Achieving cholesterol targets by individualizing starting doses of statin according to baseline low-density lipoprotein cholesterol and coronary artery disease risk category: the CANadians Achieve Cholesterol Targets Fast with Atorvastatin Stratified Titration (CanACTFAST) study.
Despite an increasing body of evidence on the benefit of lowering elevated levels of low-density lipoprotein cholesterol (LDL-C), there is still considerable concern that patients are not achieving target LDL-C levels.
The CANadians Achieve Cholesterol Targets Fast with Atorvastatin Stratified Titration (CanACTFAST) trial tested whether an algorithm-based statin dosing approach would enable patients to achieve LDL-C and total cholesterol/high-density lipoprotein cholesterol (TC/HDL-C) ratio targets quickly.
Subjects requiring statin therapy, but with an LDL-C level of 5.7 mmol/L or lower, and triglycerides of 6.8 mmol/L or lower at screening participated in the 12-week study, which had two open-label, six-week phases: a treatment period during which patients received 10 mg, 20 mg, 40 mg or 80 mg of atorvastatin based on an algorithm incorporating baseline LDL-C value and cardiovascular risk; and patients who achieved both LDL-C and TC/HDL-C ratio targets at six weeks continued on the same atorvastatin dose. Patients who did not achieve both targets received dose uptitration using a single-step titration regimen. The primary efficacy outcome was the proportion of patients achieving target LDL-C levels after 12 weeks.
Of 2016 subjects screened at 88 Canadian sites, 1258 were assigned to a study drug (1101 were statin-free and 157 were statin-treated at baseline). The proportion of subjects who achieved LDL-C targets after 12 weeks of treatment was 86% (95% CI 84% to 88%) for statin-free patients and 54% (95% CI 46% to 61%) for statin-treated patients. Overall, 1003 subjects (80%; 95% CI 78% to 82%) achieved both lipid targets.
Algorithm-based statin dosing enables patients to achieve LDL-C and TC/HDL-C ratio targets quickly, with either no titration or a single titration.
Elevated oxidized low-density lipoprotein (OxLDL) may promote inflammation, and is associated with increased risk of atherosclerotic coronary heart disease and worsening complications of diabetes mellitus. The primary objective of this study was to evaluate the efficacy of chitin-glucan (CG), alone and in combination with a potentially anti-inflammatory olive oil (OO) extract, for reducing OxLDL in subjects with borderline to high LDL cholesterol (LDL-C) levels.
This 6-week, randomized, double-blind, placebo-controlled study of a novel, insoluble fiber derived from the Aspergillus niger mycelium, CG, evaluated 130 subjects free of diabetes mellitus with fasting LDL-C 3.37-4.92?mmol/l and glucose = 6.94?mmol/l. Participants were randomly assigned to receive CG (4.5?g/day; n=33), CG (1.5?g/day; n=32), CG (1.5?g/day) plus OO extract (135?mg/day; n=30), or matching placebo (n=35).
Administration of 4.5?g/day CG for 6 weeks significantly reduced OxLDL compared with placebo (P=0.035). At the end of study, CG was associated with lower LDL-C levels relative to placebo, although this difference was statistically significant only for the CG 1.5?g/day group (P=0.019). CG did not significantly affect high-density lipoprotein cholesterol, triglycerides, glucose, insulin or F2-isoprostane levels. Adverse events did not substantively differ between treatments and placebo.
In this 6-week study, CG (4.5?g/day) reduced OxLDL, an effect that might affect the risk for atherosclerosis.
