Sherry Boschert

SAN FRANCISCO — A growing body of evidence suggests that the oral agent glyburide may not be as safe as injected insulin to treat gestational diabetes, and that perceived barriers to women using insulin are unsubstantiated.

“The standard of care was insulin. Then everybody changed to glyburide based on an underpowered study” of 404 women with gestational diabetes who were randomized to glyburide or insulin therapy, Dr. Aaron B. Caughey said at a conference on antepartum and intrapartum management sponsored by the University of California, San Francisco.

The study reported similar glycemic control and neonatal outcomes between groups (N. Engl. J. Med. 2000;343:1134–8). “A lot of people that use glyburide base it on this one prospective, randomized trial” that was too small and showed some worrisome trends, said Dr. Caughey, medical director of the Diabetes and Pregnancy Program at the university.

A closer look at the results reveals multiple trends toward worse neonatal outcomes with glyburide, although none are statistically significant, he said. In the glyburide group, 7% of babies had birth weights above 4,000 grams, compared with 4% of the insulin group. Lung complications were reported in 8% of the glyburide group and in 6% on insulin. Hypoglycemia occurred in 9% on glyburide and 6% on placebo. Hyperbilirubinemia rates were 6% on glyburide and 4% on placebo.

More recently, a retrospective cohort study of 584 women with gestational diabetes in the Kaiser Permanente system found significantly worse rates of preeclampsia (12%) and phototherapy for hyperbilirubinemia (9%) in women treated with glyburide, compared with those given insulin (6% and 5%, respectively). That study also found a nonsignificant trend toward a higher rate of birth injury with glyburide (3%) than with insulin (1%), all of which was “concerning,” he said (Am. J. Obstet. Gynecol. 2005;193:118–24).

Analyses of statewide data from the California Diabetes and Pregnancy Program (known as Sweet Success) in 2007 by Dr. Caughey's associates at the university also found some significantly worse outcomes in women given oral agents compared with insulin for gestational diabetes. They found a 35% higher risk for birth weights above 4,000 g, a 40% higher risk for admission to the neonatal intensive care unit, and a 52% higher risk for preterm delivery before 34 weeks' gestation in women taking oral agents after adjusting for the effects of maternal age, ethnicity, parity, education, gestational age at delivery or at diagnosis of gestational diabetes, body mass index, and gestational weight gain.

Among women diagnosed with gestational diabetes early in pregnancy—at less than 24 weeks' gestation—the increased risk with oral agents was even more pronounced, including more than a threefold higher risk for intrauterine fetal demise compared with the insulin group.

Some clinicians say they prefer to treat gestational diabetes with glyburide because they believe that patients with little formal education cannot understand how to use insulin, or that patients whose primary language is not English will have difficulty, noted Dr. Caughey, who said he had no conflicts of interest related to this topic. When they stratified the Sweet Success data to profile women who had less than 9 years of education or whose primary language was Spanish, those on oral agents still had significantly worse outcomes.

“In my practice, we have one person a year [who will] not be able to use insulin and [who has] to use an oral agent. It's pretty rare.” At UCSF, gestational diabetes management begins with nutritional counseling and a prescription to take a short walk after each meal. If borderline or mild glucose elevations persist, they offer the patient insulin and will consider the alternative of oral metformin, but only in patients who are unlikely to have pre-existing diabetes mellitus, who have been diagnosed with gestational diabetes at 26–32 weeks' gestation, and who have been counseled about an increased preterm delivery risk associated with metformin.

SAN FRANCISCO — A growing body of evidence suggests that the oral agent glyburide may not be as safe as injected insulin to treat gestational diabetes, and that perceived barriers to women using insulin are unsubstantiated.

“The standard of care was insulin. Then everybody changed to glyburide based on an underpowered study” of 404 women with gestational diabetes who were randomized to glyburide or insulin therapy, Dr. Aaron B. Caughey said at a conference on antepartum and intrapartum management sponsored by the University of California, San Francisco.

The study reported similar glycemic control and neonatal outcomes between groups (N. Engl. J. Med. 2000;343:1134–8). “A lot of people that use glyburide base it on this one prospective, randomized trial” that was too small and showed some worrisome trends, said Dr. Caughey, medical director of the Diabetes and Pregnancy Program at the university.

A closer look at the results reveals multiple trends toward worse neonatal outcomes with glyburide, although none are statistically significant, he said. In the glyburide group, 7% of babies had birth weights above 4,000 grams, compared with 4% of the insulin group. Lung complications were reported in 8% of the glyburide group and in 6% on insulin. Hypoglycemia occurred in 9% on glyburide and 6% on placebo. Hyperbilirubinemia rates were 6% on glyburide and 4% on placebo.

