1. THE CARDIOVASCULAR EFFECTS OF COCAINE Bryan Schwartz, MD, Shereif Rezkalla, MD, Robert Kloner, MD, PhD

2. Why should cardiologists care about cocaine?
Cocaine accounted for 31% of ER visits related to drug misuse or abuse.
Of 233 ER visits by cocaine-using patients:
56% presented with cardiovascular complaints,
40% presented with chest pain.
Cocaine users have higher incidence of MI (OR ).
Risk of MI increases by 24-fold in 1ST hr after cocaine use.
Cocaine contributes to ~1/4 MIs in persons years.
Volkow ND. National Institute on Drug Abuse
Brody SL. Am J Med 1990;88:325.
Aslibekyan S. Am J Cardiol. 2008;102:966.
Mittleman MA. Circulation. 1999;99:2737.
Qureshi AI. Circulation. 2001;103:502.

3. PATHOPHYSIOLOGY COCAINE DEATH ↑ Sympathetic output ↑ catecholamines
↓ Na transport
Local anesthetic effect
Coronary spasm /
vasoconstriction
↑ Platelet adherence /
thrombus
↑ Heart rate
↑ Blood pressure
↑ Contractility
↓ O2 supply
↑ O2 demand
Arrhythmia
QRS prolongation
QT prolongation
↓ LV function
Ischemia
Infarction
DEATH

4. PATHOPHYSIOLOGY Causes myocardial O2 supply-demand mismatch
Worsens myocardial performance
Causes cardiovascular disease
Causes clinical cardiovascular endpoints
↑Heart rate
↑Blood pressure
↓Coronary artery diameter
↓Coronary blood flow
↓Ejection fraction
↑End-systolic volume
↑End-diastolic pressure
↑Deceleration time
↑Left ventricular hypertrophy
Arrhythmias
QT prolongation
Thrombosis
Atherosclerosis
Endothelial dysfunction
Microvascular disease
Myocardial infarction
CHF
Cardiomyopathy
Aortic dissection
Endocarditis
Sudden death

5. PATHOPHYSIOLOGY Causes myocardial O2 supply-demand mismatch
Worsens myocardial performance
Causes cardiovascular disease
Causes clinical cardiovascular endpoints
↑Heart rate
↑Blood pressure
↓Coronary artery diameter
↓Coronary blood flow
↓Ejection fraction
↑End-systolic volume
↑End-diastolic pressure
↑Deceleration time
↑Left ventricular hypertrophy
Arrhythmias
QT prolongation
Thrombosis
Atherosclerosis
Endothelial dysfunction
Microvascular disease
Myocardial infarction
CHF
Cardiomyopathy
Aortic dissection
Endocarditis
Sudden death

6. COCAINE-ASSOCIATED CHEST PAIN PRESENTATION
MI occurs in ~6% of all patients with CACP
CACP and MI can result from any route of administration
Predominantly male cigarette smokers aged yrs
Cardiovascular risk factors are less prevalent than in patients with traditional MI
Presenting symptoms similar to patients with traditional MI
EKG is frequently abnormal, rarely indicates ischemia .

7. COCAINE-ASSOCIATED CHEST PAIN PRESENTATION
MI occurs in ~6% of all patients with CACP
CACP and MI can result from any route of administration
Predominantly male cigarette smokers aged yrs
Cardiovascular risk factors are less prevalent than in patients with traditional MI
Presenting symptoms similar to patients with traditional MI
EKG is frequently abnormal, rarely indicates ischemia
. NOTHING DIFFERENTIATES PATIENTS WITH CACP
WITH VS. WITHOUT MI

8. COCAINE ASSOCIATED CHEST PAIN DIAGNOSIS
High-risk patients (42/344; 12%) directly admitted
Non high-risk cocaine using patients (302) were enrolled in a 12-hour observation protocol:
Troponin at presentation and after 3, 6, and 9 hours
Continuous 12-lead ST-segment monitoring
None of 302 developed MI, arrhythmias or CHF in the observation unit and all were discharged from the unit.
At 30 days:
None died of CV causes
25% experienced recurrent chest pain
1.3% developed nonfatal MI (all 4 continued to use cocaine and had at least 2 cardiac risk factors).
Weber JE. N Engl J Med. 2003;348:510.

