Unopposed alpha-1 constriction: a critical review of beta blocker use in cocaine-associated cardiovascular events

CONTEXT: Cocaine-associated cardiovascular events pose significant challenges in primary care settings, where outpatient physicians often serve as the first point of contact for patients with both acute and chronic cardiovascular complications. Current guidelines discourage the use of beta blockers in cocaine-related acute coronary syndrome (ACS) due to concerns of unopposed alpha-1 constriction, but emerging evidence questions the validity of this caution. Primary care physicians frequently manage patients with heart failure and comorbid substance use disorders, highlighting the need for clarity on beta blocker safety and efficacy in this population. OBJECTIVES: This review aimed to systematically evaluate the evidence of unopposed alpha stimulation when prescribing beta blockers in people who utilize cocaine, as well as the safety and efficacy of beta blockers in managing heart failure in this population. METHODS: PubMed was searched from April 1968 through August 2024 utilizing the search terms "cocaine", "beta blocker", and several commonly prescribed beta blockers. The screening process was performed by two authors (CKG and JJ), with discrepancies resolved by a third reviewer (CY). The inclusion criteria encompassed original human studies examining the outcomes of patients utilizing cocaine who were treated with beta blockers. The exclusion criteria consisted of studies lacking beta blocker intervention and articles not written in English. The extracted data from each article included the study type, purpose, design, time period, data source, sample size, follow-up duration, clinical intervention, outcomes, and mortality. Critical appraisal skills programme (CASP) checklists for bias analysis were completed for each non-case study article. Different artificial intelligence (AI) bots (Gemini, Microsoft CoPilot, and ChatGPT) were utilized in helping with the completion of the checklists with comparison across the three different platforms and then cross-referenced with the article text itself. The reviewers completed the final risk-of-bias determination without the use of AI. RESULTS: The search identified 156 articles, with two duplicates being removed. The remaining 154 articles were screened for relevance, and 116 were excluded based on the inclusion and exclusion criteria outlined in the methods. Of the 38 potentially relevant articles, full-text review led to the exclusion of 12 articles, which ultimately led to 26 articles being included in this review. CONCLUSIONS: Current evidence suggests that the risk of unopposed alpha-1 constriction with beta blockers in cocaine-associated cardiovascular events may be overstated. Mixed alpha/beta blockers and beta-1 selective agents were associated with favorable hemodynamic control with minimal reported adverse events. For outpatient physicians, these findings support a more nuanced approach to beta blocker use in patients with a history of cocaine use, emphasizing the need for further randomized controlled trials to refine guidelines and optimize patient care in primary care settings.