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 Table of Contents  
Year : 2019  |  Volume : 20  |  Issue : 3  |  Page : 121-124

Cardiovascular and respiratory considerations with topical beta-blockers: is it really old news?

1 Newcastle Eye Centre, Royal Victoria Infirmary, Newcastle, UK; Ophthalmology Department, Faculty of Medicine, Minia University, Al Minia, Egypt, UK
2 Northumbria NHS Trust
3 NHS Dumfries and Galloway

Date of Submission27-May-2019
Date of Acceptance12-Jul-2019
Date of Web Publication26-Sep-2019

Correspondence Address:
PhD, FRCS Mahmoud Nassar
Royal Victoria Infirmary, Newcastle
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Source of Support: None, Conflict of Interest: None

DOI: 10.4103/DJO.DJO_27_19

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Objective The aim of this study was to identify the prevalence of prescribing topical beta-blockers (TBB) despite documented contraindications in general practice and whether patients were involved in decisions about treatment.
Design This was a primary-care-based cross-sectional descriptive study.
Introduction Glaucoma is one of the commonest causes of irreversible blindness in the United Kingdom, causing ∼5.9% of blind registration. TBB are currently considered the best adjunctive treatment and are well known for their systemic effects. The effect of concurrent prescription of TBB with systemic contraindications was found to significantly increase the rate of hospitalization and emergency room visits.
Patients and methods Electronic medical records of four primary care providers in the North East of England were searched for primary open-angle glaucoma, use of TBB, and known systemic contraindications. Included records were further searched for correspondence from ophthalmology departments to primary care. We contacted those patients whose records showed no documentation of communicating potential risks with patients and rationale of using TBB.
Results Of the 49 816 patients registered with the four primary health care providers, 798 (1.6%) had primary open-angle glaucoma. Of these, 279 (35%) were prescribed TBB; 260 (93.2%) of whom had no systemic contraindications.
Conclusion Nineteen (6.8%) patients with systemic contraindications were prescribed TBB despite alerts from electronic medical records. Furthermore, these patients were not made aware of the potential risk.

Keywords: open-angle glaucoma, systemic adverse effects, topical beta-blockers

How to cite this article:
Nassar M, Ali M, Bennett N. Cardiovascular and respiratory considerations with topical beta-blockers: is it really old news?. Delta J Ophthalmol 2019;20:121-4

How to cite this URL:
Nassar M, Ali M, Bennett N. Cardiovascular and respiratory considerations with topical beta-blockers: is it really old news?. Delta J Ophthalmol [serial online] 2019 [cited 2020 Oct 25];20:121-4. Available from: http://www.djo.eg.net/text.asp?2019/20/3/121/267942

  Introduction Top

Glaucoma is one of the commonest causes of irreversible blindness in the United Kingdom, causing ∼5.9% of blind registration in the UK [1]. Prevalence increases with age and has been reported to increase up to 10% among people aged 75 years. Risk factors include Afro-Caribbean ethnicity and family history of glaucoma. Treatment includes the use of topical agents to reduce intraocular pressure aiming to protect against further damage to the optic nerve. Prostaglandin analogs are the recommended first-line treatment for most patients; however, topical beta-blockers (TBBs) are currently considered the best adjunctive treatment [2].

TBBs have been used since 1978 and are well known for their systemic effects. Approximately 80% of a topically administered drop reaches the nasal mucosa through the nasolacrimal duct, thus entering the blood stream without going through first-pass metabolism in the liver. Thus, topical administration is considered comparable to the intravenous route, rather than to the oral route, making its systemic effect on cardiac, bronchial, and vascular beta-adrenoceptors potentially serious [3].

The use of TBB can affect normal participants. It was claimed to increase the risk of cardiac mortality by Lee et al. [4]; however, this has been recently dismissed by Pinnock et al. [5] who found no evidence of this in a recent meta-analysis. The effect of TBBs on normal respiratory function is consistently described as ‘mild bronchial obstruction’ [6],[7].

Although the effect of TBBs on normal participants is controversial, it is undebatable that TBBs are contraindicated in patients with heart block, bradycardia, or uncontrolled heart failure. National Institute for Health and Care Excellence guidelines and the British National Formulary advise that TBBs, whether cardioselective or not, should not be used in patients with asthma or obstructive airways disease, unless no alternative is available. When patients with asthma or obstructive airway disease are treated with TBB, the risk of inducing bronchospasm should be appreciated and appropriate precautions taken [2],[8].

Kaiserman et al. [9] studied the effect of concurrent prescription of TBBs with systemic contraindications and found a significant increase in the rate of hospitalization and emergency room visits.

The aim of this study was to identify the prevalence of prescribing TBB therapy for open-angle glaucoma in primary care despite recorded respiratory or cardiovascular contraindications and to determine whether (a) the rationale for beta-blocker use has been communicated and recorded, (b) patients have been counseled on potential risks and appropriate precautions, and/or (c) patients have had an opportunity to share in decision making before treatment.