More recently, a retrospective cohort study of 584 women with gestational diabetes in the Kaiser Permanente system found significantly worse rates of preeclampsia (12%) and phototherapy for hyperbilirubinemia (9%) in women treated with glyburide, compared with those given insulin (6% and 5%, respectively). That study also found a nonsignificant trend toward a higher rate of birth injury with glyburide (3%) than with insulin (1%), all of which was “concerning,” he said (Am. J. Obstet. Gynecol. 2005;193:118–24).

Analyses of statewide data from the California Diabetes and Pregnancy Program (known as Sweet Success) in 2007 by Dr. Caughey's associates at the university also found some significantly worse outcomes in women given oral agents compared with insulin for gestational diabetes. They found a 35% higher risk for birth weights above 4,000 g, a 40% higher risk for admission to the neonatal intensive care unit, and a 52% higher risk for preterm delivery before 34 weeks' gestation in women taking oral agents after adjusting for the effects of maternal age, ethnicity, parity, education, gestational age at delivery or at diagnosis of gestational diabetes, body mass index, and gestational weight gain.

Among women diagnosed with gestational diabetes early in pregnancy—at less than 24 weeks' gestation—the increased risk with oral agents was even more pronounced, including more than a threefold higher risk for intrauterine fetal demise compared with the insulin group.

Some clinicians say they prefer to treat gestational diabetes with glyburide because they believe that patients with little formal education cannot understand how to use insulin, or that patients whose primary language is not English will have difficulty, noted Dr. Caughey, who said he had no conflicts of interest related to this topic. When they stratified the Sweet Success data to profile women who had less than 9 years of education or whose primary language was Spanish, those on oral agents still had significantly worse outcomes.

“In my practice, we have one person a year [who will] not be able to use insulin and [who has] to use an oral agent. It's pretty rare.” At UCSF, gestational diabetes management begins with nutritional counseling and a prescription to take a short walk after each meal. If borderline or mild glucose elevations persist, they offer the patient insulin and will consider the alternative of oral metformin, but only in patients who are unlikely to have pre-existing diabetes mellitus, who have been diagnosed with gestational diabetes at 26–32 weeks' gestation, and who have been counseled about an increased preterm delivery risk associated with metformin.

SAN FRANCISCO — A growing body of evidence suggests that the oral agent glyburide may not be as safe as injected insulin to treat gestational diabetes, and that perceived barriers to women using insulin are unsubstantiated.

“The standard of care was insulin. Then everybody changed to glyburide based on an underpowered study” of 404 women with gestational diabetes who were randomized to glyburide or insulin therapy, Dr. Aaron B. Caughey said at a conference on antepartum and intrapartum management sponsored by the University of California, San Francisco.

The study reported similar glycemic control and neonatal outcomes between groups (N. Engl. J. Med. 2000;343:1134–8). “A lot of people that use glyburide base it on this one prospective, randomized trial” that was too small and showed some worrisome trends, said Dr. Caughey, medical director of the Diabetes and Pregnancy Program at the university.

A closer look at the results reveals multiple trends toward worse neonatal outcomes with glyburide, although none are statistically significant, he said. In the glyburide group, 7% of babies had birth weights above 4,000 grams, compared with 4% of the insulin group. Lung complications were reported in 8% of the glyburide group and in 6% on insulin. Hypoglycemia occurred in 9% on glyburide and 6% on placebo. Hyperbilirubinemia rates were 6% on glyburide and 4% on placebo.

More recently, a retrospective cohort study of 584 women with gestational diabetes in the Kaiser Permanente system found significantly worse rates of preeclampsia (12%) and phototherapy for hyperbilirubinemia (9%) in women treated with glyburide, compared with those given insulin (6% and 5%, respectively). That study also found a nonsignificant trend toward a higher rate of birth injury with glyburide (3%) than with insulin (1%), all of which was “concerning,” he said (Am. J. Obstet. Gynecol. 2005;193:118–24).

Analyses of statewide data from the California Diabetes and Pregnancy Program (known as Sweet Success) in 2007 by Dr. Caughey's associates at the university also found some significantly worse outcomes in women given oral agents compared with insulin for gestational diabetes. They found a 35% higher risk for birth weights above 4,000 g, a 40% higher risk for admission to the neonatal intensive care unit, and a 52% higher risk for preterm delivery before 34 weeks' gestation in women taking oral agents after adjusting for the effects of maternal age, ethnicity, parity, education, gestational age at delivery or at diagnosis of gestational diabetes, body mass index, and gestational weight gain.

