ASH 2007: Initial use of combination therapy effective

Preliminary results from ACCOMPLISH demonstrate BP control with combination therapy in one pill.

CHICAGO — Results of a new study show that initiating hypertension treatment with a single tablet of combination medication is safe and more than 80% effective.

“We think there’s substantial evidence here to broaden the use of combination therapy as an initial strategy for the treatment of hypertension,” said Kenneth A. Jamerson, MD, professor of the department of internal medicine at University of Michigan Health System.

Jamerson presented the results of the Avoiding Cardiovascular Events Through Combination Therapy in Patients Living with Systolic Hypertension (ACCOMPLISH) trial at the American Society of Hypertension 22nd Annual Scientific Meeting held here.

ACCOMPLISH

Jamerson said data about one of the two endpoints for the trial were available. Results on whether the combination of amlodipine-benazepril (Lotrel, Novartis) will reduce cardiovascular morbidity and mortality among patients with high-risk hypertension by 15% when compared with benazepril/hydrochlorothiazide are not yet ready.

Men and women aged 55 or older (n=11,463) are included in the study. Prior to the start of the study, 97% of patients were taking antihypertensives and 75% were taking two or more drugs. After 18 months of treatment, overall BP control rates increased from 37% to 76%, and mean systolic BP decreased from 145 mm Hg to 131 mm Hg. Benefits were noted across sex and age groups. The mean systolic BP of patients with diabetes improved to 131 mm Hg.

Adverse event rate for hypotension was 1.8%.

Jamerson said outcome data comparing the two regimens are expected approximately a year from now.

AMADEO

The Efficacy of Telmisartan Compared With Losartan in Reducing Proteinuria in Hypertensive Type 2 Diabetic Patients With Overt Nephropathy (AMADEO) study results showed that telmisartan (Micardis, Boehringer Ingelheim) reduced creatinine and BP levels after one year of treatment compared with losartan (Cozaar, Merck).

George Bakris, MD, professor of medicine and director of the Hypertension Center, section of endocrinology, diabetes and metabolism at University of Chicago, Pritzer School of Medicine, said that the researchers enrolled 860 patients with hypertension (BP >130 mm Hg/ 80 mm Hg) and overt nephropathy defined as proteinuria (spot urine ≥700 mg/g creatinine), serum creatinine ≤3 mg/dL in women and ≤3.2 mg/dL in men. After a run-in period, they randomly assigned 419 patients to 40 mg of telmisartan and 441 patients to 50 mg of losartan for two weeks, and then titrated the doses to 80 mg of telmisartan and 100 mg of losartan, for 50 weeks.

The average age of the patients in both arms was 60. Serum creatinine was 1.54 in the telmisartan group and 1.55 in the losartan group.

The primary endpoint was change from baseline in morning spot urinary protein creatinine; the telmisartan group was superior to losartan (0.71; 95% CI, 0.66-0.77 vs. 0.80; 95% CI, 0.74-0.87). No significant BP reductions were noted between the two medications.

“Telmisartan provides greater reduction in proteinuria over losartan,” said Bakris, a member of the Today in Cardiology Editorial Board.

Combinations tested

Amlodipine-olmesartan medoxomil (Azor, Daiichi-Sankyo) demonstrated greater reductions in BP compared with placebo and monotherapy, according to results of a study conducted by Steven G. Chrysant, MD, of the Oklahoma Cardiovascular and Hypertension Center and the University of Oklahoma School of Medicine, and colleagues.

In a randomized, placebo-controlled, double blind factorial study of 1,940 patients with hypertension, researchers examined whether coadministration of amlodipine at 5 mg or 10 mg per day and olmesartan medoxomil in doses ranging from 10 mg to 40 mg (10 mg, 20 mg and 40 mg) per day vs. each as monotherapy was superior. The primary endpoint of the study was change from baseline seated diastolic BP (between ≥95 mm Hg and ≤120 mm Hg). The secondary endpoint was change from baseline in seated diastolic BP.

The average age of the patients was 54 and 54.3% were men. Patients with diabetes comprised 13.5% of the population and 24.8% were black. Average systolic BP at baseline was 163.8 mm Hg and diastolic BP was 101 mm Hg.

Results of the phase-3 registration trial showed that at week eight, the greatest reduction in seated systolic and seated diastolic BP was noted with amlodipine 10 mg and olmesartan medoxomil 40 mg compared with amlodipine 10 mg (–30.1 mm Hg systolic and 19 mm Hg diastolic with the combination vs. –19.7 mm Hg systolic and –12.7 mm Hg diastolic with amlodipine 10 mg).

Adverse event profiles for each dose combination were no different from monotherapy.

“BP reductions were dose-related,” Chrysant said. “All regimens were well-tolerated.”

The results were also published in the Journal of Clinical Hypertension (2007;9:486).

A related combination study

In what he called a sister study, Joseph L. Izzo, MD, professor of medicine and pharmacology and vice chair of the department of medicine at Erie County Medical Center, Buffalo, N.Y., said results showed amlodipine-valsartan (Exforge, Novartis) is a safe and effective combination BP control strategy that was well-tolerated among patients not previously controlled with monotherapy.

All of the participants (n=894) had previously been assigned ACE inhibitors or angiotensin receptor blocker monotherapy. In the current study, 443 received amlodipine 5 mg/valsartan 160 mg and 451 received amlodipine 10 mg/valsartan 160 mg. The average age of patients was 58. One hundred forty-five patients had diabetes. The primary endpoint was BP control, defined as <140 mm Hg/<90 mm Hg for patients without diabetes and <130 mm Hg/<80 mm Hg for patients with diabetes.

After 16 weeks of treatment, the amlodipine 10 mg/valsartan 160 mg combination demonstrated the greatest reduction from baseline with a systolic BP reduction of 20.8 mm Hg (P<.001) and a –14.9 mm Hg systolic BP reduction among patients with diabetes. Almost three-quarters of each study arm population reached the set BP goals (72.7% in the amlodipine 5 mg/valsartan 160 mg group and 74.8% in the amlodipine 10 mg/valsartan 160 mg group).

“A number of us have been lobbying for [a] combination as initial drug therapy,” Izzo said during a press conference at the meeting. “I’d like to think the attitude at the FDA is changing.” – by Judith Rusk