Abraham, Neena S.

SummaryBackgroundGastrointestinal bleeding (GIB) frequently occurs following percutaneous coronary intervention (PCI) for acute coronary syndrome (ACS) with the prescription of P2Y12 inhibiting antiplatelet agents. Compared with clopidogrel, the newer P2Y12 inhibitors lower major adverse cardiac events with similar or possibly higher major bleeding events. The comparative GIB rates of these medications remain poorly understood.AimTo compare GIB rates associated with clopidogrel, prasugrel and ticagrelor using national medical and pharmacy claims data from privately insured and Medicare Advantage enrollees .MethodsPropensity score and inverse probability treatment weighting were used to balance baseline characteristics among treatment groups. The 1‐year GIB risk was calculated using weighted Cox proportional hazard models and expressed as hazard ratios (HR) with 95% confidence intervals (CI) and number needed to harm (NNH).ResultsWe identified 37 019 patients with ACS (non‐ST elevation ACS [NSTE‐ACS] and ST‐elevation myocardial infarction [STEMI]) within 14 days of a PCI (mean age 63 years and 70% male). Clopidogrel prescription was most common (69%) with prasugrel (16%) and ticagrelor (14%) prescribed less frequently. When compared with clopidogrel, ticagrelor was associated with a 34% risk reduction (HR 0.66; 95% CI: 0.54–0.81) in GIB overall and with NSTE‐ACS, and a 37% GIB risk reduction (HR 0.63; 95% CI: 0.42–0.93) in STEMI patients. When compared with clopidogrel, prasugrel was associated with a 21% risk reduction (HR 0.79; 95% CI: 0.64–0.97) overall, a 36% GIB risk reduction (HR 0.64; 95% CI: 0.49–0.85) in STEMI patients but no reduction of GIB risk in NSTE‐ACS patients.ConclusionsIn the first year following PCI, ticagrelor or prasugrel are associated with fewer GIB events than clopidogrel.

Background The introduction of non–vitamin K antagonist oral anticoagulants has been a major advance for stroke prevention in atrial fibrillation; however, outcomes achieved in clinical trials may not translate to routine practice. We aimed to evaluate the effectiveness and safety of dabigatran, rivaroxaban, and apixaban by comparing each agent with warfarin. Methods and Results Using a large US insurance database, we identified privately insured and Medicare Advantage patients with nonvalvular atrial fibrillation who were users of apixaban, dabigatran, rivaroxaban, or warfarin between October 1, 2010, and June 30, 2015. We created 3 matched cohorts using 1:1 propensity score matching: apixaban versus warfarin (n=15 390), dabigatran versus warfarin (n=28 614), and rivaroxaban versus warfarin (n=32 350). Using Cox proportional hazards regression, we found that for stroke or systemic embolism, apixaban was associated with lower risk (hazard ratio [ HR ] 0.67, 95% CI 0.46–0.98, P =0.04), but dabigatran and rivaroxaban were associated with a similar risk (dabigatran: HR 0.98, 95% CI 0.76–1.26, P =0.98; rivaroxaban: HR 0.93, 95% CI 0.72–1.19, P =0.56). For major bleeding, apixaban and dabigatran were associated with lower risk (apixaban: HR 0.45, 95% CI 0.34–0.59, P <0.001; dabigatran: HR 0.79, 95% CI 0.67–0.94, P <0.01), and rivaroxaban was associated with a similar risk ( HR 1.04, 95% CI 0.90–1.20], P =0.60). All non–vitamin K antagonist oral anticoagulants were associated with a lower risk of intracranial bleeding. Conclusions In patients with nonvalvular atrial fibrillation, apixaban was associated with lower risks of both stroke and major bleeding, dabigatran was associated with similar risk of stroke but lower risk of major bleeding, and rivaroxaban was associated with similar risks of both stroke and major bleeding in comparison to warfarin.

