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
)
Abstract. Climate change and its possible effects on water resources has become an increasingly near threat. Therefore, the study of these impacts in highly regulated systems and those suffering extreme events is essential to deal with them effectively. This study responds to the need for an effective method to integrate climate change projections into water planning and management analysis in order to guide the decision-making, taking into account drought risk assessments. Therefore, this document presents a general and adaptive methodology based on a modeling chain and correction processes, whose main outcomes are the impacts on future natural inflows, a drought risk indicator, and the simulation of future water storage in the water resources system (WRS). This method was applied in the Júcar River basin (JRB) due to its
complexity and the multiannual drought events it suffers recurrently. The
results showed a worrying decrease in future inflows, as well as a high
probability (≈80 %) of being under 50 % of total capacity of
the WRS in the near future. However, the uncertainty of the results was
considerable from the mid-century onwards, indicating that the skill of climate
projections needs to be improved in order to obtain more reliable results.
Consequently, this paper also highlights the difficulties of developing this
type of method, taking partial decisions to adapt them as far as possible
to the basin in an attempt to obtain clearer conclusions on climate change
impact assessments. Despite the high uncertainty, the results of the JRB call for action and the
tool developed can be considered as a feasible and robust method to
facilitate and support decision-making in complex basins for future water
planning and management.
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