TO THE EDITOR
Often as individuals age, medication use increases, however, the capacity of the human body to cope with medications also changes. Pharmacokinetics in the elderly is much more complex and consequently, the list of contraindicated or relatively contraindicated medications is greater. Polypharmacy, inappropriate medication prescribing and multimorbidity in the elderly result in inherent challenges. The recent coronavirus disease 2019 (COVID-19) pandemic brought the complexity of this issue into sharp focus. COVID-19 led to higher mortality and hospitalization rates in the elderly compared to the young. Frailty and comorbidities increased the likelihood of a more severe clinical course. Furthermore, COVID-19 associated illness was often accompanied by cardiovascular complications, such as arrhythmia, myopericarditis, or decompensated heart failure.
One of the most frequently used cardiac medications are beta-blockers, they have shown benefit in elderly patients with common cardiovascular diseases such as ischemic heart disease, atrial fibrillation, and heart failure. Santillo and Migale, in their review, discussed the role of beta-blocker therapy in elderly patients with COVID-19. The authors argued that although beta-blockers do not prevent infection in elderly, their use was associated with improved survival and a less severe COVID-19 clinical course. They also argued against the discontinuation of beta-blockers while having the disease. However, in their review, nine of the ten studies analysed beta-blocker subgroups which represented only 20% of the enrolled patients (range 13%–41%), which is a significant limitation in making a firm conclusion. We certainly agree with the authors' assertion that further research is needed.
To complement the published review and further enrich discussion, we would like to highlight examples where there is a potential indication for a beta-blocker, however, there may be legitimate reasons for initiation in the elderly.
Should we consider routine screening for atrial fibrillation in elderly patients with COVID-19? The GeroCovid Registry reported atrial fibrillation in 21% of elderly patients hospitalized with COVID-19, which was associated with a significant mortality rate. In the randomized multicentre STROKESTOP study, early detection of atrial fibrillation in the elderly, through routine screening, was safe and significantly reduced stroke and death. However, functional, and cognitive status in the elderly is an important factor to be considered before starting therapy. In a large cohort study (n = 15720) of nursing home residents, beta-blocker initiation after acute myocardial infarction correlated with functional decline in residents with pre-existing functional or cognitive impairment. This effect was not seen in those with intact functional and mental abilities. Needless to say, beta-blocker use yielded a significant mortality benefit in all the groups and subgroups of the study, despite its negative impact on functional and cognitive status in some.
The latter example highlights the importance of a more nuanced/selective approach to medication prescribing in the elderly. It is known that there are implicit (i.e., based on clinical judgement) and explicit (i.e., based on prespecified standards) criteria for identifying inappropriate prescribing or even determining the preferred medications to use. Such criteria have been used to develop relevant assessment tools[6,7]. Beers Criteria, for example, were examined in several studies which found a significant association between inappropriate medications and unfavourable clinical outcomes, including mortality, hospitalization, and adverse drug events and vice versa. Assessment tools are intended to alert clinicians to potential inappropriate prescribing rather than replacing clinical judgement and individualized decision-making for patients. A systematic literature search identified 46 tools that varied in methodology, clinical validation, comprehensiveness, complexity, strength, and limitations. A systematic scoping review focusing on respiratory disorders (i.e., respiratory failure, asthma, and chronic obstructive pulmonary disease) identified 19 tools. Beta-blockers were the most frequent drug class resulting in an exacerbation of respiratory diseases due to high mucus production and bronchoconstriction (i.e., β2-receptor antagonism), which worsens the respiratory condition and leads to respiratory depression. Choosing a cardio-selective beta-blocker is suggested in medical management which is consistent with what has been suggested by Santillo and Migale in their review. However, not all the tools propose therapeutic management. In the COVID-19 era, it is important to carefully assess treatment, taking account of drug interactions, and potentially inappropriate medications in the elderly to prevent the worsening of COVID-19 and other comorbidities. Although several criteria to assessing inappropriate prescribing in elderly individuals (i.e., age ≥ 65 years) are available, each has limitations, and many are outdated. Moreover, criteria for vulnerable and frail older individuals are lacking. It is probably the time to update an existing tool or develop a new one which is comprehensive and considers specific relevant criteria for the elderly including vulnerable and frail subgroups. The criteria should consider additional aspects related to COVID-19 and its treatment which is known to interact with many medications.