Among women diagnosed with gestational diabetes early in pregnancy—at less than 24 weeks' gestation—the increased risk with oral agents was even more pronounced, including more than a threefold higher risk for intrauterine fetal demise compared with the insulin group.

Some clinicians say they prefer to treat gestational diabetes with glyburide because they believe that patients with little formal education cannot understand how to use insulin, or that patients whose primary language is not English will have difficulty, noted Dr. Caughey, who said he had no conflicts of interest related to this topic. When they stratified the Sweet Success data to profile women who had less than 9 years of education or whose primary language was Spanish, those on oral agents still had significantly worse outcomes.

“In my practice, we have one person a year [who will] not be able to use insulin and [who has] to use an oral agent. It's pretty rare.” At UCSF, gestational diabetes management begins with nutritional counseling and a prescription to take a short walk after each meal. If borderline or mild glucose elevations persist, they offer the patient insulin and will consider the alternative of oral metformin, but only in patients who are unlikely to have pre-existing diabetes mellitus, who have been diagnosed with gestational diabetes at 26–32 weeks' gestation, and who have been counseled about an increased preterm delivery risk associated with metformin.

SAN FRANCISCO — Combining an ultrasound exam and quantitative beta-hCG measurements may be the most efficient and effective way to diagnose an ectopic pregnancy, said Dr. Amy “Meg” Autry.

A decision-analysis study found that performing transvaginal ultrasound, followed by measuring beta-hCG when ultrasound results were nondiagnostic, identified all ectopic pregnancies in the fastest time (1.46 days) with the fewest interrupted intrauterine pregnancies (less than 1%). Some other diagnostic strategies were faster but less sensitive or interrupted more normal pregnancies (Obstet. Gynecol. 2001;97:464–70).

“In our hospital, in reality, we're getting ultrasound and hCGs at the same time” for women with suspected ectopic pregnancy, Dr. Autry said at a conference on antepartum and intrapartum management sponsored by the University of California, San Francisco. Some ultrasounds will show evidence of intrauterine pregnancies even when the beta-hCG results are below the “discriminatory zone”—the hCG level above which a normal intrauterine pregnancy can be visualized consistently.

Combined, the ultrasound and beta-hCG results are 97%–100% sensitive and 95%–99% specific in diagnosing ectopic pregnancy. “This is predicated on a reliable and consistent ultrasonographer—whether it's an ob.gyn. or radiologist—and you have to know what your discriminatory zone is at your institution,” said Dr. Autry of the university. At her hospital, the discriminatory zone is 1,500–1,800 mIU/mL, using an endovaginal probe.

Even in patients with beta-hCG levels below the discriminatory zone, ultrasound can identify 33% of normal intrauterine pregnancies, 28% of spontaneous miscarriages, and 25% of ectopic pregnancies, a separate study found (Obstet. Gynecol. 1999;94:583–7).

In normal early pregnancies up to 41 days' gestational age, beta-hCG levels double in 48 hours. “But once you're at 6 weeks' [gestation], you should be following by ultrasound,” Dr. Autry said, because beta-hCG levels increasingly become less accurate for identifying normal pregnancies. At 41–57 days' gestation, the beta-hCG level will increase 33% in 48 hours in normal pregnancies. At 57–65 days' gestation, beta-hCG level increases only 5% in 48 hours in normal pregnancies.

Previous data have shown that 64% of women with ectopic pregnancy up to 41 days' gestation will have normal doubling of beta-hCG, emphasizing the additional value of ultrasound examination. In early pregnancy, a beta-hCG increase of less than 50% in 48 hours invariably indicates a nonviable pregnancy, but doesn't tell you where the pregnancy is.

When ultrasound results are indeterminate, the presence of echogenic material (“I call it schmutz”) in the uterus indicates a low likelihood of a normal intrauterine pregnancy, she added. Free fluid in the cul de sac suggests a moderate risk for ectopic pregnancy, a risk that increases with increased volume or echogenicity.

Other signs in indeterminate ultrasounds can be worrisome, she said. A thick endometrial stripe with a beta-hCG level below 1,000 mIU/mL predicts an increased risk for ectopic pregnancy. An empty uterus increases the risk for ectopic pregnancy fivefold. An empty uterus plus a beta-hCG rate of change of less than 66% suggests a 25-fold increased risk for ectopic pregnancy.

