Treatment preferences as basis for decision making in patients using direct oral anticoagulants in Spain.

Treatment preferences are considered a relevant decision-making driver by the main atrial fibrillation (AF) guidelines. Direct Oral Anticoagulants (DOACs), considered as similar clinically, have administration differences useful for treatment individualization. Preferences, priorities and satisfaction of DOAC users were assessed through an observational, multicentric (25 hospitals), cross-sectional study including adult AF-patients (and/or caregivers) in Spain. Three study groups were considered according to DOAC posology preferences: (A) once-daily, with water; (B) once-daily, with food; (C) twice-daily. Overall, 332 patients and 55 caregivers were included. Mean (SD) age was 73.7 (10.7) years [58.7 (13.9) for caregivers]; 51.5% women [69.1% for caregivers]; 80.7% showed comorbidities and poly-pharmacy [6.6 (3.3) drugs/day]. No statistically significant differences were shown among study groups. Once-daily administration was preferred by 274 patients (82.5%) [60.8% (Group A); 21.7% (Group B); 17.5% (Group C)], and 47 caregivers (85.5%) [58.2% (Group A); 27.3% (Group B); 14.5% (Group C)]. Once-daily DOACs were prescribed in 42.8% of the patients. Bleeding risk was the main concern for both, patients and caregivers, followed by DOAC posology and interactions. Although treatment satisfaction (patients and caregivers) was high (9.0 and 9.1 points, respectively), match between individual treatment preferences and real prescriptions was only shown in 41.0% of AF-patients, evidencing a need for patient involvement on treatment decision-making. There is not a patient profile linked to treatment preferences, and clinical criteria must be the main driver for decision-making. However, for most AF-patients (elderly patients), aged, with comorbidity, poly-pharmacy and high cardiovascular risk, once-daily DOACs would be the preferred option.

Genetic variation in the hepatic lipase gene is associated with combined hyperlipidemia, plasma lipid concentrations, and lipid-lowering drug response.

BACKGROUND: Combined hyperlipidemia (CHL) is a very frequent dyslipidemia, being lipid-lowering drugs often necessary in its management. Some genetic loci have been associated with CHL, and modulation of lipid-lowering treatment by genetic polymorphisms has been reported. We have investigated whether common polymorphisms in the hepatic lipase gene (LIPC) influence the baseline lipid concentration and the response to atorvastatin or bezafibrate in patients with CHL. METHODS: Two genetic polymorphisms in LIPC (-514C-->T and +651A-->G) were determined by polymerase chain reaction and restriction analysis in 118 subjects of the ATOMIX (Atorvastatin in Mixed dyslipidemia) study who were randomized to treatment with either atorvastatin or bezafibrate and in 114 normolipidemic controls. RESULTS: The -514T allele frequency was higher in the ATOMIX group (0.297) than in the control group (0.193) (P = .01). The -514T allele carriers in the control group showed higher high-density lipoprotein cholesterol (HDL-C) concentrations than the -514C homozygotes, 50.8 +/- 1.86 versus 45.9 +/- 1.40 mg/dL (P = .02). The +651G carriers in the ATOMIX group showed lower total cholesterol and low-density lipoprotein cholesterol than the +651A homozygotes, 274 +/- 3.72 and 181 +/- 3.50 mg/dL versus 289 +/- 4.0 and 194 +/- 3.76 mg/dL, respectively (P < .01). Homozygotes for the -514C allele on bezafibrate treatment had greater decrease in triglycerides and greater increase in HDL-C than -514T allele carriers after 12 months of bezafibrate treatment, -39.4% and +35.8% versus -25.5% and +20.4%, respectively (P = .080 and P = .007, respectively). CONCLUSIONS: A higher frequency of the -514T allele of LIPC suggests a role of this locus in the pathogenesis of CHL. The -514T allele is associated with higher HDL-C concentration in normolipidemic population. The -514C-->T polymorphism modulates the lipid-lowering response to bezafibrate, with a better effect in homozygous CC subjects.

Atorvastatin versus Bezafibrate in Mixed Hyperlipidaemia : Randomised Clinical Trial of Efficacy and Safety (the ATOMIX Study).

OBJECTIVE: Combined hyperlipidaemia is a common and highly atherogenic lipid phenotype with multiple lipoprotein abnormalities that are difficult to normalise with single-drug therapy. The ATOMIX multicentre, controlled clinical trial compared the efficacy and safety of atorvastatin and bezafibrate in patients with diet-resistant combined hyperlipidaemia. PATIENTS AND STUDY DESIGN: Following a 6-week placebo run-in period, 138 patients received atorvastatin 10mg or bezafibrate 400mg once daily in a randomised, double-blind, placebo-controlled trial. To meet predefined low-density lipoprotein-cholesterol (LDL-C) target levels, atorvastatin dosages were increased to 20mg or 40mg once daily after 8 and 16 weeks, respectively. RESULTS: After 52 weeks, atorvastatin achieved greater reductions in LDL-C than bezafibrate (percentage decrease 35 vs 5; p < 0.0001), while bezafibrate achieved greater reductions in triglyceride than atorvastatin (percentage decrease 33 vs 21; p < 0.05) and greater increases in high-density lipoprotein-cholesterol (HDL-C) [percentage increase 28 vs 17; p < 0.01 ]. Target LDL-C levels (according to global risk) were attained in 62% of atorvastatin recipients and 6% of bezafibrate recipients, and triglyceride levels <200 mg/dL were achieved in 52% and 60% of patients, respectively. In patients with normal baseline HDL-C, bezafibrate was superior to atorvastatin for raising HDL-C, while in those with baseline HDL-C <35 mg/dL, the two drugs raised HDL-C to a similar extent after adjustment for baseline values. Both drugs were well tolerated. CONCLUSION: The results show that atorvastatin has an overall better efficacy than bezafibrate in concomitantly reaching LDL-C and triglyceride target levels in combined hyperlipidaemia, thus supporting its use as monotherapy in patients with this lipid phenotype.

Effect of atorvastatin and bezafibrate on plasma levels of C-reactive protein in combined (mixed) hyperlipidemia.

C-reactive protein (CRP) is a non-specific but sensitive marker of underlying systemic inflammation. High CRP plasma levels correlate with risk for future cardiovascular events. The present study evaluated the effects of atorvastatin (10-40 mg) and bezafibrate (400 mg) on CRP concentrations after 6 and 12 months of treatment in 103 patients with combined (mixed) hyperlipidemia. The number of cardiovascular risk factors present in a given patient was associated with baseline CRP levels. After 6 months and 1 year, atorvastatin treatment was associated with significant (P<0.001) decreases from baseline of CRP concentrations by 29 and 43%, respectively, while bezafibrate-treated patients showed non-significant reductions of 2.3 and 14.6%, respectively (P=0.056 and 0.005 for the respective differences between the two treatment arms at 6 months and 1 year). The magnitude of change in CRP after 1 year was directly related to baseline CRP levels. Covariance analysis showed that CRP decreases in the atorvastatin group were unrelated to total cholesterol and LDL cholesterol reductions; however, they were directly related to triglyceride changes (r=0.28, P=0.047) and inversely related to HDL cholesterol changes (r=-0.28, P=0.045). A model including baseline CRP values and treatment effect showed that atorvastatin use was a significant predictor of change in CRP levels over time (beta=0.82, P=0.023). These results suggest a potential anti-atherosclerotic additional benefit of atorvastatin in patients at a risk of cardiovascular disease.