INTRODUCTION — Cocaine is among the most commonly used illicit recreational drugs worldwide. Because even casual use of cocaine may be associated with acute or chronic cardiovascular toxicity, the large numbers of exposed individuals may present with sequelae related to the cardiovascular system. Thus, the cardiovascular history should include questions about cocaine use, specifically focusing on symptoms associated with ischemic heart disease.
Cocaine use is more frequently associated with acute rather than chronic cardiovascular illness. Among cocaine users who present to emergency departments, cardiovascular complaints, particularly chest pain, are common [1,2]. In such patients, acute coronary syndromes (including myocardial ischemia and infarction), aortic dissection and rupture, arrhythmias, myocarditis, and vasculitis need to be considered .
The cardiovascular effects and complications of cocaine use, as well as the management of cocaine-associated ischemia, will be reviewed here. Other issues relating to cocaine use, including the general approach to patients with chest pain and a history of cocaine use, are discussed elsewhere. (See "Cocaine use disorder: Epidemiology, clinical features, and diagnosis" and "Cocaine: Acute intoxication".)
CARDIOVASCULAR PHYSIOLOGIC EFFECTS OF COCAINE — The major cardiovascular effects of cocaine appear to be caused by the inhibition of norepinephrine reuptake into the synaptic cleft by sympathetic neurons, although sodium channel blockade and stimulation of excitatory amino acids likely also contribute to the effects . Since reuptake is the major mechanism by which neurotransmitters are removed from active receptor sites, this inhibition results in potentiation of the response to sympathetic stimulation of innervated organs and to infused catecholamine. Cocaine may also enhance the release of catecholamines from central and peripheral stores [4,5]. The ensuing sympathomimetic actions (increased myocardial inotropy, heart rate, systemic blood pressure, and coronary artery constriction primarily at the capillary level) are mediated by stimulation of the alpha- and beta-adrenergic receptors and result in increased myocardial oxygen demand and decreased myocardial perfusion. (See "Cocaine: Acute intoxication", section on 'Pathophysiology'.)
Other cardiovascular effects of cocaine include promotion of thrombus formation (via activation of platelets, stimulation of platelet aggregability, and potentiation of thromboxane production) and proarrhythmia [6-8]. The cardiovascular effects produced by intravenous, intranasal, and inhaled cocaine are thought to be similar regardless of the route of ingestion.
EPIDEMIOLOGY — The precise incidence of myocardial ischemia, with or without infarction, following cocaine ingestion is difficult to quantitate. However, it is likely that the number of patients in whom cocaine use is identified as a potential causative factor and who come to medical attention is small relative to the total population of abusers. In some cases, the relationship of the ischemic event to cocaine use is unclear based upon the time of onset of symptoms and the known pharmacokinetics of cocaine and its metabolites . In one retrospective cohort of 2097 patients ≤50 years of age with type 1 acute myocardial infarction (MI) between 2000 and 2016 who were treated at one of two academic hospitals in Boston, cocaine use was identified in 99 patients (4.7 percent) .
The reported incidence of MI in patients with cocaine-associated chest pain ranges between 0.7 and 5.7 percent [11-13]. Cocaine-associated MI is particularly prevalent in younger patients as illustrated by the following observations:
●In a report from the Third National Health and Nutrition Examination Survey (NHANES) of 10,085 adults between the ages of 18 and 45, approximately 25 percent of nonfatal MIs were attributable to frequent cocaine use (frequent defined as 10 or more uses in a lifetime) .
●In another series of almost 4000 patients with acute MI, 38 (1 percent) had used cocaine within the past year . The mean age of cocaine users was significantly lower than that of nonusers (44 versus 61 years). (See "Coronary artery disease and myocardial infarction in young people".)
CLINICAL MANIFESTATIONS — Acute cocaine use is associated with arterial vasoconstriction and enhanced thrombus formation, and causes tachycardia, hypertension, increased myocardial oxygen demand, and increased vascular shearing forces. Acute cocaine use is associated with a number of cardiovascular conditions, including [2,4]:
●Myocardial ischemia or infarction
●Myocarditis and the development of a cardiomyopathy
Chronic cocaine use can cause accelerated atherogenesis and left ventricular (LV) hypertrophy, which increase the risk of myocardial ischemia or infarction and can lead to other conditions such as coronary artery aneurysm and dilated cardiomyopathy [16,17].
Chest pain — From a practical point of view, all patients with a history of chest pain and recent cocaine use should be evaluated for myocardial ischemia/infarction and aortic dissection. The characteristics of cocaine-induced myocardial ischemia are indistinguishable from other causes of myocardial ischemia. The chest pain is often accompanied by anxiety, dyspnea, palpitations, and nausea. As a result, all young patients with an acute coronary syndrome (ACS), particularly those with the above characteristics, should be carefully questioned about cocaine use [18,19].
All patients with chest pain following cocaine ingestion should promptly receive a 12-lead electrocardiogram (ECG) and frontal chest radiograph. Additional imaging is often required if there is a significant concern for aortic dissection, as the chest radiograph has limited sensitivity for the diagnosis of aortic dissection. Ultimately, however, many persons will be diagnosed as having either noncardiac or undifferentiated chest pain. The approach to these patients is discussed separately. (See "Cocaine: Acute intoxication", section on 'Clinical manifestations' and "Outpatient evaluation of the adult with chest pain".)
