Phụ lục beta blockers COPD

Beta blockers & COPD/asthma Quan Nguyen Anh, MD Structure of presentation          Case study Beta blockers – Overview COPD & heart diseases – Overview Under-use of beta-blockers in patients with ischaemic heart disease and concomitant COPD Effectiveness of beta-blocker therapy after AMI in elderly patients with COPD or asthma Use of Beta Blockers in CHF Patients with COPD and/or Asthma Cardioselective beta-blockers ? Non-cardioselective beta-blockers ? Non-selective alpha- & beta-blockers ? Case study     Male, 85 years old COPD Stent LAD1 BP: 170/80 => Isolated systolic hypertension => First line agents: - Thiazide diuretics - ARB - Long acting DHP CCB - BB (???) Case study    Male, 79 years old  Prescription at discharge: 3-vessel coronary heart disease – HF (LVEF: 28 %) – Asthma Re-admission many times due to breathlessness, well tolerated with bronchodilatory, vasodilatory agents & diuretics - Clopidogrel - Berodual, Seretide, Bambec… - Zestril, Furosemide, Nitrat… - Not BB (!!!) Case study   Male, 50 years old  Admitted to Emergency Department: Anterior MI day with bronchospasm appearance, well tolerated with bronchodilatory agents Smoking – many years; occasional breathlessness related to weather, unconfirmed asthma, no prevention His son is allergic to seafood with presentation of rash & itching -> C3: BP 130/80, HR: 85 bpm, no bronchospasm appearance at all => Use of BB??? If yes, when & how??? Beta blockers – Overview Beta blockers - contraindications      Bradycardia, especially high degree AV block Serious HF Bronchospasm pulmonary diseases (COPD, asthma) PAD Cautious in patients with DM, dyslipidemia (increase LDL-C & TG, decrease HDL-C)… Beta blockers – NOW: indications  Hypertension (not recommended for patients ≥ 60 years old without another compelling indication)     Coronary heart disease (Angina, UA, post MI) CHF (bisoprolol, metoprolol, carvedilol) Tachyarrhythmias (…) Perioperative period (…) Beta blockers – NOW: indications  In a retrospective study of more than 200,000 patients with myocardial infarction, Gottlieb et al found that beta-blockers were associated with a 40% reduction in mortality rates in patients with conditions often considered a contraindication to beta-blocker therapy, such as congestive heart failure, pulmonary disease, and older age Gottlieb SS, McCarter RJ, Vogel RA Effect of beta-blockade on mortality among high-risk and low-risk patients after myocardial infarction N Engl J Med 1998; 339:489–497 Beta blockers - classification  β1-Adrenoceptors are situated in the cardiac sarcolemma If activated, they lead to an increase in the rate and force of myocardial contraction (positive inotropic effect) by opening the calcium channels  β2-Adrenoceptors are found mainly in bronchial and vascular smooth muscles If activated, they cause broncho- and vaso-dilatation There are, however, sizable populations of β2-Adrenoceptors in the myocardium, of about 20%–25%, which leads to the cardiac effects of any β2-Adrenoceptors stimulation There is a relative up-regulation of these receptors to about 50% in heart failure Detrimental Effects of Beta-Blockers in COPD*: A Concern for Nonselective BetaBlockers Detrimental Effects of Beta-Blockers in COPD*: A Concern for Nonselective BetaBlockers Detrimental Effects of Beta-Blockers in COPD*: A Concern for Nonselective BetaBlockers  Results: - PC was significantly lower (p < 0.01) with propranolol and metoprolol treatment (geometric 20 means, 2.06 mg/mL and 2.02 mg/mL, respectively) than with placebo (3.16 mg/mL) or celiprolol (3.41 mg/mL) - FEV deteriorated only after propranolol treatment (2.08 ± 0.31 L) [mean ± SD] compared with placebo (2.24 ± 0.37 L) - The fast bronchodilating effect of formoterol was hampered by propranolol (mean increase in FEV at min, 6.7 ± 8.9%) but was unaffected by the other β-blockers (16.9 ± 9.8%, 22 ± 11.6%, and 16.9 ± 9.0% for placebo, metoprolol, and celiprolol, respectively) Detrimental Effects of Beta-Blockers in COPD*: A Concern for Nonselective BetaBlockers  Conclusions: - Pulmonary effects did not occur by celiprolol - Only propranolol reduced FEV and the bronchodilating effect of formoterol - Both metoprolol and propranolol increased AHR => Thus, different classes of β-blockers have different pulmonary effects The anticipated beneficial cardiovascular effects of a β-blocker must be weighted against the putative detrimental pulmonary effects, ie, effect on FEV , AHR, and response to additional β -agonists  A maximal dose of labetalol does not affect FEV1 in hypertensive patients with COPD George RB, Manocha K, Burford JG, Conrad SA, Kinasewitz GT Effects of labetalol in hypertensive patients with chronic obstructive pulmonary disease Chest 1983;83:457–60 • Among 89 patients with coexistent COPD or asthma and CHF, 76 tolerated