Statins reduce all-cause mortality in chronic obstructive pulmonary disease: a systematic review and meta-analysis of observational studies

Respiratory Research

Takeshi Kaneko³  Atsuhisa Ueda¹  Yoshiaki Ishigatsubo¹  Miyo Inoue²  Ryota Kojima²  Naoki Miyazawa²  Nobuyuki Horita² 

[1]Department of Internal Medicine and Clinical Immunology, Yokohama City University Graduate School of Medicine, 3-9 Fukuura, Kanazawa-ku, Yokohama 236-0004, Japan

[2]Department of Respiratory Medicine, Saiseikai Yokohamashi Nanbu Hospital, Yokohama, Japan

[3]Respiratory Disease Center, Yokohama City University Medical Center, Yokohama, Japan

关键词: Emphysema;    Inflammation;    Survival;    Prognosis;   

Others  :  1146642
DOI  :  10.1186/1465-9921-15-80

 received in 2014-03-19, accepted in 2014-07-03,  发布年份 2014

【 摘 要 】

Background

Recent observational studies have suggested that use of statins reduces mortality in patients suffering from chronic obstructive pulmonary disease. However, no meta-analysis has reported the pooled hazard ratio of statins to all-cause mortality.

Methods

We searched for eligible articles using five databases. We included randomized controlled trials and cohort studies written in English using original data reporting the hazard ratio of statins to all-cause, cardiovascular-related, cancer-related, or respiratory-related mortality. A fixed model with the confidence interval method was used. Publication bias was evaluated by funnel plot and Begg’s test, and was corrected using Duval’s trim and fill method. Sensitivity analyses were also conducted.

Results

We included 10 out of 128 articles. The pooled hazard ratio of statins to all-cause mortality involving 16269 patients was 0.81 (95% CI: 0.75-0.86, P < 0.001) with moderate heterogeneity (I2 = 52%, P = 0.032). The sensitivity analysis and funnel plot suggested the existence of publication bias. After three possibly unpublished cohorts were imputed, the pooled hazard ratio of 0.83 (95% CI: 0.78-0.88, P < 0.001) still suggested a favorable prognosis in statin-treated patients. The pooled hazard ratio of statins to cardiovascular-related, cancer-related, and respiratory-related mortality were 0.52 (95% CI: 0.27-1.01, P = 0.052), 0.57 (95% CI: 0.32-1.01, P = 0.056), and 0.55 (95% CI: 0.43-0.78, P < 0.001), respectively, although these results were not conclusive as we could not find a sufficient number of original studies dealing with those forms of mortality.

Conclusions

The use of statins for patients suffering from chronic obstructive pulmonary disease may reduce all-cause mortality. This conclusion should be re-evaluated by a registered large-scale randomized controlled trial.

【 授权许可】

   
2014 Horita et al.; licensee BioMed Central Ltd.

【 图 表 】

Figure 1.

Figure 2.

Figure 3.

Figure 4.

