Discontinuation of long-term clopidogrel therapy is associated with death and myocardial infarction after saphenous vein graft percutaneous coronary intervention.

OBJECTIVES: This study sought to examine the pattern of death and myocardial infarction (MI) after clopidogrel cessation in patients undergoing percutaneous coronary intervention (PCI) of the saphenous vein graft (SVG). BACKGROUND: The timing and incidence of adverse events by different durations of clopidogrel therapy after SVG PCI remain unknown. METHODS: This is a cohort study of patients undergoing SVG PCI between 2000 and 2009, followed for all-cause mortality or MI after stopping clopidogrel. Incidence rates were calculated across different time periods after clopidogrel cessation. Adjusted incidence rate ratios (IRR) were calculated with multivariable regression (piecewise exponential and Poisson). RESULTS: There were 603 patients who underwent SVG PCI, of which 411 were event-free at the time of clopidogrel cessation. The incidence rate (95% confidence interval: [CI])/1,000 person-days of death or MI after stopping clopidogrel in the time intervals of 0 to 90 days, 91 to 365 days, and 1 to 2 years were 1.26 (95% CI: 0.93 to 1.70), 0.41 (95% CI: 0.30 to 0.56), and 0.41 (95% CI: 0.30 to 0.55), respectively. In multivariable analyses, the overall IRR (95% CI) for death or MI in the 0- to 90-day interval after stopping clopidogrel compared with the 91- to 365-day interval was 2.58 (95% CI: 1.64 to 4.07). Similar results were observed over a broad range of clopidogrel treatment durations (<6 months, 6 months to 1 year, 1 to 2 years, or >2 years). The results were also consistent across subgroups, including sex, stent type, stent diameter, PCI period, and diabetes status. When death alone was evaluated, there remained a significant increase in the event rate in the 0- to 90-day interval compared with the 91- to 365-day interval (IRR: 2.33; 95% CI: 1.32 to 4.11). CONCLUSIONS: A clustering of events was observed in the initial 0 to 90 days after clopidogrel cessation in all treatment durations of clopidogrel investigated after SVG PCI. These results might have important implications in high-risk cohorts undergoing PCI. Additional studies are needed to elucidate the mechanisms underlying the early clustering of events after clopidogrel cessation.

Chronic hypopituitarism after traumatic brain injury: risk assessment and relationship to outcome.

OBJECTIVE: Chronic pituitary dysfunction is increasingly recognized as a sequela of traumatic brain injury. We sought to define the incidence, risk factors, and neurobehavioral consequences of chronic hormonal deficiencies after complicated mild, moderate, or severe traumatic brain injury. METHODS: Patients aged 14 to 80 years were prospectively enrolled at the time of injury and assessed at 3 and 6 to 9 months after injury for hormonal function and neurobehavioral consequences. Major and minor (subclinical) hormonal deficiencies, including growth hormone deficiency (GHD) and growth hormone insufficiency (GHI), were identified. Acute injury characteristics, neurobehavioral, and quality of life measures were compared in patients with and without major hormonal deficits by the use of multivariate analysis. RESULTS: Out of 70 patients (mean age, 32 yr; median Glasgow Coma Scale score, 7; 19% women) tested at 6 to 9 months after injury, 15 (21%) had at least one major hormonal deficiency, 20 (29%) had minor deficiencies, and 30 (43%) had major and/or minor deficiencies. Patients with major deficiencies included 16% with GHD or GHI, 10.5% with hypogonadism, and 1.4% with diabetes insipidus. None of the patients required adrenal or thyroid replacement. At 6 to 9 months after injury, patients with major hormonal deficits had more abnormal acute computed tomographic findings (P = 0.014), greater acute and chronic body mass index (P < 0.01), and a worse Disability Rating Scale score (multivariate P = 0.04). Compared with the 59 growth hormone-sufficient patients, the 11 patients with GHD or GHI had worse Disability Rating Scale scores (multivariate P = 0.04), greater rates of depression, (90 versus 53%; multivariate P = 0.06), and worse quality of life in the Short Form-36 domains of energy and fatigue (multivariate P = 0.03), emotional well-being (multivariate P = 0.02), and general health (multivariate P = 0.07). CONCLUSION: Chronic hypopituitarism warranting hormone replacement occurs in approximately 20% of patients after complicated mild, moderate, or severe traumatic brain injury and is associated with more severe brain injuries and increased disability. GHD and GHI are also associated with increased disability, poor quality of life, and a greater likelihood of depression. The clinical significance of minor hormonal deficits, which occur in almost 30% of patients, warrants further study. Given that major deficiencies are readily treatable, routine pituitary hormonal testing within 6 months of injury is indicated for this patient population.