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

Richard Grimm, Mobin Malik, Carla Yunis, Santosh Sutradhar, Attila Kursun, TOGETHER Investigators, Jon Shapiro, Mandeep Singh Oberoi, Ginger Sandler Kubala, Waymon Drummond, Dinh Van Dinh, Mark Edward Shirley, Piotr Z Imiolek, Andrew Brockmyre, Eli M Roth, Kris Manlove-Simmons, Michael Friend Wilson, Peter A Lodewick, Matthew Jay Budoff, Shelton P Hager, Fatima C Phillips, Z David Skloven, John V Bernard, Julie A Mullen, Albert Ayerst Carr, Michael R Seidner, Cynthia Becher Strout, Mel Emiel Lucas, Christopher M Chappel, Scott William Yates, Robert Jay Weiss, Richard Anthony Cottiero, Susan Levit, John P Kripsak, Prasad Gupta, Steven A Smallow, Michael Schoenwalder, Vibhuti Narain Singh, Clinton Nicolas Corder, Barry S Meyer, Robert Grady Ashley, Patrick Henry Peters, Hector G Ramirez, Philip Alan Levin, Richard Neil Marple, Dennis Stone Riff, Van Q Nguyen, Richard Allen Craven, Louis Marino, Joseph R Weinstein, Max Helman, Frederick Tannenggee, Ronald A Ronald A, Alan S Hoffman, Wentworth Grantley Jarrett, Richard Grimm, Mobin Malik, Carla Yunis, Santosh Sutradhar, Attila Kursun, TOGETHER Investigators, Jon Shapiro, Mandeep Singh Oberoi, Ginger Sandler Kubala, Waymon Drummond, Dinh Van Dinh, Mark Edward Shirley, Piotr Z Imiolek, Andrew Brockmyre, Eli M Roth, Kris Manlove-Simmons, Michael Friend Wilson, Peter A Lodewick, Matthew Jay Budoff, Shelton P Hager, Fatima C Phillips, Z David Skloven, John V Bernard, Julie A Mullen, Albert Ayerst Carr, Michael R Seidner, Cynthia Becher Strout, Mel Emiel Lucas, Christopher M Chappel, Scott William Yates, Robert Jay Weiss, Richard Anthony Cottiero, Susan Levit, John P Kripsak, Prasad Gupta, Steven A Smallow, Michael Schoenwalder, Vibhuti Narain Singh, Clinton Nicolas Corder, Barry S Meyer, Robert Grady Ashley, Patrick Henry Peters, Hector G Ramirez, Philip Alan Levin, Richard Neil Marple, Dennis Stone Riff, Van Q Nguyen, Richard Allen Craven, Louis Marino, Joseph R Weinstein, Max Helman, Frederick Tannenggee, Ronald A Ronald A, Alan S Hoffman, Wentworth Grantley Jarrett

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.

Figures

Figure 1
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
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
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
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.

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