Walter Alexander, PhD, is a medical writer living in New York.

Walter Alexander, PhD

Among the various offerings at the American Society of Hypertension's 2007 annual meeting in Chicago, several new studies strongly supported the use of fixed-dose antihypertensive combination therapy at the outset of hypertension treatment. 

A total of 12,600 hypertensive individuals with heart disease, renal disease, or target organ damage were randomized to either amlodipine and benazepril (5 mg and 20 mg) or benazepril and hydrochlorothiazide (20 mg and 12.5 mg). After one month, benazepril was increased to 40 mg in both groups. After the second month, amlodipine or thiazide doses were doubled. After the third month, investigators could add on any other drugs.  

Though ACCOMPLISH was not a diabetes trial, 60% of patients had Type 2 diabetes. Jamerson noted that even in this hard-to-treat cohort, the combo therapies dropped mean systolic blood pressure (SBP) from 145.2 mmHg to 131.5 mmHg. The proportion of patients deemed well controlled (below 140/90 mmHg) went from 37.6% to 75.6%. "We more than doubled the number who are well controlled," said Jamerson. This was accomplished, in most cases, with the fixed-dose combos alone. Only 15% of patients needed an add-on drug; only 6% needed two. Adverse-event rates were few and mild, with dizziness, cough, and edema being the most common. Roughly 2% of patients became hypotensive.  

"We assumed both combinations would reduce pressures down to target. Perhaps one is better than the other, but we are not really testing that," said Jamerson. He added, however, that combining a calcium-channel blocker (CCB) with an ACE inhibitor may increase nitric oxide production, thus improving vascular function. 

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New studies support the use of fixed dose antihypertensive combination therapy at the outset of hypertension treatment.

New data support combo therapy at outset of hypertension treatment

Analyses of the ACUITY (Acute Catheterization & Urgent Intervention Triage Strategy) trial demonstrated that bivalirudin (Angiomax, The Medicines Co.) alone in moderate- to high-risk acute coronary syndrome patients undergoing PCI (percutaneous coronary intervention) is noninferior to heparin with a glycoprotein inhibitor (GPI). But it entails much lower bleeding risk. The benefit, according to lead investigator Gregg Stone, M.D., director of research and education, Center for Interventional Vascular Therapy, Columbia University Medical Center, translates to 33 fewer major bleeds per 1,000 patients treated. One expert, however, questioned the methodology of the analysis and therefore the strength of the conclusions. 

ACUITY included 13,819 patients (mean age 63 years) randomized to heparin plus a GPI, bivalirudin plus a GPI, or bivalirudin alone. A total of 7,789 patients in this cohort underwent PCI within 20 hours of admission. At 30 days, the incidence of "composite ischemic events" (death, myocardial infarction [MI], unplanned urgent revascularization) was 8.2% for the heparin/GPI group, 9.3% for the bivalirudin/GPI group, and 8.8% for the bivalirudin monotherapy group. This fulfilled the prospectively defined criteria for "noninferiority." The slight increase (8%) in ischemic events in the bivalirudin groups was attributable primarily to higher MI rates of 6.6% and 6.5% in the bivalirudin-treated groups. Death rates were equivalent across the three groups.  

The final speaker in the ACUITY session, however, Sanjay Kaul, M.D., director of the Vascular Physiology and Thrombosis Research Laboratory at Cedars-Sinai Medical Center,  voiced strong reservations about the generally glowing conclusions. "The active control used in this trial has not been proven to be an effective and established therapy," he said. "So that undermines the whole assessment of noninferiority. Also, the noninferiority margins used in ACUITY were too broad. If we used conservative criteria, it does not meet the noninferiority standard." He objected, as well, to ACUITY's combining of safety and efficacy into a single endpoint. 

Based on evidence from anecdotal reports and a pilot study, Goldberg and colleagues conducted a 16-week study in 287 inadequately controlled diabetes patients with A1c of 7.5% to 9.5%. Mean body mass index (BMI) was high at 34.9. Patients were randomized to colesevelam (3.75 gm/ day) or placebo, continuing to take prestudy OAHs and insulin within 10% of base-line doses. Mean change in A1c was the primary endpoint, with FPG, glycemic control, lipid levels, high-sensitivity C-reactive protein (hs-CRP), and triglycerides as secondary endpoints. About 60% of patients at baseline were taking both insulin and OAHs. 

Treating heart attacks and agents affecting risk factors for heart disease were among the hot topics explored at the American Heart Association's 2006 annual meeting held recently in Chicago. Also, a program on increasing adherence to pharmacotherapy among the elderly was of interest to attendees.