A randomized, placebo-controlled trial to evaluate the efficacy, safety, and pharmacodynamic interaction of coadministered amlodipine and atorvastatin in 1660 patients with concomitant hypertension and dyslipidemia: the respond trial.
Guidelines stress the importance of the simultaneous management of multiple cardiovascular risk factors. This can in part be achieved by coadministration of lipid-lowering and antihypertensive treatments. Potential pharmacodynamic interaction between drugs should be investigated as part of developing single-pill combinations. The Respond trial assessed whether combining amlodipine to treat hypertension and atorvastatin to treat dyslipidemia affected the action of either monotherapy. A total of 1660 hypertensive patients with dyslipidemia received 1 of 15 combinations of amlodipine (placebo, 5, or 10 mg) and atorvastatin (placebo, 10, 20, 40, or 80 mg) in a 3 x 5 factorial randomized, placebo-controlled design. At 8 weeks, combination-treated patients experienced dose-related and statistically significant reductions in systolic blood pressure, low-density lipoprotein cholesterol, and Framingham risk score. Overall, coadministered atorvastatin and amlodipine was well tolerated and without adverse pharmacodynamic interaction; combination treatment did not affect the low-density lipoprotein cholesterol-lowering efficacy and safety of atorvastatin, or the systolic blood pressure-lowering efficacy and safety of amlodipine.
Division of Clinical Pharmacology Clinical Research Center, Department of Medicine, Miller School of Medicine, University of Miami, 1500 NW 12th Avenue, 15th Floor West Tower, Miami, FL 33136, USA. rpreston@med.miami.edu
Richard A
RA
Preston
Peter
P
Harvey
Ottmar
O
Herfert
Gary
G
Dykstra
J Wouter
JW
Jukema
Franklin
F
Sun
David
D
Gillen
D000410:Alanine Transaminase / Q000097:blood; D000469:Alkaline Phosphatase / Q000097:blood; D017311:Amlodipine / Q000009:adverse effects / Q000493:pharmacokinetics / Q000627:therapeutic use*; D000924:Anticholesteremic Agents / Q000009:adverse effects / Q000493:pharmacokinetics / Q000627:therapeutic use; D000959:Antihypertensive Agents / Q000009:adverse effects / Q000493:pharmacokinetics / Q000627:therapeutic use; D001219:Aspartate Aminotransferases / Q000097:blood; D000069059:Atorvastatin; D001794:Blood Pressure / Q000187:drug effects; D008078:Cholesterol, LDL / Q000097:blood; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D004347:Drug Interactions; D004359:Drug Therapy, Combination; D050171:Dyslipidemias / Q000097:blood / Q000150:complications / Q000188:drug therapy*; D005260:Female; D006538:Heptanoic Acids / Q000009:adverse effects / Q000493:pharmacokinetics / Q000627:therapeutic use*; D006801:Humans; D006973:Hypertension / Q000150:complications / Q000188:drug therapy* / Q000503:physiopathology; D008297:Male; D011758:Pyrroles / Q000009:adverse effects / Q000493:pharmacokinetics / Q000627:therapeutic use*; D016896:Treatment Outcome; D005723:gamma-Glutamyltransferase / Q000097:blood
D000924:Anticholesteremic Agents; D000959:Antihypertensive Agents; D008078:Cholesterol, LDL; D006538:Heptanoic Acids; D011758:Pyrroles; D017311:Amlodipine; D000069059:Atorvastatin; D005723:gamma-Glutamyltransferase; D001219:Aspartate Aminotransferases; D000410:Alanine Transaminase; D000469:Alkaline Phosphatase