●Chest pain with ECG evidence of ischemia – Patients with chest pain and ECG evidence of acute ischemia require admission to the hospital and should be evaluated and managed according to the standard protocol for patients with acute myocardial ischemia. One notable exception is that drugs with beta receptor blocking properties should be used with caution in cocaine abusers. (See 'Beta blockers' below and "Overview of the acute management of ST-elevation myocardial infarction" and "Overview of the acute management of non-ST-elevation acute coronary syndromes".)
●Chest pain with evidence of aortic dissection – Patients with chest pain and evidence of aortic dissection require admission to the hospital for urgent management. (See "Management of acute type B aortic dissection".)
●Chest pain without evidence of myocardial ischemia or aortic dissection – Patients with chest pain who have no evidence of myocardial ischemia or aortic dissection generally do not require admission to the hospital and can be followed up as outpatients.
Myocardial ischemia/infarction — An ACS is the most common cardiac condition associated with cocaine use and can occur with all routes of cocaine ingestion [20,21]. While the most common acute condition is myocardial ischemia, only approximately 6 percent of patients with chest pain and recent cocaine use sustain a myocardial infarction (MI). MI in this setting is unrelated to the dose or frequency of cocaine use, although approximately one-half of patients who present with cocaine-related MI have had previous episodes of chest pain . Most cocaine-associated MIs occur in the absence of high grade atherosclerotic epicardial coronary artery stenoses.
There is no evidence that preexistent cardiovascular disease or other abnormalities are prerequisites for the development of cocaine-related myocardial ischemia . Many patients who abuse cocaine also smoke cigarettes, but many have no other cardiac risk factors [9,15,23,24]. However, certain subgroups of patients may be at increased risk of manifesting cardiovascular toxicity if exposed to cocaine, including those who consume alcohol, are pregnant, or are infected with HIV .
Based principally on the ability of cocaine to inhibit norepinephrine uptake and promote thrombus formation, three mechanisms have been proposed for cocaine-induced ischemia. It is likely that more than one of these may contribute to the clinical syndrome.
●Increased myocardial oxygen demand – Increased myocardial oxygen demand results from the sympathomimetic actions of cocaine that increase myocardial inotropy, heart rate, and systemic blood pressure . This may pose a significant problem to patients in whom coronary blood flow is compromised by the presence of fixed stenoses. However, most patients with cocaine-induced myocardial ischemia do not have significant underlying coronary disease [20,23]. In a report of 92 patients with cocaine-associated MI who underwent coronary angiography, 35 (38 percent) were considered to have normal coronary arteries .
●Coronary artery vasoconstriction and spasm – Cocaine can constrict the large and small coronary vessels under some circumstances [26-29]. The vasoconstrictor effects of cocaine on the large coronary arteries are mediated primarily through stimulation of the alpha-adrenergic receptors . Cocaine is structurally similar to acetylcholine, and stimulation of cholinergic receptors in small vessels that lack endothelium or in large vessels with dysfunctional endothelium is a putative mechanism of cocaine-induced vasoconstriction and ischemia .
●Coronary artery thrombosis – Pathologic and angiographic studies have demonstrated coronary thrombi in some patients with cocaine-related MI .
MI is usually temporally related to cocaine use. In different series, approximately two-thirds of infarctions occurred within three hours of cocaine use (range one minute to four days), and approximately 25 percent occurred within 60 minutes after cocaine use [15,20]. The risk of an MI was 24 times greater than the baseline risk during the initial 60 minutes after cocaine ingestion and decreased progressively thereafter (figure 1) .
Aortic dissection — Acute aortic dissection can result from the use of cocaine and commonly presents with chest pain . Typically, the pain is severe, sharp/knife-like, causing the patient to seek medical attention within minutes to hours of onset, and categorically unlike any pain experienced before. The pain most commonly involves the anterior chest but may also be described as radiating to the back. Pain can occur in isolation or be associated with syncope, a cerebrovascular accident, ACS, heart failure (HF), or other clinical symptoms or signs.
Cocaine-associated aortic dissection is a frequent cause of dissection in younger persons and occurs more often in those with untreated or poorly controlled hypertension [25,32]. Among 3584 patients who were enrolled in the International Registry of Aortic Dissection from 1996 to 2012, cocaine use was related to aortic dissection in 63 patients (1.8 percent) . (See "Clinical features and diagnosis of acute aortic dissection".)
Coronary artery aneurysm — Coronary artery aneurysms are relatively infrequent in the general population and are most commonly associated with atherosclerosis but also are reported with collagen vascular diseases, arteritis, mycoses, trauma, and congenital disorders of connective tissue.
Potential mechanisms of coronary artery aneurysm formation due to cocaine include severe episodic hypertension and vasoconstriction with direct endothelial damage predisposing to aneurysm formation. While there is an association between coronary aneurysm and acute MI, these abnormalities are frequently detected only at the time of coronary catheterization or computed tomography (CT) angiography . Aneurysmal rupture is a theoretical concern, although it has never been documented.
