BACKGROUND
Guidelines recommend nonstatin lipid-lowering agents in patients at very high risk for major adverse cardiovascular events (MACE) if low-density lipoprotein cholesterol (LDL-C) remains ≥70 mg/dL on maximum tolerated statin treatment. It is uncertain if this approach benefits patients with LDL-C near 70 mg/dL. Lipoprotein(a) levels may influence residual risk.
OBJECTIVES
In a post hoc analysis of the ODYSSEY Outcomes (Evaluation of Cardiovascular Outcomes After an Acute Coronary Syndrome During Treatment With Alirocumab) trial, the authors evaluated the benefit of adding the proprotein subtilisin/kexin type 9 inhibitor alirocumab to optimized statin treatment in patients with LDL-C levels near 70 mg/dL. Effects were evaluated according to concurrent lipoprotein(a) levels.
METHODS
ODYSSEY Outcomes compared alirocumab with placebo in 18,924 patients with recent acute coronary syndromes receiving optimized statin treatment. In 4,351 patients (23.0%), screening or randomization LDL-C was <70 mg/dL (median 69.4 mg/dL; interquartile range: 64.3–74.0 mg/dL); in 14,573 patients (77.0%), both determinations were ≥70 mg/dL (median 94.0 mg/dL; interquartile range: 83.2–111.0 mg/dL).
RESULTS
In the lower LDL-C subgroup, MACE rates were 4.2 and 3.1 per 100 patient-years among placebo-treated patients with baseline lipoprotein(a) greater than or less than or equal to the median (13.7 mg/dL). Corresponding adjusted treatment hazard ratios were 0.68 (95% confidence interval [Cl]: 0.52–0.90) and 1.11 (95% Cl: 0.83–1.49), with treatment-lipoprotein(a) interaction on MACE (
P
interaction
= 0.017). In the higher LDL-C subgroup, MACE rates were 4.7 and 3.8 per 100 patient-years among placebo-treated patients with lipoprotein(a) >13.7 mg/dL or ≤13.7 mg/dL; corresponding adjusted treatment hazard ratios were 0.82 (95% Cl: 0.72–0.92) and 0.89 (95% Cl: 0.75–1.06), with
P
interaction
= 0.43.
CONCLUSIONS
In patients with recent acute coronary syndromes and LDL-C near 70 mg/dL on optimized statin therapy, proprotein subtilisin/kexin type 9 inhibition provides incremental clinical benefit only when lipoprotein(a) concentration is at least mildly elevated. (ODYSSEY Outcomes: Evaluation of Cardiovascular Outcomes After an Acute Coronary Syndrome During Treatment With Alirocumab;
NCT01663402
)
Spherical submicrometer-sized silica particles were prepared from a reaction mixture containing tetraethoxysilane, ammonia and ethanol, and deposited onto silicon wafers. The properties of these SiO2 particles depend on their size, size distribution and shape. Even if some of these characteristics can be perfectly controlled by appropriate synthesis conditions, several alternative approaches must be explored in order to modify the shape of silica particles. The samples were then irradiated at room temperature with Si ions at different energies (4, 6 and 8 MeV) and fluences up to 5×1015 Si/cm2, at an angle of 45° with respect to the sample surface. After the Si irradiation the spherical silica particles turned into ellipsoidal particles, as a result of the increase of the particle dimension perpendicular to the ion beam and a decrease in the parallel direction. This effect increases with the ion fluence and depends on the electronic energy loss of the impinging ions. We observed that the particle deformation decreases with the beam energy, mainly because our samples were irradiated at room temperature. Thermal effects must be studied in detail in order to elucidate the complete deformation mechanism, as the existence of additional mechanisms related to the electronic energy loss effects can not be excluded.
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