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A Question Arises in Care of Heart Patients

Graham Ramsay Joseph Ladapo

As a physician with training in decision science and health economics, I naturally gravitate toward the more technical and analytic aspects of medicine. For example, I rarely order a test without pausing to think about its diagnostic characteristics and the likelihood that a positive or negative test result will actually be accurate. In a similar vein, my thoughts often migrate toward uncertainties about the marginal effectiveness of treatments for diseases in which multiple, acceptable treatment options exist. Often, these questions have no clear answers, and management is based more on clinical judgment or preference. Yet I occasionally encounter scenarios in which multiple, acceptable management options exist and practice patterns are variable, but some treatment options seem more likely to be better for patients than others. I encountered such a situation recently on a cardiology service while managing patients with acute coronary syndrome (ACS).

ACS refers to a spectrum of cardiac ischemia syndromes distinguished by the severity of damage suffered by the heart muscle, which directly corresponds to the morbidity and mortality experienced by the patient. Patients suffering from the least malignant form of ACS suffer from unstable angina, a condition in which blood flow to the heart is intermittently compromised, with frequent cycling between states of normal heart perfusion and heart ischemia. Often, however, unstable angina can evolve to myocardial infarction, a condition in the ACS spectrum. In a heart attack, the heart is not only ischemic but it also infarcts—part of the tissue dies.

Because of the significant morbidity and mortality associated with ACS, it has attracted a significant amount of research attention. The most recent of the rapidly evolving therapies for the condition include medications aimed at inhibiting platelets, the cells that cause ACS in the first place. Aspirin remains a mainstay of treatment, but an additional antiplatelet therapy that has been adopted by mainstream practice in recent years is based on a group of drugs called thienopyridines, of which clopidogrel is most frequently used. Highly effective at improving health outcomes, the medication has been shown to decrease both morbidity and mortality in ACS patients when used in conjunction with aspirin. Moreover, though many patients with ACS ultimately undergo cardiac catheterization, clopidogrel is also extremely beneficial in patients who undergo more conservative management without the utilization of cardiac catheterization.

The main drawback of using clopidogrel, however, is directly related to its antiplatelet function: because it inhibits platelets, it also increases the risk of bleeding. This is perhaps most clinically relevant in the context of patients who receive clopidogrel prior to their catheterization and are found to have severe coronary artery disease more amenable to coronary artery bypass graft (CABG) surgery than simple stent placement. Because the risk of bleeding during surgery is higher with clopidogrel, most cardiac surgeons require that patients eligible for CABG wait several days to have their procedure to allow the effects of the clopidogrel to wane. According to Kalon Ho, HMS assistant professor of medicine at Beth Israel Deaconess Medical Center and director of quality assurance for the hospital’s Cardiovascular Division, “about 5 years ago, we had a discussion with our cardiac surgeons about clopidogrel. Patients treated with the drug clearly have more bleeding problems, but the cardiac surgeons understood that the benefits of surgery clearly outweigh the risks of bleeding on clopidogrel for patients who require their bypass surgery emergently. They don’t like operating on more stable patients until waiting five to seven days for the clopidogrel to wash out.”

Because of the risk of delaying definitive surgical treatment—though the minority of patients ultimately require CABG—some hospitals delay the administration of clopidogrel until cardiac catheterization, in which coronary anatomy can be defined and the need for CABG can be determined definitively. This practice, however, is less effective than early administration of clopidogrel for the vast majority of patients, since few patients ultimately require CABG therapy and earlier administration of clopidogrel is significantly more effective than delaying administration until catheterization. While the practice averts the need for an iatrogenically prolonged hospital stay, it comes at the price of suboptimal treatment for the vast majority of patients with unstable angina or myocardial infarction.

And yet, the decision to use or withhold clopidogrel until cardiac catheterization is not made in a systematic way, as I might have expected given the high stakes of ACS. Moreover, though the answer is unknown, my suspicion is that the benefits from early administration of clopidogrel may outweigh the costs of prolonging the hospitalization of patients ultimately found to require CABG. These are the kinds of research questions that attract my attention as a physician with training in decision science and economics, and their answers may hold solutions that will, in time, help improve the quality of life enjoyed by patients who suffer from ACS.

—Joseph Ladapo, HMS ’08, is an intern in internal medicine at Beth Israel Deaconess Medical Center.

The opinions expressed in this column are not necessarily those of Harvard Medical School, its affiliated institutions, or Harvard University.

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Copyright 2008 by the President and Fellows of Harvard College