Based on one study, coronary artery aneurysms may be relatively more common in cocaine users who undergo angiography. This was illustrated in a review of 112 consecutive patients with a history of cocaine use who underwent coronary angiography, in which 30 percent of cocaine users were noted to have coronary artery aneurysms . By contrast, only approximately 1.5 percent of unselected patients are noted to have coronary artery aneurysms at the time of coronary angiography or autopsy [35,36]. Coronary artery aneurysms can be a potential cause of MI .
Myocarditis — Myocarditis is a common autopsy finding among subjects dying from cocaine abuse, affecting as many as 20 to 30 percent of patients [1,37-40]. Myocarditis has also been reported on myocardial biopsies of active users . The precise mechanism of the myocarditis is not clear, and hypotheses range from hypersensitivity reactions leading to vasculitis and myocarditis to catecholamine-induced toxicity.
The clinical manifestations of myocarditis are highly variable, ranging from subclinical disease to fatigue, chest pain, HF, cardiogenic shock, arrhythmias, and sudden death (table 1). Many cases of myocarditis likely go undetected because they are subclinical or present with nonspecific signs. Though severe cases are potentially life-threatening, cocaine-induced myocarditis may be fully reversible if identified early in the disease process . Patients with an acute episode of myocarditis should be managed in a similar fashion to patients with noncocaine-associated myocarditis. One notable exception is that drugs with beta receptor blocking properties should be used with caution in cocaine abusers. (See 'Beta blockers' below and "Treatment and prognosis of myocarditis in adults".)
Cardiomyopathy — Dilated cardiomyopathy has been documented among cocaine users, although a cause and effect relationship has not been definitively established . In a study of 84 asymptomatic and apparently healthy cocaine users, LV systolic dysfunction was found in six (7 percent) on testing performed after two weeks of abstinence from cocaine use . As such, otherwise unexplained cardiac enlargement in a younger person without a family history of dilated cardiomyopathy should raise the possibility of cocaine abuse .
Patients with dilated cardiomyopathy following cocaine ingestion can present in a number of different ways. Symptoms of HF (progressive dyspnea with exertion, impaired exercise capacity, orthopnea, paroxysmal nocturnal dyspnea, and peripheral edema) are most common. Other presentations include the incidental detection of asymptomatic cardiomegaly and symptoms related to coexisting arrhythmia, conduction disturbance, thromboembolic complications, or sudden death. (See "Causes of dilated cardiomyopathy".)
The pathogenesis of cocaine-associated cardiomyopathy is not well defined, but the following may contribute :
●Cocaine exerts direct toxic effects on the heart, which lead to the destruction of myofibrils, interstitial fibrosis, myocardial dilation, and HF .
●The cocaine-induced hyperadrenergic state may produce contraction band necrosis in the heart and other structural changes [44-46].
●Both myocarditis and cardiomyopathy may be caused by infectious agents in patients who abuse cocaine parenterally, either through direct invasion of the myocardium or stimulation of an autoimmune reaction. (See "Myocarditis: Causes and pathogenesis".)
●Chronic ischemia or prior MI can result in a cardiomyopathy. (See "Treatment of ischemic cardiomyopathy".)
Abstaining from additional cocaine ingestion can lead to complete reversal of the myocardial dysfunction [47-49]. However, patients with permanent myocardial injury from a prior infarction may not recover normal LV function.
Arrhythmias and conduction abnormalities — While cocaine can rarely result in life-threatening ventricular tachycardia or ventricular fibrillation, arrhythmias and conduction abnormalities are generally uncommon in patients abusing cocaine. The arrhythmogenic potential of cocaine is poorly understood, but because of its pharmacologic profile and ability to induce a hyperadrenergic state, it is likely that the drug can produce or exacerbate arrhythmias and conduction abnormalities under some circumstances [9,37]. Importantly, the rhythm disturbances associated with cocaine abuse are typically transient and disappear when the drug is metabolized, although arrhythmias are also noted during withdrawal following cessation of cocaine use. (See "Cocaine: Acute intoxication", section on 'Pathophysiology'.)
The most worrisome arrhythmias associated with cocaine use are ventricular tachycardia and ventricular fibrillation, whereas the most common are supraventricular tachycardias (particularly sinus tachycardia, paroxysmal atrial tachycardia, and atrial fibrillation). A comprehensive list of the abnormalities that have been associated with cocaine use includes [1,21,50-58]:
●Polymorphic ventricular tachycardia (torsades de pointes)
●Accelerated idioventricular rhythm
●Bundle branch block
●Various supraventricular arrhythmias
●Brugada ECG pattern
Cocaine exerts class I antiarrhythmic effects, producing sodium channel blockade in the heart . Other factors contributing to the development of arrhythmias include:
●Altering automaticity by a direct effect on myocardium
●Altering autonomic balance by increasing circulating catecholamine levels
●Inducing ischemia with resultant electrical inhomogeneity
●Creating an anatomic substrate for reentrant arrhythmia
●Altering repolarization with QT prolongation 
Stroke — Stroke is defined as the sudden or rapid onset of a focal, multifocal, or global neurologic deficit attributable to ischemic or hemorrhagic lesion(s) of the central nervous system (CNS). The presenting signs and symptoms of stroke vary according to the affected CNS area. The risk of ischemic stroke may be up to sevenfold higher in cocaine users versus nonusers [60,61]. The acute management of cocaine-induced stroke is similar to that of stroke occurring in noncocaine users. This is discussed in detail separately. (See "Initial assessment and management of acute stroke".)
