Effects of Anacetrapib in Patients with Atherosclerotic Vascular Disease

BACKGROUND: Patients with atherosclerotic vascular disease remain at high risk for cardiovascular events despite effective statin-based treatment of low-density lipoprotein (LDL) cholesterol levels. The inhibition of cholesteryl ester transfer protein (CETP) by anacetrapib reduces LDL cholesterol levels and increases high-density lipoprotein (HDL) cholesterol levels. However, trials of other CETP inhibitors have shown neutral or adverse effects on cardiovascular outcomes. METHODS: We conducted a randomized, double-blind, placebo-controlled trial involving 30,449 adults with atherosclerotic vascular disease who were receiving intensive atorvastatin therapy and who had a mean LDL cholesterol level of 61 mg per deciliter (1.58 mmol per liter), a mean non-HDL cholesterol level of 92 mg per deciliter (2.38 mmol per liter), and a mean HDL cholesterol level of 40 mg per deciliter (1.03 mmol per liter). The patients were assigned to receive either 100 mg of anacetrapib once daily (15,225 patients) or matching placebo (15,224 patients). The primary outcome was the first major coronary event, a composite of coronary death, myocardial infarction, or coronary revascularization. RESULTS: During the median follow-up period of 4.1 years, the primary outcome occurred in significantly fewer patients in the anacetrapib group than in the placebo group (1640 of 15,225 patients [10.8%] vs. 1803 of 15,224 patients [11.8%]; rate ratio, 0.91; 95% confidence interval, 0.85 to 0.97; P=0.004). The relative difference in risk was similar across multiple prespecified subgroups. At the trial midpoint, the mean level of HDL cholesterol was higher by 43 mg per deciliter (1.12 mmol per liter) in the anacetrapib group than in the placebo group (a relative difference of 104%), and the mean level of non-HDL cholesterol was lower by 17 mg per deciliter (0.44 mmol per liter), a relative difference of -18%. There were no significant between-group differences in the risk of death, cancer, or other serious adverse events. CONCLUSIONS: Among patients with atherosclerotic vascular disease who were receiving intensive statin therapy, the use of anacetrapib resulted in a lower incidence of major coronary events than the use of placebo. (Funded by Merck and others; Current Controlled Trials number, ISRCTN48678192 ; ClinicalTrials.gov number, NCT01252953 ; and EudraCT number, 2010-023467-18 .)

Rank Bounds and Integrality Gaps for Cutting Planes Procedures

We present a new method for proving rank lower bounds for Cutting Planes (CP) and several procedures based on lifting due to Lova sz and Schrijver (LS), when viewed as proof systems for unsatisfiability. We apply this method to obtain the following new results: First, we prove near-optimal rank bounds for Cutting Planes and Lova ́sz- Schrijver proofs for several prominent unsatisfiable CNF examples, including random kCNF formulas and the Tseitin graph formulas. It follows from these lower bounds that a linear number of rounds of CP or LS procedures when applied to relaxations of integer linear programs is not sufficient for reducing the integrality gap. Secondly, we give unsatisfiable examples that have constant rank CP and LS proofs but that require linear rank Resolution proofs. Thirdly, we give examples where the CP rank is O(logn) but the LS rank is linear. Finally, we address the question of size versus rank: we show that, for both proof systems, rank does not accurately reflect proof size. Specifically, there are examples with polynomial-size CP/LS proofs, but requiring linear rank

Computing Shortest Resolution Proofs

EPIA Conference on Artificial Intelligence (19th. 2019. Vila Real, Portugal

Lower bounds for lovász-schrijver systems and beyond follow from multiparty communication complexity

Abstract. We prove that an ω(log 3 n) lower bound for the three-party numberon-the-forehead (NOF) communication complexity of the set-disjointness function implies an n ω(1) size lower bound for tree-like Lovász-Schrijver systems that refute unsatisfiable CNFs. More generally, we prove that an n Ω(1) lower bound for the (k + 1)-party NOF communication complexity of set-disjointness implies a 2 nΩ(1) size lower bound for all tree-like proof systems whose formulas are degree k polynomial inequalities.

Optimal Sherali-Adams Gaps from Pairwise Independence

This work considers the problem of approximating fixed predicate constraint satisfaction problems (MAX k-CSP(P)). We show that if the set of assignments accepted by P contains the support of a balanced pairwise independent distribution over the domain of the inputs, then such a problem on n variables cannot be approximated better than the trivial (random) approximation, even using Ω(n) levels of the Sherali-Adams LP hierarchy. It was recently shown [3] that under the Unique Game Conjecture, CSPs for predicates satisfying this condition cannot be approximated better than the trivial approximation. Our results can be viewed as an unconditional analogue of this result in the restricted computational model defined by the Sherali-Adams hierarchy. We also introduce a new generalization of techniques to define consistent “local distributions ” over partial assignments to variables in the problem, which is often the crux of proving lower bounds for such hierarchies