Efficacy and safety of atrasentan in patients with cardiovascular risk and early atherosclerosis.
Endothelin plays an important role in the pathogenesis of atherosclerosis. The aim of the study was to evaluate the safety and hemodynamic and metabolic responses to 6 months treatment with atrasentan, the selective endothelin-A receptor antagonist. Seventy-two patients with multiple cardiovascular risk factors and nonobstructive coronary artery disease on coronary angiogram were randomly assigned in a double-blind manner to atrasentan or placebo. Mean aortic blood pressure decreased from 92+/-10 to 80+/-10 mm Hg (P<0.001) in the atrasentan group and did not change in the placebo group (93+/-10 and 92+/-11 mm Hg; P=0.84). The difference between the groups was significant (P<0.001). No effect on heart rate was observed. In a subgroup of patients not treated with angiotensin-converting enzyme inhibitor, creatinine level decreased in the atrasentan versus the placebo group (P=0.011). Fasting glucose (P=0.026), glycosylated hemoglobin level (P=0.041), triglyceride l (P=0.013), lipoprotein-A (P=0.046), and uric acid levels (P=0.048) decreased significantly in the atrasentan group compared with the placebo group. No progression of angiographic coronary disease was observed. The most common adverse effects with atrasentan were nasal stuffiness, headache, and edema. In conclusion, 6 months of treatment with atrasentan results in a reduction of blood pressure and improvement in glucose and lipid metabolism. These findings suggest the beneficial role of atrasentan in the treatment of hypertension and metabolic syndrome.
Raichlin
Eugenia
E
Division of Cardiovascular Diseases, Center for Coronary Physiology and Imaging, Mayo Clinic, Rochester, MN 55905, USA.
Prasad
Abhiram
A
Mathew
Verghese
V
Kent
Bailey
B
Holmes
David R
DR
Pumper
Geralyn M
GM
Nelson
Rebecca E
RE
Lerman
Lilach O
LO
Lerman
Amir
A
D000328:Adult; D000959:Antihypertensive Agents / Q000008:administration & dosage* / Q000009:adverse effects; D000077868:Atrasentan; D001786:Blood Glucose / Q000378:metabolism; D001794:Blood Pressure / Q000187:drug effects; D003324:Coronary Artery Disease / Q000188:drug therapy* / Q000453:epidemiology; D004487:Edema / Q000188:drug therapy / Q000453:epidemiology; D065130:Endothelin A Receptor Antagonists; D019332:Endothelin-1 / Q000378:metabolism; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D006973:Hypertension / Q000188:drug therapy* / Q000453:epidemiology; D007668:Kidney / Q000502:physiology; D050356:Lipid Metabolism / Q000187:drug effects; D008297:Male; D024821:Metabolic Syndrome / Q000188:drug therapy / Q000453:epidemiology; D008875:Middle Aged; D011759:Pyrrolidines / Q000008:administration & dosage* / Q000009:adverse effects; D044022:Receptor, Endothelin A / Q000378:metabolism; D012307:Risk Factors; D016896:Treatment Outcome
D000959:Antihypertensive Agents; D001786:Blood Glucose; D065130:Endothelin A Receptor Antagonists; D019332:Endothelin-1; D011759:Pyrrolidines; D044022:Receptor, Endothelin A; D000077868:Atrasentan