Emerging data suggest that the 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors (statins) offer important benefits for the large population of individuals at high risk for coronary heart disease. This population encompasses a sizable portion of individuals who are also at high risk for drug-drug interactions due to their need for multiple medications. In general, statins are associated with a very small risk for myopathy (which may progress to fatal or nonfatal rhabdomyolysis); however, the potential for drug-drug interactions is known to increase this risk in specific high-risk groups. The incidence of myopathy associated with statin therapy is dose related and is increased when statins are used in combination with agents that share common metabolic pathways. Of particular concern is the potential for interactions with other lipid-lowering agents such as fibrates and niacin (nicotinic acid), which may be used in patients with mixed lipidemia, and with immunosuppressive agents, such as cyclosporine, which are commonly used in patients after transplantation. Clinicians should be alert to the potential for drug-drug interactions to minimize the risk of myopathy during long-term statin therapy in patients at high risk for coronary heart disease.

Evaluation for obesity management in primary care is limited, and successful outcomes are from intensive clinical trials in hospital settings. AimTo determine to what extent measures of success seen in intensive clinical trials can be achieved in routine primary care. Primary outcome measures were weight change and percentage of patients achieving ≥5% loss at 12 and 24 months. Design of studyProspective evaluation of a new continuous improvement model for weight management in primary care. SettingPrimary care, UK. MethodPrimary care practice nurses from 65 UK general practices delivered interventions to 1906 patients with body mass index (BMI) ≥30 kg/m 2 or ≥28 kg/m 2 with obesity-related comorbidities. ResultsMean baseline weight was 101.2 kg (BMI 37.1 kg/m 2 ); 25% of patients had BMI ≥40 kg/m 2 and 74% had ≥1 major obesity-related comorbidity. At final data capture 1419 patients were in the programme for ≥12 months, and 825 for ≥24 months. Mean weight change in those who attended and had data at 12 months (n = 642) was -3.0 kg (95% CI = -3.5 to -2.4 kg) and at 24 months (n = 357) was -2.3 kg (95% CI = -3.2 to -1.4 kg). Among attenders at specific time-points, 30.7% had maintained weight loss of ≥5% at 12 months, and 31.9% at 24 months. A total of 761 (54%) of all 1419 patients who had been enrolled in the programme for >12 months provided data at or beyond 12 months. ConclusionThis intervention achieves and maintains clinically valuable weight loss within routine primary care.

The growing number of trials that have highlighted the benefit of intensive lowering of total- and low density lipoprotein (LDL)-cholesterol levels especially with statins has created a need for more efficacious agents. Pitavastatin is a new synthetic 3-hydroxy-3-methyl glutaryl coenzyme A reductase inhibitor, which was developed, and has been available in Japan since July 2003. Metabolism of pitavastatin by the cytochrome P450 (CYP) system is minimal, principally through CYP 2C9, with little involvement of the CYP 3A4 isoenzyme, potentially reducing the risk of drug-drug interactions between pitavastatin and other drugs known to inhibit CYP enzymes. To date, human and animal studies have shown pitavastatin to be potentially as effective in lowering LDL-cholesterol levels as rosuvastatin; although, head-to-head studies are yet to be conducted.

Writing team, with contributions from other team members.Disclosures SMH, FGL, ELMcC, MAM, SM, PAN and MFQ have attended national ⁄ international meetings Linked Comment: Lean et al. Int J Clin Pract 2010; 64: 828-29.

BackgroundThere is no established primary care solution for the rapidly increasing numbers of severely obese people with body mass index (BMI) >40 kg/m 2 . AimThis programme aimed to generate weight losses of ≥15 kg at 12 months, within routine primary care. Design and settingFeasibility study in primary care. MethodPatients with a BMI ≥40 kg/m 2 commenced a micronutrient-replete 810-833 kcal/day lowenergy liquid diet (LELD), delivered in primary care, for a planned 12 weeks or 20 kg weight loss (whichever was the sooner), with structured food reintroduction and then weight-loss maintenance, with optional orlistat to 12 months. ResultsOf 91 patients (74 females) entering the programme (baseline: weight 131 kg, BMI 48 kg/ m 2 , age 46 years), 58/91(64%) completed the LELD stage, with a mean duration of 14.4 weeks (standard deviation [SD] = 6.0 weeks), and a mean weight loss of 16.9 kg (SD = 6.0 kg). Four patients commenced weight-loss maintenance omitting the food-reintroduction stage. Of the remaining 54, 37(68%) started and completed food reintroduction over a mean duration of 9.3 weeks (SD = 5.7 weeks), with a further mean weight loss of 2.1 kg (SD = 3.7 kg), before starting a long-term low-fat-diet weight-loss maintenance plan. A total of 44/91 (48%) received orlistat at some stage. At 12 months, weight was recorded for 68/91 (75%) patients, with a mean loss of 12.4 kg (SD = 11.4 kg). Of these, 30 (33% of all 91 patients starting the programme) had a documented maintained weight loss of ≥15 kg at 12 months, six (7%) had a 10-15 kg loss, and 11 (12%) had a 5-10 kg loss. The indicative cost of providing this entire programme for wider implementation would be £861 per patient entered, or £2611 per documented 15 kg loss achieved. ConclusionA care package within routine primary care for severe obesity, including LELD, food reintroduction, and weight-loss maintenance, was well accepted and achieved a 12-monthmaintained weight loss of ≥15 kg for one-third of all patients entering the programme.

