Extended-release niacin/laropiprant for lipid management: observational study in clinical practice.

AIMS: Patients with dyslipidaemia or hypercholesterolemia carry a substantially increased cardiovascular risk and need optimal treatment of this key risk factor. We aimed to investigate the utilisation, efficacy and tolerability of the single pill combination extended-release niacin/laropiprant 1000 mg/20 mg or 2000 mg /40 mg under conditions of primary care practice. METHODS: The present study was a prospective, non-interventional, observational study involving 885 primary care physicians throughout Germany. Data on adult patients treated with niacin/laropiprant one or two tablets daily within the labelled indication were documented for an average of 23 ± 7 weeks. The study was registered in the Association of research-based pharmaceutical companies (VFA) database under no. 354. RESULTS: A total of 2359 patients were analysed in the intent-to-treat population (mean age 61.1 years, 67% males) of whom 1917 could be followed up. Background statin therapy was often discontinued and only about 50% of patients received two tables niacin/laropiprant at the end of the study. Individual goal attainment rates as subjectively determined by the investigator were for LDL-C 59.4%, total cholesterol 59.5%, HDL-C 72.8% and TG 51.5%, respectively. Objective (laboratory) goal attainment rates according to NCEP ATP III criteria were lower: LDL-C <100 mg/dl goal was achieved in 17.8%, HDL-C >40 in males or >50 mg/dl in females in 37.9% and TG <150 mg/dl in 18.7%. Totally, 422 adverse events were noted in 231 patients (9.7%), of which 317 were considered drug-related. Flushing occurred in 15%. CONCLUSION: Niacin/laropiprant resulted in beneficial effects on serum lipids and was generally well tolerated. The full potential of the drug combination was not explored by most physicians due to discontinuation of statins and lack of titration of the combination. Overall, treatment effects were consistent with those seen in controlled trials.

Eplerenone improves vascular function and reduces platelet activation in diabetic rats.

Diabetes is associated with endothelial dysfunction and platelet activation, both of which contribute to increased cardiovascular risk. We investigated whether the selective mineralocorticoid receptor (MR) antagonist eplerenone improves endothelial dysfunction and reduces platelet activation in diabetic rats. Male Wistar-rats were injected with streptozotocin (50 mg/kg i.v.) to induce insulin-deficient diabetes. After 2 weeks, treatment with eplerenone (100 mg/kg/day) or vehicle was initiated for 2 weeks. Aortic superoxide production determined by lucigenin-enhanced chemiluminescence and 2-hydroxyethidium formation was significantly increased in rats with diabetes and reduced by treatment with eplerenone (chemiluminescence: control 2045+/-227, STZ-placebo 3977+/-340, p<0.05 vs. control, STZ-eplerenone 1762+/-307, p<0.05 vs. STZ-placebo). Endothelium-dependent vasorelaxation was significantly attenuated in diabetic rats and was normalized by eplerenone (maximum relaxation in % of precontraction: control 95+/-3, STZ-placebo 82+/-3, p<0.01 vs. control, STZ-eplerenone 99+/-1, p<0.01 vs. STZ-placebo). Treatment with the selective MR antagonist significantly reduced fibrinogen-binding on activated GPIIb/IIIa (immunofluorescence: control 161+/-7, STZ-placebo 208+/-16, p<0.05 vs. control, STZ-eplerenone 173+/-6, p<0.05 vs. STZ-placebo). Eplerenone improves endothelial function by reducing superoxide formation and increasing NO bioavailability in diabetic rats. Platelet activation was significantly reduced by eplerenone. Selective MR blockade may constitute a useful therapeutic approach for treatment of vascular dysfunction in diabetes.

Improving antiplatelet therapy for atherothrombotic disease: preclinical results with SCH 530348, the first oral thrombin receptor antagonist selective for PAR-1.

Morbidity and mortality in patients with atherothrombotic disease remain high despite the use of antiplatelet therapy with aspirin and an ADP receptor antagonist. Selective inhibition of the principal protease-activated receptor (PAR)-1 for thrombin, the most potent agonist for platelet activation, represents a promising novel strategy to reduce thrombosis and ischaemic events. SCH 530348, a potent thrombin receptor antagonist (TRA) selective for PAR-1, has been evaluated in preclinical studies, demonstrating complete and sustained inhibition of thrombin/TRAP-induced platelet aggregation without a concomitant increase in the risk of bleeding. Phase 2 studies in patients undergoing non-urgent or urgent PCI showed that treatment with SCH 530348 in addition to the standard of care (aspirin plus an ADP receptor antagonist) is not associated with an increased risk of TIMI bleeding and is well tolerated, with a rate of adverse events comparable to standard therapy alone. These studies also demonstrated that the use of SCH 530348 in combination with aspirin and an ADP receptor antagonist may reduce the incidence of major adverse cardiac events, specifically periprocedural myocardial infarction, vs aspirin plus an ADP receptor antagonist alone. On the basis of these encouraging results, 2 ongoing large phase 3 randomized trials are evaluating the efficacy and safety of SCH 530348 in combination with the standard-of-care therapy in approximately 35,000 patients with NSTE ACS or established atherosclerosis.

[Antihypertensive first-line and add-on treatment with a fixed controlled release combination of metoprololsuccinate/hydrochlorothiazide. Prospective doctor's office observational study in 14,964 patients]. / Antihypertensive First-line- und Add-on-Therapie mit einer Metoprololsuccinat-Hydrochlorothiazid-Retardkombination. Prospektive Beobachtungsstudie mit 14,964 Patienten in der hausärztlichen Praxis.

AIM: To evaluate the efficacy and tolerability of a single daily dose of a fixed combination of 95 mg metoprololsuccinate (MS) and 12.5 mg hydrochlorothiazide (HCTZ) in the first-line treatment of non-pretreated hypertensives, or additional (add-on) to ongoing antihypertensive medication. METHOD: 14,964 patients aged 18 years or older treated by 2808 family doctors in Germany were included in a noncontrolled observational study. Most patients had at least one concurrent disease or concomitant medication of one kind or another. The primary target parameters for efficacy was the lowering of the systolic blood pressure (SBP) and diastolic blood pressure (DBP) after 8 weeks and for tolerability the number of patients reporting adverse events (AE). RESULTS: 65.4% of the patients received MS/HCTZ in the form of first-line treatment, the remainder as add-on therapy. The mean blood pressure decrease for the overall group by the end of the study was -24.5/-13.6 mmHg (baseline: 166.7/97.3 mmHg; p < 0.0001 for SBP and DBP). 92.2% of the patients experienced a decrease in SBP of > or = 10 mmHg. The mean heart rate decreased by 10.2 beats (baseline 81.4; p < 0.0001). The blood pressure decreased both in patients receiving MS/HCTZ alone and in those receiving it as an add-on to other antihypertensives. Only 1.4 of the patients reported AE. CONCLUSION: The MS/HCTZ controlled release combination was safe, efficacious and well-tolerated both as first-line and add-on therapy for essential hypertension.