Meta-analysis of Short-term Randomized Controlled Trials of Inhaled Anticholinergics vs Control for Major Adverse Cardiovascular Outcomes Composite

Cardiovascular outcomes composite indicates cardiovascular death, myocardial infarction, and stroke. Short-term indicates 6 weeks to 6 months. Size of the data markers indicates weight of the study. CI indicates confidence interval.

Table 4. Results of Meta-analysis on Individual End Points of Cardiovascular Death, Myocardial Infarction (MI), Stroke, and All-Cause Mortality With Inhaled Anticholinergics
Table 4. Results of Meta-analysis on Individual End Points of Cardiovascular Death, Myocardial Infarction (MI), Stroke, and All-Cause Mortality With Inhaled Anticholinergics
Table 4. Results of Meta-analysis on Individual End Points of Cardiovascular Death, Myocardial Infarction (MI), Stroke, and All-Cause Mortality With Inhaled Anticholinergics
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