“Routine screening for drug use should be considered in cardiology intensive care units”

LONDON ^_ Patients admitted to a Cardiac Intensive Care Unit (CICU) with a recent history of recreational drug use (cannabis, opioids, cocaine, amphetamines, 3,4-methylenedioxymethamphetamine [MDMA]) have a three times higher risk of having a new serious cardiac event in the year following a first accident, according to new French research presented at the ESC 2024 congress^[1] in London.

The Dr Raphaël Mirailles (Lariboisière hospital, Paris), first author of the study, sheds light on these results Medscape French edition.

Medscape French edition: Why this study?

Dr Raphaël Mirailles: This study was born in 2021 with a first project which was led by Dr Théo Pezel faced with the increase in recreational drug use around the world, particularly in the United States with the opioid crisis.

In addition, we had numerous data on overdose and the risk of mortality, particularly respiratory with opioids, but less data available on the cardiovascular prognosis of patients.

However, in cardiology, we still have experience of a fairly large number of heart attacks linked to the use of cannabis or cocaine in fairly young subjects.

In many Parisian SICUs, we welcome patients under the age of 40 who have genuine heart attacks, sometimes with fairly severe lesions linked to drug use in patients who have no other factors. risk apart from smoking.

Until then, several works had been carried out but often retrospective with declarative data.

The objective was to have a more precise idea of ​​the reality among patients admitted to the CICU, to have an inventory of drug use.

With our new study, the objective was to then see if one year after a cardiovascular event, patients retained an increased risk compared to others.

The incidence of acute coronary syndromes was 1.3% among non-users and 5.1% among drug users.

What was the study methodology?

Dr Raphaël Mirailles: In this study, all patients admitted to cardiology intensive care units for two weeks in April 2021 in 39 centers in France were included. Screening for recreational drug use was carried out by systematic urine tests. One-year follow-up consisted of a clinical visit or direct contact with the patient and the referring cardiologist. The primary composite outcome was the occurrence of a serious cardiac event, whether cardiovascular death, nonfatal myocardial infarction, or stroke. A subgroup analysis was performed in patients initially hospitalized for acute coronary syndrome (non-fatal heart attack/angina lasting more than 20 minutes).

In terms of drugs consumed, what have you observed?

Dr Raphaël Mirailles: Of the 1499 patients screened, 93% had a complete one-year follow-up. Among them, 11% had a first positive test for recreational drug use (cannabis, opioids, cocaine, amphetamines, 3,4-methylenedioxymethamphetamine [MDMA]).

The most widely used drug, by far, was cannabis. 10% of patients who were admitted tested positive for cannabis, followed by opioids (2.3%), cocaine (1.7%); amphetamines (0.6%), and MDMA (active ingredient in ecstasy, 0.6%). More than a quarter of patients (28.7%) tested positive for at least two of these drugs.

Among the drugs tested, the risk of serious CV events increased 4.1-fold for MDMA, 3.6-fold for heroin and other opioids, and 1.8-fold for cannabis.

What are the main results on the cardiovascular level?

Dr Raphaël Mirailles: Over one year of follow-up, the incidence of cardiovascular events was 13% in patients whose test was positive versus 6% in non-drug users. After adjusting for different confounding factors, recreational drug use was independently associated with a three-fold increased risk of serious cardiovascular events.

Specifically, among the 1,392 patients examined, the incidence of cardiovascular death was 4.5% among non-users compared to 5.7% among recreational drug users. That of acute coronary syndromes was 1.3% among non-users and 5.1% among drug users. And that of strokes was 0.6% among non-users and 1.9% among drug users.

Among the recreational drugs tested, the risk of serious cardiovascular events was increased 4.1-fold for MDMA, 3.6-fold for heroin and other opioids, and 1.8-fold for cannabis. Other types of drugs did not have a statistically significant relationship with serious cardiovascular events.

We observed an 11% prevalence of drug use among patients who are admitted to the NICU, which is quite astonishing.

Does your study have any limitations?

Dr Raphaël Mirailles: It should be remembered that this is an observational study but the data were adjusted for several factors, including age, sex, diabetes, smoking, history of cardiovascular disease before hospitalization, known chronic kidney disease, history of cancer, primary diagnosis at admission, baseline systolic blood pressure, and baseline heart rate.