9. COCAINE ASSOCIATED CHEST PAIN PROGNOSIS
COHORT MI
Death
CHF
Supraventri cular
tachy- arrhythmia
Sust- ained VT
Brady- arrhythm ia
246 presented to ED with CP 6% 1%
1.6%
1.2%
250 with CP 0%
0.4%
0.8%
302 presented to ED with CP
101 hospitalized with CP
70 hospitalized with CP
31%
1.4%
91 with MI
100% 3% 7%
10%
136 with MI 4%
19%

10. AVOID BETA-BLOCKERS IN COCAINE USING PATIENTS
Beta-blockade can leave alpha-stimulation unopposed → pronounced systemic and coronary vasoconstriction.
In animal studies of acute cocaine toxicity, propranolol worsened the seizure threshold and expedited death.
In humans, propranolol exacerbated cocaine-induced coronary artery vasoconstriction
Esmolol increased blood pressure in 2 of 7 cocaine- using patients (in 1 from 200/120 to 230/180)
Catravas JD. J Pharmacol Exp Ther. 1981;217:350.
Lange RA. Ann Intern Med. 1990;112:897.
Sand IC. Am J Emerg Med. 1991;9:161.

11. AVOID BETA-BLOCKERS IN COCAINE-USING PATIENTS
Labetalol and carvedilol offer the theoretical advantage of blocking both α- and β -receptors.
Labetalol did not reverse cocaine-induced coronary artery vasoconstriction.
In pheochromocytoma labetalol caused severe hypertension.
Combined with cocaine, carvedilol 25mg tended to increase BP.
Boehrer JD. Am J Med. 1993;94:608.
Briggs RS. Lancet. 1978;1:1045.
Sofuoglu M. Drug Alcohol Depend. 2000;60:69.

12. AVOID BETA-BLOCKERS IN COCAINE USING PATIENTS
Risk of exacerbating
cocaine-induced coronary and systemic vasoconstriction (reduce myocardial O2 supply and exacerbate hypertension)
Benefit unproven in cocaine-using patients.
Without beta-blockers complications are low, including death, CHF, arrhythmias.

13. AVOID BETA-BLOCKERS IN COCAINE USING PATIENTS
Risk of exacerbating
cocaine-induced coronary and systemic vasoconstriction (reduce myocardial O2 supply and exacerbate hypertension)
Benefit unproven in cocaine-using patients.
Without beta-blockers complications are low, including death, CHF, arrhythmias.
ALWAYS AVOID BETA-BLOCKERS IN THE ACUTE SETTING
PRESCRIBE BETA-BLOCKERS AT DISCHARGE ONLY AFTER
CAREFUL RISK-BENEFIT ASSESSMENT

14. COCAINE ASSOCIATED CHEST PAIN TREATMENT ALGORITHM
CACP
Aspirin
Benzodiazepine
Nitroglycerin
ST-segment elevation?
Yes No
Yes
Chest pain persists?
Antithrombotic therapy
Antiplatelet therapy
Cath lab available? No
Primary PCI
Yes No
Consider thrombolytic therapy only if unequivocal evidence of STEMI
Discharge therapy according to published guidelines, including:
12 hours observation: serial EKGs and troponins.
NSTEMI or unstable angina?
Aspirin
Statin
Clopidogrel
ACE I No
Yes
Antithrombotic therapy
Antiplatelet therapy
Consider cardiac catheterization
Rule out MI
DC from observation unit
Timely cardiology follow up
Encourage cessation of
cocaine and cigarettes
Drug abuse counseling

15. COCAINE ASSOCIATED CHEST PAIN TREATMENT ALGORITHM
CACP
Aspirin
Benzodiazepine
Benzodiazepines:
Improved BP, HR, acidemia and hyperthermia in dogs
Improved chest pain as much as NTG in humans
Nitroglycerin
ST-segment elevation?
Yes No
Yes
Chest pain persists?
Antithrombotic therapy
Antiplatelet therapy
Cath lab available? No
Primary PCI
Yes No
Consider thrombolytic therapy only if unequivocal evidence of STEMI
Discharge therapy according to published guidelines, including:
12 hours observation: serial EKGs and troponins.
NSTEMI or unstable angina?
Aspirin
Statin
Clopidogrel
ACE I No
Yes
Antithrombotic therapy
Antiplatelet therapy
Consider cardiac catheterization
Rule out MI
DC from observation unit
Timely cardiology follow up
Encourage cessation of
cocaine and cigarettes
Drug abuse counseling