The etiology of cocaine-induced brain ischemia is multifactorial:
●Cocaine stimulates vasospasm, presumably by increasing levels of extracellular monoamines, particularly dopamine [62,63].
●Long-term cocaine use may cause pathologic changes in the cerebral vasculature (vasculitis) that impair cellular oxygenation by exacerbating nonlaminar blood flow and sludging in the vessels, with consequent increase in platelet aggregation and thrombus formation [3,65].
●Cocaine may stimulate arterial dissection, during which blood enters the arterial wall through an intimal tear and activates the coagulation cascade at the site of endothelial damage. This has been attributed to cocaine-induced hypertension and other factors and has been reported for the coronary and renal arteries and the aorta. When this involves the extracranial or intracranial vessels, stroke may occur through thromboembolic or hemodynamic mechanisms. Preclinical studies have indicated that cocaine may cause apoptosis of cells in the vascular wall, thus weakening the vascular wall and resulting in a dissection per prone state .
Regardless of the precise mechanism, cocaine-induced cerebral ischemia can cause marked hypoperfusion abnormalities associated with severe neurologic deficits. More subtle cognitive deficits can also occur . Over time, repeated ischemic episodes and subsequent reperfusion can weaken vessel walls, thereby increasing the likelihood of cerebral hemorrhage .
Cocaine abuse is also associated with intracerebral and subarachnoid hemorrhage. (See "Spontaneous intracerebral hemorrhage: Pathogenesis, clinical features, and diagnosis" and "Nonaneurysmal subarachnoid hemorrhage".)
Miscellaneous cardiac complications — Cocaine abuse can produce a variety of other cardiac complications, including LV hypertrophy, infectious endocarditis among intravenous users, and mesenteric ischemia [22,69]. Accelerated atherosclerosis has also been reported [16,17]. (See "Right-sided native valve infective endocarditis" and "Overview of intestinal ischemia in adults".)
DIAGNOSTIC EVALUATION — The evaluation of a patient with chest pain following cocaine ingestion is similar to that of nonusers with chest pain and includes (see "Initial evaluation and management of suspected acute coronary syndrome (myocardial infarction, unstable angina) in the emergency department" and "Evaluation of emergency department patients with chest pain at low or intermediate risk for acute coronary syndrome" and "Outpatient evaluation of the adult with chest pain"):
●Complete history and physical examination
●Serial serum biomarkers (ie, troponin T or troponin I)
Additionally, toxicology assays for cocaine or its metabolites may be useful if exposure to cocaine is suspected or requires confirmation. (See "Cocaine: Acute intoxication", section on 'Laboratory and radiographic evaluation'.)
Electrocardiogram — In general, we obtain a resting ECG in all adults with chest pain following cocaine ingestion, unless the chest pain has an obvious noncardiac cause. The interpretation of the ECG for evidence of acute ischemia and/or infarction, which is the same as for patients who have chest pain without cocaine ingestion, is discussed in greater detail separately. (See "Initial evaluation and management of suspected acute coronary syndrome (myocardial infarction, unstable angina) in the emergency department", section on 'Electrocardiogram assessment'.)
Radiologic studies — Based on the clinical presentation of the patient, ECG findings, and cardiac biomarkers, coronary computed tomography angiography (CCTA) may be needed in select patients to document large vessel coronary pathology. In most instances, CCTA has the equivalent diagnostic value to invasive coronary angiography. However, if an acute coronary syndrome is highly suspected, invasive coronary angiography, at a site that can provide the option to revascularize affected vessels if needed, is the preferred approach.
If aortic dissection is suspected, a chest radiograph or transthoracic echocardiograph may provide diagnostic clues. However, definitive diagnosis of dissection usually requires CT angiography or a similar advanced imaging modality (eg, transesophageal echocardiography, magnetic resonance imaging, etc). The approach to diagnosis of aortic dissection is discussed in detail separately. (See "Clinical features and diagnosis of acute aortic dissection", section on 'Cardiovascular imaging'.)
Serum markers — We obtain serial biomarker testing with troponin (T or I) in all adults with chest pain following cocaine ingestion. The presence of circulating troponin in serum is specific for damage to the myocardium [70,71]. By contrast, other markers such as myoglobin, CK, and CK-MB may be elevated in the absence of infarction if skeletal muscle injury, rhabdomyolysis, or increased motor activity has occurred . As such, we do not routinely measure myoglobin, CK, or CK-MB to assess for myocardial injury.
The role of serial troponin testing is discussed in detail separately. (See "Troponin testing: Clinical use".)
DIAGNOSIS — For patients with suspected cardiac pathology following cocaine ingestion, the optimal approach to confirming a specific diagnosis will vary according to the diagnosis:
●Acute myocardial ischemia/infarction – Rise of cardiac biomarkers, along with supportive evidence in the form of typical symptoms, suggestive ECG changes, or imaging evidence of new loss of viable myocardium or new regional wall motion abnormality.
●Aortic dissection – Suspected clinically based upon the presence of high-risk clinical features, but confirmation requires cardiovascular imaging that demonstrates the dissection flap separating a false lumen from the true lumen.
●Myocarditis – Suggestive symptoms along with rise in cardiac biomarkers (eg, troponin), ECG changes suggestive of acute myocardial injury, arrhythmia, or abnormalities of cardiac function, particularly if the clinical findings are new and unexplained.