  Patients and methods Top

A primary-care-based cross-sectional descriptive study was conducted by analyzing electronic medical records (EMR) in June 2016 in four primary care providers in the North East of England. Patients were included based on the criteria outlined in [Table 1].
Table 1 Inclusion criteria

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Following an initial search, we excluded patients prescribed cardioselective beta-blockers, as these are likely to be prescribed with caution for patients with mild to moderate chronic obstructive pulmonary disease (COPD). We also excluded patients with heart failure from the final analysis, as oral beta-blockers are frequently prescribed in these cases; therefore, TBBs are currently not a contraindication in controlled heart failure.

The electronic records of patients who met our inclusion criteria were searched for correspondence from ophthalmology departments to primary care. Relevant correspondence was examined for references to beta-blocker therapy to determine the following:
  1. Whether any known contraindication to TBB therapy had been acknowledged and a reason for use recorded.
  2. Whether any advice on necessary caution and precautions had been communicated.
  3. Whether patients’ involvement in shared decision making on off-label use had been documented.

Patients lacking the aforementioned factors were then telephoned by the clinical pharmacist and asked to participate in a short interview as follows:
  1. Introductory questions about general well-being and adherence to topical and systemic medications.
  2. Direct questioning about recall of discussions about possible adverse effects and potential systemic effects of eye drops at the time therapy was initiated.
  3. Exploration of potential beta-blocker related adverse effects, with direct questioning about experience of the following:
    1. Giddiness, spells of syncope, and/or fainting among patients with documented bradycardia or heart block.
    2. Increased wheeze, increased use of inhalers, sleep disturbance, or interference with routine daily activities among patients with asthma or COPD.

For patients with no recall of discussions about systemic adverse effects and no experience of specific adverse effects, an alert was added to the EMR, to prompt discussion at the next routine medication review in the general practice. Patients reporting any of the specific adverse effects were offered a scheduled medical review with a general practitioner or a clinical pharmacist within 4 weeks.

The initial EMR search was done anonymously. A written informed consent was obtained from patients who were approached for further information or recalled for discussions about systemic adverse effects. This study has obtained approval from the Local Research Ethics Committee and has been conducted with adherence to the tenets of the Declaration of Helsinki.

  Results Top

Among the 49 816 patients registered with the four primary health care providers, there were 798 (1.6%) above 35 years of age with a diagnosis of primary open-angle glaucoma. Of these, 279 (35%) were prescribed TBB; 260 (93.2%) of whom had no systemic contraindications. Details of potential contraindications recorded for the remaining 19 (6.8%) patients are shown in [Table 2].
Table 2 Patients on topical beta-blockers with systemic contraindications

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In none of these cases was there any documentation in practice records or ophthalmology letters indicating that the decision to treat primary open-angle glaucoma with a beta-blocker despite a known contraindication had been taken with the informed involvement of the patient, balancing known risks against likely benefits.

All 19 patients were contacted by telephone. None of the patients were aware of the potential risks associated with TBB use. Seven patients (36.8% of those with systemic contraindications and 2.5% of total TBB users) reported worsening symptoms related to their systemic condition and were offered an appointment within 4 weeks. Results are to be shared with the relevant ophthalmology departments.

The four primary health care providers involved used either EmisWeb or SystmOne EMR software. Both systems have built-in drug interaction and contraindication alerts, which are triggered by coded entries in patient records. Interestingly, the records for all patients with relevant comorbidities triggered automatic alerts highlighting drug interactions, contraindications, and potential risks but these were not acted upon or explained.

  Discussion Top

TBB are the second most common drops used for open-angle glaucoma [2]; our cohort found over one-third (35%) of patients with glaucoma using them. Additionally, 93.2% of TBBs were prescribed to patients with no systemic contraindications, which is in agreement with Shiuey and Eisenberg [10], who described ophthalmologists as ‘more aware than cardiologists’ of potential TBB complications.

The use of cardioselective beta-blockers is considered safe with minimal or no effect on the respiratory system [11]; therefore, we have excluded patients with glaucoma using them as it indicates a knowledgeable response to a systemic contraindication. Interestingly, a recent report found a significant shift to greater use of nonselective TBBs owing to the introduction of fixed combination drops [12].

UK regulators explicitly contraindicate TBB use in bradycardia, reactive airway disease, and severe COPD. Shared decision making and informed consent are core ingredients of a patient-centered approach to health care and likely to be needed in any truly precautionary approach to risk. Nevertheless, we found that 6.8% of patients prescribed a nonselective TBB for open-angle glaucoma had one of these three acknowledged contraindications, being lower than previous studies recording concurrent prescription of TBB, with contraindications to range between 27.3 and 45.7% [13],[14]. This can be explained by increasing use of EMR with built-in alert system. Morales et al. [15] documented a fall in the prevalence of concurrent use from 23.0 to 13.4% between 2000 and 2012.Nearly all primary care providers in the UK rely on an EMR system. The four participating practices in this study are not an exception. The efficiency of their built-in drug interaction and contraindication alerts is as good as the validity of the database, which is participant to entry errors and incomplete or missing data; we consider this the main limitation of the present study. The efficiency of EMR in reducing the prescription of TBB in high-risk patients was studied by Vinker et al. [16] who recommended the use of a central EMR (i.e. shared by primary and secondary care) as being more efficient than local EMR (i.e. in primary care only) owing to shared patient medical history.

