Prescribing humility 

By Samuel Durso, MD, MBA, Johns Hopkins Medicine 

I’m an internist-geriatrician. Most of my experience, either initiating or stopping beta-blockers, occurs in the context of my office practice and to a lesser extent in the hospital. Other sources of information and experience with beta-blocker use are weekly medicine grand rounds, weekly teaching rounds with medical students and house staff, regular participation in resident morning report and attempts to keep current with self-study programs (e.g., American College of Medicine Medical Knowledge Self-Assessment Program). I scan a small fraction of the articles that are relevant to older adults with heart disease and most articles that I read are prompted by questions that arise in the context of patients’ concerns and their care. I have no expertise regarding clinical trials or other evidence supporting guidelines for the management of patients after myocardial infarction.  

Also, let me share the lens through which I read the results of clinical trials: 1) most of my patients have a phenotype that is poorly represented in most cardiovascular clinical trials (generalizability), 2) I’m struck that very often preventive interventions that demonstrate a positive or negative outcome result in a small absolute benefit or harm (high number needed to treat or harm), and 3) reflection on the complex human organism leads me to conclude that there are a myriad ways that a biologically plausible intervention might not work or work differently than expected (life’s not simple).    

In this light I will explain my reaction when asked to share thoughts on a new study published in the European Heart Journal titled: “Beta-blockers after myocardial infarction: effects according to sex in the REBOOT trial. “The study finds that for “. . . MI patients managed according to contemporary standards, beta-blocker therapy was associated with evidence of harm in women—particularly those with preserved LVEF and receiving higher doses—an effect not observed in men.” The harm observed was “an excess absolute risk of approximately 0.9% per year of the composite endpoint of all-cause death, MI, or HF hospitalization among women receiving beta-blockers compared with those not receiving them.”  

My first reaction is that a finding of harm that differs by sex is plausible, as the authors note. The reasons are likely complex and may include differences in biology, comorbidity, practice patterns, and clinical biases leading to differences in therapeutic interventions. My next reaction is to ask: “What do I know about beta-blockers after a myocardial infarction?” The answer: very little. I know that that they’re part of guideline directed care for men and women after MI, are standard care for patients with heart failure with reduced ejection fraction, and I know a bit of pharmacology and physiology. Furthermore, I’m not likely to be the physician deciding whether to use or not use beta-blockers in the setting of an acute MI. More likely I will be the one reviewing a patient’s medications in the post-hospital phase of care, responding questions about their health, addressing symptoms—including possible medication side effects—and other concerns related to their future care.     

Therefore, with respect to weighing new evidence for or against the current practice of post-myocardial management, I must lean heavily on colleagues who are experts in caring for patients with myocardial infarction and sophisticated in interpreting the results of clinical trials, such as this one. I’m cautious that there may be elements of study design or other factors that I don’t know. For example, patients that had an absolute indication for beta-blocker use were excluded. What were those conditions? In addition, I must also weigh my personal experience with individual patients—most of whom have multiple significant chronic conditions (some of which are not accounted for in this study’s population), and they have their own unique experience, life-circumstances, and preferences.  

A few final thoughts 

Beta-blockers given after myocardial infarction to men and women with preserved ejection fraction (> 50%) appear to confer no benefit and this new study found evidence of absolute harm in 0.9% of women per year (number needed to harm, 111). 

I’m eager to hear what my cardiology colleagues say. Does this information change their practice, if so, how so, and if there are exceptions, what are they? 

The study authors consider their findings hypothesis-generating and deserving of further study. So, I expect more to come. 

That some of my patients, men and women, experience fatigue and other symptoms associated with beta-blocker use, and many (but not all) want to limit the number of medications they take, having a rationale for not starting or possibly stopping one more medicine, aside from no apparent benefit or even harm—is a benefit. 

And on reading this study and others like it, I’m reminded that what’s “standard of care” is open to change. There are many examples of practices that made sense and were once standard of care that later were stopped when proven ineffective, dangerous, or required use with substantial qualification (e.g., routine administration of lidocaine to prevent premature ventricular contractions after MI, or post-menopausal estrogen replacement therapy to reduce cardiovascular disease risks). In fact, an analysis of highly cited clinical trials published in high impact journals—most of which were in the cardiovascular literature—found with surprising frequency that subsequent trials refuted or demonstrated positive outcomes that were less impactful than the initial trial. As a result, I approach guidelines, standards care, and new findings with justifiable caution and a good measure of humility about what I think I “know.”  

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This piece expresses the views solely of the author. It does not necessarily represent the views of any organization, including Johns Hopkins Medicine.