Background In comparison to warfarin, non–vitamin K antagonist oral anticoagulants ( NOAC s) have the advantages of ease of dosing, fewer drug interactions, and lack of need for ongoing monitoring. We sought to evaluate whether these advantages translate to improved adherence and whether adherence is associated with improved outcomes in patients with atrial fibrillation. Methods and Results We performed a retrospective cohort analysis by using a large US commercial insurance database to identify 64 661 patients with atrial fibrillation who initiated warfarin, dabigatran, rivaroxaban, or apixaban treatment between November 1, 2010, and December 31, 2014. During a median of 1.1 y of follow‐up, 47.5% of NOAC patients had a proportion of days covered of ≥80%, compared with 40.2% in warfarin patients ( P <0.001). Patients with CHA 2 DS 2 ‐ VAS c (risk based on the presence of congestive heart failure, hypertension age 65–74 y, age ≥75 y, diabetes mellitus, prior stroke or transient ischemic attack, vascular disease, sex category) score ≥4 were at increased risk of stroke when they were not taking anticoagulation ≥1 month versus <1 week (1–3 months: hazard ratio [ HR ] 1.96, 3–6 months: HR 2.64, ≥6 months: HR 3.66; all P <0.001). Patients with CHA 2 DS 2 ‐ VAS c score 2 or 3 were at increased risk of stroke when they were not taking anticoagulation ≥6 months ( HR 2.73, P <0.001). In these patients with CHA 2 DS 2 ‐ VAS c score ≥2, nonadherence was not associated with intracranial hemorrhage. Among patients with CHA 2 DS 2 ‐ VAS c score 0 or 1, time not taking anticoagulation was not associated with stroke, but not taking anticoagulation ≥3 months was associated with a significant reduction of bleeding. Conclusions Adherence to anticoagulation is poor in practice and may be modestly improved with NOAC s. Adherence to therapy appears to be most important in patients with CHA 2 DS 2 ‐ VAS c score ≥2, whereas the benefits of anticoagulation may not outweigh the harms in patients with CHA 2 DS 2 ‐ VAS c score 0 or 1.

Background— Complex antithrombotic therapy (CAT) prescribed to elderly patients increases the risk of gastrointestinal bleeding. We quantified upper (UGIE) and lower gastrointestinal (LGIE) events, transfusions, and hospitalizations in a national cohort of elderly veterans prescribed CAT. Methods and Results— Veterans ≥60 years of age prescribed anticoagulant-antiplatelet, aspirin (ASA)-antiplatelet, ASA-anticoagulant, or triple therapy (ie, TRIP, anticoagulant-antiplatelet-ASA) were identified from the national pharmacy database (October 1, 2002 to September 30, 2008). Prescription-fill data were linked to Veteran Affairs and Medicare encounter files, each person-day of follow-up was assessed for CAT exposure, and outcomes were defined by using diagnostic code algorithms derived following chart abstraction. Incidence density ratios (compared with the reference category of no CAT) and survival analysis was conducted. Among 78 133 veterans (98.6% white; mean age, 72.3 [standard deviation 7.7]), 64% were prescribed ASA-antiplatelet and anticoagulant-antiplatelet and 6% were prescribed TRIP. The incidence of UGIE was 20.1/1000 patient-years, and the incidence of LGIE was 70.1/1000 patient-years. ASA-anticoagulant and TRIP were associated with the highest incidence of transfusion and hospitalization. A 40% to 60% increased risk of UGIE was observed with all strategies. LGIE was 30% higher with anticoagulant-antiplatelet, and transfusion increased with ASA-anticoagulant (hazard ratio, 6.1; 95% confidence interval, 5.2–7.1) and TRIP (hazard ratio, 5.0; 95% confidence interval, 4.2–5.8). Increased risk of hospitalization was noted with all strategies. The number needed to harm for UGIE or LGIE ranged from 52 to 65 and 15 to 23, respectively. The number needed to harm for hospitalization was 39 (anticoagulant-antiplatelet), 34 (ASA-anticoagulant), 67 (ASA-antiplatelet), and 45 (TRIP) patients. Conclusions— Among elderly patients, CAT-related LGIE and UGIE are clinically relevant risks resulting in increased hospitalizations and transfusions.