Other predictors of ectopic pregnancy include a history of ectopic pregnancy or miscarriage, older age, and bleeding. Dr. Autry said she has no conflicts of interest related to these topics.

Combined, ultrasound and beta-hCG were 95%–99% specific for diagnosis.

Source DR. AUTRY

SAN FRANCISCO — Combining an ultrasound exam and quantitative beta-hCG measurements may be the most efficient and effective way to diagnose an ectopic pregnancy, said Dr. Amy “Meg” Autry.

A decision-analysis study found that performing transvaginal ultrasound, followed by measuring beta-hCG when ultrasound results were nondiagnostic, identified all ectopic pregnancies in the fastest time (1.46 days) with the fewest interrupted intrauterine pregnancies (less than 1%). Some other diagnostic strategies were faster but less sensitive or interrupted more normal pregnancies (Obstet. Gynecol. 2001;97:464–70).

“In our hospital, in reality, we're getting ultrasound and hCGs at the same time” for women with suspected ectopic pregnancy, Dr. Autry said at a conference on antepartum and intrapartum management sponsored by the University of California, San Francisco. Some ultrasounds will show evidence of intrauterine pregnancies even when the beta-hCG results are below the “discriminatory zone”—the hCG level above which a normal intrauterine pregnancy can be visualized consistently.

Combined, the ultrasound and beta-hCG results are 97%–100% sensitive and 95%–99% specific in diagnosing ectopic pregnancy. “This is predicated on a reliable and consistent ultrasonographer—whether it's an ob.gyn. or radiologist—and you have to know what your discriminatory zone is at your institution,” said Dr. Autry of the university. At her hospital, the discriminatory zone is 1,500–1,800 mIU/mL, using an endovaginal probe.

Even in patients with beta-hCG levels below the discriminatory zone, ultrasound can identify 33% of normal intrauterine pregnancies, 28% of spontaneous miscarriages, and 25% of ectopic pregnancies, a separate study found (Obstet. Gynecol. 1999;94:583–7).

In normal early pregnancies up to 41 days' gestational age, beta-hCG levels double in 48 hours. “But once you're at 6 weeks' [gestation], you should be following by ultrasound,” Dr. Autry said, because beta-hCG levels increasingly become less accurate for identifying normal pregnancies. At 41–57 days' gestation, the beta-hCG level will increase 33% in 48 hours in normal pregnancies. At 57–65 days' gestation, beta-hCG level increases only 5% in 48 hours in normal pregnancies.

Previous data have shown that 64% of women with ectopic pregnancy up to 41 days' gestation will have normal doubling of beta-hCG, emphasizing the additional value of ultrasound examination. In early pregnancy, a beta-hCG increase of less than 50% in 48 hours invariably indicates a nonviable pregnancy, but doesn't tell you where the pregnancy is.

When ultrasound results are indeterminate, the presence of echogenic material (“I call it schmutz”) in the uterus indicates a low likelihood of a normal intrauterine pregnancy, she added. Free fluid in the cul de sac suggests a moderate risk for ectopic pregnancy, a risk that increases with increased volume or echogenicity.

Other signs in indeterminate ultrasounds can be worrisome, she said. A thick endometrial stripe with a beta-hCG level below 1,000 mIU/mL predicts an increased risk for ectopic pregnancy. An empty uterus increases the risk for ectopic pregnancy fivefold. An empty uterus plus a beta-hCG rate of change of less than 66% suggests a 25-fold increased risk for ectopic pregnancy.

Other predictors of ectopic pregnancy include a history of ectopic pregnancy or miscarriage, older age, and bleeding. Dr. Autry said she has no conflicts of interest related to these topics.

Combined, ultrasound and beta-hCG were 95%–99% specific for diagnosis.

Source DR. AUTRY

SAN FRANCISCO — Combining an ultrasound exam and quantitative beta-hCG measurements may be the most efficient and effective way to diagnose an ectopic pregnancy, said Dr. Amy “Meg” Autry.

A decision-analysis study found that performing transvaginal ultrasound, followed by measuring beta-hCG when ultrasound results were nondiagnostic, identified all ectopic pregnancies in the fastest time (1.46 days) with the fewest interrupted intrauterine pregnancies (less than 1%). Some other diagnostic strategies were faster but less sensitive or interrupted more normal pregnancies (Obstet. Gynecol. 2001;97:464–70).