16. COCAINE ASSOCIATED CHEST PAIN TREATMENT ALGORITHM
CACP
Aspirin
Benzodiazepine
None of 302 non-high-risk patients developed MI, CHF or arrhythmias in the observation unit and all were discharged from the unit.
Nitroglycerin
ST-segment elevation?
Yes No
Yes
Chest pain persists?
Antithrombotic therapy
Antiplatelet therapy
Cath lab available? No
Primary PCI
Yes No
Consider thrombolytic therapy only if unequivocal evidence of STEMI
Discharge therapy according to published guidelines, including:
12 hours observation: serial EKGs and troponins.
NSTEMI or unstable angina?
Aspirin
Statin
Clopidogrel
ACE I No
Yes
Antithrombotic therapy
Antiplatelet therapy
Consider cardiac catheterization
Rule out MI
DC from observation unit
Timely cardiology follow up
Encourage cessation of
cocaine and cigarettes
Drug abuse counseling

17. COCAINE ASSOCIATED CHEST PAIN TREATMENT ALGORITHM
CACP
Aspirin
Benzodiazepine
Nitroglycerin relieves chest pain in ~1/2 of patients.
Nitroglycerin reversed the coronary vasoconstriction induced by cocaine.
Nitroglycerin
ST-segment elevation?
Yes No
Yes
Chest pain persists?
Antithrombotic therapy
Antiplatelet therapy
Cath lab available? No
Primary PCI
Yes No
Consider thrombolytic therapy only if unequivocal evidence of STEMI
Discharge therapy according to published guidelines, including:
12 hours observation: serial EKGs and troponins.
NSTEMI or unstable angina?
Aspirin
Statin
Clopidogrel
ACE I No
Yes
Antithrombotic therapy
Antiplatelet therapy
Consider cardiac catheterization
Rule out MI
DC from observation unit
Timely cardiology follow up
Encourage cessation of
cocaine and cigarettes
Drug abuse counseling

18. COCAINE ASSOCIATED CHEST PAIN TREATMENT ALGORITHM
CACP
Aspirin
Benzodiazepine
2nd-line therapy for hypertension
Ca channel blockers: abolished cocaine’s effects on BP and coronary vasoconstriction in humans
Nitroglycerin
ST-segment elevation?
Yes No
Yes
Chest pain persists?
Antithrombotic therapy
Antiplatelet therapy
Cath lab available? No
Primary PCI
Yes No
Consider thrombolytic therapy only if unequivocal evidence of STEMI
Discharge therapy according to published guidelines, including:
12 hours observation: serial EKGs and troponins.
NSTEMI or unstable angina?
Aspirin
Statin
Clopidogrel
ACE I No
Yes
Antithrombotic therapy
Antiplatelet therapy
Consider cardiac catheterization
Rule out MI
DC from observation unit
Timely cardiology follow up
Encourage cessation of
cocaine and cigarettes
Drug abuse counseling

19. COCAINE ASSOCIATED CHEST PAIN TREATMENT ALGORITHM
CACP
Aspirin
Benzodiazepine
2nd-line therapy for hypertension
Phentolamine: abolished cocaine’s effects on HR, BP, coronary vasoconstriction and coronary sinus blood flow
Nitroglycerin
ST-segment elevation?
Yes No
Yes
Chest pain persists?
Antithrombotic therapy
Antiplatelet therapy
Cath lab available? No
Primary PCI
Yes No
Consider thrombolytic therapy only if unequivocal evidence of STEMI
Discharge therapy according to published guidelines, including:
12 hours observation: serial EKGs and troponins.
NSTEMI or unstable angina?
Aspirin
Statin
Clopidogrel
ACE I No
Yes
Antithrombotic therapy
Antiplatelet therapy
Consider cardiac catheterization
Rule out MI
DC from observation unit
Timely cardiology follow up
Encourage cessation of
cocaine and cigarettes
Drug abuse counseling

20. COCAINE ASSOCIATED CHEST PAIN TREATMENT ALGORITHM
CACP
Aspirin
Benzodiazepine
Nitroglycerin
ST-segment elevation?
Yes No
Yes
Chest pain persists?
Antithrombotic therapy
Antiplatelet therapy
Cath lab available? No
Primary PCI
Yes No
Consider thrombolytic therapy only if unequivocal evidence of STEMI
Discharge therapy according to published guidelines, including:
12 hours observation: serial EKGs and troponins.
NSTEMI or unstable angina?
Aspirin
Statin
Clopidogrel
ACE I No
Yes
Antithrombotic therapy
Antiplatelet therapy
Consider cardiac catheterization
Rule out MI
DC from observation unit
Timely cardiology follow up
Encourage cessation of
cocaine and cigarettes
Drug abuse counseling

