A Systematic Review and Meta-analysis of Randomized Controlled Trials of Cardiovascular Toxicity of Medical Cannabinoids

Abstract Aim The objective of this study was to evaluate the cardiovascular toxicity associated with medical use of cannabinoids. Methods A two-stage systematic review (SR) approach was undertaken to assess current evidence on cannabinoid-associated cardiovascular events reported among randomized controlled trials (RCT). First, we searched for SRs in multiple sources until June 2019. Second, RCTs identified from SRs were included if they assessed medical cannabis and reported cardiovascular events. The outcomes of interest were all types of cardiovascular events. Data were extracted by two independent reviewers. Study quality was assessed using the Cochrane risk of bias. A statistical test of heterogeneity was performed. The summary risk ratios and 95% Confidence Intervals (CIs) were calculated using a random-effects model. Results A total of 47 studies involving 2,800 patients were included. The median duration of cannabinoid use was 15.8 days (range 1 to 322) and 45% of studies excluded patients with underlying cardiovascular diseases. Cannabinoid use was significantly associated with increased risks of orthostatic hypotension (RR 3.16; 95% CI 2.27 – 4.40; I2 = 2.3%), and hypotension (RR 3.55; 95% CI 1.45 – 8.71; I2 = 31.8%) with a trend of increased risk of tachycardia (RR 1.94; 95% CI 0.81 – 4.64; I2 = 48.6%). No study reported serious cardiovascular events. Conclusions Cannabinoid use was associated with tachycardia, hypotension, and orthostatic hypotension. There is a paucity of data for other cardiovascular events among medical cannabis users. More data especially long-term effects among patients with existing cardiovascular diseases are needed.