First United Kingdom Heart and Renal Protection (UK-HARP-I) study: biochemical efficacy and safety of simvastatin and safety of low-dose aspirin in chronic kidney disease.
BACKGROUND: Patients with chronic kidney disease are at increased risk for cardiovascular disease, but the efficacy and safety of simvastatin and aspirin are unknown in this patient group. METHODS: Patients were randomly assigned in a 2 x 2 factorial design to the administration of: (1) 20 mg of sim...
| Main Authors: | , , , , , , , , , , , , , , , , |
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| Format: | Journal article |
| Language: | English |
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2005
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| _version_ | 1797080433755684864 |
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| author | Baigent, C Landray, M Leaper, C Altmann, P Armitage, J Baxter, A Cairns, H Collins, R Foley, R Frighi, V Kourellias, K Ratcliffe, P Rogerson, M Scoble, J Tomson, C Warwick, G Wheeler, D |
| author_facet | Baigent, C Landray, M Leaper, C Altmann, P Armitage, J Baxter, A Cairns, H Collins, R Foley, R Frighi, V Kourellias, K Ratcliffe, P Rogerson, M Scoble, J Tomson, C Warwick, G Wheeler, D |
| author_sort | Baigent, C |
| collection | OXFORD |
| description | BACKGROUND: Patients with chronic kidney disease are at increased risk for cardiovascular disease, but the efficacy and safety of simvastatin and aspirin are unknown in this patient group. METHODS: Patients were randomly assigned in a 2 x 2 factorial design to the administration of: (1) 20 mg of simvastatin daily versus matching placebo, and (2) 100 mg of modified-release aspirin daily versus matching placebo. RESULTS: Overall, 448 patients with chronic kidney disease were randomly assigned (242 predialysis patients with a creatinine level > or = 1.7 mg/dL [> or =150 micromol/L], 73 patients on dialysis therapy, and 133 patients with a functioning transplant). Compliance with study treatments was 80% at 12 months. Allocation to treatment with 100 mg of aspirin daily was not associated with an excess of major bleeds (aspirin, 4 of 225 patients [2%] versus placebo, 6 of 223 patients [3%]; P = not significant [NS]), although there was a 3-fold excess of minor bleeds (34 of 225 [15%] versus 12 of 223 patients [5%]; P = 0.001). Among those with predialysis renal failure or a functioning transplant at baseline, aspirin did not increase the number of patients who progressed to dialysis therapy (7 of 187 [4%] versus 6 of 188 patients [3%]; P = NS) or experienced a greater than 20% increase in creatinine level (63 of 187 patients [34%] versus 56 of 188 patients [30%]; P = NS). After 12 months of follow-up, allocation to 20 mg of simvastatin daily reduced nonfasting total cholesterol levels by 18% (simvastatin, 163 mg/dL [4.22 mmol/L] versus placebo, 196 mg/dL [5.08 mmol/L]; P < 0.0001), directly measured low-density lipoprotein cholesterol levels by 24% (89 mg/dL [2.31 mmol/L] versus 114 mg/dL [2.96 mmol/L]; P < 0.0001), and triglyceride levels by 13% (166 mg/dL [1.87 mmol/L] versus 186 mg/dL [2.10 mmol/L]; P < 0.01), but there was no significant effect on high-density lipoprotein cholesterol levels (2% increase; P = NS). Allocation to simvastatin therapy was not associated with excess risk for abnormal liver function test results or elevated creatine kinase levels. CONCLUSION: During a 1-year treatment period, simvastatin, 20 mg/d, produced a sustained reduction of approximately one quarter in low-density lipoprotein cholesterol levels, with no evidence of toxicity, and aspirin, 100 mg/d, did not substantially increase the risk for a major bleeding episode. Much larger trials are now needed to assess whether these treatments can prevent vascular events. |
| first_indexed | 2024-03-07T00:59:58Z |
| format | Journal article |
| id | oxford-uuid:896190ac-ade4-4764-802b-eee167387a04 |
| institution | University of Oxford |
| language | English |
| last_indexed | 2024-03-07T00:59:58Z |
| publishDate | 2005 |
| record_format | dspace |
