ABSTRACT & COMMENTARY

Get Thee to the Pharmacy! Delays in Clopidogrel After Coronary Stenting Can be Deadly

By Jeffrey Zimmet, MD, PhD

Associate Professor of Medicine, University of California, San Francisco, Director, Cardiac Catheterization Laboratory, San Francisco VA Medical Center

Dr. Zimmet reports no financial relationships relevant to this field of study.

This article originally appeared in the July 2014 issue of Clinical Cardiology Alert. It was edited by Michael H. Crawford, MD, and peer reviewed by Susan Zhao, MD. Dr. Crawford is Professor of Medicine, Lucie Stern Chair in Cardiology, Director, Cardiology Fellowship Program, Chief of Clinical Cardiology, University of California, San Francisco, and Dr. Zhao is Director, Adult Echocardiography Laboratory, Associate Chief, Division of Cardiology, Department of Medicine, Santa Clara Valley Medical Center. Dr. Crawford and Dr. Zhao report no financial relationships relevant to this field of study.

Source: Cruden NL, et al. Delay in filling first clopidogrel prescription after coronary stenting is associated with an increased risk of death and myocardial infarction. J Am Heart Assoc 2014;3:e000669.

During my final year of interventional cardiology training, a woman in her 60s was brought emergently to the cath lab in cardiogenic shock, with diffuse ST-segment elevations. She had undergone PCI of the RCA and LAD coronary arteries just over a week earlier at an outside hospital. During her catheterization procedure, both stents were found to be occluded with clot. After successfully treating both vessels and inserting an intra-aortic balloon pump, we met with the family to go over her condition and review her history. There in the neatly organized discharge folder the family had brought in from her recent hospitalization was her prescription for clopidogrel, unfilled.

We all know that dual antiplatelet therapy after coronary stenting is an essential component of avoiding stent thrombosis and related downstream events. Issues with medication adherence are an underappreciated source of poor outcomes. In this study, Cruden and colleagues reviewed records from all patients receiving coronary stents in British Columbia from 2004-2006. Data from cardiac revascularization reports, community pharmacy, and hospital administrative records were reviewed, yielding information on 15,629 patients post-stent, with data out to 2 years. Among this group, 3599 patients had at least one drug-eluting stent (DES) placed, while the remaining 12,030 patients received only bare-metal stents (BMS). While the median elapsed time from hospital discharge to filling of the first clopidogrel prescription was 1 day, a substantial proportion took considerably longer. In fact, approximately 30% of patients in both the DES and BMS groups failed to fill their clopidogrel within 3 days of discharge.

Patients who delayed filling their prescriptions by at least 3 days were older, had a higher burden of comorbidities, and were more likely to have been treated for ST-elevation myocardial infarction (MI) compared to those who filled their prescriptions without that delay. Using a regression analysis, delayed filling of clopidogrel prescriptions by > 3 days was associated with an increased probability for death, repeat admission for MI, and the combined endpoint of death and recurrent MI (hazard ratio [HR], 2.4; 95% confidence interval [CI], 1.7-3.4; HR, 2.0; 95% CI, 1.5-2.7; and HR, 2.0; 95% CI, 1.6-2.6, respectively, for DES; HR, 2.2; 95% CI, 1.9-2.6; HR, 1.8; 95% CI, 1.5-2.1; and HR, 2.0; 95% CI, 1.8-2.3, respectively, for BMS). As seen from these data, the increased risks associated with delay in filling clopidogrel prescriptions were similarly increased for both BMS and for DES. The effect was greatest in the first 30 days after hospital discharge, but a delay in filling the clopidogrel prescription remained a predictor of death and MI out to 2 years of follow-up. The authors concluded that delays in filling the first prescription for clopidogrel after coronary stenting are common and associated with adverse clinical outcomes, regardless of stent type.

COMMENTARY

Nothing about this study should be particularly surprising. It is well-known that stopping dual antiplatelet therapy early is an important predictor of poor outcomes including stent thrombosis, MI, and death. As the risk of stent thrombosis is greatest early after stent implantation, when endothelialization is least complete, it stands to reason that a failure to initiate outpatient treatment in a timely fashion can have disastrous results.

Previous work has looked at similar data but with smaller sample sets, or with only a single stent type. Nevertheless, the overall findings are similar. A prior study in the United States found that one in six patients had a significant delay in filling post-discharge clopidogrel prescriptions, but questions were raised about the completeness of their pharmacy data. In the current study performed in a province-wide fashion in Canada, nearly one in three patients delayed filling their prescriptions. This should put us all on alert, and refocus our efforts to do those things that have been proven to improve post-hospitalization medication adherence: namely, good discharge planning and patient education, ensuring close telephone and clinic follow-up, and addressing barriers to obtaining and affording medications. Some hospital systems have taken to supplying patients with medications at the time of discharge, thus bypassing the need to go to the pharmacy themselves soon after a hospital admission. More and better systems’ approaches to this problem are needed or more cardiologists will not place a stent if they are concerned that the patient will not be compliant.