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 -blocker in patients with coexistent HF and reactive airway disease Time: 95.1.11 ( 三 ) Reporter: 張秀美 藥師.

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Presentation on theme: " -blocker in patients with coexistent HF and reactive airway disease Time: 95.1.11 ( 三 ) Reporter: 張秀美 藥師."— Presentation transcript:

1  -blocker in patients with coexistent HF and reactive airway disease Time: ( 三 ) Reporter: 張秀美 藥師

2 Background Beta blockers are recommended for the treatment of all patients (in NYHA class II-IV) with stable, mild, moderate, and severe HF from ischaemic or non-ischaemic cardiomyopathies and reduced LVEF on standard treatment, including diuretics and ACEI, unless there is a contraindication. (evidence class IA) Beta blockers therapy reduce hospitalizations (all, CV and HF), improves the functional class and leads to less worsening of HF. (Reduction all-cause mortality) (evidence class IA) ESC guideline for CHF; 2005.

3 The patient should be in a relatively stable condition, without the need of intravenous inotropic therapy and without signs of marked fluid retention. Differences in clinical effects may be present between different beta-blockers in patients with HF. Only bisoprolol, carvedilol, metoprolol succinate, and nebivolol can be recommended. (evidence class IA) ESC guideline for CHF; Background

4 Contraindications to beta-blockers Asthma bronchiale Severe bronchial disease (ex: COPD) Symptomatic bradycardia or hypotension Background ESC guideline for CHF; 2005.

5 P.I.C.O. Patients (P) Intervention (I) Comparison (C) Outcome (O) HF with airway disease beta-blockersPlacebo FEV1 change P’t symptom Mortality

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8 Database Search Cochrane Library key word: heart failure and airway disease and beta-blocker Found: 2/9 related results * Cardioselective beta-blockers for chronic obstructive pulmonary disease. * Cardioselective beta-blockers for reversible airway disease.

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11 Database Search Bandolier key word: heart failure, airway disease, COPD, beta-blocker Found: No related result

12 Database Search ACP Journal Club key word: heart failure, airway disease, COPD, beta-blocker Found: No related result

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14 Database Search EMBASE-- Drugs & Pharmacology key word: heart failure, airway disease, beta-blockers Found: 2/42 related results

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17 Database Search Pub-Med Clinical Queries-systematic review key word: heart failure, airway disease Found: 3/26 related results

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21 Database Search Pub-Med key word: heart failure, airway disease,Carvedilol Found: 2 related results

22 EMBASE

23 Results…. Cardioselective  -blockers for reversible airway disease or COPD Non-selective ,  -blocker—Carvedilol, use in p’ts with HF and COPD or Asthma Conclusion

24 Cardioselective beta-blockers for reversible airway disease S Salpeter, T Ormiston, E Salpeter, R Wood-Baker The Cochrane Database of Systematic Reviews 2005 Issue 4 Copyright © 2005 The Cochrane Collaboration. Published by John Wiley & Sons, DOI: / CD This version first published online: 21 October 2002 in Issue 4, 2002

25 Objectives To assess the effect of cardioselective beta-blockers in patients with asthma or chronic obstructive pulmonary disease (COPD). Selection criteria Randomized, blinded, placebo-controlled trials of single dose or continued treatment of the effects of cardioselective beta- blockers in patients with reversible airway disease. Data collection and analysis We divided beta1-blockers into those with or without intrinsic sympathomimetic activity (ISA). Interventions were: administration of single dose or continued beta1-blocker(3-28 days), and response to beta2-agonist given after the study drug. Main results 19 studies on single-dose treatment and 10 studies on continued treatment met the inclusion criteria.

26 Result —beta-blocker v.s placebo: Single dose The Cochrane Database of Systematic Reviews 2005 Issue 4

27 beta-blocker v.s placebo: Single dose— FEV1 treatment

28 The Cochrane Database of Systematic Reviews 2005 Issue 4 beta-blocker v.s placebo: Single dose— FEV1 treatment

29 Beta-blocker categories The Cochrane Database of Systematic Reviews 2005 Issue 4 Carvedilol (+ alpha block)Carteolol (Mikelan) * * * * * * *

30 The Cochrane Database of Systematic Reviews 2005 Issue 4 beta-blocker v.s placebo: Single dose— subgroup: COPD--FEV1

31 The Cochrane Database of Systematic Reviews 2005 Issue 4 beta-blocker v.s placebo: Single dose— subgroup: CVD--FEV1

32 The Cochrane Database of Systematic Reviews 2005 Issue 4 Result — beta-blocker+agonist v.s placebo+agonist: Single dose

