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 Academic Article uri icon

abstract

  • BACKGROUND:Statins reduce LDL cholesterol and prevent vascular events, but their net effects in people at low risk of vascular events remain uncertain. 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. 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. 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. FUNDING:British Heart Foundation; UK Medical Research Council; Cancer Research UK; European Community Biomed Programme; Australian National Health and Medical Research Council; National Heart Foundation, Australia.

authors

  • Mihaylova, B
  • Emberson, J
  • Blackwell, L
  • Keech, A
  • Simes, J
  • Barnes, EH
  • Voysey, M
  • Gray, A
  • Collins, R
  • Baigent, C
  • De Lemos, J
  • Braunwald, E
  • Blazing, M
  • Murphy, S
  • Downs, JR
  • Gotto, A
  • Clearfield, M
  • Holdaas, H
  • Gordon, D
  • Davis, B
  • Koren, M
  • Dahlof, B
  • Poulter, N
  • Sever, P
  • Knopp, RH
  • Fellstrom, B
  • Jardine, A
  • Schmieder, R
  • Zannad, F
  • Goldbourt, U
  • Kaplinsky, E
  • Colhoun, HM
  • Betteridge, DJ
  • Durrington, PN
  • Hitman, GA
  • Fuller, J
  • Neil, A
  • Wanner, C
  • Krane, V
  • Sacks, F
  • Moye, L
  • Pfeffer, M
  • Hawkins, CM
  • Kjekshus, J
  • Wedel, H
  • Wikstrand, J
  • Barter, P
  • Tavazzi, L
  • Maggioni, A
  • Marchioli, R
  • Tognoni, G
  • Franzosi, MG
  • Bloomfield, H
  • Robins, S
  • Armitage, J
  • Parish, S
  • Peto, R
  • Sleight, P
  • Pedersen, TR
  • Ridker, PM
  • Holman, R
  • Meade, T
  • MacMahon, S
  • Marschner, I
  • Tonkin, A
  • Shaw, J
  • Serruys, PW
  • Nakamura, H
  • Knatterud, G
  • Marschner, I
  • Byington, R
  • MacFarlane, P
  • Cobbe, S
  • Ford, I
  • Murphy, M
  • Blauw, GJ
  • Packard, C
  • Shepherd, J
  • Wilhelmsen, L
  • Cannon, C
  • Bowman, L
  • Peto, R
  • Landray, M
  • La Rosa, J
  • Rossouw, J
  • Probstfi Eld, J
  • Flather, M
  • Kastelein, J
  • Newman, C
  • Shear, C
  • Tobert, J
  • Varigos, J
  • White, H
  • Yusuf, S
  • Mellies, M
  • McGovern, M
  • Barclay, J
  • Belder, R
  • Mitchel, MY
  • Musliner, T

publication date

  • August 2012

published in