Cocaine and Beta Blockers: All It’s Cracked Up to Be?

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Author: Brent N. Reed, PharmD, BCPS-AQ Cardiology, FAHA

Note: The use of beta blockers in the setting of cocaine abuse is one of the most controversial topics in cardiovascular medicine. The following are my perspectives based on the available evidence, and refer to their use for compelling indications (e.g., myocardial infarction, heart failure, etc.), not in the acute management of cocaine toxicity.

Beta blockers remain a cornerstone in the management of several cardiovascular disorders, including myocardial infarction (MI) and heart failure – two conditions where they have been associated with improvements in survival as well as a myriad of other clinical outcomes (1, 2). However, because of the theoretical risks attributed to their use in the setting of cocaine abuse, many clinicians are reluctant to administer them despite these well-established benefits.

The pharmacologic basis for these fears is unopposed alpha-mediated effects – that is, that beta blockers occupy post-synaptic beta receptors and shunt excitatory neurotransmitters (present in excess concentrations as a result of cocaine-inhibited reuptake) toward alpha receptors, resulting in vasoconstriction. While this is certainly a plausible mechanism for myocardial injury, more recent research has indicated that cocaine-induced cardiotoxicity is complex, involving pro-thrombotic effects, progressive atherosclerosis, and ventricular remodeling (3) – all scenarios where beta blockers may actually be helpful. Furthermore, beta blockers are not associated with worsening outcomes in other hyperadrenergic states (e.g. heart failure, acute coronary syndromes), so why in the setting of cocaine abuse?

While the risk of using beta blockers in the setting of cocaine abuse is often discussed, data to support a clinically meaningful interaction is slim at best. The pharmacologic mechanism mentioned above was first hypothesized from a single case report in 1985 involving a patient with cocaine toxicity who experienced a mild increase in blood pressure and decrease in heart rate after being treated with propranolol (4). Much of the remaining evidence has been derived from experimental or animal models. Evidence of cocaine-provoked vasospasm was thought to be observed in early cardiac catheterization studies but has since been challenged by more recent investigations, including some that have involved direct administration of cocaine (5). Even when vasospasm has been observed, it has not been associated with defects in coronary perfusion. In fact, in a case series of patients with MI in the setting of cocaine use, the vast majority of patients had clear evidence of thrombosis during percutaneous coronary intervention, indicating that the pro-thrombotic effects of cocaine may have been the underlying etiology (6).

The limited evidence to support an interaction between cocaine and beta blockers often involves propranolol, a non-selective beta blocker that is used only rarely in contemporary clinical practice. Carvedilol and labetalol, two beta blockers with concomitant alpha-blocking activity, have been proposed as a reasonable alternative in patients who continue to use cocaine, as they would provide similar clinical benefits while moderating the theoretical alpha-mediated effects of cocaine. In fact, patients receiving labetalol in the setting of cocaine use experienced improvements in blood pressure without evidence of coronary vasoconstriction (7). Additionally, in a small prospective trial comparing labetalol to calcium channel blockers among patients presenting with an acute coronary syndrome in the setting of active cocaine use, administration of labetalol was associated with favorable changes in hemodynamics and inflammatory mediators without increasing the incidence of adverse cardiovascular events (8).

Two retrospective studies of patients presenting to the emergency department have also cast doubt on the risk attributed to beta blockers in the setting of cocaine abuse (9, 10). In one trial, use of beta blockers was associated with a reduction in MI; in patients for whom the admission was their first event, a reduction in in-hospital mortality was also observed with beta blocker use (9). In another trial, beta blockers were not associated with increased mortality among patients presenting with chest pain following cocaine abuse; in fact, after adjustment for potential confounders, beta blocker use was associated with a reduction in cardiovascular death (10). Obviously, these retrospective analyses are not without limitations, including notable differences in baseline characteristics, use of urine toxicology data as evidence of cocaine abuse, and inability to assess interim behaviors following hospital discharge. While conclusions cannot be made based on these results alone, I do think it is enough to call into question a concept that has become a widely held notion in cardiovascular medicine (despite having only minimal evidence to support its existence).

So what should clinicians do with this seemingly discordant information? As is often the case in clinical practice, one should probably consider the potential risk versus benefit in an individual patient. Although the studies to date are helpful in clarifying the role of beta blockers in this setting, I am not sure enough evidence exists to support their indiscriminate use in cocaine-induced myocardial injury. For young, otherwise healthy patients, it is unlikely that beta blockers will provide much benefit (although I remain doubtful that there is an increased risk associated with their use). However, beta blockers should be considered in those patients who are at high risk for coronary artery disease or MI, given the complex cardiotoxicity of cocaine and the potential for benefit in these conditions. In fact, in the studies mentioned above, the patients who seemed to benefit most were those who were at increased risk for cardiovascular events, either by having established ischemic heart disease at baseline or multiple cardiovascular risk factors (e.g., advanced age, hypertension). I think similar arguments can be made for patients with heart failure.

I recognize that some may remain reluctant to use beta blockers in the setting of cocaine abuse as a result of professional liability concerns. However, a certain degree of personal responsibility should also be expected of the patient. As health care professionals, we should make available to patients the tools necessary to improve their condition, whether it be in the form of education (including substance abuse counseling and/or therapies, if indicated), therapeutic lifestyle changes, invasive procedures, or medications. However, whether a patient chooses to use these tools – or similarly, avoid those activities that might put them at risk – that is ultimately up to them.