Single-pill lipid and BP lowering effective in blacks; other research supports diuretics in hypertensives with metabolic syndrome

Shelley Wood

June 26, 2006

June 26, 2006

Atlanta, GA - Both black and white patients benefit from an atorvastatin/amlodipine single-pill combination (Caduet, Pfizer), although more whites than blacks reached treatment goals in a recent comparative study [ 1 ]. Dr John Flack (Wayne State University School of Medicine, Detroit, MI), who presented the results at the International Society of Hypertension in Blacks (ISHIB) 2006 meeting, says the important message from the study is that the combination pill produces impressive results in both groups.

Flack et al's analysis was conducted by comparing the results from the CAPABLE study, conducted in African Americans only, with results from non-African Americans who participated in the GEMINI study.

"Despite the fact that, in GEMINI, the non-African Americans had higher control, the bottom line is that in both groups, the control rates were actually pretty impressive and should not be lost in the relative contrast between the groups," Flack told renalwire .

While the two trials were not identical?most notably, GEMINI was a 14-week, open-label, noncomparative trial, while CAPABLE was comparative and 20 weeks in duration?they had the same entry criteria (patients with concomitant hypercholesterolemia and hypertension) and permitted dosing according to health status. Goal attainment in both trials was derived from the JNC 6 and 7 recommendations for blood-pressure goals and NCEP ATP III for cholesterol goals.

Reaching goals

As Flack reported, 48.5% of blacks reached blood pressure- and lipid-lowering goals, while 58.5% of whites reached goals on single-pill therapy, up from 0.8% and 0.6%, respectively, at study onset. Changes were statistically significant in both groups. Of note, black patients tended to be on higher doses of the combination pill, and the discontinuation rate was significantly higher in CAPABLE than in GEMINI, which may have played a role in decreasing the numbers of blacks who reached goals, compared with whites, Flack said.

"I doubt very seriously that it had anything to do with race differences in response of those people taking the drug, but you can't really tell that very easily when you're looking at a big trial," he observed. "The real message here is that you can get much better control rates with a combination pill to treat both high BP and dyslipidemia in a single pill, which reduces pill burden. People just don't like to take extra numbers of pills, so it's better if you can give them the same number of medications with fewer pills."

While the study did not look explicitly at the broader issue of medication discontinuation, Flack speculated to renalwire that combination pills reduce rates of stopping therapy and may even have the effect of increasing attainment of lipid-lowering goals.

"Patients discontinue lipid-lowering therapy a lot sooner than they do their hypertension therapy; I've always thought that by combining a statin with a commonly used, well-tolerated antihypertension agent [in a single pill], you would probably eliminate more of the people dropping off therapy with a statin than you would if you prescribed them individually," Flack said.

The reasons for this are complex, he added, but they have less to do with side effects and more to do with how cholesterol and hypertension are viewed by patients and physicians alike.

"People are afraid of high blood pressure because of its clear link to stroke; for cholesterol, they're not as immediately afraid," Flack explained. "They go on a statin, they take it for a while, but it's really a condition where the drug probably doesn't make them feel any different. And doctors tend to not be as aggressive with cholesterol as they are with blood pressure."

New ALLHAT analysis clarifies role of diuretics in metabolic syndrome

In separate research also presented at the ISHIB meeting, Dr Jackson T Wright (Case Western Reserve University, Cleveland, OH) and colleagues used data from the landmark ALLHAT trial to examine the role of different antihypertensive drugs in patients with metabolic syndrome [ 2 ].

As Wright acknowledged in an interview with renalwire , metabolic syndrome was not even a health designation at the time ALLHAT was designed and launched, but it has become, in the ensuing years, an important consideration for physicians selecting drugs for the treatment of hypertension in the setting of other diseases and conditions. In recent years, use of drugs that have more favorable metabolic profiles, such as alpha-blockers (ARBs), calcium-channel blockers, and ACE inhibitors have been advocated over other classes of antihypertensive drugs in patients with metabolic syndrome, despite findings from the original ALLHAT study that supported diuretics as first-line therapy.

To address this issue, Wright et al analyzed ALLHAT data according to metabolic-syndrome status, looking specifically at ARBs?suggested in recent studies to be the best choice for preventing new-onset diabetes?as compared with the thiazide-type diuretic chlorthalidone.

In all, 13 209 ALLHAT study participants met the criteria for metabolic syndrome, of whom almost 4200 were black. As per the main ALLHAT study, all of the patients were hypertensive, so the definition of metabolic syndrome was given if they also had at least two of the following: fasting glucose >100 mg/dL, BMI >30, fasting triglycerides >150 mg/dL, and HDL cholesterol <40 mg/dL for men or <50 mg/dL for women.

As Wright and colleagues report, among ALLHAT patients with metabolic syndrome, blood-pressure levels at 36 months were lower in diuretic-treated patients than in patients treated with the ARB doxazosin, yet serum glucose, cholesterol, and incident diabetes levels were lower in the ARB group than in the chlorthalidone group overall. More important, however, overall outcomes, in terms of heart failure, nonfatal MI, stroke, and combined cardiovascular disease, were worse in the ARB-treated patients than in the diuretic-treated patients with metabolic syndrome.

"The bottom line is that despite the much more favorable metabolic profile, antihypertension treatment initiated with the alpha-blocker was not superior to one initiated with the diuretic, including in patients with metabolic syndrome. This provides further evidence of the need to consider intermediate outcomes in the selection of antihypertensive agents, even in those with the metabolic syndrome," Wright commented to renalwire .


Flack receives consulting fees and speaker's honoraria for Pfizer, as well as competing companies. Wright reports doing research for many of the major companies that make ACE inhibitors, ARBs, and calcium-channel blockers, but not diuretics.



  1. Flack JM, Victor R, Watson K, et al. A comparison of goal attainment between African Americans and non-African Americans treated with amlodipine/atorvastatin single-pill therapy: A post-hoc comparison of the CAPABLE and GEMINI trials. ISHIB 2006; June 23-26, 2006; Atlanta, GA.

  2. Wright JT, Davis BR, Haywood J et al. Clinical outcomes by race in participants with the metabolic syndrome in the antihypertensive and lipid-lowering treatment to prevent heart attack trial on doxazosin vs chlorthalidone. ISHIB 2006; June 23-26, 2006; Atlanta, GA.