PracticeUpdate: Cardiology

AHA 2016

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Two treatment strategies of rivaroxaban reduce rehospitalisation in patients with AF undergoing intracoronary stenting In patients with atrial fibrillation who underwent intracoronary stenting, two rivaroxaban strategies reduced rehospitalisations potentially attributable to either bleeding or cardiovascular events. T his outcome of a study comparing rivaroxaban plus a P2Y12 inhibitor monotherapy or rivaroxaban plus dual antiplatelet therapy was reported at the AHA Scientific Sessions 2016. Michael Gibson, MS, MD, of Beth Israel Deaconess Medical Center, Boston, Massachusetts, explained that patients with atrial fibrillation who undergo intracoronary stenting traditionally are treated with a vitamin K antagonist plus dual antiplatelet therapy, though this treatment leads to high risk of bleeding. Dr Gibson and colleagues hypothesised that a regimen of rivaroxaban plus a P2Y12 inhibitor monotherapy or rivaroxaban plus dual antiplatelet therapy would reduce bleeding and exert a favourable impact on all-cause mortality and the need for rehospitalisation. Stented subjects with nonvalvular atrial fibrillation (n=2124) were randomised 1:1:1 to: • Group 1: reduced-dose rivaroxaban 15 mg daily plus a P2Y12 inhibitor for 12 months. • Group 2: rivaroxaban 2.5 mg twice daily with stratification to a prespecified duration of dual antiplatelet therapy of 1, 6, or 12 months. • Group 3: the reference arm of dose-adjusted vitamin K antagonist daily with similar dual antiplatelet therapy stratification. Post hoc analysis assessed the endpoint of all-cause mortality or recurrent hospitalisation for an adverse event, which was further classified as the result of bleeding, a cardiovascular, or another cause blinded to treatment assignment. The risk of all-cause mortality or recurrent hospitalisation was 34.9% in Group 1 (hazard ratio 0.79, 95% CI 0.66–0.94, P = 0.008 vs Group 3, number needed to treat 15); 31.9% in Group 2 (hazard ratio 0.75; 95% CI 0.62–0.90; P = 0.002 vs Group 3, number needed to treat 10); and 41.9% in Group 3 (vitamin K antagonist + dual antiplatelet therapy). Both all-cause death plus hospitalisation potentially resulting from bleeding (Group 1, 8.6% [P = 0.032 vs Group 3]; Group 2, 8.0% [P = 0.012 vs Group 3]; and Group 3, 12.4%); and all- cause death plus rehospitalisation potentially resulting from a cardiovascular cause (Group 1, 21.4% [P = 0.001 vs Group  3], Group 2, 21.7% [P = 0.011 vs Group 3]; and Group 3, 29.3%) were reduced in the rivaroxaban arms vs the vitamin K antagonist arm, but other forms of rehospitalisation were not. Dr Gibson concluded that among patients with atrial fibrillation undergoing intracoronary stenting, administration of either rivaroxaban 15 mg daily plus P2Y12 inhibitor monotherapy or 2.5 mg rivaroxaban twice daily plus dual antiplatelet therapy was associated with a reduced risk of all- cause mortality or recurrent hospitalisation for adverse events vs standard-of-care vitamin K antagonism plus dual antiplatelet therapy. grafting does not add further clinical benefit but may increase the risk of sternal wound complication especially in at risk populations. >9 In summary, adding onemore IMA graft to patients undergoing CABGwith LIMA

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Reconstituted apolipoprotein A-I CSL112 enhances cholesterol efflux after acute MI The reconstituted, infusible, plasma-derived apolipoprotein A-I has been shown to enhance choles- terol efflux after acute myocardial infarction, with no significant alterations in liver or kidney function or other safety concern, reports the Apo-I Event Reducing in Ischemic Syndromes I (AEGIS-I) trial. M ichael Gibson, MS, MD, of Beth Israel Deaconess Medical Center, Boston, of 5%. CSL112 was associated with increases in apolipoprotein A-I and ex vivo cholesterol efflux similar to that achieved in patients with stable coronary artery disease.

Coprimary safety endpoints were the occurrence of either a hepatic safety event (an increase in alanine transaminase more than three times the upper limit of normal or an increase in total bilirubin more than twice the upper limit of normal) or a renal safety event (an increase in serum creatinine >1.5 times the baseline value or a new requirement of renal replacement therapy). A total of 1258 patients were randomised, and 91.2% received all four infusions. The difference in incidence rates for an increase in alanine transaminase or total bilirubin between both CSL112 arms and placebo was within the protocol-defined noninferiority margin of 4%. Similarly, the difference in incidence rates of an increase in serum creatinine or a new requirement for renal replacement therapy was within the protocol-defined noninferiority margin

assachusetts, explained that human or recombinant apolipoprotein A-I has been shown to increase high-density lipoprotein – mediated cholesterol efflux capacity and to regress atherosclerotic disease in animal and clinical studies. CSL112 is an infusible, plasma-derived apolipoproteinA-I that has been studied in normal subjects or those with stable coronary artery disease. AEGIS-I was a multicentre, randomised, double-blind, placebo- controlled, dose-ranging phase 2b trial. Patients with myocardial infarction were stratified by renal function and randomised 1:1:1 to CSL112 (2 g apolipoprotein A-I per dose) and high- dose CSL112 (6 g apolipoprotein A-I per dose), or placebo for four consecutive weekly infusions.

With regard to the secondary efficacy endpoint, the risk for the composite of major adverse cardiovascular events among the groups was similar. Dr Gibson concluded that among patients with acute myocardial infarction, four weekly infusions of CSL112 were shown to be feasible, well tolerated, and not associated with any significant alterations in liver or kidney function or other safety concern. The ability of CSL112 to acutely enhance cholesterol efflux was confirmed. The potential benefit of CSL112 to reduce major adverse cardiovascular events needs to be assessed in an adequately powered phase 3 trial.

VOL. 1 • No. 3 • 2016