Efficacy and safety of coadministered amlodipine and atorvastatin in patients with hypertension and dyslipidemia: results of the AVALON trial

Abstract

The AVALON study was a randomized, multicenter trial to assess the efficacy and safety of coadministered amlodipine and atorvastatin in patients with hypertension and dyslipidemia. Phase one was an 8-week, double-blind, double-dummy, placebo-controlled period whereby patients received amlodipine 5 mg, atorvastatin 10 mg, amlodipine 5 mg and atorvastatin 10 mg, or placebo. Thereafter, all patients received single-blind amlodipine 5 mg and atorvastatin 10 mg for 8-weeks, followed by 12 weeks of open-label treatment where doses could be titrated to improve low-density lipoprotein cholesterol and blood pressure control. A total of 847 patients entered the double-blind phase. At Week 8, 45% of the patients receiving amlodipine 5 mg and atorvastatin 10 mg reached both their blood pressure and low-density lipoprotein cholesterol goals, compared with 8.3% with amlodipine (p < 0.001), 28.6% with atorvastatin (p < 0.001), and 3.5% with placebo. At 28 weeks, 67.1% of patients coadministered amlodipine and atorvastatin (mean doses, 7.6 mg and 28.4 mg, respectively) achieved both targets. Framingham estimated 10-year risk of coronary heart disease declined from baseline levels of 15.1% to 6.9% at Week 28. Following coadministered treatment, the adverse events reported were similar to either agent alone. Concomitant administration of amlodipine and atorvastatin is an effective and well tolerated treatment for coexisting hypertension and dyslipidemia.

Figure 1

Study design and patient disposition. AE=adverse event; Other=reported lack of efficacy of drug, laboratory abnormalities, or patient defaulted (includes lack of treatment compliance); ITT=intent‐to‐treat; *duration 2–6 weeks depending on medication previously administered; **one patient randomized to treatment but did not receive drug; ^†amlodipine (AML) 5 mg and atorvastatin (ATV) 10 mg o.d. × 8‐week, single‐blind period, then up‐titrated to a maximum dose of AML 10 mg × ATV 80 mg, if required, during subsequent 12 weeks to achieve goals

Figure 2

Percentage of patients within the four different treatment groups that reached target levels for both blood pressure and low‐density lipoprotein cholesterol at Week 8 (left panel) and Week 28 (right panel, stratified by the original randomized double‐blind treatment groups); data for risk groups I, II, and III combined. At Week 28, all patients were receiving coadministered amlodipine (AML) and atorvastatin (ATV). *p<0.001 vs. amlodipine alone; **p<0.001 vs. atorvastatin alone

Figure 3

Percentage of patients within the four different treatment groups that reached target levels for both blood pressure and low‐density lipoprotein cholesterol at Week 8 (left panel) and Week 28 (right panel, stratified by the original randomized double‐blind treatment groups); data for risk groups I, II, and III combined. At Week 28, all patients were receiving coadministered amlodipine (AML) and atorvastatin (ATV). *p<0.001 vs. amlodipine alone; **p<0.001 vs. atorvastatin alone

Figure 4

Percentage of patients within the four different treatment groups that reached target levels for low‐density lipoprotein cholesterol at Week 8 (left panel) and Week 28 (right panel, stratified by the original randomized double‐blind treatment groups); data for risk groups I, II, and III combined. At Week 28, all patients were receiving coadmin‐istered amlodipine (AML) and atorvastatin (ATV). *p<0.001 vs. amlodipine alone

Figure 5

Least square mean changes in systolic blood pressure (SBP) and diastolic blood pressure (DBP) among the four treatment groups; data for groups I, II, and III combined. *p<0.001 vs. placebo; **p<0.001 vs. atorvastatin alone; ^†all patients received coadministered amlodipine (AML) 5 mg and atorvastatin (ATV) 10 mg; ^†all patients received coadministered AML 5–10 mg and ATV 10‐80 mg titrated to achieve goals