Multifaceted Intervention to Improve P2Y12 Inhibitor Adherence After Percutaneous Coronary Intervention: A Stepped Wedge Trial.

Background P2Y12 inhibitor medications are critical following percutaneous coronary intervention (PCI); however, adherence remains suboptimal. Our objective was to assess the effectiveness of a multifaceted intervention to improve P2Y12 inhibitor adherence following PCI. Methods and Results This was a modified stepped wedge trial of 52 eligible hospitals, of which 15 were randomly selected and agreed to participate (29 hospitals declined, and 8 eligible hospitals were not contacted). At each intervention hospital, patient recruitment occurred for 6 months and enrolled patients were followed up for 1 year after PCI. Three control groups were used: patients at intervention hospitals undergoing PCI (1) before the intervention period (preintervention); (2) after the intervention period (postintervention); or (3) at the 8 hospitals not contacted (concurrent controls). The intervention consisted of 4 components: (1) P2Y12 inhibitor delivered to patients' bedside after PCI; (2) education on importance of P2Y12 inhibitors; (3) automated reminder telephone calls to refill medication; and (4) outreach to patients if they delayed refilling P2Y12 inhibitor. The primary outcomes were as follows: (1) proportion of patients with delays filling P2Y12 inhibitor at hospital discharge and (2) proportion of patients who were adherent in the year after PCI using pharmacy refill data. Primary analysis compared intervention with preintervention control patients. There were 1377 (intent-to-treat) potentially eligible patients, of whom 803 (per protocol) were approached at intervention sites versus 5910 preintervention, 2807 postintervention, and 4736 concurrent control patients. In the intent-to-treat analysis, intervention patients were less likely to delay filling P2Y12 at hospital discharge (-3.4%; 98.3% CI, -1.2% to -5.6%) and more likely to be adherent to P2Y12 (4.1%; 98.3% CI, 1.0%-7.1%) at 1 year, but had more clinical events (3.2%; 98.3% CI, 2.3%-4.1%) driven by repeated PCI compared with preintervention patients. In post hoc analysis looking at myocardial infarction, stroke, and death, intervention patients had lower event rates compared with preintervention patients (-1.7%; 98.3% CI, -2.3% to -1.1%). Conclusions A 4-component intervention targeting P2Y12 inhibitor adherence was difficult to implement. The intervention produced mixed results. It improved P2Y12 adherence, but there was also an increase in repeat PCI. Registration URL: https://www.clinicaltrials.gov; Unique identifier: NCT01609842.

Potential association of thyrotoxicosis with vitamin B and folate deficiencies, resulting in risk for hyperhomocysteinemia and subsequent thromboembolic events.

OBJECTIVE: To describe a patient with severe thyrotoxicosis attributable to Graves' disease who had a thrombotic cerebrovascular accident and hyperhomocysteinuria, which resolved on correction of the thyrotoxicosis, and to present findings in a pilot study undertaken to investigate the relationship among thyrotoxicosis, homocysteine, folate, and vitamin B(12). METHODS: We present a case report of the index case, with clinical and laboratory details. For the investigative analysis, 21 patients who were 18 to 50 years old and had newly diagnosed, untreated Graves' disease and 10 age-and sex-matched euthyroid control subjects were studied. Of the patients with Graves' disease, 11 underwent studies both at diagnosis and after treatment. Fasting blood tests were performed for thyrotropin, free thyroxine, homocys-teine, vitamin B(12), folate, and methylmalonic acid, a marker of vitamin B(12) deficiency. RESULTS: Vitamin B(12), folate, homocysteine, and methylmalonic acid levels were not significantly different between the thyrotoxic and control or posttreatment groups. In patients with thyrotoxicosis, however, free thyroxine was positively correlated with both homocysteine (r = 0.67; P = 0.03) and methylmalonic acid (r = 0.89; P = 0.003). CONCLUSION: The positive correlation between free thyroxine levels and both homocysteine and methylmalonic acid suggests that thyrotoxicosis may be associated with functional vitamin B(12) deficiency. Such a deficiency may result in clinically important hyperhomocysteine-mia.