Efficacy and safety of LDL‐lowering therapy among men and women: meta‐analysis of individual data from 174,000 participants in 27 randomised trials

Background There has been debate about whether statin therapy is as effective in women as men, especially for primary prevention. Methods Meta‐analyses were performed on data from 22 trials of statin therapy vs. control (n=134 537) and five trials of more intensive vs. less intensive statin therapy (n=39 612). Effects on major vascular events, major coronary events, stroke, coronary revascularisation and mortality were weighted per 1∙0 mmol/L reduction in LDL cholesterol and effects in men and women compared using a Cox model that adjusted for non‐gender differences. For subgroup analyses, 99% confidence intervals were used to make allowance for the multiplicity of comparisons. Findings Overall, 46675 (27%) of 174,149 randomised participants were women. Allocation to a statin had similar absolute effects on 1‐year lipid concentrations in both men and women (LDL cholesterol reduced by ~1∙1mmol/L in statin vs. control trials and ~0∙5mmol/L in more vs. less trials). The proportional reductions per 1∙0 mmol/L reduction in LDL cholesterol in major vascular events were similar in women (RR 0∙84, 99% CI 0∙78‐0∙91) and men (RR 0∙78, 99% CI 0∙75‐0∙81), both overall (adjusted p value for heterogeneity by gender=0∙33) and among those at <10% predicted 5‐year risk (adjusted heterogeneity p=0∙11). Likewise, the proportional reductions in major coronary events, coronary revascularisation and stroke did not differ by gender. Since there were similar proportional reductions in vascular mortality in women (RR 0∙92, 99% CI 0∙82‐1∙03) and men (RR 0∙87, 99% CI 0∙82‐0∙92) (adjusted heterogeneity p=0∙84), but no apparent effect on non‐vascular deaths in either sex, all‐cause mortality was reduced in both women (RR 0∙91, 99% CI 0∙84‐0∙99) and men (RR 0∙90, 99% CI 0∙86‐0∙95). Interpretation Other things being equal, statin therapy is of comparable effectiveness for the prevention of major vascular events in women as in men, even among those at low risk of vascular disease

Efficacy and safety of LDL‐lowering therapy among men and women: meta‐analysis of individual data from 174,000 participants in 27 randomised trials

Background There has been debate about whether statin therapy is as effective in women as men, especially for primary prevention. Methods Meta‐analyses were performed on data from 22 trials of statin therapy vs. control (n=134 537) and five trials of more intensive vs. less intensive statin therapy (n=39 612). Effects on major vascular events, major coronary events, stroke, coronary revascularisation and mortality were weighted per 1∙0 mmol/L reduction in LDL cholesterol and effects in men and women compared using a Cox model that adjusted for non‐gender differences. For subgroup analyses, 99% confidence intervals were used to make allowance for the multiplicity of comparisons. Findings Overall, 46675 (27%) of 174,149 randomised participants were women. Allocation to a statin had similar absolute effects on 1‐year lipid concentrations in both men and women (LDL cholesterol reduced by ~1∙1mmol/L in statin vs. control trials and ~0∙5mmol/L in more vs. less trials). The proportional reductions per 1∙0 mmol/L reduction in LDL cholesterol in major vascular events were similar in women (RR 0∙84, 99% CI 0∙78‐0∙91) and men (RR 0∙78, 99% CI 0∙75‐0∙81), both overall (adjusted p value for heterogeneity by gender=0∙33) and among those at <10% predicted 5‐year risk (adjusted heterogeneity p=0∙11). Likewise, the proportional reductions in major coronary events, coronary revascularisation and stroke did not differ by gender. Since there were similar proportional reductions in vascular mortality in women (RR 0∙92, 99% CI 0∙82‐1∙03) and men (RR 0∙87, 99% CI 0∙82‐0∙92) (adjusted heterogeneity p=0∙84), but no apparent effect on non‐vascular deaths in either sex, all‐cause mortality was reduced in both women (RR 0∙91, 99% CI 0∙84‐0∙99) and men (RR 0∙90, 99% CI 0∙86‐0∙95). Interpretation Other things being equal, statin therapy is of comparable effectiveness for the prevention of major vascular events in women as in men, even among those at low risk of vascular disease

A Polypill for primary prevention of cardiovascular disease: A feasibility study of the World Health Organization

