SHARP Data Analyzed for Cost-Effectiveness of Simvastatin plus Ezetimibe

Results of SHARP (Study of Heart and Renal Protection) demonstrated that in patients with moderate to severe chronic kidney disease (CKD), lowering low-density lipoprotein (LDL) cholesterol by 0.85 mmol/L with a combination of simvastatin, 20 mg, plus ezetimibe, 10 mg, daily reduced the risk of major atherosclerotic events. There were no adverse events associated with the intervention.

The Kidney Disease: Improving Global Outcomes clinical practice guideline for lipid management in CKD recommends that treatment with a statin or a statin plus ezetimibe be initiated in all CKD non-dialysis-dependent and nontransplantation patients ≥50 years of age and in younger patients with elevated cardiovascular risk. The 2013 American College of Cardiology and American Heart Association guidelines recommend statin therapy for non-dialysis-dependent CKD patients at increased risk for cardiovascular disease.

SHARP provided clear evidence that simvastatin plus ezetimibe is effective for prevention of atherosclerotic events in patients with CKD; however, there are few data on the cost-effectiveness of the treatment. Borislava Mihaylova, DPhil, and colleagues conducted an analysis to examine the cost-effectiveness of the intervention in relation to the cardiovascular risk of patients with CKD, the severity of kidney disease, and the cost of treatment. In scenario analyses, the relevance of other high-intensity statin regimens was investigated. Results were reported in the American Journal of Kidney Diseases [2016;67(4):576-584].

A total of 9270 patients from 18 countries were randomly assigned to receive simvastatin plus ezetimibe (n=4650) or placebo (n=4620) in SHARP. Those in the simvastatin plus ezetimibe group had a mean reduction of 0.85 mmol/L in LDL cholesterol, yielding a 17% proportional reduction (rate ratio [RR], 0.83; 95% confidence interval [CI], 0.72-0.95; P=.007) in all (first and subsequent) major atherosclerotic events, corresponding to a 20% proportional reduction (RR, 0.80; 95% CI, 0.68-0.94) per 1-mmol/L LDL cholesterol level reduction.

Overall, allocation to the intervention group yielded a 16% proportional reduction (RR, 0.84; 95% CI, 0.74-0.96; P=.01) in atherosclerotic hospital episodes and an 11% reduction (RR, 0.84; 95% CI, 0.79-0.99; P=.04) in nonatherosclerotic vascular episodes. These events resulted in a 15% proportional reduction (RR, 0.85; 95% CI, 0.75-0.97; P=.01) in mean costs of all vascular hospital episodes (corresponding to 17% proportional reduction [RR, 0.83; 95% CI, 0.72-0.96] per 1-mmol/L LDL cholesterol reduction).

There was no significant effect of the intervention on renal hospital episodes or other nonvascular and nonrenal hospital episodes, so the researchers excluded the costs of both from subsequent calculation of cost-effectiveness. There were no significant differences in the costs of routine dialysis or in the use of medications other than nonstudy lipid-lowering medications; those costs were also excluded.

The mean cost per patient of simvastatin plus ezetimibe needed to achieve the reduction in LDLD cholesterol achieved in SHARP during the study period was £1319. Among those at higher 5-year risk for cardiovascular disease, there was a trend toward lower costs of treatment, due to shorter duration of treatment among those at higher risk for death.

The cost per patients was lowest among patients with more severe CKD (£1182 among those at stage 5 not on dialysis and £1214 among those on dialysis) and highest among those with CKD stage 3 (£1454).

The net cost of avoiding a major atherosclerotic event ranged from £157,600 among patients at low cardiovascular risk to £15,230 among those at high risk and from £47,280 among patients in CKD stage 3 to £28,180 among patients on dialysis therapy.

In scenario analyses, the researchers assumed that high-intensity statin regimens other than simvastatin plus ezetimibe would produce effects on major atherosclerotic events and hospital costs that were in proportion to their relative potency in reducing LDL cholesterol levels compared with simvastatin plus ezetimibe and that they would not result in additional adverse events. The net cost per major atherosclerotic event avoided with such a regimen would be similar to the study intervention if it were available at identical cost.

The researchers cited not studying high-intensity statin-alone regimens as a limitation to this analysis of SHARP data.

The researchers concluded, “Simvastatin plus ezetimibe prevents atherosclerotic events in SHARP, but other less costly statin regimens are likely to be more cost-effective for reducing cardiovascular risk in CKD.”

Takeaway Points

  1. SHARP trial results demonstrated the beneficial effects of simvastatin, 20 mg, plus ezetimibe, 10 mg, daily in reducing major atherosclerotic events in patients with moderate to severe chronic kidney disease.
  2. Researchers in the United Kingdom conduced an analysis of SHARP data to assess the cost-effectiveness of the simvastatin plus ezetimibe regimen.
  3. In scenario analyses, generic high-intensity statin regimens were estimated to yield similar benefits at substantially lower cost.