| spelling | oxford-uuid:896190ac-ade4-4764-802b-eee167387a042022-03-26T22:24:17ZFirst United Kingdom Heart and Renal Protection (UK-HARP-I) study: biochemical efficacy and safety of simvastatin and safety of low-dose aspirin in chronic kidney disease.Journal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:896190ac-ade4-4764-802b-eee167387a04EnglishSymplectic Elements at Oxford2005Baigent, CLandray, MLeaper, CAltmann, PArmitage, JBaxter, ACairns, HCollins, RFoley, RFrighi, VKourellias, KRatcliffe, PRogerson, MScoble, JTomson, CWarwick, GWheeler, DBACKGROUND: Patients with chronic kidney disease are at increased risk for cardiovascular disease, but the efficacy and safety of simvastatin and aspirin are unknown in this patient group. METHODS: Patients were randomly assigned in a 2 x 2 factorial design to the administration of: (1) 20 mg of simvastatin daily versus matching placebo, and (2) 100 mg of modified-release aspirin daily versus matching placebo. RESULTS: Overall, 448 patients with chronic kidney disease were randomly assigned (242 predialysis patients with a creatinine level > or = 1.7 mg/dL [> or =150 micromol/L], 73 patients on dialysis therapy, and 133 patients with a functioning transplant). Compliance with study treatments was 80% at 12 months. Allocation to treatment with 100 mg of aspirin daily was not associated with an excess of major bleeds (aspirin, 4 of 225 patients [2%] versus placebo, 6 of 223 patients [3%]; P = not significant [NS]), although there was a 3-fold excess of minor bleeds (34 of 225 [15%] versus 12 of 223 patients [5%]; P = 0.001). Among those with predialysis renal failure or a functioning transplant at baseline, aspirin did not increase the number of patients who progressed to dialysis therapy (7 of 187 [4%] versus 6 of 188 patients [3%]; P = NS) or experienced a greater than 20% increase in creatinine level (63 of 187 patients [34%] versus 56 of 188 patients [30%]; P = NS). After 12 months of follow-up, allocation to 20 mg of simvastatin daily reduced nonfasting total cholesterol levels by 18% (simvastatin, 163 mg/dL [4.22 mmol/L] versus placebo, 196 mg/dL [5.08 mmol/L]; P < 0.0001), directly measured low-density lipoprotein cholesterol levels by 24% (89 mg/dL [2.31 mmol/L] versus 114 mg/dL [2.96 mmol/L]; P < 0.0001), and triglyceride levels by 13% (166 mg/dL [1.87 mmol/L] versus 186 mg/dL [2.10 mmol/L]; P < 0.01), but there was no significant effect on high-density lipoprotein cholesterol levels (2% increase; P = NS). Allocation to simvastatin therapy was not associated with excess risk for abnormal liver function test results or elevated creatine kinase levels. CONCLUSION: During a 1-year treatment period, simvastatin, 20 mg/d, produced a sustained reduction of approximately one quarter in low-density lipoprotein cholesterol levels, with no evidence of toxicity, and aspirin, 100 mg/d, did not substantially increase the risk for a major bleeding episode. Much larger trials are now needed to assess whether these treatments can prevent vascular events. |
| spellingShingle | Baigent, C Landray, M Leaper, C Altmann, P Armitage, J Baxter, A Cairns, H Collins, R Foley, R Frighi, V Kourellias, K Ratcliffe, P Rogerson, M Scoble, J Tomson, C Warwick, G Wheeler, D First United Kingdom Heart and Renal Protection (UK-HARP-I) study: biochemical efficacy and safety of simvastatin and safety of low-dose aspirin in chronic kidney disease. |
| title | First United Kingdom Heart and Renal Protection (UK-HARP-I) study: biochemical efficacy and safety of simvastatin and safety of low-dose aspirin in chronic kidney disease. |
| title_full | First United Kingdom Heart and Renal Protection (UK-HARP-I) study: biochemical efficacy and safety of simvastatin and safety of low-dose aspirin in chronic kidney disease. |
| title_fullStr | First United Kingdom Heart and Renal Protection (UK-HARP-I) study: biochemical efficacy and safety of simvastatin and safety of low-dose aspirin in chronic kidney disease. |
| title_full_unstemmed | First United Kingdom Heart and Renal Protection (UK-HARP-I) study: biochemical efficacy and safety of simvastatin and safety of low-dose aspirin in chronic kidney disease. |
| title_short | First United Kingdom Heart and Renal Protection (UK-HARP-I) study: biochemical efficacy and safety of simvastatin and safety of low-dose aspirin in chronic kidney disease. |
| title_sort | first united kingdom heart and renal protection uk harp i study biochemical efficacy and safety of simvastatin and safety of low dose aspirin in chronic kidney disease |
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