Triple Therapy for the Management of COPD: A Review

Figures & data

Figure 1.  Quorum diagram.

Table 1.  Study characteristics

	Inclusion criteria				Interventions and Sample Size (n)
Author, year, (study duration)	Age	FEV1	Smoke Hx	Exacerbation	Triple therapy	Dual or combination therapy	Monotherapy	No inhaled therapy	Primary Outcome	Concomitant drugs allowed
Aaron, 2007 [28] 12 months	≥35 years	<65% predicted	≥10 pack-years	At least 1 in previous 12 months requiring antibiotics or steroids	18 μg tio OD plus FPS 500/50 μg/puff 1P BID (n = 145)	18 μg tio OD plus S 25 μg/puff 2P BID (n = 148)	18 μg tio OD plus placebo 2 P BID (n = 156)	NA	Proportion of patients experiencing at least 1 exacerbation	Albuterol, oxygen, antileukotrienes, methylxanthines
Welte, 2009 [27] 3 months	≥40 years	≤50% predicted	≥ 10 pack- years	History requiring antibiotics or steroids	18 μg tio OD plus BDF 320/9 μg/puff 1P BID(n = 329)	NA	18 μg tio OD plus placebo1P BID(n = 331)	NA	FEV1	Terbutlaine
Cazzola, 2007 [26] 3 months	≥50 years	<70% predicted	≥20 pack-years/current smoker	Not a criterion	18 μg tio OD plus FPS 250/25 μg/puff 2P BID (n = 29)	FPS 500/50 μg/puff 1P BID plus placebo 1P OD (n = 26)	18 μg tio OD plus placebo 1 P BID (n = 26)	NA	FEV1	Salbutamol, theophylline
Fang, 2008 [25] 12 months	NR	25%–70% predicted	Not a criterion	At least 1 in previous 36 months requiring antibiotics or steroids	18 μg tio OD plus FPS 250/50 μg/puff BID (n = 33)	FPS 250/50 μg/puff BID (n = 32)	18 μg tio OD (n = 32)	(n = 29)	FEV1	Albuterol

FEV₁ = forced expiratory volume in the first second of expiration; Hx = history; NA = not applicable; NR = not reported; μg = micrograms; tio = tiotropium; OD = once daily; P = puff; BID = twice daily; FPS = fluticasone/salmeterol; BDF = budesonide/formoterol; S = salmeterol.

Figure 2.  Pooled estimate for severe/acute exacerbations. Tio = tiotropium, LABA = long-acting beta-agonist bronchodilator; ICS = inhaled corticosteroid; CI = confidence interval.

Figure 3.  Pooled estimate for lung function. Tio = tiotropium, LABA = long-acting beta-agonist bronchodilator; ICS = inhaled corticosteroid; CI = confidence interval.

Figure 4.  Pooled estimate for changes in quality of life scores. Tio = tiotropium, LABA = long-acting beta-agonist bronchodilator; ICS = inhaled corticosteroid; CI = confidence interval.

Figure 5.  Pooled estimate for mortality. Tio = tiotropium, LABA = long-acting beta-agonist bronchodilator; ICS = inhaled corticosteroid; CI = confidence interval.

Figure 6.  Pooled estimate for adverse event. Tio = tiotropium, LABA = long-acting beta-agonist bronchodilator; ICS = inhaled corticosteroid; CI = confidence interval.

Aaron SD, Vandemheen KL, Fergusson D, Maltais F, Bourbeau J, Goldstein R, Balter M, O'Donnell D, McIvor A, Sharma S, Bishop G, Anthony J, Cowie R, Field S, Hirsch A, Hernandez P, Rivington R, Road J, Hoffstein V, Hodder R, Marciniuk D, McCormack D, Fox G, Cox G, Prins HB, Ford G, Bleskie D, Doucette S, Mayers I, Chapman K, Zamel N, FitzGerald M. Tiotropium in combination with placebo, salmeterol, or fluticasone- salmeterol for treatment of chronic obstructive pulmonary disease: a randomized trial. Ann Intern Med 2007; 146(8):545–555.

 PubMed Web of Science ®Google Scholar

Welte T, Miravitlles M, Hernandez P, Eriksson G, Peterson S, Polanowski T, Kessler R. Efficacy and tolerability of budesonide/formoterol added to tiotropium in COPD patients. Am J Respir Crit Care Med 2009 August 13; 180:741–750.

 PubMed Web of Science ®Google Scholar

Cazzola M, Ando F, Santus P, Ruggeri P, Di Marco F, Sanduzzi A, D'Amato M. A pilot study to assess the effects of combining fluticasone propionate/salmeterol and tiotropium on the airflow obstruction of patients with severe-to-very severe COPD. Pulm Pharmacol Ther 2007; 20(5):556–61.

 PubMed Web of Science ®Google Scholar

Fang LZ, Liang X, Zhang JQ, Liu L, Fu WP, Zhao ZH, Dai LM. Combination of inhaled salmeterol/fluticasone and tiotropium in the treatment of chronic obstructive pulmonary disease: a randomised controlled trial [in Chinese]. Zhonghua Jie He He Hu Xi Za Zhi 2008; 31(11):811–814.

 PubMedGoogle Scholar