Carvedilol Likely Safe for Heart Failure With Cocaine Use Disorder

By Marilynn Larkin

September 03, 2019

NEW YORK (Reuters Health) - Carvedilol is likely safe for heart failure (HF) patients with a cocaine use disorder and may be effective for those with a reduced ejection fraction, a single-center retrospective study suggests.

"The use of beta-blockers is strongly recommended among patients with HF with a depressed left ventricular function/ejection fraction (EF)," Dr. Raza Alvi of Massachusetts General Hospital in Boston told Reuters Health by email. "However, current HF guidelines, citing a lack of data, note that the safety and efficacy of beta-blockers among individuals with recent or active cocaine use is unclear."

"Our aim was to address this knowledge gap," he said. "Our data suggested that prescribing carvedilol to individuals with HF with a cocaine use disorder did not result in worse outcomes compared to those not on carvedilol and may be associated with a lower rate of adverse cardiovascular events among those with a reduced EF."

Dr. Alvi and colleagues analyzed data from health records of patients hospitalized with HF in a medical center in New York City. Cocaine use was self-reported or by positive urine toxicology. Patients were divided by carvedilol prescription, and subgroup analyses were performed by EF strata (40%, 41% to 49%, or 50% or less). Major adverse cardiovascular events (MACE) were cardiovascular mortality and 30-day HF readmission.

As reported online in JACC Heart Failure, 2,578 patients hospitalized with HF in 2011 were included in the analysis. Mean age was about 60; about half were women; 40% were African American; 39%, Hispanic; and 20%, other ethnicities.

Among them, 503 patients were identified as also having a cocaine use disorder, of whom 404 (80%) were prescribed carvedilol. Patients who did or did not get carvedilol had similar characteristics; however, the carvedilol group had a lower LVEF, heart rate, and N-terminal pro-B-type natriuretic peptide concentrations at admission and on discharge, as well as more coronary artery disease.

Over a median follow-up of 19 months, 169 MACEs occurred. MACE rates were similar between the carvedilol and the non-carvedilol groups (32% vs. 38%, respectively) and between those with a preserved EF in both groups (30% vs. 33%).

However, MACE rates were lower in patients with a reduced EF who were taking carvedilol versus those who were not (34% vs. 58%).

In a multivariate model, carvedilol therapy was associated with lower MACE among patients with HF with a cocaine use disorder (hazard ratio: 0.67).

Further research is needed to confirm the benefits of carvedilol and replicate the results prospectively, he added, "as well as to find out if these findings hold true for other psycho-stimulants and other beta blockers besides carvedilol."

Dr. Robert Page of the University of Colorado in Aurora, coauthor of a related editorial, commented by email, "Even at low doses, cocaine acts not only as a potent sympathomimetic by directly stimulating central sympathetic outflow, but also as a presynaptic reuptake inhibitor of norepinephrine and dopamine."

"Thus, the use of an evidenced-based, second-generation beta-1 selective beta-blocker such as metoprolol succinate or bisoprolol could lead to coronary artery vasoconstriction and hypertension exacerbation as catecholamines are shunted to the alpha-adrenergic receptor," he told Reuters Health.

"Based on this assumption," he said, "providers have typically chosen carvedilol, a third-generation alpha and beta-blocker, even though limited to no data exist."

This study is important, he noted. "First, these data provide reassurance to providers that carvedilol can be safely used in patients with HF and cocaine use disorder - a fact that we have always known based on the pathophysiology of cocaine use disorder and the pharmacology of carvedilol, but we did not have the data to officially back up this recommendation."

"Additionally, the advantages of carvedilol lie in its lipophilic nature and ability to cross the blood brain barrier," he said. "Thus, it may attenuate the behavioral and psychological response to cocaine."

"Second, compared to other non-evidenced third generation beta-blockers, carvedilol is much cheaper," he said.

"Theoretically, these data suggest that carvedilol could also be safe in patients with HF and concomitant opiate and/or psycho-stimulants withdrawal syndrome, as the pathophysiology is similar to cocaine use disorder," he added. "However, limited to no data exist in this population and larger studies are needed to fully answer this specific question."


JACC Heart Failure 2019.