Practice Update: Cardiology

AHA 2016 29

Dr Ben Scirica presents his top abstracts from AHA 2016, including ORION 1, MILANO-PILOT and ATHENAHF

The analysis focused on the 7875 (57%) patients enrolled based on prior lower extremity revascularisation. Patients could not be enrolled within 30 days of their most recent revascularisation, and patients with an indication for dual antiplatelet therapy were excluded. The primary efficacy endpoint was a composite of cardiovascular death, myocardial infarction, or ischaemic stroke. The primary safety endpoint was major bleeding. Patients who had undergone prior revascularisation were a mean age of 66 years, 73% were male, and median baseline ankle-brachial index was 0.78. After adjustment for baseline characteristics, patients enrolled based on prior revascularisation experienced similar rates of the primary composite endpoint (hazard ratio 1.10, 95%CI 0.98–1.23) and statistically significantly higher rates of myocardial infarction (hazard ratio 1.29, 95% CI 1.08–1.55, P = 0.005) and acute limb ischaemia (hazard ratio 4.23, 95% CI 2.86–6.25, P < 0.001) than patients enrolled based on ankle-brachial index criteria. No differences in ticagrelor- versus clopidogrel-treated patients were observed for the primary efficacy endpoint (11.4% vs 11.3%, hazard ratio 1.01, 95% CI 0.88–1.15); all-cause mortality (9.2% vs 9.2%, hazard ratio 0.99, 95% CI 0.86–1.15); acute limb ischaemia (2.5% vs 2.5%; hazard ratio 1.03, 95% CI 0.78–1.36); or major bleeding (1.9% vs 1.8%; hazard ratio 1.15, 95% CI 0.83–1.59). The median duration of follow-up was approximately 30 months. Dr Jones said that after adjustment for baseline characteristics, patients enrolled based on prior revascularisation for peripheral artery disease experienced higher rates of myocardial infarction and acute limb ischaemia with similar composite rates of cardiovascular death, myocardial infarction, and stroke versus patients enrolled based on the ankle-brachial index criterion. No significant differences between ticagrelor and clopidogrel were observed in reduction of cardiovascular or acute limb events. The findings suggest that patients with prior revascularisation have a substantial residual rate of cardiovascular and acute limb events, despite high adherence to antiplatelet and statin medications, and require further study. The findings not only add context to knowledge of antiplatelet monotherapy after revascularisation for peripheral artery disease, but they also highlight the need for more trials of antithrombotic agents after revascularisation. Specifically, whether patients should be treated with one or two antiplatelet agents, which agents should be used, the duration of antiplatelet monotherapy or dual therapy, and whether antithrombotics that utilise different mechanistic pathways (for example, P2Y12 receptor antagonists, factor Xa inhibitors) should be used in isolation or in combination for these complex patients to reduce their long-term rates of cardiovascular events and acute limb ischaemia have not been determined. Finally, while the optimal antiplatelet medication regimen is being studied and developed, the impact of disease presenta- tion, anatomic burden of disease, and type of revascularisation procedures need to be understood. “While ticagrelor was no more effective in reducing risk than clopidogrel,” Dr Schuyler Jones said, “we learned valuable in- formation about this population, specifically, that patients with a history of lower extremity revascularisation are at higher risk of acute limb events and cardiovascular events.”

Benjamin Morgan Scirica MD Associate Professor of Medicine, Harvard Medical School and PracticeUpdate Cardiology Editorial Board member, recommended the following papers presented at this year’s

AHA Scientific Sessions. LBCT.01: Big trials for big questions EUCLID – Effects of ticagrelor compared with clopidogrel in patients with peripheral artery disease. MR Patel, FGR Fowkes, JS Berger, et al • The EUCLID trial was designed to test if long-term monother- apy treatment with ticagrelor would be superior to clopidogrel at preventing cardiovascular death, myocardial infarction, or ischaemic stroke in patients with symptomatic PAD. • This is a very large trial comparing cardiovascular outcomes with three commonly used NSAIDs in high-cardiovascular risk patients. LBCT.03: Insights from new therapeutic trials for lipids ORION 1 – Inhibition of PCSK9 synthe- sis via RNA interference: 90 day data fromOrion-1 – a multi-centre phase-2 randomized controlled trial. KK Ray, U Landmesser, LA Leiter, et al • ORION1 will provide information on safety and efficacy of using RNA interference quarterly or biannually to target intracellular PCSK9 production as a means to lower LDL-C in a large patient cohort. PRECISION – Cardiovascular outcomes with celecoxib vs ibuprofen or naproxen: the PRECISION trial. SE Nissen

GLAGOV – effect of evolocumab on progression of coronary athero- sclerosis in statin-treated patients: a placebo-controlled intravascular ultrasound trial. SE Nissen • This trial is the first to assess the effects of a PCSK9 inhibitor on the regression or progression of coro- nary atherosclerosis as assessed by intravascular ultrasound. MILANO-PILOT – impact of infusion of an ApoA-I HDL mimetic on regression of coronary atherosclerosis in acute coronary syndrome patients: The MILANO- PILOT Study. S Nicholls, S Nissen, D Kallend, et al • This trial was designed to evaluate whether infusions of a HDL mimetic containing apia-I Milano would promote regression of coronary atherosclerosis. LBCT.04: Guiding the momentum to effect HF outcomes – ironing out the wrinkles ATHENA HF – Aldosterone Targeted NeuroHormonal CombinEd with Natriuresis TherApy in Heart Failure (ATHENA-HF) trial. J Butler, MA Konstam, M Felker, et al • This trial assesses the use of high-dose spironolactone versus standard of care in patients with acute heart failure.

DECEMBER 2016