【 参考文献 】

• [1]Global Strategy for the Diagnosis, Management and Prevention of COPD, Global Initiative for Chronic Obstructive Lung Disease (GOLD) http//www.goldcopd.org/uploads/users/files/GOLD_Report_2011_Feb21.pdf webcite
• [2]Young RP, Hopkins RJ: Update on the potential role of statins in chronic obstructive pulmonary disease and its co-morbidities. Expert Rev Respir Med 2013, 7:533-544.
• [3]Young RP, Hopkins R, Eaton TE: Pharmacological actions of statins: potential utility in COPD. Eur Respir Rev 2009, 18:222-232.
• [4]Young RP, Hopkins R, Eaton TE: Potential benefits of statins on morbidity and mortality in chronic obstructive pulmonary disease: a review of the evidence. Postgrad Med J 2009, 85:414-421.
• [5]Ishida W, Kajiwara T, Ishii M, Fujiwara F, Taneichi H, Takebe N, Takahashi K, Kaneko Y, Segawa I, Inoue H, Satoh J: Decrease in mortality rate of chronic obstructive pulmonary disease (COPD) with statin use: a population-based analysis in Japan. Tohoku J Exp Med 2007, 212:265-273.
• [6]Janda S, Park K, FitzGerald JM, Etminan M, Swiston J: Statins in COPD: a systematic review. Chest 2009, 136:734-743.
• [7]Dobler CC, Wong KK, Marks GB: Associations between statins and COPD: a systematic review. BMC Pulm Med 2009, 9:32.
• [8]Wang MT, Lo YW, Tsai CL, Chang LC, Malone DC, Chu CL, Liou JT: Statin use and risk of COPD exacerbation requiring hospitalization. Am J Med 2013, 126:598-606.
• [9]Frost FJ, Petersen H, Tollestrup K, Skipper B: Influenza and COPD mortality protection as pleiotropic, dose-dependent effects of statins. Chest 2007, 131:1006-1012.
• [10]Søyseth V, Brekke PH, Smith P, Omland T: Statin use is associated with reduced mortality in COPD. Eur Respir J 2007, 29:279-283.
• [11]van Gestel YR, Hoeks SE, Sin DD, Simsek C, Welten GM, Schouten O, Stam H, Mertens FW, van Domburg RT, Poldermans D: Effect of statin therapy on mortality in patients with peripheral arterial disease and comparison of those with versus without associated chronic obstructive pulmonary disease. Am J Cardiol 2008, 102:192-196.
• [12]van Gestel YR, Hoeks SE, Sin DD, Hüzeir V, Stam H, Mertens FW, van Domburg RT, Bax JJ, Poldermans D: COPD and cancer mortality: the influence of statins. Thorax 2009, 64:963-967.
• [13]Rutten FH, Zuithoff NP, Hak E, Grobbee DE, Hoes AW: Beta-blockers may reduce mortality and risk of exacerbations in patients with chronic obstructive pulmonary disease. Arch Intern Med 2010, 170:880-887.
• [14]Short PM, Lipworth SI, Elder DH, Schembri S, Lipworth BJ: Effect of beta blockers in treatment of chronic obstructive pulmonary disease: a retrospective cohort study. BMJ 2011, 342:d2549.
• [15]Bartziokas K, Papaioannou AI, Minas M, Kostikas K, Banya W, Daniil ZD, Haniotou A, Gourgoulianis KI: Statins and outcome after hospitalization for COPD exacerbation: a prospective study. Pulm Pharmacol Ther 2011, 24:625-631.
• [16]Lawes CM, Thornley S, Young R, Hopkins R, Marshall R, Chan WC, Jackson G: Statin use in COPD patients is associated with a reduction in mortality: a national cohort study. Prim Care Respir J 2012, 21:35-40.
• [17]Young RP, Hopkins RJ, Chan W, Thornley S, Gamble GD: Effect of statin therapy on mortality in COPD: analysis of cause specific deaths in a National Cohort Study. Am J Respir Crit Care Med 2013, 187:A6017.
• [18]Sheng X, Murphy MJ, MacDonald TM, Schembri S, Simpson W, Winter J, Winter JH, Wei L: Effect of statins on total cholesterol concentrations, cardiovascular morbidity, and all-cause mortality in chronic obstructive pulmonary disease: a population-based cohort study. Clin Ther 2012, 34:374-384.
• [19]Ekström MP, Hermansson AB, Ström KE: Effects of cardiovascular drugs on mortality in severe chronic obstructive pulmonary disease. Am J Respir Crit Care Med 2013, 187:715-720.
• [20]Tashkin DP, Celli B, Senn S, Burkhart D, Kesten S, Menjoge S, Decramer M, UPLIFT Study Investigators: A 4-year trial of tiotropium in chronic obstructive pulmonary disease. N Engl J Med 2008, 359:1543-1554.
• [21]Karner C, Chong J, Poole P: Tiotropium versus placebo for chronic obstructive pulmonary disease. Cochrane Database Syst Rev 2012, 7:CD009285.
• [22]Beri A, Sural N, Mahajan SB: Non-atheroprotective effects of statins: a systematic review. Am J Cardiovasc Drugs 2009, 9:361-370.
• [23]Greenland S: Quantitative methods in the review of epidemiologic literature. Epidemiol Rev 1987, 9:1-30.
• [24]Higgins JP, Thompson SG, Deeks JJ, Altman DG: Measuring inconsistency in meta-analyses. BMJ 2003, 327:557-560.
• [25]Begg CB, Mazumdar M: Operating characteristics of a rank correlation test for publication bias. Biometrics 1994, 50:1088-1101.
• [26]Duval S, Tweedie R: Trim and fill: A simple funnel-plot-based method of testing and adjusting for publication bias in meta-analysis. Biometrics 2000, 56:455-463.
• [27]Sutton AJ, Duval SJ, Tweedie RL, Abrams KR, Jones DR: Empirical assessment of effect of publication bias on meta-analyses. BMJ 2000, 320:1574-1577.
• [28]Altman DG, Bland JM: Interaction revisited: the difference between two estimates. BMJ 2003, 326:219.
• [29]Ray KK, Seshasai SR, Erqou S, Sever P, Jukema JW, Ford I, Sattar N: Statins and all-cause mortality in high-risk primary prevention: a meta-analysis of 11 randomized controlled trials involving 65,229 participants. Arch Intern Med 2010, 170:1024-1031.
• [30]Mancini GB, Etminan M, Zhang B, Levesque LE, FitzGerald JM, Brophy JM: Reduction of morbidity and mortality by statins, angiotensin-converting enzyme inhibitors, and angiotensin receptor blockers in patients with chronic obstructive pulmonary disease. J Am Coll Cardiol 2006, 47:2554-2560.
• [31]Mortensen EM, Copeland LA, Pugh MJ, Restrepo MI, de Molina RM, Nakashima B, Anzueto A: Impact of statins and ACE inhibitors on mortality after COPD exacerbations. Respir Res 2009, 10:45.
• [32]Lahousse L, Loth DW, Joos GF, Hofman A, Leufkens HG, Brusselle GG, Stricker BH: Statins, systemic inflammation and risk of death in COPD: the Rotterdam study. Pulm Pharmacol Ther 2013, 26:212-217.
• [33]DeAngelis CD, Drazen JM, Frizelle FA, Haug C, Hoey J, Horton R, Kotzin S, Laine C, Marusic A, Overbeke AJ, Schroeder TV, Sox HC, Van Der Weyden MB, International Committee of Medical Journal Editors: Clinical trial registration: a statement from the International Committee of Medical Journal Editors. JAMA 2004, 292:1363-1364.
• [34]ClinicalTrials.gov database 2014. http://www.clinicaltrials.gov webcite
• [35]Stroup DF, Berlin JA, Morton SC, Olkin I, Williamson GD, Rennie D, Moher D, Becker BJ, Sipe TA, Thacker SB: Meta-analysis of observational studies in epidemiology: a proposal for reporting. Meta-analysis Of Observational Studies in Epidemiology (MOOSE) group. JAMA 2000, 283:2008-2012.
• [36]Danaei G, Tavakkoli M, Hernán MA: Bias in observational studies of prevalent users: lessons for comparative effectiveness research from a meta-analysis of statins. Am J Epidemiol 2012, 175:250-262.