Endothelin is a powerful vasoconstrictor peptide derived from the endothelium. The contribution of endothelin to blood-pressure regulation in patients with hypertension was as-sessed by studying the effect of an endothelin-receptor antagonist, Bosentan. In the study, 293 patients with mild to moderate hypertension were randomized to receive one of four oral doses of Bosentan (100, 500, 1000, or 2000 mg daily), a placebo, or the ACE (angiotensin-convertin
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Endothelin is a powerful vasoconstrictor peptide derived from the endothelium. The contribution of endothelin to blood-pressure regulation in patients with hypertension was as-sessed by studying the effect of an endothelin-receptor antagonist, Bosentan. In the study, 293 patients with mild to moderate hypertension were randomized to receive one of four oral doses of Bosentan (100, 500, 1000, or 2000 mg daily), a placebo, or the ACE (angiotensin-converting enzyme) inhibitor enalapril (an established antihypertensive drug) [18]. The reported mean changes in systolic blood pressure (SBP) over a 24-hour period are shown in Table 11.23.
Table 11.23 Mean change in SBP over 24 hours
| Group | Mean Change | Bosentan dose (mg) | ln(dose) |
| Placebo | -0.9 | 1 | 0 |
| 100mg bosentan | -2.5 | 100 | 4.61 |
| 500 mg bosentan | -8.4 | 500 | 6.21 |
| 1000 mg bosentan | -7.4 | 1000 | 6.91 |
| 2000 mg bosentan | -10.3 | 2000 | 7.60 |
11.61 What test can be used to assess whether the mean change in SBP is significantly related to ln(dose) of Bosentan? My answer: Model Utility Test
11.62 Implement the method in Problem 11.61, and report a two-tailed p-value. My answer: p-value is 0.04067
11.63 What is the estimated mean change in SBP for an average patient taking 2000 mg of Bosentan? Provide a 95% confidence interval corresponding to this estimate. My answer: Estimated mean change in SBP is -8.889642. 95% CI = (-16.62807 -1.151212)
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