Impact of Switching From High-Efficacy Lipid-Lowering Therapies to Generic Simvastatin on LDL-C Levels and LDL-C Goal Attainment Among High-Risk Primary and Secondary Prevention Populations in the United Kingdom

Cao X, Ejzykowicz F, Ramey DR
Clin Ther. 2015 Jan 24. doi: 10.1016/j.clinthera.2014.12.01. [Epub ahead of print]

Background

High total cholesterol is one of the major modifiable risk factors for CVD morbidity and mortality. In the Cholesterol Treatment Trialists’ Collaboration meta-analysis, statins have been reported to yield a relative risk reduction of about 20% for major vascular events, and a reduction of 20% of total mortality per 1-mmol/L lowering of LDL-c in patients treated with statins, irrespective of baseline risk [1].
Use of less costly generic medications instead of trade name medications may have financial benefits for health care systems, if the same efficacy can be maintained. There is, however, little research on whether patients were switching to equipotent generic simvastatin or what the effect on LDL-c levels and LDL-c goal attainment is upon such switching.
This study examined the impact of switching from high-efficacy lipid-lowering therapies (HETs: e.g. atorvastatin [ator], rosuvastatin [rosu] and simvastatin/ezetimibe [sim/eze]) to generic simvastatin monotherapy on LDL-c levels and LDL-c goal attainment, in high-risk primary and secondary prevention populations in the United Kingdom. This study explored historical data (from the Clinical Practice Research Datalink (CPRD) database), so as to reinforce the appropriateness of the prescription recommendation change in the new Joint British Societies’ guidelines on prevention of CV disease in clinical practice (JBS3) [2].

Main results

• There was no difference in average baseline LDL-c levels between switchers and nonswitchers on sim/eze and on rosu, but there was for those on ator (switchers: 2.04 vs. 2.08 mmol/L in non-switchers, P<0.0001).
• During 12 months of follow-up, switchers had higher LDL-c levels than nonswitchers (mean difference from baseline: 0.36 vs. 0.04 mmol/L, P<0.0001 in the sim/eze group and 0.24 vs. -0.03 mmol/L, P<0.0001 in the rosu group). In the ator group, LDL-c of switchers improved more than that of nonswitchers (mean LDL-c difference from baseline: -0.07 vs. 0.01, P<0.0001).
• LDL-C goal attainment rate in the baseline period was ~70% across switchers and nonswitchers in each HET group, with a significant difference between switchers (71.0%) and nonswitchers (67.3%) in the ator group.
  During follow-up the goal attainment rate remained significantly higher in switchers than in nonswitchers in the ator group (73.2% vs. 67.6%, P<0.0001), but it was lower among switchers than nonswitchers in the sim/eze (52.7% vs. 70.4%, P=0.0006) and the rosu group (62.4% vs. 71.6%, P=0.0008).
• All patients in the sim/eze group switched to a lower-than-equivalent dose of simvastatin, and 96.8% of patients did so in the rosu group. In the ator group 89.1% of patients received equivalent or higher doses of simva.
• Adjusted regression analyses showed that switchers in the sim/eze group had a greater mean increase in LDL-c than nonswitchers (difference 18.7%, 95%CI: 8.6-28.9, P<0.001), and in the rosu group this was a 16.7% (95%CI: 12.8-20.6, P<0.001) greater increase. No such difference was seen between switchers and nonswitchers in the ator group.
• Switchers in the sim/eze and rosu groups were less likely to attain LDL-c goals at follow-up than were nonswitchers (adjOR: 0.40, 95%CI: 0.23-0.70 for sim/eze and 0.36, 95%CI: 0.26-0.51 for rosu). In the ator-treated patients, no such difference was seen.  

Conclusion

This study in high-risk CVD patients in the United Kingdom showed that people who switch from high-efficacy simvastatin/ezetimibe or rosuvastatin treatment, to generic simvastatin monotherapy had an increase in LDL-c levels and were less likely to attain LDL-c goals. Patients switching from atorvastatin to generic simvastatin maintained LDL-c values and goal attainment rates. These data, although historical, demonstrate the appropriateness of the new JBS3 guidelines, in which the incentive of starting simvastatin 40 mg is no longer included.

Find this article online at Clinical Therapeutics

References

1. Cholesterol Treatment Trialists’ (CTT) Collaborators. Mihaylova B, Emberson J, Blackwell L, et al, 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. Lancet. 2012;380:581–590.
2. JBS3 Board. Joint British Societies’ consensus recommendations for the prevention of cardiovascular disease (JBS3). Heart. 2014;100(Suppl2):ii1–ii67.