| 1. |
- Bakris, George L, et al.
(författare)
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Divergent results using clinic and ambulatory blood pressures report of a darusentan-resistant hypertension trial
- 2010
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Ingår i: Hypertension. - 0194-911X .- 1524-4563. ; 56:5, s. 824-830
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Tidskriftsartikel (refereegranskat)abstract
- Patients with resistant hypertension are at increased risk for cardiovascular events. The addition of new treatments to existing therapies will help achieve blood pressure (BP) goals in more resistant hypertension patients. In the current trial, 849 patients with resistant hypertension receiving ≥3 antihypertensive drugs, including a diuretic, at optimized doses were randomized to the selective endothelin A receptor antagonist darusentan, placebo, or the central α-2 agonist guanfacine. The coprimary end points of the study were changes from baseline to week 14 in trough, sitting systolic BP, and diastolic BP measured in the clinic. Decreases from baseline to week 14 in systolic BP for darusentan (−15±14 mm Hg) were greater than for guanfacine (−12±13 mm Hg; P<0.05) but not greater than placebo (−14±14 mm Hg). Darusentan, however, reduced mean 24-hour systolic BP (−9±12 mm Hg) more than placebo (−2±12 mm Hg) or guanfacine (−4±12 mm Hg) after 14 weeks of treatment (P<0.001 for each comparison). The most frequent adverse event associated with darusentan was fluid retention/edema at 28% versus 12% in each of the other groups. More patients withdrew because of adverse events on darusentan as compared with placebo or guanfacine. We conclude that darusentan provided greater reduction in systolic BP in resistant hypertension patients as assessed by ambulatory BP monitoring, in spite of not meeting its coprimary end points. The results of this trial highlight the importance of ambulatory BP monitoring in the design of hypertension clinical studies.
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| 2. |
- Weber, Michael A, et al.
(författare)
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A selective endothelin-receptor antagonist to reduce blood pressure in patients with treatment-resistant hypertension : a randomised, double-blind, placebo-controlled trial
- 2009
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Ingår i: The Lancet. - : Elsevier. - 0140-6736 .- 1474-547X. ; 374:9699, s. 1423-1431
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Tidskriftsartikel (refereegranskat)abstract
- BackgroundHypertension cannot always be adequately controlled with available drugs. We investigated the blood-pressure-lowering effects of the new vasodilatory, selective endothelin type A antagonist, darusentan, in patients with treatment-resistant hypertension.MethodsThis randomised, double-blind study was undertaken in 117 sites in North and South America, Europe, New Zealand, and Australia. 379 patients with systolic blood pressure of 140 mm Hg or more (≥130 mm Hg if patient had diabetes or chronic kidney disease) who were receiving at least three blood-pressure-lowering drugs, including a diuretic, at full or maximum tolerated doses were randomly assigned to 14 weeks' treatment with placebo (n=132) or darusentan 50 mg (n=81), 100 mg (n=81), or 300 mg (n=85) taken once daily. Randomisation was made centrally via an automated telephone system, and patients and all investigators were masked to treatment assignments. The primary endpoints were changes in sitting systolic and diastolic blood pressures. Analysis was by intention to treat. The study is registered with ClinicalTrials.gov, number NCT00330369.FindingsAll randomly assigned participants were analysed. The mean reductions in clinic systolic and diastolic blood pressures were 9/5 mm Hg (SD 14/8) with placebo, 17/10 mm Hg (15/9) with darusentan 50 mg, 18/10 mm Hg (16/9) with darusentan 100 mg, and 18/11 mm Hg (18/10) with darusentan 300 mg (p<0·0001 for all effects). The main adverse effects were related to fluid accumulation. Oedema or fluid retention occurred in 67 (27%) patients given darusentan compared with 19 (14%) given placebo. One patient in the placebo group died (sudden cardiac death), and five patients in the three darusentan dose groups combined had cardiac-related serious adverse events.InterpretationDarusentan provides additional reduction in blood pressure in patients who have not attained their treatment goals with three or more antihypertensive drugs. As with other vasodilatory drugs, fluid management with effective diuretic therapy might be needed.
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