As the main users of TBB are elderly patients who normally have comorbidities and polypharmacy, a number of challenges and potential risks should be taken into account. It is important that prescribers are aware of potential risk when dealing with patients with concomitant conditions. A more holistic approach and accurate history should be taken. Furthermore, a more informed patient-shared decision should be considered with explanation of the risk/benefit concept. This also has shown the importance of more effective communication between primary care and specialty, which can potentially reduce adverse effects and nonadherence. It is essential to communicate and link regular monitoring to current patient’s conditions and medications with effective use of available electronic recording systems. Unfortunately, none of our high-risk patients could recall any advice about the rationale for overriding explicit contraindications, the risks associated with such off-label use, precautions to be taken or action in case of adverse effects, and no relevant discussions were recorded on general practitioner computer systems.

  Conclusion Top

In this study, 6.8% of patients with systemic contraindications were prescribed TBBs despite alerts from EMR. Furthermore, these patients were not made aware of the potential risk.

Systemic adverse effects of TBB can be avoided by increased awareness and improved communication between primary and secondary care. There is a need to improve patient-shared decision making on polypharmacy and comorbidity. Furthermore, if an alert is generated by EMR, reasons for overriding it should be documented.

Financial support and sponsorship


Conflicts of interest

There are no conflicts of interest.

  References Top

Liew G, Michaelides M, Bunce C. A comparison of the causes of blindness certifications in England and Wales in working age adults (16–64 years), 1999–2000 with 2009–2010. BMJ Open 2014; 4:e004015.  Back to cited text no. 1
National Institute for Health and Care Excellence. Glaucoma: diagnosis and management [Internet]. London: NICE; 2017.  Back to cited text no. 2
Han JA, Frishman WH, Wu Sun S, Palmiero PM, Petrillo R. Cardiovascular and respiratory considerations with pharmacotherapy of glaucoma and ocular hypertension. Cardiol Rev 2008; 16:95–108.  Back to cited text no. 3
Lee AJ, Wang JJ, Kfley A, Mitchell P. Open-angle glaucoma and cardiovascular mortality: The Blue Mountains Eye Study. Ophthalmology 2006; 113:1069–1076.  Back to cited text no. 4
Pinnock C, Yip J, Khawaja A, Luben R, Hayat S, Broadway D et al. Topical beta-blockers and cardiovascular mortality: systematic review and meta-analysis with data from the epic-norflk cohort study. Ophthalmic Epidemiol 2016; 23:277–284.  Back to cited text no. 5
Sadiq SA, Fielding K, Vernon SA. The effect of timolol drops on respiratory function. Eye (Lond) 1998; 12 (Part 3a):386–389.  Back to cited text no. 6
Waldock A, Snape J, Graham CM. Effects of glaucoma medications on the cardiorespiratory and intraocular pressure status of newly diagnosed glaucoma patients. Br J Ophthalmol 2000; 84:710–713.  Back to cited text no. 7
Joint Formulary Committee. British National Formulary (BNF). 70th ed. London: BMJ Group and Pharmaceutical Press 2015.  Back to cited text no. 8
Kaiserman I, Fendyur A, Vinker S. Topical beta blockers in asthmatic patients − is it safe? Curr Eye Res 2009; 34:517–522.  Back to cited text no. 9
Shiuey Y, Eisenberg MJ. Cardiovascular effects of commonly used ophthalmic medications. Clin Cardiol 1996; 19:5–8.  Back to cited text no. 10
Salpeter S, Ormiston T, Salpeter E. Cardioselective beta-blockers for reversible airway disease. Cochrane Database Syst Rev 2002; 2002:CD002992.  Back to cited text no. 11
Xu K, Campbell EL, Gill SS, Nesdole R, Campbell RJ. Impact of combination glaucoma therapies on β-blocker exposure. J Glaucoma 2017; 26:e107–e109.  Back to cited text no. 12
Valuck RJ, Perlman JI, Anderson C, Wortman GI. Co-prescribing of medications used to treat obstructive lung disease, congestive heart failure and depression among users of topical beta blockers: estimates from three US Veterans Affairs Medical Centers. Pharmacoepidemiol Drug Saf 2000; 10:511–516.  Back to cited text no. 13
O’Sullivan EP, Malhotra R, Migdal C. Prescription of eye drops. Postgrad Med J 2001; 77:654–655.  Back to cited text no. 14
Morales DR, Dreischulte T, Lipworth BJ, Donnan PT, Jackson C, Guthrie B. Respiratory effect of beta-blocker eye drops in asthma: population-based study and meta-analysis of clinical trials. Br J Clin Pharmacol 2016; 82:814–822.  Back to cited text no. 15
Vinker S, Kaiserman I, Waitman DA, Blackman S, Kitai E. Prescription of ocular beta-blockers in patients with obstructive pulmonary disease: does a central electronic medical record make a difference? Clin Drug Investig 2006; 26:495–500.  Back to cited text no. 16


  [Table 1], [Table 2]


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