33 The Cochrane Database of Systematic Reviews 2005 Issue 4 beta-blocker+agonist v.s placebo+agonist: Single dose FEV1 treatment

34 The Cochrane Database of Systematic Reviews 2005 Issue 4 beta-blocker+agonist v.s placebo+agonist: Single dose FEV1 treatment

35 The Cochrane Database of Systematic Reviews 2005 Issue 4 Result —beta-blocker v.s placebo: Longer duration

36 The Cochrane Database of Systematic Reviews 2005 Issue 4 Result — beta-blocker+agonist v.s placebo+agonist: Longer duration

37 The Cochrane Database of Systematic Reviews 2005 Issue 4 beta-blocker+agonist v.s placebo+agonist: Longer duration FEV1 treatment

38 Beta-blockers reduce mortality in patients with hypertension, heart failure and coronary arterial disease. Traditionally they have not been given to patients with reversible airway disease (asthma or COPD with a reversible obstructive component). This review of randomized controlled trials, that evaluated cardioselective beta-blocker given in mild to moderate reversible airway disease or COPD, do not produce adverse respiratory effects in the short term, these agents should not be withheld from such patients. Long term safety (especially their impact during an acute exacerbation) still needs to be established. Conclusion The Cochrane Database of Systematic Reviews 2005 Issue 4

39 Cardioselective beta-blockers for chronic obstructive pulmonary disease S Salpeter, T Ormiston, E Salpeter The Cochrane Database of Systematic Reviews 2005 Issue 4 Copyright © 2005 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.DOI: / CD pub2 This version first published online: 19 October 2005 in Issue 4, 2005

40 Objectives To assess the effect of cardioselective beta-blockers on respiratory function of patients with COPD. Selection criteria Randomised, blinded, controlled trials of single dose or longer duration that studied the effects of cardioselective beta-blockers on the forced expiratory volume in 1 second (FEV1) or symptoms in patients with COPD. Main results 11 studies of single-dose treatment and 9 of treatment for longer durations, ranging from 2 days to 12 weeks. The Cochrane Database of Systematic Reviews 2005 Issue 4

41 Results P=0.2 P=1.0 P=0.2 P=1.0

42 The Cochrane Database of Systematic Reviews 2005 Issue 4 P=0.8 P=0.3 P=0.5 P=0.6 P=0.5 P=0.1

43 Results The Cochrane Database of Systematic Reviews 2005 Issue 4 P=0.8 P=0.7

44 The available data from controlled trials suggest that cardioselective beta-blocker use in patients with COPD has no significant adverse effects on FEV1, respiratory symptoms or response to beta2-agonists, even for those with severe chronic airways obstruction. This finding was consistent whether patients had severe airways obstruction or a reversible obstructive component. Cardioselective beta-blockers should not be withheld from patients with COPD. Conclusion The Cochrane Database of Systematic Reviews 2005 Issue 4

45 Carvedilol (+ alpha block)Carteolol (Mikelan) * * * * * * * Nebivolol

46 Tolerability of Carvedilol in patients with HF and concomitant COPD or asthma Kotlyar, Eugene a ; Keogh, Anne M. a ; Macdonald, Peter S. a ; Arnold, Ruth H. a ; McCaffrey, Dermot J. a ; Glanville, Allan R. a J Heart Lung Transplant 2002; 21:

47 Background Little information exists on the tolerability of carvedilol in patients with chronic obstructive pulmonary disease (COPD). In this study, we assessed the tolerability and efficacy of carvedilol in patients with CHF and concomitant COPD or asthma. Methods Between 1996 and 2000, a total of 487 patients began receiving open-label carvedilol. 43 (9%) had COPD (n = 31) or asthma (n = 12). 60% began carvedilol therapy in the hospital and underwent measurement of peak expiratory flow rates (PEFR) before and after dosing. Patients were observed for a mean of 2.4 years.

48 17% increase (p=0.04) in PEFR in patients with COPD and a non-significant increase of 4% in patients with asthma (p=0.29). J Heart Lung Transplant 2002; 21: Result

49 J Heart Lung Transplant 2002; 21: patient (3.2%) was withdrawn from carvedilol therapy because of an exacerbation of the pulmonary disease. Four other patients (12.9%), intolerant of carvedilol, ceased therapy because of worsening heart failure.

50 J Heart Lung Transplant 2002; 21: In patients who tolerated carvedilol, echocardiography at 12 months demonstrated a statistically improvement in LV dimensions and function accompanied by improvement in NYHA functional class in 68%.