●Cardiomyopathy – Reduced myocardial contractility and ventricular function as seen on cardiovascular imaging.
●Arrhythmias – Symptoms (eg, palpitations, presyncope, syncope) may or may not be present, but diagnosis is confirmed by ECG findings on 12-lead ECG or continuous ECG monitoring.
●Stroke – Typical symptoms and physical examination findings, usually with confirmatory imaging study such as computed tomography or magnetic resonance imaging.
Additionally, the diagnosis of recent cocaine ingestion can be confirmed by testing the urine for cocaine and its metabolites. The possibility that adulterants and contaminants may be contributing to the cardiovascular effects observed in cocaine abusers must always be considered. Various substances are frequently added to trafficked cocaine supplies , some of which may have significant cardiovascular toxicities. For example, levamisole, an antihelminthic for use in animals, has been speculated to enhance the euphoric effects of cocaine and is a frequently identified adulterant that has been associated with acute coronary syndrome . (See "Cocaine: Acute intoxication", section on 'Laboratory and radiographic evaluation'.)
TREATMENT OF COCAINE-RELATED MYOCARDIAL ISCHEMIA/INFARCTION — Patients with cocaine-related unstable angina, non-ST elevation myocardial infarction (NSTEMI), or ST elevation MI (STEMI) are, for the most part, managed in a manner similar to other patients with these diagnoses. One notable exception is the use of beta blockers, which are not recommended in the early phases of acute coronary syndromes (ACS) in patients with recent cocaine use. This section will highlight the ways in which treatment differs for patients with myocardial ischemia or infarction in the setting of acute cocaine intoxication. The treatment of ACS and the management of cocaine-associated chest pain, including the use of beta blockers, are discussed elsewhere. (See "Overview of the acute management of non-ST-elevation acute coronary syndromes" and "Overview of the acute management of ST-elevation myocardial infarction" and "Cocaine: Acute intoxication".)
There have been no well-designed, randomized, prospective clinical trials to compare treatment strategies for cocaine-associated myocardial ischemia, and thus evidence comes from observations in animals, experimental trials in the catheterization laboratory, observational studies, case series, and case reports . Our approach and recommendations are generally similar to those made in the American Heart Association scientific statement on the management of cocaine-associated chest pain and MI and the guidelines for the management of patients with unstable angina/NSTEMI [11,75,76].
Our approach to the treatment of other cocaine-related cardiac pathologies (eg, aortic dissection, myocarditis, arrhythmias, stroke, etc) is similar to the approach to these entities in nonusers of cocaine. (See "Management of acute type B aortic dissection" and "Treatment and prognosis of myocarditis in adults" and "Overview of the acute management of tachyarrhythmias" and "Initial assessment and management of acute stroke".)
Initial medical therapies — The medical management of patients with an ACS and recent cocaine use is similar to that in the broad population of patients with an ACS. One notable exception is the use of drugs with beta receptor blocking properties, which are generally NOT recommended in the early phases of ACS in patients with recent cocaine use. An expanded discussion of the early treatment of cocaine-associated chest pain is presented separately. (See "Cocaine: Acute intoxication", section on 'Chest pain'.)
Aspirin — Aspirin is an important part of the early treatment of chest pain associated with cocaine use, particularly given the propensity of cocaine to induce thrombus formation via the activation of platelets, stimulation of platelet aggregability, and potentiation of thromboxane production. Unless there is also a high suspicion for acute aortic dissection, aspirin 325 mg (nonenteric coated) should be given to the patient to chew and swallow. (See "Acute non-ST-elevation acute coronary syndromes: Early antiplatelet therapy".)
Nitroglycerin and calcium channel blockers — Sublingual or intravenous (IV) nitroglycerin (NTG) and/or oral calcium channel blockers are safe and effective medications for patients with ischemic chest discomfort and ST-segment elevation or depression. These can also be used for patients with normal ECGs or minimal ST-segment deviation. (See "Nitrates in the management of acute coronary syndrome".)
●For the patient presenting to the emergency department with chest pain that may be due to cardiac ischemia, sublingual NTG is commonly administered at a dose of 0.3 to 0.4 mg every five minutes until chest pain is relieved, up to a total of three doses. Up to 0.6 mg per dose may be given to patients with refractory angina, particularly those with hypertension. After the administration of sublingual NTG, assessment should be made about the need for IV NTG.
●Calcium channel blockers are used as adjunctive therapy in patients with ongoing or recurrent symptoms of ischemia despite optimal therapy with NTG. We generally start with IV diltiazem (0.25 mg/kg; average dose 20 mg IV; may repeat after 15 minutes if needed) or verapamil (usual dose 2.5 to 5 mg IV; may repeat after 15 minutes if needed), given their widespread availability and ease of use, although other IV (eg, nicardipine) or oral (eg, extended-release nifedipine, amlodipine) calcium channel blockers could also be used. Patients who respond after one or two bolus doses can usually be transitioned directly to oral dosing for ongoing management. (See "Overview of the acute management of ST-elevation myocardial infarction" and "Overview of the acute management of non-ST-elevation acute coronary syndromes".)