21. COCAINE ASSOCIATED CHEST PAIN TREATMENT ALGORITHM
CACP
Aspirin
Benzodiazepine
Primary PCI is more preferable in cocaine-using patients than traditional STEMI patients because of diagnostic uncertainty;
5-8% risk of stent thrombosis
Nitroglycerin
ST-segment elevation?
Yes No
Yes
Chest pain persists?
Antithrombotic therapy
Antiplatelet therapy
Cath lab available? No
Primary PCI
Yes No
Consider thrombolytic therapy only if unequivocal evidence of STEMI
Discharge therapy according to published guidelines, including:
12 hours observation: serial EKGs and troponins.
NSTEMI or unstable angina?
Aspirin
Statin
Clopidogrel
ACE I No
Yes
Antithrombotic therapy
Antiplatelet therapy
Consider cardiac catheterization
Rule out MI
DC from observation unit
Timely cardiology follow up
Encourage cessation of
cocaine and cigarettes
Drug abuse counseling

22. COCAINE ASSOCIATED CHEST PAIN TREATMENT ALGORITHM
CACP
Aspirin
Benzodiazepine
Primary PCI is more preferable in cocaine-using patients than traditional STEMI patients because of diagnostic uncertainty;
5-8% risk of stent thrombosis
Nitroglycerin
ST-segment elevation?
Yes No
Yes
Chest pain persists?
Antithrombotic therapy
Antiplatelet therapy
Cath lab available? No
Primary PCI
Yes No
Consider thrombolytic therapy only if unequivocal evidence of STEMI
Discharge therapy according to published guidelines, including:
12 hours observation: serial EKGs and troponins.
NSTEMI or unstable angina?
Aspirin
Statin
Clopidogrel
ACE I No
Yes
Antithrombotic therapy
Antiplatelet therapy
Consider cardiac catheterization
Rule out MI
DC from observation unit
Timely cardiology follow up
Encourage cessation of
cocaine and cigarettes
Drug abuse counseling

23. COCAINE ASSOCIATED CHEST PAIN TREATMENT ALGORITHM
CACP
Aspirin
Benzodiazepine
Nitroglycerin
ST-segment elevation?
Yes No
Yes
Chest pain persists?
Antithrombotic therapy
Antiplatelet therapy
Cath lab available? No
Primary PCI
Yes No
Consider thrombolytic therapy only if unequivocal evidence of STEMI
Discharge therapy according to published guidelines, including:
12 hours observation: serial EKGs and troponins.
NSTEMI or unstable angina?
Aspirin
Statin
Clopidogrel
ACE I No
Yes
Antithrombotic therapy
Antiplatelet therapy
Consider cardiac catheterization
Rule out MI
DC from observation unit
Timely cardiology follow up
Encourage cessation of
cocaine and cigarettes
Drug abuse counseling

24. COCAINE ASSOCIATED CHEST PAIN TREATMENT ALGORITHM
CACP
Aspirin
Benzodiazepine
For patients who discontinue cocaine:
MI and death are rare
incidence of recurrent chest pain
is reduced
Nitroglycerin
ST-segment elevation?
Yes No
Yes
Chest pain persists?
Antithrombotic therapy
Antiplatelet therapy
Cath lab available? No
Primary PCI
Yes No
Consider thrombolytic therapy only if unequivocal evidence of STEMI
Discharge therapy according to published guidelines, including:
12 hours observation: serial EKGs and troponins.
NSTEMI or unstable angina?
Aspirin
Statin
Clopidogrel
ACE I No
Yes
Antithrombotic therapy
Antiplatelet therapy
Consider cardiac catheterization
Rule out MI
DC from observation unit
Timely cardiology follow up
Encourage cessation of
cocaine and cigarettes
Drug abuse counseling

25. COCAINE ASSOCIATED CHEST PAIN CONCLUSION
Predominantly young male cigarette smokers
Of patients in ER with CACP: ~6% have MI
Evaluate non-high-risk patients with 12 hr observation
Cocaine-induced MI: complications are very low, including death, CHF, arrhythmias
Avoid all beta-blockers in the acute setting
Treat CACP with benzodiazepines, NTG, standard Tx
PCI even more preferable than in traditional patients
Cocaine cessation is primary therapeutic goal