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

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

Rechenstoepselkarten - 1. Schuljahr

Available from: Lehr- und Arbeitsmittel Heide Kraft, Muenster (Germany, F.R.) / FIZ - Fachinformationszzentrum Karlsruhe / TIB - Technische InformationsbibliothekSIGLEDEGerman

Comparative analysis of genome-wide association studies signals for lipids, diabetes, and coronary heart disease: Cardiovascular Biomarker Genetics Collaboration

To evaluate the associations of emergent genome-wide-association study-derived coronary heart disease (CHD)-associated single nucleotide polymorphisms (SNPs) with established and emerging risk factors, and the association of genome-wide-association study-derived lipid-associated SNPs with other risk factors and CHD events

Cancer incidence and cancer mortality in all 27 trials, by site.

<p>Excluding death from cancers known to have been first diagnosed prior to randomisation. ICD-9 cancer codes: Gastrointestinal (140–159); Lip, mouth or pharynx (140–149); Oesophageal (150); Stomach (151); Large bowel or intestine (152–154); Liver (155); Gall bladder or bile-ducts (156); Pancreas (157); Other gastrointestinal (158,159); Genitourinary (179–189); Prostate (185); Penis/Scrotum (187); Uterus (179,180,182); Ovarian (183); Other genitourinary (181,184,186); Bladder (188); Kidney (189); Respiratory (160–163,165); Trachea/Lung (162); Other respiratory (160,161,163,165); Female breast (174); Haematological (200–208); Melanoma (172); Other/unspecified ([Neurological (191,192); Other known site (164,170,171,175,176,190,193–195); Unspecified (196–199, 209)]); All cancer (140–209 excluding 173). If the ICD9 cause of death was 173 or 210–239 then both cancer incidence and cancer death was coded as unknown cancer. P-values are continuity corrected.</p

Effects of statin therapy on cancer incidence and mortality, by duration of treatment.

<p>Symbols and conventions as in <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0029849#pone-0029849-g001" target="_blank">Figure 1</a>.</p

Effects of statin therapy on cancer incidence in each study.

<p>In the left panel, unweighted rate ratios (RRs) are plotted for each trial of the comparison of first event rates between randomly allocated treatment groups, along with their 99% confidence intervals (CIs). Trials are ordered according to the absolute reduction in LDL cholesterol at 1 year within each type of trial comparison (statin versus control and more versus less statin). In the right panel, rate ratios are weighted per 1 mmol/L LDL cholesterol difference at 1 year. Totals and subtotals, together with their 95% CIs, are indicated by open diamonds.</p