Benzodiazepines — Early in their care, patients with recent cocaine ingestion should receive adequate doses of benzodiazepines, as needed, for sedation and control of blood pressure and heart rate. Some patients require large cumulative doses of benzodiazepines. (See "Cocaine: Acute intoxication", section on 'Psychomotor agitation'.)
No study has clearly demonstrated whether benzodiazepines or nitrates are more efficacious in the management of cocaine-associated chest pain [77,78]. In one prospective controlled trial, 12 patients with cocaine-associated chest pain randomly assigned to receive sublingual NTG and lorazepam had significantly more rapid and more complete relief of pain than the 15 patients assigned to treatment with NTG alone .
Acute therapy — In patients with cocaine-associated myocardial ischemia or infarction, we recommend not using beta blockers prior to elimination of the cocaine from the patient’s body. This proscription is based principally upon theoretical concerns of coronary artery vasoconstriction and systemic hypertension, which can result from unopposed alpha-adrenergic stimulation. This proscription against beta blockade includes labetalol (a mixed alpha/beta antagonist with predominantly beta-blocking effects), although several articles suggest that mixed alpha/beta blockers, including labetalol and carvedilol, may be safe and effective for clinical use [79-81]. We acknowledge that available evidence pertaining directly to this clinical scenario is weak [82-84]. However, we also recognize that death rates for patients with cocaine-associated MI are low, and thus the usual benefit from beta blockers after MI may be diminished [11,85].
A number of human studies have found that the administration of beta blockers worsens or does not change cocaine-induced coronary artery vasoconstriction [86,87], and beta-blocker therapy has been associated with poor hemodynamic responses or poor clinical outcomes in patients with acute cocaine intoxication in case reports and case series [82,88-90]. In addition, there is no high quality evidence to support the safety or efficacy of beta-blocker therapy in the setting of acute cocaine intoxication. Although several retrospective studies, case reports, and reviews argue that beta blockade in the setting of cocaine-associated cardiovascular complications is safe and effective [79,80,82,91-94], many of these studies suffer from methodologic shortcomings, including lack of evidence of clinical intoxication at the time of beta-blocker administration, potential selection bias of patients receiving beta blockers, and asymmetric use of ancillary medications (eg, NTG and aspirin) [95-99].
Nevertheless, evidence pertaining to the role of beta blockers in the treatment of cocaine-related cardiovascular complications is limited. Data from prospective studies accounting for 175 patients exposed to cocaine and then treated with beta blockers reported four adverse events (2.3 percent), suggesting a slightly safer profile than previously assumed . According to registry data, the majority of patients with cocaine-associated ACS receive beta blockers within the first 24 hours of hospitalization .
Nevertheless, some clinicians may choose to give beta blockers as part of their management of acute cocaine-related cardiovascular complications. If beta blockers are given, they should be used in situations where benefits outweigh risks (eg, remote from cocaine exposure), and mixed alpha/beta blockers (eg, labetalol and carvedilol) should be used rather than nonselective beta blockers. Additionally, beta blockers should ideally be used in combination with an alpha antagonist or some other vasodilator without beta-blocking effects (eg, NTG or nitroprusside), and under close observation, including frequent measurements of vital signs and serial ECGs. Of note, the use of labetalol for the treatment of cocaine-associated chest pain appears in an update of the American College of Cardiology/American Heart Association guidelines for the management of patients with unstable angina and NSTEMI as a "Class IIb (may be considered)" recommendation in specific circumstances (eg, hypertension with systolic blood pressure >150 mmHg or sinus tachycardia >100 bpm), provided the patient has received a vasodilator, such as NTG or a calcium channel blocker, within close temporal proximity (ie, within the previous hour) .
The general use of beta blockers in the settings of ACS and coronary heart disease is reviewed separately, as is the detailed management of patients presenting to the emergency department with acute cocaine intoxication. (See "Acute myocardial infarction: Role of beta blocker therapy" and "Beta blockers in the management of chronic coronary syndrome" and "Cocaine: Acute intoxication", section on 'Initial management'.)
Long-term therapy — Whether a beta blocker should be started after the elimination of cocaine in patients with a documented MI remains unclear. The likelihood of recurrent cocaine use argues against such a strategy. An observational study of 2578 patients hospitalized at a single center with heart failure, including 503 patients with cocaine use, suggested that long-term therapy with carvedilol was safe and associated with reduced major adverse cardiac events (compared with not taking a beta blocker), particularly in patients with heart failure and reduced left ventricular (LV) ejection fraction . We suggest that patients with LV systolic dysfunction or ventricular arrhythmias be considered for beta blockers at the time of discharge but only if the risk of recurrent cocaine use is low . (See "Primary pharmacologic therapy for heart failure with reduced ejection fraction", section on 'Beta blocker'.)
Reperfusion and revascularization — The management of patients with a history of recent cocaine use, in whom an acute NSTEMI or STEMI is likely or definitively diagnosed, is similar to that in the broad population of patients with acute MI. This includes the use of an early invasive strategy in some patients with NSTEMI, early reperfusion strategies in patients with STEMI, and the appropriate use of antithrombotic drugs. (See "Overview of the acute management of non-ST-elevation acute coronary syndromes" and "Overview of the acute management of ST-elevation myocardial infarction".)
