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.
Preston
Richard A
RA
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
Harvey
Peter
P
Herfert
Ottmar
O
Dykstra
Gary
G
Jukema
J Wouter
JW
Sun
Franklin
F
Gillen
David
D
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