Propranolol in cardiovascular diseases: The jack of all trades
Propranolol is a competitive beta-adrenergic receptor antagonist that was developed by Sir James Black around six decades ago for the treatment of angina (1). Since then, its indications have expanded not only to several cardiovascular disorders but also non-cardiac disease processes like migraine, anxiety, portal hypertension etc.
With the advent of more cardio-selective beta-blockers in the last few decades, it is notable that propranolol still holds its unique place in the therapeutic armamentarium of every physician. The following review aims to summarise the unique pharmacokinetic profile and versatile indications of this drug that make it a relevant clinician's choice in the modern era.
Why propranolol is still relevant after the emergence of cardio-selective beta-blockers?
The non-selective beta-blocking action (2) and high lipophilicity (3) of this molecule makes it a suitable choice for many cardiovascular diseases. A study found propranolol to be as beneficial as carvedilol for benefiting left ventricular volume and function after primary coronary stenting in acute myocardial infarction. (4)
The mind-heart healer: Dual benefits by sympatholytic action
Another arena where propranolol has an edge over other available beta-blockers is in the treatment of coexisting anxiety disorders in cardiac patients. Among patients with cardiovascular disease, anxiety and formal anxiety disorders are common and associated with poor cardiovascular health, including the development and progression of coronary artery disease and heart failure. (5)
Following an acute coronary syndrome, 20-30% of patients experience elevated levels of anxiety (6). While post-ACS anxiety may be transient for some patients, in half of cases anxiety persists for up to 1-year post-event. Anxiety has been associated with the incidence and in some cases progression, of cardiovascular disease. In patients without existing cardiac disease, anxiety has been linked to the subsequent development of CAD (5). (Figure 1)
In such settings, a non-selective beta-blocker, by blocking the anxiety-driven issympathetic drive is beneficial while cardioselective beta-blockers which do not cross the blood-brain barrier are rendered less useful.
How management of co-existing psychiatric disorders improves outcomes in CVD patients?
Given their links to poor outcomes, the diagnosis and treatment of anxiety disorders is critical. With careful diagnosis and appropriate treatment, anxious patients can have improved quality of life, functioning, and cardiac health. The autonomic hyperactivity and hyperarousal associated with anxiety disorders respond well to propranolol. Propranolol is used to suppress the physical symptoms associated with a generalised anxiety disorder that is caused by noradrenergic stimulation such as tachycardia, palpitations, sweating, and tremors. (7)
Indications for propranolol in CVD- Angina, hypertension, arrhythmias.
Post myocardial infarction: The Beta-Blocker Heart Attack Trial was a landmark trial in the history of propranolol. This multicentre, randomized, double-blind, placebo-controlled trial was designed to evaluate whether administration of propranolol post-myocardial infarction led to a reduction in mortality. Results were encouraging with statistically significant reductions with propranolol vs placebo for total mortality ( 9.8% vs 7.2%, P < 0.005), cardiovascular mortality (8.9% vs 6.6% , P < 0.01), mortality due to arteriosclerotic heart disease (8.5% vs 6.2%, P < 0.01), and sudden death ( 4.6% vs 3.3%, P < 0.05). The drug also had an acceptable safety profile. The results also showed that propranolol has an antiarrhythmic effect which may, at least in part, be responsible for the observed reduction in sudden cardiac death. (8) The positive results of this study led to widespread use of propranolol for a reduction in morbidity and mortality associated with myocardial infarction. (9)
Antiplatelet effects: Besides the effects on hypertension and heart rate, Bonten et al. in a meta-analysis found that betablockers also decreased platelet aggregation significantly which can partly explain their effects in coronary artery disease patients. What is more interesting is that this effect was more pronounced with lipophilic beta antagonists like propranolol. (10)
Hypertension: Propranolol has been extensively used for the management of essential hypertension. Although the exact mechanism of its antihypertensive effect is not known, propranolol is known to work through several mechanisms including peripheral vasodilation, central sympathetic blockage, cardiac output reduction, and renin–angiotensin–aldosterone–sympathetic axis inhibition. (11) Further, the anxiolytic effect of propranolol is also well known. (7) Based on all these factors, presently, propranolol is being considered for the treatment of resistant arterial hypertension.
The versatility of propranolol
Due to non-selective beta-blocking and lipophilic nature of the drug, uses of propranolol extend beyond cardiovascular diseases. It is used as a means of migraine prophylaxis, treatment of restless leg syndrome, essential tremors, and has even been of great success in treating infantile hemangiomas. (12) Thus, any cardiac patient with overlapping symptoms like migraine, essential tremors etc is an appropriate candidate for propranolol therapy.
Conclusion
The multifaceted beneficial profile of propranolol makes it a relevant and highly efficacious option for the management of cardiovascular disorders even in today's age, especially so when co-existing psychiatric disorders like anxiety exist in almost a third of such patients. (5) Added to this is its low cost and wide availability that makes it an attractive option for clinicians. This review serves to summarise important clinical scenarios where therapy with propranolol will be of utmost benefit to cardiac patients.
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