By Betty S. Riggs
NEW ORLEANS -- May 20, 2008 -- According to findings from the Caduet in Untreated Subject Population (CUSP) Trial, 4 weeks of therapy with the combination of amlodipine/atorvastatin plus therapeutic lifestyle changes (TLC) resulted in significantly more patients reaching blood pressure and cholesterol goals than treatment with TLC alone.
Joel M. Neutel, MD, Associate Professor of Medicine, University of California, Irvine, California, and Medical Director of Clinical Pharmacology at Orange County Research Center, Tustin, California, and colleagues reported their findings on May 16 at the 23rd Annual Scientific Meeting of the American Society of Hypertension (ASH[HYP]).
CUSP was a double-blind, randomised, placebo-controlled study that was designed to assess whether patients at cardiovascular (CV) risk might benefit from simultaneous initiation of combined antihypertensive/lipid-lowering treatment together with TLC compared with TLC alone. Patients qualified for the study were randomised to either amlodipine/atorvastatin (5/20 mg daily) plus TLC or to placebo plus TLC for 8 weeks. TLC included patient counselling regarding diet, exercise, and smoking cessation. Add-on therapy for blood pressure and/or lipid-lowering was allowed, if needed, after 4 weeks of double-blind therapy.
Adult patients of either gender with hypertension and dyslipidaemia were eligible for the study if they had not been treated for the 2 conditions for at least 3 months prior to screening. Hypertension was defined as systolic blood pressure (SBP) of 140 to 169 mm Hg and/or diastolic blood pressure (DBP) 90 to 105 mm Hg at screening, or SBP of 140 to 159 mm Hg and/or DBP 90 to 99 mm Hg at randomisation. Low-density lipoprotein cholesterol (LDL-C) had to be 110 to 160 mg/dL at screening. Patients were excluded if they had a history of diabetes, coronary heart disease (CHD), peripheral vascular disease, cardiac arrhythmias, liver disease, or fasting triglycerides >500 mg/dL.
The primary endpoint was the proportion of patients attaining both the blood pressure goal (<140/90 mm Hg) and LDL-C goal (<100 mg/dL) at week 4. A number of secondary endpoints were evaluated, including the proportion of patients attaining the combined BP and LDL-C goals at week 8, and the 10-year Framingham Risk of CHD Score at weeks 4 and 8.
Statistical analysis of efficacy parameters was based on the Full Analysis Set (FAS) of all randomised patients who received study medication and had at least one postbaseline assessment for BP and LDL-C. For the primary endpoint, an odds ratio (OR) estimate, 95% confidence intervals (CI), and P values were calculated based on a Cochran-Mantel-Haenszel (CMH) test, controlling for baseline BP and LDL-C.
There were 123 patients in the FAS population. At baseline, the mean age was 53 years, and slightly more than 50% of patients were white males. The 10-year Framingham Risk Score was 7, and 71% of patients were treatment-naive for both hypertension and dyslipidaemia.
At week 4 of double-blind treatment, 47.6% of patients treated with amlodipine/atorvastatin reached BP and LDL-C goals compared with only 1.7% of the placebo-treated patients (OR 59.8; 95% CI, 7.4-486; P < .001). At week 8, the percentages increased to 55.6% and 5%, respectively (OR 23.8; 95% CI, 6.7-85; P < .001).
The 10-Year Framingham Risk Score worsened by an average of 4.1% in the placebo arm at weeks 4 and 8. However, the score improved by an average of 33% after 4 weeks of treatment with amlodipine/atorvastatin and by 38% at week 8 (P < .001).
Adverse events, most of which were mild to moderate, were reported in 31.8% of patients in the amlodipine/atorvastatin group compared to 34.4% of patients in the placebo group. No serious adverse events were observed. Discontinuation occurred in 2 patients in the active group and in 1 patient in the placebo group.
According to Dr. Neutel, "The previously published ASCOT Study demonstrated that hypertensive patients with moderate cholesterol elevations are undertreated." He added that the CUSP study demonstrates that amlodipine/atorvastatin in a single tablet provides a convenient and effective way to treat both hypertension and cholesterol.
Investigators concluded that improvements in goal attainment with simultaneous initiation of amlodipine/atorvastatin plus TLC compared with TLC alone may provide a more comprehensive preventive approach to CVD.
The CUSP Trial was sponsored by Pfizer Inc.
[Presentation title: Benefits of Amlodipine/Atorvastatin Single Pill in the Caduet in Untreated Subject Population (CUSP) Trial. Abstract P-288]
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