American Society of Hypertension 26th Annual Scientific Meeting and Exposition

May 21-24, 2011; New York, NY
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Combination of Azilsartan/Chlorthalidone Effective at Reducing Systolic Blood Pressure

New York, NY—A late-breaking oral abstract presented at the ASH annual meeting found that 3 months of combination therapy with newly approved azilsartan medoxomil (AZL-M) plus chlorthalidone (CLD) produced steeper drops in systolic blood pressure (BP) than the combination of olmesartan medoxomil (OLM) and hydrochlorothiazide (HCTZ). At a press conference, lead investigator William C. Cushman, MD, Veterans Affairs Medical Center, Memphis, TN, described the randomized phase 3 trial as “the first, large forced-titration study of an angiotensin-receptor blocker/chlorthalidone fixed-dose-combination therapy.”

Investigators enrolled 1071 adults age ≥18 years (mean age, 57 years) with seated systolic BP ranging from 160 to 190 mmHG, as measured in the clinic. Many participants were already taking antihypertensives, so the study began with a 3- to 4-week washout period, which was followed by 2 weeks of placebo use. Patients were then randomized to 12 weeks of AZL-M/CLD once daily, titrated to 40/25 mg (n = 355) or to 80/25 mg (n = 352), or they received once-daily OLM/HCTZ (n = 364), titrated to 40/25 mg, which is the highest dose approved for this regimen. Cushman said that they paired AZL-M with CLD based on emerging data that suggest CLD, a diuretic similar to thiazide, lowers systolic BP by an additional 5 to 10 mm Hg compared with HCTZ.

The study’s primary end point was change from baseline in systolic BP. A secondary end point was change in 24-hour ambulatory BP. Investigators also evaluated the safety and effectiveness of each regimen. At 4-, 8-, and 12-week follow-up visits, patients receiving either dose of AZL-M/CLD demonstrated significantly greater declines in systolic BP versus those randomized to OLM/HCTZ (P <.001). Seated systolic BP declined a mean of 42.5 mm Hg in the AZL-M/CLD 40/25-mg group compared with 44 mm Hg for the AZL-M/CLD 80/25-mg arm and 37.1 mm Hg for the OLM/HCTZ group. On the secondary end point of change in 24-hour systolic BP, patients in the AZL-M/CLD 40/25-mg group experienced a mean drop of 33.9 mm Hg compared with 36.3 mm Hg for the AZL-M/CLD 80/25-mg group and 27.5 mm Hg for the OLM/HCTZ trial arm, also considered significant (P <.001).

Cushman said that the 70% rate of adverse events among patients randomized to AZL-M/CLD and the 60% rate observed in the OLM/HCTZ group correlated with rates observed in other trials. Patients taking AZL-M/CLD were slightly more likely to discontinue due to adverse events, but hypokalemia was not problematic with AZL-M. Cushman said that this was likely because AZL-M offset the negative effect of CLD on potassium levels.

Cushman said that although the use of different diuretics with the angiotensin II receptor blockers made it harder to determine which agent was responsible for the declines in systolic BP, trials directly comparing AZL-M and OLM have shown that AZL-M decreases systolic BP by 2 to 3 mm Hg more than OLM. He called the findings encouraging. “This combination of azilsartan medoxomil plus chlorthalidone, especially in the 40-to 25-mg dosage, offers the promise of a very effective and well-tolerated treatment for hypertensive patients,” he concluded at the press conference.

 Funding by Takeda Global Research & Development Center Inc.
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Poster

Elderly Patients With Comorbidities Less Likely to Achieve Blood Pressure Control

New York, NY—A review of medical records for elderly patients with hypertension found that most were prescribed antihypertensive medications in accordance with guideline recommendations for their relevant comorbid diseases and risk factors. Individuals with the greatest number of relevant conditions and compelling indications (RCCIs) for antihypertensive treatments, however, were less likely to achieve reductions in blood pressure (BP) that met therapeutic goals. Investigators from the Analysis Group Inc, Boston, MA, and Novartis Pharmaceuticals Corporation, East Hanover, NJ, presented data from the retrospective study in a poster session at the ASH annual meeting.

The research team examined medical records from four primary care centers in the United States for community-dwelling patients ≥65 years of age whose diagnosis of hypertension was established with ≥1 BP reading at a clinic visit on or after January 1, 2007, and confirmed during ≥1 follow-up visit. Patients found to have received care for a hypertensive emergency or terminal illness were ineligible. Investigators randomly selected 357 patients (mean age, 78.3+7.0 years) from among the list of individuals who met eligibility criteria and analyzed records from the patient’s first clinic visit to his or her last clinic visit.

