Publications by Year: 2016

IMPORTANCE: Dual antiplatelet therapy after percutaneous coronary intervention (PCI) reduces ischemia but increases bleeding.

OBJECTIVE: To develop a clinical decision tool to identify patients expected to derive benefit vs harm from continuing thienopyridine beyond 1 year after PCI.

DESIGN, SETTING, AND PARTICIPANTS: Among 11,648 randomized DAPT Study patients from 11 countries (August 2009-May 2014), a prediction rule was derived stratifying patients into groups to distinguish ischemic and bleeding risk 12 to 30 months after PCI. Validation was internal via bootstrap resampling and external among 8136 patients from 36 countries randomized in the PROTECT trial (June 2007-July 2014).

EXPOSURES: Twelve months of open-label thienopyridine plus aspirin, then randomized to 18 months of continued thienopyridine plus aspirin vs placebo plus aspirin.

MAIN OUTCOMES AND MEASURES: Ischemia (myocardial infarction or stent thrombosis) and bleeding (moderate or severe) 12 to 30 months after PCI.

RESULTS: Among DAPT Study patients (derivation cohort; mean age, 61.3 years; women, 25.1%), ischemia occurred in 348 patients (3.0%) and bleeding in 215 (1.8%). Derivation cohort models predicting ischemia and bleeding had c statistics of 0.70 and 0.68, respectively. The prediction rule assigned 1 point each for myocardial infarction at presentation, prior myocardial infarction or PCI, diabetes, stent diameter less than 3 mm, smoking, and paclitaxel-eluting stent; 2 points each for history of congestive heart failure/low ejection fraction and vein graft intervention; -1 point for age 65 to younger than 75 years; and -2 points for age 75 years or older. Among the high score group (score ≥2, n = 5917), continued thienopyridine vs placebo was associated with reduced ischemic events (2.7% vs 5.7%; risk difference [RD], -3.0% [95% CI, -4.1% to -2.0%], P < .001) compared with the low score group (score <2, n = 5731; 1.7% vs 2.3%; RD, -0.7% [95% CI, -1.4% to 0.09%], P = .07; interaction P < .001). Conversely, continued thienopyridine was associated with smaller increases in bleeding among the high score group (1.8% vs 1.4%; RD, 0.4% [95% CI, -0.3% to 1.0%], P = .26) compared with the low score group (3.0% vs 1.4%; RD, 1.5% [95% CI, 0.8% to 2.3%], P < .001; interaction P = .02). Among PROTECT patients (validation cohort; mean age, 62 years; women, 23.7%), ischemia occurred in 79 patients (1.0%) and bleeding in 37 (0.5%), with a c statistic of 0.64 for ischemia and 0.64 for bleeding. In this cohort, the high-score patients (n = 2848) had increased ischemic events compared with the low-score patients and no significant difference in bleeding.

CONCLUSION AND RELEVANCE: Among patients not sustaining major bleeding or ischemic events 1 year after PCI, a prediction rule assessing late ischemic and bleeding risks to inform dual antiplatelet therapy duration showed modest accuracy in derivation and validation cohorts. This rule requires further prospective evaluation to assess potential effects on patient care, as well as validation in other cohorts.

TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT00977938.

BACKGROUND: Contemporary rates of oral anticoagulant (OAC) therapy and associated outcomes among patients undergoing percutaneous coronary intervention (PCI) have been poorly described.

METHODS AND RESULTS: Using data from an integrated health care system from 2009 to 2014, we identified patients on OACs within 30 days of PCI. Outcomes included in-hospital bleeding and mortality. Of 9566 PCIs, 837 patients (8.8%) were on OACs, and of these, 7.9% used non-vitamin K antagonist agents. OAC use remained stable during the study (8.1% in 2009, 9.0% in 2014; P=0.11), whereas use of non-vitamin K antagonist agents in those on OACs increased (0% in 2009, 16% in 2014; P<0.01). Following PCI, OAC-treated patients had higher crude rates of major bleeding (11% versus 6.5%; P<0.01), access-site bleeding (2.3% versus 1.3%; P=0.017), and non-access-site bleeding (8.2% versus 5.2%; P<0.01) but similar crude rates of in-hospital stent thrombosis (0.4% versus 0.3%; P=0.85), myocardial infarction (2.5% versus 3.0%; P=0.40), and stroke (0.48% versus 0.52%; P=0.88). In addition, prior to adjustment, OAC-treated patients had longer hospitalizations (3.9±5.5 versus 2.8±4.6 days; P<0.01), more transfusions (7.2% versus 4.2%; P<0.01), and higher 90-day readmission rates (22.1% versus 13.1%; P<0.01). In adjusted models, OAC use was associated with increased risks of in-hospital bleeding (odds ratio 1.50; P<0.01), 90-day readmission (odds ratio 1.40; P<0.01), and long-term mortality (hazard ratio 1.36; P<0.01).

