Guidelines for Chest Pain and Myocardial Infarction: One Size Does Not Fit All

Across most disciplines in medicine, the implementation of evidence-based guidelines has been repeatedly demonstrated to reduce morbidity, mortality, length of intensive care unit and hospital stay, and the overall cost of health care. However, it is inevitable that either the homogeneity of patients included in studies that form the basis of guideline preparation, or the heterogeneity of actual patients will prevent the inclusion of every applicable patient into an appropriate guideline. While it is incumbent on us to apply well-designed guidelines to all appropriate patients, it is equally essential that we identify those outlying patients for whom the guidelines were never intended. Furthermore, when large subsets of patients are identified who fall outside the realm of a particular guideline, then either the guideline should be modified, or a new one created. In this issue of Circulation, the scientific statement from the AHA Acute Cardiac Care Committee summarizes the unique pathophysiology of cocaine-induced myocardial ischemia and infarction and provides a thorough analysis of the existing data that offers clinicians a logical and concise approach to the management of patients with cocaine-associated chest pain and myocardial infarction.

Although cocaine use began in South America as early as the 6th century [1], it was not until 1982 that Coleman and colleagues recognized an association between cocaine and myocardial infarction.[2] While the first case series suggested that nearly one-third of cocaine-using patients with chest pain developed myocardial infarction [3], this estimate was probably erroneously high because of selection bias. Much of the next decade was consumed by debate over the actual incidence of myocardial infarction in cocaine users, and the need to admit and observe patients with cocaine-associated chest pain.[4-6] We now recognize, based on Emergency Department data, that close to 100,000 cocaine-using patients will be seen each year with complaints referable to the cardiovascular system, that more than half will be admitted to the hospital at a cost of approximately 83 million dollars, and that only about 6% of them will have suffered a myocardial infarction.[7,8] Data extrapolation from the Third National Health and Nutrition Examination Survey provides an even more concerning analysis of the impact of cocaine use on cardiovascular disease. This survey suggests that frequent users of cocaine have a nearly sevenfold increased likelihood of myocardial infarction over nonusers and that one out of every four nonfatal myocardial infarctions in patients between the ages of 18 and 45 can be attributed to frequent cocaine use.[9]

Because of the magnitude of this problem, it is critical to ensure that therapies provided to typical patients with acute coronary syndromes (ACS) are also safe and effective in cocaine users. Unfortunately, the large randomized clinical trials (RCTs) that provide the core data from which we derive an understanding of the benefits of antiplatelet, antithrombotic, and antiadrenergic therapy in ACS patients failed to systematically evaluate their patients for cocaine use. Studies of known cocaine users are quite small by comparison, and ethical concerns over enrollment as well as difficulties with regard to compliance and follow-up hamper the development of large-scale RCTs in this patient population.

Existing data are limited to sound animal models, human volunteer studies, small case series, case reports, and just a few small RCTs. Despite these limitations, the Acute Cardiac Care Committee identified three areas where there is support for individualized care of cocaine users. First, benzodiazepines have an essential role in the early management of patients with chest pain. While the use of benzodiazepines for acute cocaine toxicity should be familiar to most clinicians, it is interesting to note that most patients who present to health care with cocaine-associated chest pain lack the typical adrenergic findings of severe hypertension, tachycardia, and psychomotor agitation that are expected in acute cocaine overdose.[6] Whereas benzodiazepines may treat some residual adrenergic excess, it is also possible that they help alleviate ischemia and reperfusion injury through their direct effects on peripheral (myocardial) benzodiazepine receptors.[10]

Second, beta-blockers should be avoided acutely. This is a critical issue in light of the emphasis placed on early beta-blockade by national organizations that monitor quality of care.[11,12] Though this recommendation was not based on data from RCTs, it is supported by controlled animal data, human volunteer studies, case series, and case reports accurately summarized by the Acute Cardiac Care Committee. Opponents of this position [13,14] will point to archaic approaches abandoned by their own authors [15-17], poorly documented cases of perceived benefit [18], and a single recent study [19] whose extensive flaws are addressed elsewhere.[20] Also missing from the analysis is a recent fatality attributed to the use of beta-blockers in the setting of cocaine-associated myocardial infarction.[21] Although for some readers this issue may remain unresolved, a risk:benefit analysis provides further insight. It is difficult to imagine a substantial benefit for the routine administration of beta-blockers in patients with cocaine-associated chest pain when the following facts are appreciated: Only about 6% will demonstrate evidence of myocardial injury [6,7]; short-term (in-hospital) mortality is exceedingly low in patients with documented myocardial infarction [22]; and long-term follow-up demonstrates an exceedingly low morbidity and mortality, especially if cocaine abstinence can be achieved.[23] Given this minimal benefit, the risk and expense of routine beta-blockade seem unwarranted. The challenge for clinicians is to accurately identify cocaine-using patients. Though it is certain that history alone will not be sufficient to identify all cocaine users [24,25], it is uncertain if routine urine testing is warranted in all or any subset of patients with chest pain.

The final recommendation for individualized care stresses the need for referral for cocaine detoxification. Maintaining long-term abstinence is a daunting task even under the best of circumstances. The high rate of recidivism in cocaine users attests both to the highly addicting properties of the drug and to the lack of social support for so many of those addicted. Data support the benefits modifying this recognized risk factor for cardiovascular disease [23], and detoxification should be integrated into a comprehensive primary care program that identifies and modifies additional risk factors such as cigarette smoking, which is highly prevalent in this population.[26] For those patients who can maintain cocaine abstinence and have clear indications for beta-blockade, long-term beta-blocker therapy is unstudied but may be indicated.

A remaining unanswered critical question in this small subpopulation is to identify the interval required to ensure the safety of beta-blocker administration following recent cocaine use. A single study demonstrated episodes of ST-segment elevation on Holter monitoring that persisted for weeks during the immediate cocaine detoxification period.[27] It is unclear whether this represents a change in receptor sensitivity or the presence of a metabolite (benzoylecgonine) that is known to persist for days to weeks [28], does not cross the blood-brain barrier to produce clinically evident sympathomimetic effects [29,30], yet is a potent vasoconstrictor.[31] This study suggests, however, that the absence of clinical cocaine toxicity is insufficient to suggest that beta-blockade is safe.