Patients were stratified according to number of RCCIs, which were assessed using guidelines from “The Seventh Report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure” (JNC-7). Only 68 patients had no RCCIs (0-RCCI); 132 were categorized as 1-RCCI, and 157 were classified as ≥2RCCI. Overall, 72.8% of patients were at high risk of coronary disease. Records showed that at the first visit, mean systolic BP was significantly higher among patients in the ≥2-RCCI group, at 141.2 mm Hg, compared with 131.4 mm Hg for the 0-RCCI group and 137.4 mm Hg for the 1-RCCI arm (P <.001).

JNC-7 guidelines outline treatment recommendations for patients with uncomplicated hypertension and for those with a high risk of coronary disease or who have conditions (eg, diabetes, chronic kidney disease) considered compelling indicators for starting therapy with medication from a specific class of antihypertensive drugs. During the initial visit, 96.1% of patients were prescribed an antihypertensive medication, and 66.5% of these patients received combination therapy. Therapeutics were typically prescribed in accordance with JNC-7 guidelines, although less commonly for patients who had a history of stroke or diabetes.

Follow-up visits were recorded every 3 months and showed that treatment regimens were modified for 61.8% of patients in the ≥2-RCCI group, 57.6% in the 1-RCCI arm, and 55.9% in the 0-RCCI group. Patients with ≥2-RCCIs were least likely to attain BP goals, with only 15% of patients in this group demonstrating satisfactory BP levels during the 75% to 100% of clinic visits where BP was measured. The proportion of patients who attained BP goals over time increased significantly in the 1-RCCI group and the 0-RCCI arm (33% and 50%, respectively). The authors concluded that their review indicates “the need for more aggressive hypertension management in elderly patients.”

Analysis Group, Inc., received the research support for this study from Novartis Pharmaceuticals Corporation, East Hanover, NJ.
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Poster

Elderly Patients Highly Adherent to Home Blood Pressure Monitoring Intervention

New York, NY—Researchers from Health-Partners Research Foundation in Minneapolis, MN, reported high rates of adherence to an experimental intervention designed to help patients with uncontrolled hypertension monitor blood pressure (BP) at home. In a preliminary analysis of data for the 160 patients with uncontrollable BP who participated in the interventional trial for at least 24 weeks, Tessa J. Kerby, MPH, and colleagues reported mean adherence rates as high as 90% among individuals age ≥65 years. Six-month findings were presented in a poster session at the ASH annual meeting.

Home BP monitoring has been endorsed by ASH, the American Heart Association, and the Preventive Cardiovascular Nurses Association for people with hypertension or borderline hypertension, but adherence is essential if it is to be effective. “We evaluated telemedicine as a transformational care management tool that allows comprehensive assessment of hypertension and improves care,” Kerby told Clinical Geriatrics.

Persons age ≥21 years whose BP measured >140/90 mm Hg at their two most recent visits to a HealthPartners Medical Group clinic and during a trial screening were eligible for the study. Kerby said, “Most [participants] were aware of their hypertension status and motivated to enter into an intensive intervention.” 

Patients were randomized to the telemonitoring intervention or usual care with their primary care physician. Individuals in the telemonitoring group were given a home BP telemonitor and told to measure their BP at least six times each week, transmitting results electronically to the pharmacist case manager. They were also required to partake in telephone consultations with the pharmacist every 2 weeks and to visit the research clinic 6 months after randomization.

Individuals who recorded six or more BP readings weekly for ≥17 weeks (70% of study duration) were considered adherent to the telemonitoring intervention. Overall, 83% of participants were adherent. Some participants completed all six required BP readings for only 4% of the 24 weeks, whereas others did so all 24 weeks. The overall mean proportion of weeks for which at least six BP measurements were documented was 80%.

Patients who were white, employed part-time, or ≥65 years of age were significantly more likely to adhere to the telemonitoring protocol. The rate of adherence was 85% for whites compared with 66% for non-whites (P = .04). Only 77% of individuals <65 years of age were adherent versus 90% of adults age ≥65 years (P = .03). Stratifying adherence according to employment status revealed that 77% of full-time employees were adherent, compared with 95% of part-time employees, 88% of retirees, and 67% of unemployed persons (P = .05). Neither gender nor education level affected the likelihood of adherence. A multivariate analysis found that older age significantly predicted likelihood of adherence (P = .04). Approximately 90% of participants completed all six mandatory phone calls with study pharmacists, and 94% visited the research clinic at 6 months.

Despite the intensive study protocol, adherence rates were high. Kerby attributed the high rate to “motivated participants and a well-articulated schedule of readings and telephone visits with their case managers.” She said that the telemedicine protocol has positive implications for patient care. “If patients were able to adhere to a blood pressure monitoring regimen, BP control could be improved by allowing reliable BP data to be conveyed to healthcare providers, who can then close the feedback loop by making appropriate therapeutic adjustments.”

The ongoing study is being conducted in collaboration with the National Heart, Lung, and Blood Institute.