Prescribing Patterns of Proprotein Convertase Subtilisin-Kexin Type 9 Inhibitors in Eligible Patients With Clinical Atherosclerotic Cardiovascular Disease or Heterozygous Familial Hypercholesterolemia.

Two proprotein convertase subtilisin-kexin type 9 (PCSK9) inhibitors are approved for patients with atherosclerotic cardiovascular disease or heterozygous familial hypercholesterolemia who require additional low-density lipoprotein cholesterol (LDL-C) lowering. This retrospective study sought to determine differences between eligible patients who were prescribed and those who were not prescribed a PCSK9 inhibitor. Patients from an electronic medical record database were included in the analysis, and their demographic, clinical, and treatment characteristics were evaluated. Of 368,624 PCSK9 inhibitor-eligible patients, 1,752 (<0.5%) received a PCSK9 inhibitor prescription. Patients who received a PCSK9 inhibitor were more frequently associated with a higher cardiovascular disease risk category and a higher baseline LDL-C level (139.4 vs 103.5 mg/dl; p <0.0001) compared with those who did not. Patients with a PCSK9 inhibitor prescription were significantly more likely to be on ezetimibe, alone or in combination with a statin, at baseline compared with those without (29% vs 5%; p <0.0001). The use of a PCSK9 inhibitor was very low in the 2 groups of patients identified as PCSK9 inhibitor-eligible based on the American College of Cardiology Expert Consensus Decision Pathway. In conclusion, this study demonstrates that most PCSK9 inhibitor-eligible patients do not receive a PCSK9 inhibitor prescription, highlighting that many high-risk patients could benefit from additional LDL-C lowering with a PCSK9 inhibitor.

Association Between Hospitalization for Heart Failure and Dipeptidyl Peptidase 4 Inhibitors in Patients With Type 2 Diabetes: An Observational Study.

OBJECTIVE: To examine, among patients with type 2 diabetes, the association between hospitalization for heart failure (hHF) and treatment with dipeptidyl peptidase 4 inhibitors (DPP-4is) versus sulfonylureas (SUs), and treatment with saxagliptin versus sitagliptin. RESEARCH DESIGN AND METHODS: This was a retrospective, observational study using a U.S. insurance claims database. Patients initiated treatment between 1 August 2010 and 30 August 2013, and had no use of the comparator treatments in the prior 12 months (baseline). Each comparison consisted of patients matched 1:1 on a propensity score. Time to each outcome was compared between matched groups using Cox models. Analyses were stratified by the presence of baseline cardiovascular disease (CVD). Secondary analyses examined associations between comparator treatments and other selected cardiovascular events. RESULTS: After matching, the study included 218,556 patients in comparisons of DPP-4i and SU, and 112,888 in comparisons of saxagliptin and sitagliptin. The hazard ratios (HRs) of hHF were as follows: DPP-4i versus SU (reference): HR 0.95 (95% CI 0.78-1.15), P = 0.580 for patients with baseline CVD; HR 0.59 (95% CI 0.38-0.89), P = 0.013 for patients without baseline CVD; saxagliptin versus sitagliptin (reference): HR 0.95 (95% CI 0.70-1.28), P = 0.712 for patients with baseline CVD; HR 0.99 (95% CI 0.56-1.75), P = 0.972 for patients without baseline CVD. Comparisons of the individual secondary and composite cardiovascular outcomes followed a similar pattern. CONCLUSIONS: In patients with type 2 diabetes, there was no association between hHF, or other selected cardiovascular outcomes, and treatment with a DPP-4i relative to SU or treatment with saxagliptin relative to sitagliptin.

Synthesis and biological evaluation of menthol-based derivatives as inhibitors of plasminogen activator inhibitor-1 (PAI-1).

Compound 1 was identified by high throughput screening as a novel PAI-1 inhibitor. Optimization of the B and C-segments of 1 resulted in a series of structurally simplified compounds with improved potency. The synthesis and SAR data of these compounds are presented here.

Automated parallel solid-phase synthesis of non-peptide CCR1 receptor antagonists.

An automated, parallel, solid-phase synthesis and screening strategy using commercially available aryl acetic acids as starting materials has discovered novel, non-peptide CCR1 antagonists (K(i) < 100 nM).