What is striking is that usually when we adjust for usual prognostic factors, we lose the power of the effect. However, in our study, it is the opposite. After this adjustment, recreational drug use was independently associated with a three-fold increased risk of serious cardiovascular events versus an excess risk of 2.5 before adjustment. This is because the patients are much younger. They do not have other risk factors, dyslipidemia or hypertension, for example.

From a more general point of view, we know that there is always a psychosocial effect associated with taking drugs and it is always difficult to distinguish between a real cardiovascular effect and the social component because drug users are often less well followed. They have more difficult access to care.

We were also quite surprised to see that opioids were clearly associated with cardiovascular events.

Were you surprised by your results?

Dr Raphaël Mirailles: The results are quite astonishing. We observed an 11% prevalence of drug use among patients admitted to the NICU, which is something that we did not necessarily expect. Also, about a year after a cardiovascular event, we were quite surprised to see that there was still a much higher percentage of events in these patients with drug use.

We were also quite surprised to see that opioids were clearly associated with cardiovascular events. Cocaine and cannabis are well known as risk factors for myocardial infarction. But the association between CV events and opioids is less known apart from the association between heroin and infective endocarditis.

What could be the underlying mechanisms?

Dr Raphaël Mirailles: For cannabis, there is a well-described effect on platelet activation and therefore the development of atherosclerotic plaques and the occurrence of type 1 infarctions. For cocaine, there are 2 mechanisms. A fairly acute mechanism, with a capacity to promote the rupture of plaques. There may be a vasospasm in which the smooth muscle cells on the coronary arteries contract in patients who are often also smokers. Moreover, the AHA has developed recommendations for the management of chest pain in patients who use cocaine. This is a real public health problem in the United States.

At the same time, there is a more chronic effect. Autopsy data in patients who died of a heart attack at a relatively young age and who had reported cocaine use during their life show atherosclerotic plaques.

So there is probably also a pro-atheromatous effect of cocaine use, an effect on platelet activation.

For opioids, it is much less well described. Some speak of interactions with antiplatelet agents, which could be an explanation in our study given that these are patients who have already had a cardiovascular event. Half of the patients had suffered heart attacks.

Finally, there are notions of hormonal changes which also moderately promote atherosclerosis. But these are only hypotheses, avenues for reflection.

We really need to ask ourselves the question of monitoring patients who take therapeutic cannabis, particularly on the cardiovascular level.

Is there enough information and prevention on the somatic effects of cannabis, cocaine, and opioids?

Dr Raphaël Mirailles: There are currently two debates, a first debate on legalization, which is a public health problem. The fact of legalization can promote a safer, less dangerous approach in terms of infection or even violence.

Otherwise, there is another debate on the medicinal virtues, in particular of cannabis for analgesic purposes. However, this debate is focused on medicinal properties or addiction but it completely overlooks the increased cardiovascular risk.

We really need to ask ourselves the question of monitoring patients who take therapeutic cannabis, particularly on the cardiovascular level. Danish observational data have shown an increased risk of AF in patients consuming therapeutic cannabis for analgesic purposes.

We need to do prevention with patients and tell them: “you are 30 years old, you have no cardiovascular risk factors and you may be affected if you use drugs frequently.”

Routine screening for drug use should be considered in cardiac intensive care units.

What should be done in practice?

Dr Raphaël Mirailles: Despite the underreporting of recreational drug use, systematic screening is not recommended by current recommendations. However, it could improve patient risk stratification and personalized care to promote drug withdrawal. Therefore, routine screening for drug use should be considered in cardiology intensive care units.

Are there other newer drugs that worry you?

Dr Raphaël Mirailles: Yes, the recent explosion in the use of synthetic cannabinoids. These synthetic cannabinoids have a much higher concentration of THC than that present in the cannabis plant. The risk of overdose is therefore very high. Young people are admitted to intensive care units just after using these drugs for consciousness disorders, respiratory disorders and sometimes ventricular rhythm disorders. We do not yet have any perspective on the chronic effects of this use, but the high concentration of THC is not reassuring. The danger is that these drugs are developed in chemical laboratories, there is no need for large, more easily detectable cultures. They are easily accessible online on the internet.