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.

Pleiotrophic and anti-inflammatory effects of pioglitazone precede the metabolic activity in type 2 diabetic patients with coronary artery disease.

We investigated MMP-9 levels and inflammatory markers during pioglitazone treatment in type 2 diabetic patients with cardiovascular disease. In this randomized multicenter, double blinded, placebo controlled study, 92 type 2 diabetic patients with angiographically proven CHD were randomly assigned to pioglitazone or placebo treatment. At baseline and during a 28 days observational period MMP-9, MCP1, hsCRP, IL-6, sCD40, and P-selectin were monitored. During Pioglitazone treatment, a 12% reduction in MMP-9 and a 18% reduction in hsCRP levels (p<0.05, respectively) could be observed already after 3 days. MCP-1 levels were reduced by 14% after 10 days of treatment (p<0.0001). At the end of the study, these parameters were significantly lower in the pioglitazone group as compared to the placebo group (MMP-9: 392+/-286 versus 427+/-166 ng/ml; hsCRP: 1.9+/-1.7 versus 3.1+/-2.3 ng/L; MCP-1: 413+/-115 versus 471+/-146 pg/ml; p<0.05, respectively). sCD40 levels decreased by 32.5% (p<0.05) and P-selectin decreased by 3.2% (p=0.053) in the pioglitazone group. No change could be found with regard to the other study endpoints. No changes in these parameters could be observed during placebo treatment. Even before effects on glucose metabolism could be obtained, pioglitazone exerts immediate effects on plasma markers of plaque vulnerability and inflammation.

Improved assessment of intravascular Doppler coronary flow velocity profile.

Easy and safe in-vivo flow velocity studies in small coronary arteries have become feasible using a 0.014 'or 0.018' guidewire with an integrated Doppler probe in its tip (FloWire, Cardiometrics). Assessment of the flow velocity profile by the ratio of diastolic to systolic flow velocity (DSVR) is used as a diagnostic parameter. However, DSVR is a coarse quantifier of the flow velocity profile, and is subject to large physiologic variance and depends crucially on the quality of the Doppler signal. The aim of our study was to test parameters derived from statistical time series analysis for monitoring the quality of the instantaneous peak velocity (IPV) signal. Improvement of quantification of changes in quality and shape of flow velocity profiles by these parameters as compared to DSVR was a second goal. We investigated analog-digital converted IPV-signals and video registrations of corresponding greyscale spectra of intracoronary Doppler flow velocity signals. The signals were analyzed by using the autocorrelation function (ACF) in the time domain and a fast Fourier transform (FFT) in the frequency domain (standard time series statistics). The first minimum of autocorrelation function turned out to be very sensitive to signal quality, and Fisher's g of the periodogram was the parameter of choice for shape analysis. In 11 patients with coronary artery disease, pre and post PTCA, the sensitivity of DSVR and signal to noise ratio to changes in shape and quality of the flow velocity signals was compared to that of the new parameters. Nineteen Doppler flow velocity samples of good quality from measurements in nonstenotic vessels and 7 flow velocity tracings with visible artefacts were used to assess the value of these parameters in monitoring signal quality. By comparison with corresponding parameters in use (SNR and DSVR) a significantly improved performance of the new statistical parameters was observed with respect to sensitivity to changes in signal quality and flow profile. In view of these results and because of the short calculation time of these variables they should be used for on-line quality control and analysis of flow velocity profiles.