OBJECTIVES: Lipid-lowering drugs as 3-hydroxy-3-methyl glutaryl coenzyme A (HMG-CoA) reductase inhibitors and cholestyramine are effective in reducing cardiovascular morbidity both in primary and secondary prevention. Patient compliance is an important determinant of the outcome of therapy. This study was designed to compare compliance with tolerance and lipid-lowering effectiveness of pravastatin and/or cholestyramine in primary care. DESIGN: Nine hundred and eighty nine women and 1047 men were randomized to treatment at 100 primary-care centres in Sweden. After dietary intervention, an eligible patient was randomly assigned to one of four programs of daily treatment: group Q, 16 g cholestyramine, group QP, 8 g cholestyramine and 20 mg pravastatin, group P20, 20 mg pravastatin or group P40, 40 mg pravastatin. RESULTS: In group Q, group QP, group P20 and group P40 the reductions in low density lipoprotein (LDL)-cholesterol were 26%, 36%, 27% and 32%. The dose actually taken was 91-95% of the prescribed for the pravastatin treatment groups and 77-88% for the cholestyramine groups. In the pravastatin and cholestyramine groups 76-78% and 44-53%, respectively, completed the trial. Only 8-27% of the patients reached a serum cholesterol target level of 5.2 mmol L-1. There was no difference in lipid-lowering effect between women and men. CONCLUSION: Pravastatin alone is efficacious and compliance is high, independent of dose. Combined treatment with cholestyramine and pravastatin had a better cholesterol lowering effect (although not statistically significant) than 40 mg pravastatin. Despite this, only 8-27% of the patients actually reached a serum cholesterol level of 5.2 mmol L-1. No unexpected serious adverse events were detected in any of the treatment groups. As predicted, the gastrointestinal disturbances were more common on cholestyramine treatment. These two factors suggest that an increase in the dosage of the HMG-CoA reductase inhibitor may be appropriate. Results from other studies indicate that there also might be other positive effects of statin treatment beyond cholesterol lowering.
Development of femoral atherosclerosis in hypercholesterolemic patients during treatment with cholestyramine and probucol/placebo: Probucol Quantitative Regression Swedish Trial (PQRST): a status report.
The Probucol Quantitative Regression Swedish Trial is being performed to investigate the effects of probucol on atherosclerosis in the femoral artery. Probucol is combined with cholestyramine and dietary management in hypercholesterolemic patients, and the effects of atheroma developing in the femoral artery will be followed by a quantitative angiographic technique. A randomly selected control group is also being managed by dietary therapy and cholestyramine, but receives placebo instead of probucol. The treatment time in this double-blind trial is 3 years, and femoral angiography is performed yearly. Detailed lipoprotein and apolipoprotein analysis are performed at monthly intervals. The basic study design is described here, and some results from the open prerandomization phase of the study are presented.
National guidelines recommend strict control of blood pressure (BP) and plasma low-density lipoprotein cholesterol (LDL) in type 2 diabetes (T2DM), aiming at a BP = 130/80 mmHg and an LDL concentration = 2.5 mmol/l. Angiotensin-converting enzyme inhibitors (ACEI) or angiotensin II-receptor blockers (ARB) are recommended as primary antihypertensive therapy (AHT). To which extent these targets are met in Danish primary care is unknown.
This study was based on data from 2,057 patients with T2DM who were randomly selected from 64 general practitioners (GPs) from different regions of Denmark. Data were collected from the GPs' electronic records.
The mean age ± standard deviation was 66.2 ± 11.6 years; 58.7% were male. The mean systolic BP ± standard deviation was 132.6 ± 14.6 mmHg and the mean diastolic BP ± standard deviation was 78.1 ± 9.0 mmHg. 47.7% of the patients met the BP target. 79.5% of the patients were on AHT. 55.1% of the untreated and 46.0% of the treated patients met the BP target. 83.4% of the treated patients received ACEI or ARB. The median LDL was 2.2 (1.7-2.7) mmol/l. 63.7% of the patients met the LDL target. 73.7% of the patients received lipid-lowering therapy. 32.8% of the untreated and 74.4% of the treated patients met the LDL target.
AHT including ACEI and ARB and lipid-lowering therapy are widely used in T2DM in Danish primary care, but only half of the patients are at target for BP and two thirds are at target for LDL. Increased use of diuretics may improve BP control.
This study was funded by a grant from Boehringer Ingelheim, Denmark. The grant covered costs related to data collection, time spent by the general practitioners and data analysis by the DTU.
