Secondary prevention of MI still calls for a careful balancing act between risks and benefits.
Anna GarrettA recently published study showed that patients who received dual antiplatelet therapy two years post-myocardial infarction (MI) had a 15% lower risk of MI, stroke, or CV death compared with patients who received placebo plus aspirin during a median of 33 months follow-up.
Study patients were randomized to low-dose ticagrelor (60 mg twice daily), high-dose ticagrelor (90 mg twice daily), or placebo plus aspirin. The efficacy end point was virtually the same with low-dose or high-dose ticagrelor. However, patients had a 2.3-fold and 2.6-fold higher risk of clinically significant bleeding and a 3.0-fold and 3.7-fold higher risk of transfusion with low-dose and high-dose ticagrelor, respectively, compared with patients in the placebo group. The drug was also associated with an approximate 3-fold greater risk of dyspnea. Roughly 30% of patients discontinued the study drug.
Secondary prevention of MI still remains a careful balancing act between risks and benefits. These results suggest that low-dose ticagrelor plus aspirin may be a viable alternative for secondary MI prevention in patients for whom the benefits outweigh the risks of bleeding.
Source: Bonaca MP, Bhatt DL, Cohen M. Long-term use of ticagrelor in patients with prior myocardial infarction. NEJM 2015.http://bit.ly/Ltuticag. Published online March 14, 2015.
Polymorphisms in two genes, CYP2C9 and VKORC1, account for about 40% of the variability in patients' responses to warfarin. Use of FDA-approved initial-dosing recommendations based on these genetic tests increases time in the therapeutic range, but genotype-based dosing hasn't been shown to improve clinical outcomes. Testing is not reimbursed by Medicare.
In a previous trial (ENGAGE AF-TIMI 48), 21,105 adults with nonvalvular atrial fibrillation were randomized to receive warfarin (INR of 2.0–3.0) or daily edoxaban (30 or 60 mg) for a median of 2.8 years. Genotyping was done for more than 14,000 of these patients, who were then stratified as having a normal, sensitive, or highly sensitive response to warfarin (62%, 35%, and 3%, respectively).
In the first 90 days of treatment, those patients with a highly sensitive or sensitive response had supratherapeutic warfarin levels a greater proportion of time (18.3% and 8.4%, respectively) than did those with a normal response (2.2%), and were at excess risk for bleeding complications.
In patients with a highly sensitive or sensitive response, bleeding risk was reduced more for those who received edoxaban (compared with warfarin) than it was in a normal response. After 90 days, the difference in bleeding risk between edoxaban and warfarin was similar in all genotype groups.
Source: Mega JL, Walker JR, Ruff, CT et al. Genetics and the clinical response to warfarin and edoxaban: Findings from the randomised, double-blind ENGAGE AF-TIMI 48 trial. Lancet 2015. http://bit.ly/clinwarfedox. Published online March 10, 2015.
Newer anticoagulants offer advantages in treatment of patients with venous thromboembolism (VTE) because injectable bridging therapy and routine laboratory monitoring are not required. A recent retrospective claims analysis compared the hospitalization rate of patients treated with rivaroxaban after its introduction with what costs would have been before the introduction of rivaroxaban.
Adult patients with a primary diagnosis of deep vein thrombosis (DVT) treated with rivaroxaban or low-molecular-weight heparin (LMWH) transitioned to warfarin during the first day of hospital evaluation were included in the study. All rivaroxaban-treated patients (n = 134) in the database were matched 4:1 with historical LMWH/warfarin-treated patients (n = 536). Sixty percent of the patients on rivaroxaban were admitted to the hospital, compared to 82% of the historical controls.
This difference was statistically significant and corresponded to a 27% reduction in hospital admissions. Hospitalization rates adjusted for time-trend analyses also led to similar results. The authors concluded that the availability of rivaroxaban significantly reduced the hospitalization rates in patients with DVT.
Source: Merli GJ, Hollander JE, Lefebvre P et al. Rates of hospitalization among patients with deep vein thrombosis before and after the introduction of rivaroxaban. Hosp Pract. 2015;43:85–93.