Brain Penetrant Calcium Channel Blockers Were Not Associated With Reduced Alcohol Consumption: Converging Results From Two Large Independent Cohort Studies Using Electronic Health Records.
Christopher T Rentsch, Vanessa A Palzes, Mingjian Shi, Michael R Setzer, Samantha G Malone, Andrea H Kline-Simon, Emma L Winterlind, Lorenzo Leggio, Vincent Lo Re, David A Fiellin, John Tazare, Mehdi Farokhnia, Stacy Sterling, Henry R Kranzler, Joshua C Gray
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Abstract
Purpose: Alcohol use disorder (AUD) remains a major public health problem, with few effective treatments. L-type calcium channel blockers (LTCCBs) have genetic and preclinical support as potential treatments for AUD.
Methods: We evaluated whether brain penetrant (BP)-LTCCBs are associated with reduced alcohol consumption in two preregistered observational cohort studies using electronic health records from the US Department of Veterans Affairs (VA) and Kaiser Permanente Northern California (KPNC). New users of BP-LTCCBs (nifedipine or felodipine) were compared with new users of a non-BP-LTCCB (amlodipine) and with unexposed patients from the same clinics, requiring a 180-day washout and ≥ 60 days' supply. Propensity score matching was performed across all exposure contrasts. The primary outcome was change in drinks per week from pre-index to end of follow-up using difference-in-differences (DiD) models, with prespecified subgroup analyses by AUD diagnosis, drinking level, and sex.
Results: Across both health systems, BP-LTCCB initiation was not associated with greater reductions in drinks per week than either comparator, with broadly consistent findings across all subgroups; though some subgroups were small and imprecise. In the VA, the DiD comparing BP-LTCCB with non-BP-LTCCB was 0.14 drinks/week (95% CI -0.06, 0.34), and versus unexposed was 0.00 (95% CI -0.18, 0.19). Similar results were observed in KPNC (BP-LTCCB vs. non-BP-LTCCB: 0.31, 95% CI -0.48, 1.11; BP-LTCCB vs. unexposed: 0.16, 95% CI -0.67, 0.99).
Conclusions: In two large, preregistered EHR-based cohorts, we found no evidence that BP-LTCCBs were associated with reduced drinking relative to comparators. Despite compelling genetic and preclinical evidence, these findings do not support repurposing BP-LTCCBs for AUD and instead prioritize alternative pharmacologic targets.
期刊介绍：
The aim of Pharmacoepidemiology and Drug Safety is to provide an international forum for the communication and evaluation of data, methods and opinion in the discipline of pharmacoepidemiology. The Journal publishes peer-reviewed reports of original research, invited reviews and a variety of guest editorials and commentaries embracing scientific, medical, statistical, legal and economic aspects of pharmacoepidemiology and post-marketing surveillance of drug safety. Appropriate material in these categories may also be considered for publication as a Brief Report.
Particular areas of interest include:
design, analysis, results, and interpretation of studies looking at the benefit or safety of specific pharmaceuticals, biologics, or medical devices, including studies in pharmacovigilance, postmarketing surveillance, pharmacoeconomics, patient safety, molecular pharmacoepidemiology, or any other study within the broad field of pharmacoepidemiology;
comparative effectiveness research relating to pharmaceuticals, biologics, and medical devices. Comparative effectiveness research is the generation and synthesis of evidence that compares the benefits and harms of alternative methods to prevent, diagnose, treat, and monitor a clinical condition, as these methods are truly used in the real world;
methodologic contributions of relevance to pharmacoepidemiology, whether original contributions, reviews of existing methods, or tutorials for how to apply the methods of pharmacoepidemiology;
assessments of harm versus benefit in drug therapy;
patterns of drug utilization;
relationships between pharmacoepidemiology and the formulation and interpretation of regulatory guidelines;
evaluations of risk management plans and programmes relating to pharmaceuticals, biologics and medical devices.
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