Dual antiplatelet therapy lowers risk of CV death in MI secondary prevention

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.

See also: Warfarin does not decrease stroke risk in dialysis patients

Pharmacogenetic testing worthwhile for newer anticoagulants

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.

See also: Oral anticoagulation may not help all AF patients

Rivaroxaban saves on hospital admissions for DVT

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.