The combination of scientific and regulatory messaging on a national level supplemented by personal letters to patients and their primary health care providers on a local level can affect clopidogrel use, according to a single-center study published online, October 23, 2012, ahead of print in Circulation: Cardiovascular Quality and Outcomes. With more communication, patients receiving drug-eluting stents (DES) are more likely to adhere to dual antiplatelet therapy.

Concerns were raised in 2006 that DES patients on 6 months or less of clopidogrel had higher risk of late stent thrombosis and potentially poorer outcomes compared with BMS patients. A US Food and Drug Administration hearing soon followed, and broader public health campaigns related to clopidogrel use after DES were initiated.

Eric L. Eisenstein, DBA, and colleagues at Duke University Medical Center (Durham, NC) sought to assess whether sending letters directly to patients and providers could augment the effect of nationwide efforts. Beginning in December 2006, the letters outlined available evidence and suggested patients contact their physicians to evaluate their use of dual antiplatelet therapy. Outcomes from before and after 2006 were compared in patients with significant coronary artery disease who received an intracoronary DES (n = 2,989) or BMS (n = 336) between April 2004 and December 2007.

Extra Notification Pays Off

The combination of public and provider direct notification was associated with an increase in the percentage of DES patients reporting clopidogrel use at 6 months (16.55%; P = 0.010) and 12 months (15.33%; P = 0.004) but a less pronounced change at 24 months (4.64%; P = 0.295). During the same period, there was no change in the percent of BMS patients reporting clopidogrel use at 6 months (-3.73%; P = 0.654), 12 months (-5.98%; P = 0.389), or 24 months (-5.16%; P = 0.708).

Although mortality rates through 24-month follow-up seemed to decrease after the letters began, these changes were not significant (P = 0.086 for DES; P = 0.296 for BMS).

Several factors were identified as associated with clopidogrel use at 12 months: stent implantation after December 2006 (OR 3.042; 95% CI 2.460-3.761), history of diabetes (OR 0.770; 95% CI 0.609-0.973), and prior MI (OR 1.325; 95% CI 1.073-1.635). There were no associations between patient-reported clopidogrel use and age, race, sex, or ACS status at admission.

Beginning with the second quarter of 2006, the percentage of stented patients receiving DES declined rapidly and remained lower than that of patients receiving BMS through 2007.

Local Strategy Just a Start

“Gaps between medical discovery and practice change are well known and their effects become amplified when there are safety concerns regarding a drug or device,” Dr. Eisenstein and colleagues write.

Even though it has been proven that poor dissemination of drug knowledge to physicians is associated with medical errors, the authors acknowledge that remaining up-to-date with every new drug can be difficult. “[B]lack box warnings cannot provide the context [physicians] require to individualize risks and benefits to their patients, and Dear Doctor letters often do not clearly and effectively communicate labeling changes suggesting their effectiveness may be limited,” they write. 

While the study indicates that additional notification efforts increase clopidogrel adherence, the “below target levels” of patient-reported use at 6 and 12 months are concerning, they say. “More focused methods may be required to solicit more adherence beyond these thresholds.”

In a telephone interview with TCTMD, Dr. Eisenstein said the study "demonstrates the value of supplementing national and regulatory messaging with local direct communication to patients and their physicians." With the increased prevalence of electronic health records and personal health record systems, he added, it will become more feasible over time to implement such interventions.

Study Tells an ‘Old Story’

On the other hand, Sorin J. Brener, MD, of Weill Cornell Medical College (New York, NY), told TCTMD in a telephone interview that though well designed and conducted, the study has minimal to no clinical implications. “This study is just in 1 place, [and involves] 1 attempt, so I’m not sure what that means,” he said, adding that the lack of control group is an important limitation.

“All we know is that there was a huge uproar in the community at large [in 2006] and then they sent these letters and the utilization increased, although not that much. It’s not like it doubled or something like that,” Dr. Brener said, noting, “What’s really remarkable is the incredible decline in DES use at that time. That’s pretty impressive.”

The study tells “such an old story that to report on it now . . . is oblique,” he concluded. “It’s something that happened literally 5 years ago. Now [the earlier concern] seems to be less and less relevant since we think that 3-month dual antiplatelet therapy is fine.”

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