In patients with persistent ST-segment elevation, after treatment with NTG and calcium channel blockers, we agree with published society guidelines to proceed with immediate coronary angiography and percutaneous coronary intervention (if indicated) [11,70,76]. Fibrinolytic therapy is an acceptable alternative when timely coronary angiography is not possible. (See "Acute ST-elevation myocardial infarction: The use of fibrinolytic therapy".)
Two specific management issues merit special attention in patients with cocaine-associated MI: the choice of early reperfusion strategy and the choice of stent type.
Early reperfusion — As in any patient with a suspected ACS, early reperfusion is an important part of the management of an ACS associated with cocaine use. In patients with STEMI and recent cocaine use, we proceed with coronary angiography and primary percutaneous coronary intervention (if indicated by the usual criteria and when locally available) rather than fibrinolysis for two reasons:
●As the specificity of ST-segment elevation on the ECG is lower in young people due to the common finding of benign early repolarization (J-point elevation), the inappropriate use of fibrinolytic therapy becomes more likely.
●There are reports of a higher rate of intracranial hemorrhage after fibrinolytic therapy in patients who use cocaine .
General indications for the use of reperfusion in patients with STEMI and NSTEMI are discussed separately. (See "Non-ST-elevation acute coronary syndromes: Selecting an approach to revascularization", section on 'Summary and recommendations' and "Primary percutaneous coronary intervention in acute ST elevation myocardial infarction: Determinants of outcome", section on 'Summary and Recommendations'.)
Stent placement — Clinicians frequently have concerns about long-term compliance with medical therapies in patients with a history of cocaine use. Of particular concern is the patient’s likelihood to comply with long-term dual antiplatelet therapy following coronary stent placement. In addition, there is a several-fold increased rate of coronary stent thrombosis with both bare-metal and drug-eluting stents reported in patients with cocaine-associated myocardial ischemia [103,104]. (See "Coronary artery stent thrombosis: Incidence and risk factors".)
●In patients with ACS, the risk of stent thrombosis should be compared with the risk of a conservative management strategy with intensive medical therapy. The choice between the two strategies should be made on the basis of an individual patient's clinical characteristics.
●In patients in whom there are significant concerns about medication compliance, bare-metal stents should be considered in preference to drug-eluting stents when a decision has been made to place a stent .
Wide complex QRS arrhythmias — Cocaine can produce two distinct wide QRS-complex arrhythmias. The first is a sinus rhythm with tricyclic antidepressant (TCA)-like QRS changes caused by the class IA antidysrhythmic effects of cocaine (blockade of cardiac fast sodium channels). The second is ventricular tachycardia. Accurate recognition is important, as the treatment of the two entities differs. The diagnostic criteria for these ECG findings are discussed elsewhere. (See "Tricyclic antidepressant poisoning", section on 'Electrocardiogram' and "Brugada syndrome: Clinical presentation, diagnosis, and evaluation".)
TCA-like wide QRS arrhythmias — When the wide QRS-complex arrhythmia is attributable to sodium channel blockade, treatment is sodium bicarbonate. A sodium bicarbonate challenge in such patients can be both diagnostic and therapeutic, as the QRS complex will often narrow after bicarbonate treatment. Dosing is similar to the treatment of patients with QRS widening due to TCA poisoning. (See "Tricyclic antidepressant poisoning", section on 'Sodium bicarbonate for cardiac toxicity'.)
Acute ventricular arrhythmias — Rarely, cocaine can result in acute life-threatening ventricular tachycardia or ventricular fibrillation. In general, we manage these arrhythmias in a manner similar to other patients. (See "Overview of the acute management of tachyarrhythmias", section on 'Wide QRS complex tachyarrhythmias'.)
We use amiodarone if clinically indicated despite theoretical concerns regarding a potential negative interaction with cocaine. Both cocaine and amiodarone are potent sodium channel blockers. We are not aware of any clinical reports of this potential adverse interaction. (See 'Arrhythmias and conduction abnormalities' above.)
Secondary cardiovascular disease prevention — Patients who have been treated for an ACS following cocaine ingestion should be treated for secondary prevention of atherosclerotic cardiovascular disease (CVD). Typically, patients will require therapy with an antiplatelet drug (usually aspirin) and a statin (eg, atorvastatin, rosuvastatin, etc). Patients may require additional medical therapies depending upon the extent of damage from the ACS (eg, therapy for heart failure and/or reduced LV systolic function, etc). Additionally, patients should be counselled regarding the importance of a healthy diet, weight reduction (if overweight), regular exercise, and smoking cessation. (See "Prevention of cardiovascular disease events in those with established disease (secondary prevention) or at very high risk".)
Cessation of cocaine use — Cessation of cocaine use is essential for secondary prevention, although modification of other risk factors, in particular tobacco smoking, may also play a role. Unfortunately, among patients with cocaine-associated chest pain, approximately 60 percent admit to continued cocaine use in the year after a symptomatic episode . (See "Substance use disorders: Clinical assessment".)
PROGNOSIS — Complications of cocaine-associated myocardial infarction (MI) may be more frequent than MI in the absence of cocaine use. As an example, one prospective study of 479 patients aged 50 or younger with acute coronary syndrome identified 24 patients who tested positive for cocaine on admission . Cocaine users had significantly higher troponin levels (53 versus 23 ng/mL), lower ejection fractions post-MI (45 versus 52 percent), and higher in-hospital mortality (8.3 versus 0.8 percent) than nonusers.