BACKGROUND AND PURPOSE: Beta-adrenergic blockade has in several studies been shown to improve survival after myocardial infarction. In animal experiments beta-blockers have also shown an antiatherosclerotic effect. The aim of this study was to test the hypothesis that the beta-blocker metoprolol succinate controlled release/extended release (CR/XL), when given to patients with hypercholesterolemia on concomitant lipid-lowering therapy, provides an additional antiatherosclerotic effect to that provided by the statins, measured as carotid intima-media thickness (IMT). METHODS: We conducted a randomized, double-blind, placebo-controlled, single center trial to compare the effect of metoprolol CR/XL (100 mg once daily) and placebo on the progression of carotid IMT during 36 months of treatment in patients with hypercholesterolemia and signs of early atherosclerosis in the carotid artery. Most patients were prescribed lipid-lowering treatment with statins. RESULTS: A highly significant difference in the progression rate of the composite variable of carotid bulb IMT+common carotid IMT was observed between the metoprolol CR/XL and placebo groups after 1 year of treatment (-0.08 versus -0.01 mm; P=0.004), an effect that was sustained after 3 years of follow-up (-0.06 versus +0.03 mm; P=0.011). The patients had high levels of total cholesterol at randomization: 9.4 mmol/L in the metoprolol CR/XL group and 8.6 mmol/L in the placebo group. During the study the 2 randomization groups were treated with lipid-lowering drugs, mainly statins, to a similar extent, and total cholesterol was reduced to 6.4 mmol/L at end of follow-up in both groups. CONCLUSIONS: The results from the present study in patients with hypercholesterolemia under concomitant lipid-lowering therapy are the first clinical data to show an antiatherosclerotic effect of beta-blockade as additional therapy to statins. The data indicate that statin treatment and treatment with beta-blockers affect different mechanisms in the atherosclerotic process and have additive beneficial effects.
Greater effect of enhanced pharmacist care on cholesterol management in patients with diabetes mellitus: a planned subgroup analysis of the Study of Cardiovascular Risk Intervention by Pharmacists (SCRIP).
To determine the effect of enhanced pharmacist care on cholesterol management in patients with and without diabetes mellitus.
We conducted a planned subgroup analysis of the Study of Cardiovascular Risk Intervention by Pharmacists (SCRIP), a 54-center randomized trial of pharmacist intervention compared with usual care in patients at high risk for cardiovascular events. The patients involved had atherosclerotic disease or diabetes. We compared the effect of pharmacist intervention in patients with and without diabetes. The primary end point was a composite of performing a fasting cholesterol profile, or adding or increasing the dosage of a cholesterol-lowering drug. Secondary end points were individual components of the primary end point and change in 10-year risk for cardiovascular events, using the Framingham risk equation.
Of the 675 patients enrolled in the SCRIP study, 294 (44%) had diabetes. Enhanced pharmacist care had a more beneficial effect on cholesterol management in those with diabetes (odds ratio [OR] 4.8) than without diabetes (OR 2.1), p=0.01. Secondary end points showed similar trends, and reduction in Framingham risk was greater in patients with diabetes than without.
Pharmacist intervention for dyslipidemia appears to have a greater impact in patients with diabetes. Results of this substudy suggest that pharmacists should target this patient group for interventions in cholesterol risk management.
We previously found that the use of ezetimibe increased rapidly with different patterns between the United States (US) and Canada prior to the landmark Ezetimibe and Simvastatin in Hypercholesterolemia Enhance Atherosclerosis Regression (ENHANCE) trial, which was reported in January 2008, and failed to show that the drug slowed the progression of atherosclerosis. What is not known is how practice in the 2 countries changed after the ENHANCE trial. We examined ezetimibe use trends in the US and Canada before and after the reporting of the ENHANCE trial.
We conducted a population-based, retrospective, time-series analysis using the data collected by IMS Health in the US and CompuScript in Canada from January 1, 2002, to December 31, 2009. The main outcome measure was monthly number of prescriptions for ezetimibe-containing products.
The monthly number of ezetimibe prescriptions/100,000 population rose from 6 to 1,082 in the US from November 2002 to January 2008, then significantly declined to 572/100,000 population by December 2009 after the release of the ENHANCE trial, a decrease of 47.1% (P
The authors considered whether the difference in body fat distribution between men and women, measured as waist:hip ratio, might explain part of the sex difference in coronary heart disease incidence in prospective population studies of 1,462 women and 792 men. In these studies, conducted in Sweden, men were found to have about four times higher odds for coronary heart disease than women during a 12-year follow-up period (men, 1967 to 1979; women, 1968-1969 to 1980-1981). Controlling for differences in blood pressure, serum cholesterol, smoking, and body mass index only marginally altered the magnitude of the male-female difference. When waist:hip ratio, which predicted coronary heart disease rates in both sexes, was also considered, the sex difference in coronary heart disease risk was significantly reduced and virtually disappeared (odds ratios = 1.0-1.1; nonsignificant). The findings suggest that body fat distribution or a factor highly correlated with waist:hip ratio (genetic, hormonal, or behavioral) may help to explain the sex differences in coronary heart disease.
Comment In: Am J Epidemiol. 1993 Jan 15;137(2):261-28452133