“In our hospital, in reality, we're getting ultrasound and hCGs at the same time” for women with suspected ectopic pregnancy, Dr. Autry said at a conference on antepartum and intrapartum management sponsored by the University of California, San Francisco. Some ultrasounds will show evidence of intrauterine pregnancies even when the beta-hCG results are below the “discriminatory zone”—the hCG level above which a normal intrauterine pregnancy can be visualized consistently.

Combined, the ultrasound and beta-hCG results are 97%–100% sensitive and 95%–99% specific in diagnosing ectopic pregnancy. “This is predicated on a reliable and consistent ultrasonographer—whether it's an ob.gyn. or radiologist—and you have to know what your discriminatory zone is at your institution,” said Dr. Autry of the university. At her hospital, the discriminatory zone is 1,500–1,800 mIU/mL, using an endovaginal probe.

Even in patients with beta-hCG levels below the discriminatory zone, ultrasound can identify 33% of normal intrauterine pregnancies, 28% of spontaneous miscarriages, and 25% of ectopic pregnancies, a separate study found (Obstet. Gynecol. 1999;94:583–7).

In normal early pregnancies up to 41 days' gestational age, beta-hCG levels double in 48 hours. “But once you're at 6 weeks' [gestation], you should be following by ultrasound,” Dr. Autry said, because beta-hCG levels increasingly become less accurate for identifying normal pregnancies. At 41–57 days' gestation, the beta-hCG level will increase 33% in 48 hours in normal pregnancies. At 57–65 days' gestation, beta-hCG level increases only 5% in 48 hours in normal pregnancies.

Previous data have shown that 64% of women with ectopic pregnancy up to 41 days' gestation will have normal doubling of beta-hCG, emphasizing the additional value of ultrasound examination. In early pregnancy, a beta-hCG increase of less than 50% in 48 hours invariably indicates a nonviable pregnancy, but doesn't tell you where the pregnancy is.

When ultrasound results are indeterminate, the presence of echogenic material (“I call it schmutz”) in the uterus indicates a low likelihood of a normal intrauterine pregnancy, she added. Free fluid in the cul de sac suggests a moderate risk for ectopic pregnancy, a risk that increases with increased volume or echogenicity.

Other signs in indeterminate ultrasounds can be worrisome, she said. A thick endometrial stripe with a beta-hCG level below 1,000 mIU/mL predicts an increased risk for ectopic pregnancy. An empty uterus increases the risk for ectopic pregnancy fivefold. An empty uterus plus a beta-hCG rate of change of less than 66% suggests a 25-fold increased risk for ectopic pregnancy.

Other predictors of ectopic pregnancy include a history of ectopic pregnancy or miscarriage, older age, and bleeding. Dr. Autry said she has no conflicts of interest related to these topics.

Combined, ultrasound and beta-hCG were 95%–99% specific for diagnosis.

Source DR. AUTRY

Results of two separate pivotal trials of the investigational drug denosumab show significant decreases in the risk of fractures during 36 months of twice-yearly injections in 7,868 postmenopausal women with osteoporosis and in 1,468 men receiving androgen deprivation therapy for prostate cancer, compared with placebo injections.

The two randomized, double-blind, multicenter trials were published in the New England Journal of Medicine (2009 [doi:10.1056/NEJM0a0809493doi;10.1056/NEJM0a0809003

The FDA's Reproductive Health Drugs Advisory Committee has recommended approval of the drug for treating osteoporosis in postmenopausal women but not for preventing it. (See story, p. 8.)

The benefits of denosumab therapy have the potential to extend beyond osteoporosis to the management of rheumatoid arthritis.

Rheumatologist Robin Dore noted in an interview with Rheumatology News that patients with rheumatoid arthritis are at increased risk of fracture even if they have never received glucocorticoid therapy due to the chronic inflammatory state seen in these patients. If a phase III trial in RA patients “confirms the findings of our smaller phase II study [Arthritis Rheum 2008;58;1299-309], in my opinion denosumab could be used as a therapy to treat both the [RA] and low bone mass seen in this population of patients,” she said.

“Our phase II study was too small to evaluate the efficacy of denosumab to reduce fractures in patients [with RA] but it was found to increase bone mineral density in patients [with RA] both with and without glucocorticoid treatment and with and without bisphosphonate treatment.”

Although a phase III study in RA patients (if performed) would be larger, “it still would not have the power to demonstrate fracture reduction in this population,” said Dr. Dore of the University of California, Los Angeles.

