Incremental cholesterol reduction with ezetimibe/simvastatin, atorvastatin and rosuvastatin in UK General Practice (IN-PRACTICE): randomised controlled trial of achievement of Joint British Societies (JBS-2) cholesterol targets

Terry Mccormack (1) , Peter Harvey (2) , Richard Gaunt (3) , Victoria Allgar (4) , Robert Chipperfield (5) , Paul Robinson (6)

1 Whitby Group Practice
2 The Crouch Oak Family Practice
3 Rowden Medical Practice
4 Hull York Medical School
5 Medical
6 Merck Sharp & Dohme Ltd

Aim: To compare ezetimibe/simvastatin combination therapy with intensified statin monotherapy as alternative treatment strategies to achieve the JBS-2 and NICE low-density-lipoprotein cholesterol (LDL-C) target of <2 mmol/l for secondary prevention or JBS-2 LDL-C target of <2 mmol/l for primary prevention in high-risk patients who have failed to reach target with simvastatin 40 mg. Methods: Prospective, double-blind study in 34 UK primary care centres; 1748 patients with established cardiovascular disease (CVD), diabetes or high risk of CVD who had been taking simvastatin 40 mg for ≥6 weeks were screened and 786 (45%) with fasting LDL-C ≥2.0 mmol/l (and <4.2 mmol/l) at screening and after a further 6-week run-in period on simvastatin 40 mg were randomised to ezetimibe/simvastatin 10/40 mg (as a combination tablet; n=261), atorvastatin 40 mg (n=263) or rosuvastatin 5 mg (n=73) or 10 mg (n=189) once daily for 6 weeks. Rosuvastatin dose was based on UK prescribing instructions. The primary outcome measure was the proportion of patients achieving LDL-C <2 mmol/l at the end of the study. Results: The percentage of patients (adjusted for baseline differences) achieving LDL-C <2 mmol/l was 69.4% with ezetimibe/simvastatin 10/40 mg, compared with 33.5% for atorvastatin 40 mg (odds ratio 4.5 [95% CI 3.0 to 6.8]; p<0.001) and 14.3% for rosuvastatin 5 or 10 mg (odds ratio 13.6 [95% CI 8.6 to 21.6]; p<0.001). Similar results were observed for achievement of total cholesterol <4.0 mmol/l. All study treatments were well tolerated. Conclusion: Approximately 45% of patients screened had not achieved LDL-C <2 mmol/l after ≥12 weeks of treatment with simvastatin 40 mg. In this group, treatment with ezetimibe/simvastatin 10/40 mg achieved target LDL-C levels in a significantly higher proportion of patients during a 6-week period than switching to either atorvastatin 40 mg or rosuvastatin 5–10 mg. Trial registration: NCT 00462748 (www.clinicaltrials.gov)

Mots clés: Medicine

Terry Mccormack, Peter Harvey, Richard Gaunt, Victoria Allgar, Robert Chipperfield, et al.. Incremental cholesterol reduction with ezetimibe/simvastatin, atorvastatin and rosuvastatin in UK General Practice (IN-PRACTICE): randomised controlled trial of achievement of Joint British Societies (JBS-2) cholesterol targets. International Journal of Clinical Practice, 2010, 64 (8), pp.1052. ⟨10.1111/j.1742-1241.2010.02429.x⟩. ⟨hal-00552661⟩