51 CONCLUSION 1. Patients with CHF and COPD tolerated carvedilol well with no significant reversible airflow limitation, but patients with CHF and asthma tolerated carvedilol poorly. 2.The effect of carvedilol on LV dimensions and function in patients with concomitant airway diseases was similar to that seen in our general group of patients. 3.Asthma remains a contraindication to  -blockade. J Heart Lung Transplant 2002; 21:

52 Selective beta-1-adrenergic blockade is routinely preferred to non-selective blockade in patients with coexistent COPD and CHF to minimize the risk of inducing bronchoconstriction. Recent limited evidence indicates that combined non-selective beta- and alpha-adrenergic blockade is well tolerated by patients with COPD who do not have reversible airway obstruction. Alpha-1-adrenergic-blocking agents such as phentolamine and indoramine produce mild bronchodilation in patients with obstructive airway disease and abolish propranolol- induced bronchoconstriction. Alpha -1-blocking activity of carvedilol and labetalol may be sufficient to offset beta-adrenergic blockade-induced bronchoconstriction in patients with COPD, but not in patients with asthma. JACC 2004; 44(3):

53 Selective beta-1-blockade or non-selective beta- combined with alpha-adrenergic blockade should not be withheld in patients with CHF and COPD without reversible airway obstruction. In patients with CHF and COPD with reversible airway obstruction, selective beta-1-blockade remains the preferred approach in the absence of safety data on agents combining non- selective beta- with alpha-adrenergic blockade. Selective beta-1-blockade and non-selective beta- combined with alpha-adrenergic blockade should be avoided during COPD exacerbation until safety data are available. JACC 2004; 44(3):

54 總 結 Cardioselective-nonISA beta-blocker agent (Atenolol, Bisoprolol, Metoprolol, Practolol) for reversible airway disease Total reversible airway d’s p’t FEV1 Sub: COPD FEV1 Sub: CVD FEV1 P’t symptom 併 beta- agonist FEV1 Single dose (v.s placebo) ↓ ↓ WMD –9.14 [-11.31, -6.97] P< ↓ ↓ WMD –5.28 [-10.03, -0.54] P=0.03 ↓ ↓ WMD –6.83 [-11.46, -2.20] P=0.004 No significant RD 0.00 [-0.03, 0.03]; p= 1 ↑ ↑ WMD 6.59 [4.18, 9.01] P< Longer duration (v.s placebo) No significant WMD –3.22 [7.79, 1.36]; p= 0.2 No significant WMD –6.20 [-16.37, 3.97]; p= 0.2 No significant WMD –1.40 [-8.10, 5.31]; p= 0.7 No significant RD 0.01 [-0.02, 0.04]; p=0.5 ↑ ↑ WMD 12.0 [4.12, 19.87] P< RD: Risk difference WMD: Weighted Mean Difference

55 總 結 Cardioselective beta-blocker agent (Atenolol, Bisoprolol, Metoprolol, Practolol, Celiprolol) for COPD Total COPD p’t FEV1 P’t symptom Severe COPD FEV1 Reversible ai rway disease FEV1 CVD FEV1 併 beta- agonist FEV1 Single dose (v.s placebo) WMD –2.08 [-5.25, 1.09] P= 0.2 WMD 0.00 [-0.04, 0.04] P= 1 WMD –0.71 [-5.69, 4.27] P= 0.8 WMD –1.8 [-7.01, 3.41] P= 0.5 WMD –1.8 [-7.01, 3.41] P= 0.5 WMD –1.21 [-10.97, 8.56] P= 0.8 Longer duration (v.s placebo) WMD –2.39 [-5.69, 0.91] P= 0.2 WMD 0.00 [-0.05, 0.05] P= 1 WMD –3.11 [-8.62, 2.41] P= 0.3 WMD –1.26 [-5.78, 3.25] P= 0.6 WMD –4.2 [-9.32, 0.92] P= 0.1 WMD 1.12 [-4.97, 7.20] P= 0.7

56 系統性文獻回顧顯示,Cardioselective  -blocker 的使用不影響 airway disease 病患之 FEV1,respiratory symptom, 在併用  2 - agonist 時也不影響其作用 ( 部分資料顯示對 FEV1 有正面效益 ). 對於 HF 合併 airway disease (COPD, Asthma 等 ) 患者, 依目前文 獻搜尋結果仍建議持續使用具心臟選擇性的  -blocker. ( 除非 病患正處於 airway disease exacerbation 狀態時 ). 具有改善 HF 疾病 outcome 之 non-selective ,  -blocker— Carvedilol 由於目前佐證其用於 COPD 併 HF 之臨床試驗數據有限, 故當 CHF 合併 airway disease 時, 仍優先建議使用 Cardioselective  - blocker (prefer use Bisoprolol (Concor)® ). 總 結

57 Thanks …


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