<p>Abstract</p> <p>Background</p> <p>The feasibility of conducting a large-scale Polypill clinical trial in developing countries remains unclear. More information is needed regarding the efficacy in reducing the risk factors of cardiovascular disease (CVD), side effects, improvement in adherence and physician/patient "acceptability" of the Polypill.</p> <p>Methods</p> <p>We conducted an open-label, parallel-group, randomized clinical trial involving three sites in Sri Lanka that enrolled a total of 216 patients without established CVD. The trial compared a Polypill (75 mg aspirin, 20 mg simvastatin, 10 mg lisinopril and 12.5 mg hydrochlorothiazide) to Standard Practice. After randomization, patients were followed monthly for three months. Pre-specified primary outcomes included reduction in systolic blood pressure, total cholesterol and estimated 10-year CVD risk. We also evaluated the recruitment process and acceptability of the Polypill by both physicians and patients.</p> <p>Results</p> <p>Patients were recruited in a six-month period as planned. Two hundred three patients (94.0%) completed the treatment program and returned for their three-month follow-up visits. No safety concerns were reported. These findings suggest a high rate of patient acceptability, a finding that is bolstered by the majority of patients completing the trial (90%) indicating that they would take the Polypill "for life" if proven to be effective in reducing CVD risk. Approximately 86% of the physicians surveyed agreed with and supported use of the Polypill for primary prevention and 93% for secondary prevention of CVD. Both the Polypill and Standard Practice resulted in marked reductions in systolic blood pressure, total cholesterol and 10-year risk of CVD. However, the differences between the treatment groups were not statistically significant.</p> <p>Conclusions</p> <p>We successfully completed a Polypill feasibility trial in Sri Lanka. We were able to document high acceptability of the Polypill to patients and physicians. We were unable to estimate the risk factor reductions on the Polypill because the control group received similar treatment with individual drugs. The Polypill was however simpler and achieved comparable risk factor reductions, highlighting its potential usefulness in the prevention of CVD.</p> <p>Trial registration number</p> <p>ISRCTN: <a href="http://www.controlled-trials.com/NCT00567307">NCT00567307</a></p

The Causes and Consequences of Low Levels of High Density Lipoproteins in Patients with Diabetes

Type 2 diabetes is commonly accompanied by a low level of high density lipoprotein cholesterol (HDL-C) that contributes to the increased cardiovascular risk associated with this condition. Given that HDLs have the ability to improve increase the uptake of glucose by skeletal muscle and to stimulate the secretion of insulin from pancreatic beta cells the possibility arises that a low HDL concentration in type 2 diabetes may also contribute to a worsening of diabetic control. Thus, there is a double case for raising the level of HDL-C in patients with type 2 diabetes: to reduce cardiovascular risk and to improve glycemic control. Approaches to raising HDL-C include lifestyle factors such as weight reduction, increased physical activity and stopping smoking. Of currently available drugs, the most effective is niacin. Newer formulations of niacin are reasonably well tolerated and have the ability to increase HDL-C by up to 30%. The effect of niacin on cardiovascular events in type 2 diabetes is currently being tested in a large-scale clinical outcome trial

Efficacy and safety of LDL-lowering therapy among men and women: meta-analysis of individual data from 174,000 participants in 27 randomised trials

Background Whether statin therapy is as effective in women as in men is debated, especially for primary prevention. We undertook a meta-analysis of statin trials in the Cholesterol Treatment Trialists' (CTT) Collaboration database to compare the effects of statin therapy between women and men. Methods We performed meta-analyses on data from 22 trials of statin therapy versus control (n=134 537) and five trials of more-intensive versus less-intensive statin therapy (n=39 612). Effects on major vascular events, major coronary events, stroke, coronary revascularisation and mortality were weighted per 1·0 mmol/L reduction in LDL cholesterol and effects in men and women compared with a Cox model that adjusted for non-sex differences. For subgroup analyses, we used 99% CIs to make allowance for the multiplicity of comparisons. Findings 46 675 (27%) of 174 149 randomly assigned participants were women. Allocation to a statin had similar absolute effects on 1 year lipid concentrations in both men and women (LDL cholesterol reduced by about 1·1 mmol/L in statin vs control trials and roughly 0·5 mmol/L for more-intensive vs less-intensive therapy). Women were generally at lower cardiovascular risk than were men in these trials. The proportional reductions per 1·0 mmol/L reduction in LDL cholesterol in major vascular events were similar overall for women (rate ratio [RR] 0·84, 99% CI 0·78–0·91) and men (RR 0·78, 99% CI 0·75–0·81, adjusted p value for heterogeneity by sex=0·33) and also for those women and men at less than 10% predicted 5 year absolute cardiovascular risk (adjusted heterogeneity p=0·11). Likewise, the proportional reductions in major coronary events, coronary revascularisation, and stroke did not differ significantly by sex. No adverse effect on rates of cancer incidence or non-cardiovascular mortality was noted for either sex. These net benefits translated into all-cause mortality reductions with statin therapy for both women (RR 0·91, 99% CI 0·84–0·99) and men (RR 0·90, 99% CI 0·86–0·95; adjusted heterogeneity p=0·43). Interpretation In men and women at an equivalent risk of cardiovascular disease, statin therapy is of similar effectiveness for the prevention of major vascular events.UK Medical Research Council, British Heart Foundation, Australian National Health and Medical Research Council, European Community Biomed Program

Diabetes and stroke

The association between diabetes and stroke is well established. Recent large‐scale, international population studies suggest that diabetes is one of the most important modifiable risk factors for cerebrovascular disease. Despite this, we still have a relative paucity of evidence around the management of diabetes in stroke. The landscape is evolving and recent studies are helping establish best practice and suggesting new therapeutic opportunities. It is possible to develop a practical and clinical synthesis of the evidence around managing diabetes in adult patients with stroke and cerebrovascular disease, based on large trials, systematic reviews and guidelines, and focusing on the scenarios most often encountered in clinical practice. It is also important to recognise that there are common situations where robust evidence is lacking, but practical guidance for clinicians can be suggested