Efficacy and safety of statin therapy in older people: a meta-analysis of individual participant data from 28 randomised controlled trials

Australian National Health and Medical Research CouncilMRCBritish Heart Foundation

Effect of rosuvastatin on outcomes in chronic haemodialysis patients - Design and rationale of the AURORA study.

Background Cardiovascular disease (CVD) is the leading cause of death in patients with end-stage renal disease (ESRD). Aims AURORA (A study to evaluate the Use of Rosuvastatin in subjects On Regular haemodialysis: an Assessment of survival and cardiovascular events) is the first large-scale international trial to assess the effects of statins on cardiovascular outcomes in patients with ESRD on chronic haemodialysis. Preliminary baseline data from the randomised population are presented. Methods A total of 2,775 patients from 280 centres in 25 countries were randomised into the study. Patients aged 50–80 years on regular chronic haemodialysis for at least 3 months before screening were eligible for inclusion. They were randomised 1:1 to receive either rosuvastatin 10 mg or placebo daily and assessed throughout the study. Results The mean age at baseline was 64 years. Most patients were male (62%) and 85% were white. The median time since commencing renal replacement was 32 months. Mean total cholesterol (TC) and low-density lipoprotein cholesterol (LDL-C) levels were 4.53 mmol/l (175 mg/dl) and 2.57 mmol/l (99 mg/dl), respectively. Conclusion Results from the AURORA trial will impact on the current guidelines and use of statins in this patient population

The effects of lowering LDL cholesterol with statin therapy in people at low risk of vascular disease: meta-analysis of individual data from 27 randomised trials

<p>Background: Statins reduce LDL cholesterol and prevent vascular events, but their net effects in people at low risk of vascular events remain uncertain.</p> <p>Methods: This meta-analysis included individual participant data from 22 trials of statin versus control (n=134 537; mean LDL cholesterol difference 1·08 mmol/L; median follow-up 4·8 years) and five trials of more versus less statin (n=39 612; difference 0·51 mmol/L; 5·1 years). Major vascular events were major coronary events (ie, non-fatal myocardial infarction or coronary death), strokes, or coronary revascularisations. Participants were separated into five categories of baseline 5-year major vascular event risk on control therapy (no statin or low-intensity statin) (<5%, ≥5% to <10%, ≥10% to <20%,≥20% to <30%, ≥30%); in each, the rate ratio (RR) per 1·0 mmol/L LDL cholesterol reduction was estimated.</p> <p>Findings: Reduction of LDL cholesterol with a statin reduced the risk of major vascular events (RR 0·79, 95% CI 0·77—0·81, per 1·0 mmol/L reduction), largely irrespective of age, sex, baseline LDL cholesterol or previous vascular disease, and of vascular and all-cause mortality. The proportional reduction in major vascular events was at least as big in the two lowest risk categories as in the higher risk categories (RR per 1·0 mmol/L reduction from lowest to highest risk: 0·62 [99% CI 0·47—0·81], 0·69 [99% CI 0·60—0·79], 0·79 [99% CI 0·74—0·85], 0·81 [99% CI 0·77—0·86], and 0·79 [99% CI 0·74—0·84]; trend p=0·04), which reflected significant reductions in these two lowest risk categories in major coronary events (RR 0·57, 99% CI 0·36—0·89, p=0·0012, and 0·61, 99% CI 0·50—0·74, p<0·0001) and in coronary revascularisations (RR 0·52, 99% CI 0·35—0·75, and 0·63, 99% CI 0·51—0·79; both p<0·0001). For stroke, the reduction in risk in participants with 5-year risk of major vascular events lower than 10% (RR per 1·0 mmol/L LDL cholesterol reduction 0·76, 99% CI 0·61—0·95, p=0·0012) was also similar to that seen in higher risk categories (trend p=0·3). In participants without a history of vascular disease, statins reduced the risks of vascular (RR per 1·0 mmol/L LDL cholesterol reduction 0·85, 95% CI 0·77—0·95) and all-cause mortality (RR 0·91, 95% CI 0·85—0·97), and the proportional reductions were similar by baseline risk. There was no evidence that reduction of LDL cholesterol with a statin increased cancer incidence (RR per 1·0 mmol/L LDL cholesterol reduction 1·00, 95% CI 0·96—1·04), cancer mortality (RR 0·99, 95% CI 0·93—1·06), or other non-vascular mortality.</p> <p>Interpretation: In individuals with 5-year risk of major vascular events lower than 10%, each 1 mmol/L reduction in LDL cholesterol produced an absolute reduction in major vascular events of about 11 per 1000 over 5 years. This benefit greatly exceeds any known hazards of statin therapy. Under present guidelines, such individuals would not typically be regarded as suitable for LDL-lowering statin therapy. The present report suggests, therefore, that these guidelines might need to be reconsidered.</p&gt