Marijuana Ups Bleeding, CVA Risks in PCI Patients: Registry Data

Marijuana use may impact PCI outcomes, according to data from a Michigan-based registry. While the study showed increases in both bleeding and cerebrovascular accident (CVA) rates, there also was a small but significant decrease in acute kidney injury (AKI).

As more and more US states are legalizing marijuana for recreational and medicinal use, its cardiovascular impact is a clinically relevant issue, lead author Sang Gune K. Yoo, MD (University of Michigan, Ann Arbor), and colleagues write in JACC: Cardiovascular Interventions.

“The thing that surprised me most about this space is how little we still know,” Devraj Sukul, MD (University of Michigan), the study’s senior author, told TCTMD. “There are probably benefits and there are probably harms, and it’s up to us to figure it out.” Cardiologists should be up front about this uncertainty when speaking with their patients, he advised. “And frankly, as with any observational work, my own included, I think we need further research to corroborate these findings.”

Marijuana activates the cannabinoid receptors, which are expressed on multiple organs, including hematologic, vascular, and myocardial tissues, and this activation has been linked to atherosclerosis and to the precipitation of ACS, the researchers explain in their paper. Marijuana has also been shown to cause endothelial injury and modulate the immune system and platelet function.

Then there’s the potential for drug-drug interactions, an accompanying editorial points out, since “cannabis may interfere with many of the metabolic pathways of antithrombotic agents used in patients to treat cardiovascular disease.” Among them are warfarin, direct oral anticoagulants, and clopidogrel.

Yet, as noted by a 2020 American Heart Association (AHA) scientific statement, less is known about marijuana’s effects on CV outcomes. The document concludes that, if anything, there appear to be substantial risks and no benefit from cannabis use. For instance, one study has suggested it’s linked to periprocedural MI after elective surgery, while others found no rise in arrhythmias post-MI. The overall picture remains cloudy.

Sukul hopes their work will inspire further basic science and clinical research, something that has been hindered thus far by cannabis still being classified by the US Drug Enforcement Administration as a Schedule I controlled substance. “As supported by the recent AHA statement, we need more research to understand the effects of marijuana use so that we can more appropriately counsel our patients,” he said, adding, “With every incremental study, we’ll hopefully get more to the truth of these associations.”

BMC2 PCI Registry

Yoo et al pulled data from the Blue Cross Blue Shield of Michigan Cardiovascular Consortium (BMC2) PCI registry for the years 2013 through 2016. Marijuana use was reported by 3,970 patients in the 113,477-person data set. The marijuana group tended to be younger (mean 53.9 vs 65.8 years), have fewer cardiovascular comorbidities, and be more likely to use tobacco (73.0% vs 26.8%) and present with STEMI (27.3% vs 15.9%).

Among 3,803 propensity-matched pairs, self-described marijuana users were more likely to experience bleeding and CVA, especially hemorrhagic stroke, but less apt to develop AKI. The heightened bleeding risk was seen both at the access site and elsewhere. There were no differences seen for transfusion, death, hemodynamically significant arrhythmias, or stent thrombosis.

Risk by Marijuana Use: Propensity-Matched Analysis

“It is important to note that the confidence intervals around the higher risk of CVA were very large due to the very small absolute number of events, as post-PCI CVA is a relatively rare complication,” Sukul said. “The finding of a lower risk of post-PCI AKI was an interesting and surprising finding.” He pointed out that marijuana’s influence here may vary by the method and timing of intake as well as the amount used.

Mamas A. Mamas, BMBCh, DPhil (Keele University/Royal Stoke University Hospital, Stoke-on-Trent, England), and Pablo Lamelas, MD (Instituto Cardiovascular de Buenos Aires, Argentina, and McMaster University, Hamilton, Canada), writing in the editorial, draw attention to these details.

For the current analysis, “marijuana use was determined from the patient’s medical record at the time of PCI and was defined as the use of marijuana at any time within 1 month prior to index PCI,” they note. With patients not specifically asked the question, “this is likely to have resulted in underestimation of marijuana use in this cohort, particularly given that the study period was prior to the legalization of marijuana for recreational use in Michigan (which occurred in 2018).”

Also making interpretation difficult, the researchers observe, is that marijuana use might also be a proxy for nontraditional cardiac risk factors, such as insurance status, race, and barriers to substance abuse treatment. “Of note, we were unable to account for differential environmental stressors such as structural racism, discrimination, and disparities in socioeconomic status and geography. Furthermore, there are likely unmeasured or unmeasurable cardiac risk factors associated with patients’ social experience that may affect outcomes,” the investigators acknowledge.

‘Frank Conversations’ Needed

Even with the knowledge gaps, it’s time for cardiologists to be cognizant of cannabis, said Sukul, and their data open the door by offering a real-world picture. “First, we should ask our patients about marijuana use and record it in the medical record just as we do for tobacco, alcohol, and other medication/drug use. Next, we should have frank conversations with our patients about what is and isn’t known about the health effects of marijuana or cannabis use,” he advised.

Mamas and Lamelas agree that these are conversations worth having and suggest concrete steps to deal with the risks.

“Given the potential effects on the coagulation cascade, platelet biology, and drug metabolism, physicians should record the history of marijuana use as they would smoking history and advise patients regarding potential risks, particularly in the context of treatment with antithrombotic regimens,” they write. Not only is there increased vulnerability to bleeding, there also could be more ischemic events, the editorialists note. “Bleeding avoidance strategies such as the radial-first approach should be adopted, and antithrombotic regimes (both type and duration) should be personalized at the individual patient level taking into consideration their overall balance of ischemic and bleeding risk and whether patients are likely to adhere to therapies.”