Simultaneous treatment to attain blood pressure and lipid goals and reduced CV risk burden using amlodipine/atorvastatin single-pill therapy in treated hypertensive participants in a randomized controlled trial

Abstract

TOGETHER investigated whether targeting multiple cardiovascular (CV) risk factors using single-pill amlodipine/atorvastatin (AML/ATO) and therapeutic lifestyle changes (TLC) results in greater blood pressure (BP)/lipid control and additional reduction in estimated cardiovascular disease (CVD) risk compared with blood pressure intervention only using amlodipine (AML) + TLC. TOGETHER was a 6-week, randomized, double-blind, double-dummy trial using hypertensive participants with additional CV risk factors without CVD/diabetes. Participants were randomized to either AML/ATO (5 to 10/20 mg) + TLC or AML (5 to 10 mg) + TLC. The primary end point was the difference in proportion of participants attaining both BP (<140/90 mm Hg) and low-density lipoprotein cholesterol (LDL-C) (<100 mg/dL) goals at week 6. At week 6, 67.8% of participants receiving AML/ATO + TLC attained the combined BP/LDL-C goal versus 9.6% with AML + TLC (RD [A-B]: 58.2; 95% CI [48.1 to 68.4] P < 0.001; OR: 19.0; 95% CI 9.1 to 39.6; P < 0.001). Significant reductions from baseline in LDL-C, total cholesterol and triglycerides and estimated 10-year Framingham risk were also observed. Treatment with AML/ATO was well tolerated. In conclusion, a multifactorial CV management approach is more effective in achieving combined BP/LDL-C targets as well as CV risk reduction compared with BP intervention only in this patient population.

Keywords: blood pressure; calcium channel blocker; low-density lipoprotein cholesterol; statin.

Figure 1

Trial design and flow of participants through the trial. Notes: ^aOne participant was randomized, but did not receive any study medication, and was excluded from all analyses. Group A, prior amlodipine 5 mg + controlled BP; Group B, prior amlodipine 5 mg + uncontrolled BP; Group C, prior amlodipine 10 mg + controlled BP. Abbreviations: AML, amlodipine; ATO, atorvastatin; TLC, therapeutic lifestyle changes.

Figure 2

Attainment of combined BP/LDL-C goal. Notes: ^aPrimary efficacy measure. The BP goal used in this analysis was <140/90 mm Hg described by the Seventh Report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure. The LDL-C goal used was 100 mg/dL, an optimal threshold defined by the National Cholesterol Education Program Adult Treatment Panel II. Abbreviations: AML, amlodipine; ATO, atorvastatin; OR, odds ratio; RD, risk difference; TLC, therapeutic lifestyle changes.

Figure 3

Attainment of LDL-C goal. Notes: The LDL-C goal used for this analysis was <100 mg/dL, an optimal threshold defined by the National Cholesterol Education Program Adult Treatment Panel III. Abbreviations: AML, amlodipine; ATO, atorvastatin; OR, odds ratio; RD, risk difference; TLC, therapeutic lifestyle changes.

Figure 4

Attainment of SBP/DBP goal. Notes: The SBP/DBP goal used in this analysis was <140/90 mm Hg described by the Seventh Report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure. Abbreviations: AML, amlodipine; ATO, atorvastatin; OR, odds ratio; RD, risk difference; TLC, therapeutic lifestyle changes; SBP, systolic blood pressure; DBP, diastolic blood pressure.