Ilan Matok,Rotenberg Yakir  MD, Palliative team, Hadassah – Hebrew University, Medical center, Jerusalem, Israel,Elyad Davidson, Anesthesiology and Pain

Background and aim: Anthracyclines are cornerstone of contemporary chemotherapeutic regimens for a variety of solid tumors and hematological malignancies cancers. However, one of the major side effect of Anthracyclines use is a significant dose-dependent irreversible cardiotoxicity. The prediction of long-term cardiovascular prognosis is frequently challenging because patients with cancer typically receive multiple cardiotoxic drugs, with the potential for synergistic cardiotoxic effects.

Medical cannabis is wildly used among cancer patients. The two major components in terms of relative concentration and pharmacological knowledge about their effects are THC -tetrahydrocannabinol-9-Δ and CBD- Cannabidiol. One of most controversial safety concerns regarding the use of cannabis is its association with cardiotoxicity and the correlation between THC/CBD ratio and cardiovascular outcomes. There is a lack of knowledge about the benefits and risks of medical cannabis use particularly in patients that are administered anthracycline.

Study objectives: To study the cardiovascular effect of cannabis consumption in patients treated with an anthracyclines including change in left ventricular [LV] ejection fraction and arrhythmia. We will also assess the differences between cannabis composition (THC / CBD ratio) and cardiovascular outcomes.

Methods:  The study will contain two phases: retrospective study and a prospective cohort study. In the retrospective study data on cannabis license will be extracted from the Israeli Medical Cannabis Agency (Yaqar). This database will be linked with data extracted from computerized records of the Hadassah medical center (HMC) and the Israeli Ministry of health registry, documenting cardiac events. We will compare patients with the combined treatment of anthracycline and medical cannabis vs. anthracycline alone users from 08.2013. The patients will be followed until diagnosis of a cardiac disease, death or until September 31, 2020.

Exclusion criteria: Patients with less than six months of follow-up in the HMC, patients who had previously, before administration of anthracycline, a medical cannabis license, and patients age<18 years old will be excluded as well.

In a prospective cohort, oncology patients who will start a new treatment with anthracycline in HMC will be recruited. These patients will be followed until diagnosis of cardiotoxicity after cohort entry, death, or until the end of the study after 2 years of follow up, we will compare patients with the combined treatment of anthracycline and medical cannabis vs. anthracycline alone users. Cox proportional hazard ratios with time-varying analysis will be constructed to estimate the hazard ratios of medical cannabis exposure to cardiotoxicity. Our analysis will control for potential confounders, such as gender, age, comorbidities, tobacco use, consumption of alcohol and drugs, and concomitant cardiotoxic drugs.

Importance to Medicine: Since no data is available on the association between the combined use of medical cannabis and anthracycline and the risk for cardiotoxicity, This study will give important tool about the meticulous interaction between antracyclines, cannabis subtypes and cardiotoxicity.

Capabilities for Scientific Collaborations and Services: performance of meta-analysis, meta regression and bid-data analysis