A retrospective descriptive analysis of patient adherence to dabigatran at a large academic medical center.

BACKGROUND: Clinical trials evaluating the efficacy of dabigatran followed a very strict protocol, which included close monitoring and follow-up. Patients followed in this controlled environment had an average medication possession ratio (MPR) greater than 0.95. However, very few studies have evaluated patient adherence to dabigatran in a real-world setting. Other studies of chronic medications indicate patients are not reliably adherent to twice daily regimens. Adherence to therapy is particularly important for direct thrombin inhibitors because there may be a risk of increased thromboembolic events associated with poor adherence to these agents.  OBJECTIVE: To identify the MPR for patients prescribed dabigatran at a large academic medical center and affiliated clinics.  METHODS: This retrospective descriptive study evaluated the MPR for patients prescribed dabigatran between January 1, 2012, and December 31, 2012. Patients included in this study had to receive dabigatran for a minimum of 3 months, have a primary care physician or cardiologist at the medical center or affiliated clinics, and must not use a mail order pharmacy. Patient MPR was calculated based on prescriptions picked up from the patient. RESULTS: After screening 400 patients, 159 patients met eligibility criteria. The mean MPR for the patients in this study was 0.63. Overall, 43% of the patients had an MPR of less than 0.80, and the mean MPR for this subgroup was 0.39 ± 0.27; 57% of the study population had an MPR of 0.80 or higher, with a mean MPR of 0.94 ± 0.08. There was a significantly higher proportion of men (67.7%, P = 0.0112) and a larger number of "as needed medications" prescribed (1.73 vs. 0.86, P = 0.0039) in patients with an MPR less than 0.80. There were 5 patients hospitalized during the study period (3 for bleeding, 1 for confusion, and 1 death not related to dabigatran therapy).  CONCLUSIONS: The relatively low mean MPR seen in this study may indicate that there is a need for improved anticoagulation services and follow-up for patients taking dabigatran.

Specific antibody titer alters the effectiveness of intrathecal enzyme replacement therapy in canine mucopolysaccharidosis I.

Intrathecal enzyme replacement therapy is an experimental option to treat central nervous system disease due to lysosomal storage. Previous work shows that MPS I dogs receiving enzyme replacement with recombinant human alpha-l-iduronidase into the cisterna magna showed normal brain glycosaminoglycan (GAG) storage after three or four doses. We analyzed MPS I dogs that received intrathecal enzyme in a previous study using an assay that detects only pathologic GAG (pGAG). To quantify pGAG in MPS I, the assay measures only those GAG which display terminal iduronic acid residues on their non-reducing ends. Mean cortical brain pGAG in six untreated MPS I dogs was 60.9±5.93 pmol/mg wet weight, and was 3.83±2.64 in eight normal or unaffected carrier animals (p<0.001). Intrathecal enzyme replacement significantly reduced pGAG storage in all treated animals. Dogs with low anti-iduronidase antibody titers showed normalization or near-normalization of pGAG in the brain (mean 8.17±6.17, n=7), while in dogs with higher titers, pGAG was reduced but not normal (mean 21.9±6.02, n=4). Intrathecal enzyme therapy also led to a mean 69% reduction in cerebrospinal fluid pGAG (from 83.8±26.3 to 27.2±12.3 pmol/ml CSF). The effect was measurable one month after each dose and did not differ with antibody titer. Prevention of the immune response to enzyme may improve the efficacy of intrathecal enzyme replacement therapy for brain disease due to MPS I.