Vascular viewpoint

Abstract

Question: To determine by how much statins reduce serum concentrations of low density lipo-protein (LDL) cholesterol according to drug, dose, and duration of treatment.

Population: Patients included in randomized, placebo-controlled trials of six statins (atorvastatin, fluvastatin, lovastatin, pravastatin, simvastatin, rosuvastatin).

Design and methods: Meta analysis of 164 short-term, randomized trials including 24 000 drug-treated and 14000 placebo-treated patients. Studies were found by searching Medline, the Cochrane Collaboration, Web of Science databases, and BMJ.com. All double-blind, placebo-controlled trials were considered eligible. Excluded trials were those with no placebo group, any which lasted less than 2 weeks, those that used titrated doses, those that used combination drugs to lower cholesterol, crossover trials, or those with chronic renal failure patients. The efficacy of each statin was defined as the reduction of LDL for a given dose of a statin expressed as the change in the treated group minus that in the placebo group.

Results: The doses of atorvastatin, lovastatin, rosuvastatin and simvastatin used to lower LDL by an absolute amount of 1.8 mmol=l or 40% are shown in the table. Pravastatin and fluvastatin were a less effective treatment, with maximum doses (80 mg=day) lowering LDL by 1.58 mmol=l and 1.60 mmol=l, respectively. Statins increased high density lipoprotein cholesterol by 0.07 mmol=l on average with no dose effects observed. For safety outcomes, 1063=14 197 statin patients compared with 923=10 568 control patients reported one or more symptoms possibly associated with the drug. Rhabdomyolysis was observed in eight statin patients compared with five placebo patients.

Statin	Number of patients studied	Dose (mg/day)	LDL lowering(mmol/l)
Atorvastatin	4268	10	1.80
Fluvastatin*	4729	80	1.58
Lovastatin	10648	40	1.80
Pravastatin*	9856	80	1.60
Rosuvastatin	555	5	1.80
Simvastatin	8839	40	1.80

Conclusion: Statins can lower the LDL cholesterol concentration by an average of 1.8 mmol=l, and the LDL lowering effect varies across statin type and dose: simvastatin, lovastatin, atorvastatin and rosuvastatin appearing more effective, and fluvastatin and pravastatin appearing less effective.