CONCLUSIONS: Chronic OAC therapy is frequent among contemporary patients undergoing PCI. After adjustment for potential confounders, OAC-treated patients experienced greater in-hospital bleeding, more readmissions, and decreased long-term survival following PCI. Efforts are needed to reduce the occurrence of adverse events in this population.

OBJECTIVES: The purpose of this study was to describe temporal trends and determine the comparative effectiveness of bivalirudin versus unfractionated heparin (UFH) during percutaneous coronary intervention (PCI) for ST-segment elevation myocardial infarction (STEMI).

BACKGROUND: Several clinical trials have compared the safety and effectiveness of bivalirudin versus UFH during PCI for STEMI, but results have been conflicting.

METHODS: Trends in anticoagulant use were examined among 513,775 PCIs for STEMI from July 2009 through December 2014 within the National Cardiovascular Data Registry CathPCI Registry. We conducted an instrumental variable analysis comparing bivalirudin with UFH, using operator preference for bivalirudin as the instrument. We used a test of mediation to determine the extent to which differences in outcomes between anticoagulants were due to differences in use of glycoprotein IIb/IIIa inhibitors (GPI). Primary outcomes were in-hospital bleeding and mortality.

RESULTS: Bivalirudin use increased from 2009 through 2013, followed by a new decline. GPIs were used in 74.7% of UFH PCIs versus 26.5% of bivalirudin PCIs. In unadjusted analyses, bivalirudin was associated with decreased bleeding (risk difference [RD]: -4.2%; p < 0.001) and mortality (RD: -0.84%; p < 0.001). After instrumental variable analyses, bivalirudin remained associated with less bleeding (RD: -3.75%; p < 0.001), but not mortality (RD: -0.10%; p = 0.280). The higher rate of GPI use with UFH was responsible for more than one-half of bivalrudin's bleeding reduction (GPI-adjusted RD: -1.57%; p < 0.001). Bleeding reductions were negligible for transradial PCI (RD: -0.11%; p = 0.842).

CONCLUSIONS: The use of bivalirudin during STEMI has decreased. Bivalirudin was associated with reduced bleeding and no mortality difference. The bleeding reduction with bivalirudin was largely explained by the greater use of GPIs with UFH.

BACKGROUND: Bleeding is associated with poor outcomes after percutaneous coronary intervention (PCI). Although arterial closure devices (ACDs) are widely used in clinical practice, whether they are effective in reducing bleeding complications during transfemoral PCI is uncertain. The objective of this study was to evaluate the effectiveness of ACDs for the prevention of vascular access site complications in patients undergoing transfemoral PCI using an instrumental variable approach.

METHODS AND RESULTS: We performed a retrospective analysis of the CathPCI Registry from 2009 to 2013 at 1470 sites across the United States. Variation in the proportion of ACDs used by each individual physician operator was used as an instrumental variable to address potential confounding. A 2-stage instrumental variable analysis was used as the primary approach. The main outcome measure was vascular access site complications, and nonaccess site bleeding was used as a falsification end point (negative control) to evaluate for potential confounding. A total of 1 053 155 ACDs were used during 2 056 585 PCIs during the study period. The vascular access site complication rate was 1.5%. In the instrumental variable analysis, the use of ACDs was associated with a 0.40% absolute risk reduction in vascular access site complications (95% confidence interval, 0.31-0.42; number needed to treat=250). Absolute differences in nonaccess site bleeding were negligible (risk difference, 0.04%; 95% confidence interval, 0.01-0.07), suggesting acceptable control of confounding in the comparison.

CONCLUSIONS: ACDs are associated with a modest reduction in major bleeding after PCI. The number needed to treat with ACDs to prevent 1 major bleeding event is high.