Cannabis use and acute coronary syndrome

Abstract Introduction: Cannabis smoking can result in elevation of heart rate and blood pressure immediately after use, possibly from sympathetic nervous system stimulation and parasympathetic nervous system inhibition. Vascular inflammation, platelet activation, and carboxyhemoglobin generation have also been proposed as potential side effects of cannabis smoking. As such, an association between cannabis use and acute coronary syndrome has been postulated. Objective: The objective of our study was to analyze systematically the medical literature pertaining to this putative association. Methods: PubMed, Google Scholar, and OpenGrey were queried using a unique search string. All human trials, case series, or case reports of cannabis use and acute coronary syndrome in any language were considered in the literature search. The definition of acute coronary syndrome represented a penumbra that included chest pain, angina pectoris, unstable angina, myocardial infarction, myocardial ischemia, and cardiac arrest. Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) guidelines were followed. Our final search strategy included free-text words (TW): (“cannabis”[TW] OR "marijuana"[TW]) AND ("acute coronary syndrome"[TW] OR “myocardial” OR “ischemia”[TW] OR “infarction”[TW] OR “chest pain”[TW] OR “cardiac arrest”[TW] OR “angina”[TW]). To remain consistent over a span of five decades, we specifically did not include any publications with non-phytogenic, non-smoked cannabis as the sole etiology, as these are relatively recent and may possess additional pharmacologic characteristics compared to phytogenic cannabinoids. Therefore, for the purpose of this review, the term “cannabis” refers to the smoked phytogenic form. The search resulted in 325 articles. References in each selected publication were carefully hand-searched for any additional reports having relevance, and a total of 12 publications were identified in this manner. Following comparison and discussion amongst the co-authors, duplicate and non-relevant publications were removed, and a total of 85 publications involving 541,518 human subjects were selected for inclusion. Results were synthesized and reviewed by the authors for relevance. Clinical trials, observational studies, retrospective studies, case series, and case reports were graded using Oxford Centre for Evidence-based Medicine guidelines. Results: There were no Level I randomized blinded controlled studies specifically addressing the cannabis/acute coronary syndrome association. However, there were five Level I systematic reviews, 14 Level II studies with 83,961 subjects, and 14 Level III studies with 457,495 subjects. Conclusions from 28 of these 33 studies highlighted an increased risk of both acute coronary syndrome and chronic cardiovascular disease from cannabis use. The systematic reviews were wide-ranging in topic and scale, and none specifically focused on the association between cannabis use and acute coronary syndrome. The dissenting studies included two systematic reviews, one concluding there was limited and weak evidence for association of cardiovascular disease and acute coronary syndromes with cannabis use, and another citing the evidence was inconclusive. The other dissenting articles were two longitudinal prospective studies and a retrospective review concluding cannabis users had lower post-myocardial infarction mortality. There were 51 case series (Level IV) and case reports (Level V) with 62 subjects. Six cases were female (10%). Average age was 31 ± 12 years, reported maximum heart rate was 88 ± 21 bpm, systolic blood pressure was 125 ± 32 mmHg, and diastolic blood pressure was 80 ± 17 mmHg. ST-segment elevation was documented on 37 (60%) electrocardiograms, and the most common angiographic finding was left anterior descending coronary arterial occlusion and/or stenosis in 22 (35%) patients. Concomitant cardiomyopathy was described in 21 (34%) cases. There were 14 (23%) deaths attributed to acute coronary syndrome associated with cannabis use. Conclusion: There were five Level I systematic reviews, 14 Level II studies with 83,961 subjects, and 14 Level III studies with 457,495 subjects. All but five Level I–III publications highlighted an increased risk of both acute coronary syndrome and chronic cardiovascular disease associated with cannabis use.