carvedilol well for at least three months Why the remaining 13 patients did not tolerate carvedilol, or how many of them had reversible airway obstruction, was not commented on Krum H, Ninio D, MacDonald P Baseline predictors of tolerability to carvedilol in patients with chronic heart failure Heart 2000;84:615–9 Tolerability of carvedilol in patients with heart failure and concomitant chronic obstructive pulmonary disease or asthma Kotlyar E, Keogh AM, Macdonald PS, Arnold RH, McCaffrey DJ, Glanville AR Heart Lung Transplant 2002;21:1290–5 J Tolerability of carvedilol in patients with HF and concomitant COPD or asthma  Methods - Between 1996 and 2000, a total of 487 patients began receiving open-label carvedilol - 43 patients (9%) had COPD (n = 31) or asthma (n = 12) - Spirometry supported clinical diagnosis in all, and full pulmonary function testing supported diagnosis in 71% - Sixty percent began carvedilol therapy in the hospital and underwent measurement of peak expiratory flow rates (PEFR) before and after dosing Tolerability of carvedilol in patients with HF and concomitant COPD or asthma       Results:      In patients with asthma: In patients with COPD: mean FEV1 was 62% ± 13% predicted reversibility was 4% ± 4% with bronchodilators FEV1/FVC was 62% ± 8% Mean PEFR was 325 ± 115 liter/min before the dose and increased by 17% hours after the carvedilol dose (p = 0.04) mean FEV1 was 80% ± 17% predicted reversibility was 13% ± 7% FEV1/FVC was 74% ± 11% Mean PEFR was 407 ± 161 liter/min before the dose with no significant change hours after the dose Tolerability of carvedilol in patients with HF and concomitant COPD or asthma  1/31 patients with coexistent CHF and COPD without reversible airflow obstruction did not tolerate carvedilol because of exacerbation of pulmonary disease (a mean dose of 29 ± 19 mg daily; followed for a mean duration of 2.4 years)  3/12 patients with coexistent CHF and asthma, did not tolerate carvedilol because of wheezing At the time of carvedilol withdrawal patients were receiving 6.25, 12.5, and 50 mg of carvedilol, respectively  Survival at 2.5 years was 72% In survivors, left ventricular end-diastolic diameter decreased from 76 ± 11 mm to 72 ± 14 mm (p = 0.01), left ventricular end-systolic diameter decreased from 65 ± 13 mm to 60 ± 15 mm (p = 0.01), and fractional shortening increased from 14% ± 7% to 17% ± 7% (p = 0.05) at 12 months Tolerability of carvedilol in patients with HF and concomitant COPD or asthma  Conclusions: - Patients with CHF and COPD tolerated carvedilol well with no significant reversible airflow limitation, but patients with CHF and asthma tolerated carvedilol poorly - The effect of carvedilol on left ventricular dimensions and function in patients with concomitant airway diseases was similar to that seen in our general group of patients Asthma remains a contraindication to β-blockade  All current evidence on combined nonselective beta-and alpha-blockade is observational, and it is not yet clear whether this class of beta-blockers is better tolerated due to alphablockade or merely because nonselective beta-blockers themselves are well tolerated Take home messages  Patients with COPD have a high incidence of cardiac events, necessitating careful consideration of prophylactic treatment The benefits of beta blockade in this group would therefore appear to outweigh any potential risk of side-effects, according to the available evidence  Many patients with a diagnosis of COPD have no objective evidence to support the diagnosis and are denied the prognostic benefits of BB when presenting with ACS Before withholding beta-blockers, COPD and reversibility should be ascertained by pulmonary function testing Take home messages  Evaluation of BB therapy in patients with COPD requires a detailed classification of patients according to the severity of their lung disease Guidelines from the ACC/AHA specify ‘severe’ COPD as a contraindication to BB therapy, rather than the mere presence of the condition, regardless of its severity  If needed, selective beta-blockers should be used A safe approach is to initiate cardioselective BBs at a low dose and titrate them up as tolerated during the hospital admission Thanks for your attention ... patients with COPD or asthma Use of Beta Blockers in CHF Patients with COPD and/or Asthma Cardioselective beta -blockers ? Non-cardioselective beta -blockers ? Non-selective alpha- & beta -blockers ?...       Case study Beta blockers – Overview COPD & heart diseases – Overview Under-use of beta -blockers in patients with ischaemic heart disease and concomitant COPD Effectiveness of beta-blocker... with presentation of rash & itching -> C3: BP 130/80, HR: 85 bpm, no bronchospasm appearance at all => Use of BB??? If yes, when & how??? Beta blockers – Overview Beta blockers - contraindications