SOCIETY GUIDELINE LINKS — Links to society and government-sponsored guidelines from selected countries and regions around the world are provided separately. (See "Society guideline links: Cocaine use and cocaine use disorder" and "Society guideline links: Stimulant use disorder and withdrawal".)
SUMMARY AND RECOMMENDATIONS
●Cocaine is among the most commonly used illicit recreational drugs worldwide, and even casual use of cocaine may be associated with acute or chronic cardiovascular toxicity. Acute coronary syndromes (ACS; including myocardial ischemia and infarction), aortic dissection and rupture, arrhythmias, myocarditis, and vasculitis are potential toxicities related to cocaine ingestion. (See 'Introduction' above.)
●The major cardiovascular effects of cocaine appear to be caused by the inhibition of norepinephrine reuptake into the synaptic cleft by sympathetic neurons. Since reuptake is the major mechanism by which neurotransmitters are removed from active receptor sites, this inhibition results in potentiation of the response to sympathetic stimulation of innervated organs and to infused catecholamine. Cocaine may also enhance the release of catecholamines from central and peripheral stores. (See 'Cardiovascular physiologic effects of cocaine' above.)
●An ACS is the most common cardiac condition associated with cocaine use. The mechanisms of cocaine-associated myocardial ischemia include coronary artery spasm, a prothrombotic state in the coronary circulation, and increases in heart rate and blood pressure which increase myocardial oxygen consumption. Myocardial infarction (MI) affects approximately 6 percent of patients with chest pain and recent cocaine use, and is unrelated to the dose or frequency of use. Most cocaine-associated MIs occur in the absence of high grade atherosclerotic epicardial coronary artery stenoses. (See 'Epidemiology' above and 'Myocardial ischemia/infarction' above.)
●Acute aortic dissection can result from the use of cocaine and commonly presents with severe chest pain that is sharp/knife-like, causing the patient to seek medical attention within minutes to hours of onset, and categorically unlike any pain experienced before. Cocaine-associated aortic dissection is a frequent cause of dissection in younger persons and occurs more often in those with untreated or poorly controlled hypertension. (See 'Aortic dissection' above.)
●A variety of other clinical manifestations may rarely occur in cocaine users, including coronary artery aneurysm, myocarditis, cardiomyopathy, stroke, and a variety of arrhythmias. (See 'Myocarditis' above and 'Clinical manifestations' above.)
●The diagnostic approach to the patient with chest pain following cocaine ingestion is the same as the approach in nonusers and includes a complete history and physical examination, ECG, radiologic studies, and serial serum markers searching for evidence of MI. (See 'Diagnostic evaluation' above.)
●Patients with cocaine-related unstable angina, non-ST elevation MI (NSTEMI), or ST elevation MI (STEMI) are, for the most part, managed in a manner similar to other patients with these diagnoses.
•Aspirin is an important part of the early treatment of chest pain associated with cocaine use. Unless there is also a high suspicion for acute aortic dissection, aspirin 325 mg (nonenteric coated) should be given to the patient to chew and swallow. (See 'Aspirin' above and "Acute non-ST-elevation acute coronary syndromes: Early antiplatelet therapy".)
•For the patient presenting to the emergency department with chest pain that may be due to cardiac ischemia, sublingual nitroglycerin (NTG) is commonly administered at a dose of 0.3 to 0.4 mg every five minutes until chest pain is relieved, up to a total of three doses. (See 'Nitroglycerin and calcium channel blockers' above.)
•Calcium channel blockers are used as adjunctive therapy in patients with ongoing or recurrent symptoms of ischemia despite optimal therapy with NTG. We generally start with intravenous (IV) diltiazem (average dose 20 mg IV) or verapamil (usual dose 2.5 to 5 mg IV), given their widespread availability and ease of use. (See 'Nitroglycerin and calcium channel blockers' above.)
•For cocaine-induced agitation, we suggest treatment with benzodiazepines (eg, diazepam 5 to 10 mg IV every 3 to 5 minutes until agitation is controlled) (Grade 2C). (See "Cocaine: Acute intoxication", section on 'Psychomotor agitation'.)
•In patients with cocaine-associated myocardial ischemia or infarction, we recommend not using beta blockers prior to elimination of the cocaine from the patient’s body (Grade 1C). This proscription is based principally upon theoretical concerns of coronary artery vasoconstriction and systemic hypertension, which can result from unopposed alpha-adrenergic stimulation. Nevertheless, some clinicians may choose to give beta blockers as part of their management of acute cocaine-related cardiovascular complications. If beta blockers are given, they are used in situations where benefits outweigh risks (eg, remote from cocaine exposure), and mixed alpha/beta blockers (eg, labetalol and carvedilol) should be used rather than nonselective beta blockers. (See 'Beta blockers' above.)
•As in any patient with a suspected ACS, early reperfusion is an important part of the management of an ACS associated with cocaine use. In patients with STEMI and recent cocaine use, we proceed with coronary angiography and primary percutaneous coronary intervention (if indicated by usual criteria and when locally available) rather than fibrinolysis because of the decreased specificity of ECG findings and safety concerns. However, fibrinolytic therapy is an acceptable alternative when timely coronary angiography is not possible. (See 'Reperfusion and revascularization' above.)
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