BackgroundStroke is associated with the development of cognitive impairment and dementia. We assessed the effect of intensive blood pressure (BP) and/or lipid lowering on cognitive outcomes in patients with recent stroke in a pilot trial.MethodsIn a multicentre, partial-factorial trial, patients with recent stroke, absence of dementia, and systolic BP (SBP) 125–170 mmHg were assigned randomly to at least 6 months of intensive (target SBP <125 mmHg) or guideline (target SBP <140 mmHg) BP lowering. The subset of patients with ischaemic stroke and total cholesterol 3.0–8.0 mmol/l were also assigned randomly to intensive (target LDL-cholesterol <1.3 mmol/l) or guideline (target LDL-c <3.0 mmol/l) lipid lowering. The primary outcome was the Addenbrooke’s Cognitive Examination-Revised (ACE-R).ResultsWe enrolled 83 patients, mean age 74.0 (6.8) years, and median 4.5 months after stroke. The median follow-up was 24 months (range 1–48). Mean BP was significantly reduced with intensive compared to guideline treatment (difference –10·6/–5·5 mmHg; p<0·01), as was total/LDL-cholesterol with intensive lipid lowering compared to guideline (difference –0·54/–0·44 mmol/l; p<0·01). The ACE-R score during treatment did not differ for either treatment comparison; mean difference for BP lowering -3.6 (95% CI -9.7 to 2.4), and lipid lowering 4.4 (95% CI -2.1 to 10.9). However, intensive lipid lowering therapy was significantly associated with improved scores for ACE-R at 6 months, trail making A, modified Rankin Scale and Euro-Qol Visual Analogue Scale. There was no difference in rates of dementia or serious adverse events for either comparison.ConclusionIn patients with recent stroke and normal cognition, intensive BP and lipid lowering were feasible and safe, but did not alter cognition over two years. The association between intensive lipid lowering and improved scores for some secondary outcomes suggests further trials are warranted.Trial RegistrationISRCTN ISRCTN85562386

Switching to Eze/Simva 10/40 mg is projected to be a cost-effective treatment (vs. double-statin) in UK patients with ACS.

OBJECTIVE -To compare effects of different oral hypoglycemic drugs as first-line therapy on lipoprotein subfractions in type 2 diabetes.RESEARCH DESIGN AND METHODS -Sixty overweight type 2 diabetic patients not on lipid-lowering therapy were randomized to metformin, pioglitazone, or gliclazide after a 3-month dietary run-in. Drug doses were uptitrated for 3 months to optimize glycemia and were kept fixed for a further 3 months. LDL subfractions (LDL 1 , LDL 2 , and LDL 3 ) were prepared by density gradient ultracentrifugation at randomization and study end. Triglycerides, cholesterol, total protein, and phospholipids were measured and mass of subfractions calculated. HDL subfractions were prepared by precipitation. The primary end point was change in proportion of LDL as LDL 3 .RESULTS -HbA 1c , triglycerides, glucose, and cholesterol were comparable across groups at baseline and over time. LDL 3 mass and the LDL 3 -to-LDL ratio fell with pioglitazone (LDL 3 mass 36.2 to 28.0 mg/dl, P Ͻ 0.01; LDL 3 -to-LDL 19.2:13.3%, P Ͻ 0.01) and metformin (42.7 to 31.5 mg/dl, P Ͻ 0.01; 21.3:16.2%, P Ͻ 0.01, respectively) with no change on gliclazide. LDL 3 reductions were associated with reciprocal LDL 1 increases. Changes were independent of BMI, glycemic control, and triglycerides. Total HDL cholesterol increased on pioglitazone (1.28 to 1.36 mmol/l, P ϭ 0.02) but not gliclazide (1.39 to 1.37 mmol/l, P ϭ NS) or metformin (1.26 to 1.18 mmol/l, P ϭ NS), largely due to an HDL 2 increase (0.3 to 0.4 mmol/l, P Ͻ 0.05). HDL 3 cholesterol fell on metformin (0.9 to 0.85 mmol/l, P Ͻ 0.01). On pioglitazone and metformin, the HDL 2 -to-HDL 3 ratio increased compared with no change on gliclazide.CONCLUSIONS -For the same improvement in glycemic control, pioglitazone and metformin produce favorable changes in HDL and LDL subfractions compared with gliclazide in overweight type 2 diabetic patients. Such changes may be associated with reduced atherosclerosis risk and may inform the choice of initial oral hypoglycemic agent. Diabetes Care 27:41-46, 2004P atients with type 2 diabetes are frequently overweight with associated hypertension and a characteristic dyslipidemia with raised triglycerides and low HDL cholesterol. This cluster of abnormalities partly explains their increased risk of macrovascular disease. Targeting and treating the hypertension and dyslipidemia improves long-term outcomes (1-3). However, despite intervention, these patients remain at increased risk, suggesting that other factors contribute.A proportion of the increased risk may be explained by qualitative changes in lipoprotein subfraction. Although LDL cholesterol may not be elevated in type 2 diabetes, the dyslipidemia is characterized by an increased proportion of LDL as small, dense LDL or LDL 3 (4). Increased LDL 3 has been shown to be associated with increased risk of myocardial infarction (5-7). Risk may also be increased by qualitative changes in HDL subfractions (8), with an increased proportion of HDL occurring as smaller, denser HDL 3 , which is believed t...