In osteoporotic postmenopausal women aged 60-90 years with a baseline bone mineral density T score of less than −2.5 but not less than −4.0 at the lumbar spine or total hip, the cumulative incidence of new vertebral fractures was 2.3% on denosumab and 7.2% on placebo, a relative decrease of 68%.

Reduction in new vertebral fracture was the primary end point of the FREEDOM (Fracture Reduction Evaluation of Denosumab in Osteoporosis Every 6 Months) trial. The primary outcomes of HALT (Hormone Ablation Bone Loss Trial) showed significantly improved lumbar density at 24 months in the denosumab group (an increase of 5.6%), compared with the placebo group, (which had a bone density loss of 1%,) in men receiving androgen deprivation therapy for prostate cancer. The age range of the denosumab group was 48-92 years and the age range of the placebo group was 50-97 years. The original 2-year study protocol was extended to 3 years for further evaluation. One of the secondary end points showed significantly decreased risk for new vertebral fractures at 36 months on denosumab (1.5%), compared with placebo (3.9%), a relative improvement of 62%.

Amgen, the company that is developing the drug for the United States, has applied for FDA approval for denosumab (to be marketed as Prolia) to treat postmenopausal osteoporosis and to prevent bone loss in patients undergoing hormone ablation for prostate or breast cancer. A previous study found that denosumab was associated with increased bone mineral density in women receiving aromatase-inhibitor therapy for breast cancer (J. Clin. Oncol. 2008;26:4875-82).

Dr. Steven R. Cummings of the University of California, San Francisco, and his associates in the FREEDOM trial noted that rare adverse effects associated with other osteoporosis therapies—necrosis of the jaw and fractures of the femoral shaft—were not seen with denosumab. However, theoretical concerns have been raised previously about a possible increase in the risk of cancer or infection with denosumab because of the drug's potential effects on the immune system.

Dr. Cummings reported no significant increase in the rate of serious infections, but did find significant increases in risks for eczema (3% vs. 1.7% on placebo), cellulitis (0.3% vs. less than 0.1%), and flatulence (2.2% vs. 1.4%).

Dr. Matthew R. Smith of Massachusetts General Hospital, Boston, and his associates in HALT reported that rates of adverse events were similar between groups. However, rates were higher in the denosumab group, compared with placebo, for serious adverse events (34.6% vs. 30.6%), serious adverse events related to infection (5.9% vs. 4.6%), and cataracts (4.7% vs. 1.2%), although none of the cataracts was considered to be related to the drug treatment.

In an accompanying editorial, Dr. Sundeep Khosla of the Mayo Clinic, Rochester, Minn., noted that a previous study of 314 women with low bone mineral density found that neoplasms developed in six patients randomized to denosumab therapy and in none on placebo, and serious infections developed in three patients on the drug and none on placebo (N. Engl. J. Med. 2006;354:821-31). “Although not statistically significant, such findings support ongoing surveillance of patients receiving denosumab,” Dr. Khosla suggested (N. Engl. J. Med. 2009 [doi:10.1056NEJMe0905480]).

The studies were funded by Amgen. Dr. Cummings has received fees and/or grant support from Amgen, Eli Lilly, GlaxoSmithKline, Organon, Pfizer, and Novartis. Dr. Smith has received fees from Amgen, Novartis, and GTx. Their study associates work for, are invested in, and/or receive support from Amgen and other companies. Dr. Khosla reported having no potential conflicts of interest related to these topics. Dr. Dore reported receiving funding from Amgen for clinical trials, is a consultant to Amgen, and participates on their speakers bureau.

Denosumab use was not associated with jaw osteonecrosis or femoral shaft fractures seen with other agents.

Source DR. CUMMINGS

Results of two separate pivotal trials of the investigational drug denosumab show significant decreases in the risk of fractures during 36 months of twice-yearly injections in 7,868 postmenopausal women with osteoporosis and in 1,468 men receiving androgen deprivation therapy for prostate cancer, compared with placebo injections.

The two randomized, double-blind, multicenter trials were published in the New England Journal of Medicine (2009 [doi:10.1056/NEJM0a0809493doi;10.1056/NEJM0a0809003

The FDA's Reproductive Health Drugs Advisory Committee has recommended approval of the drug for treating osteoporosis in postmenopausal women but not for preventing it. (See story, p. 8.)

The benefits of denosumab therapy have the potential to extend beyond osteoporosis to the management of rheumatoid arthritis.

Rheumatologist Robin Dore noted in an interview with Rheumatology News that patients with rheumatoid arthritis are at increased risk of fracture even if they have never received glucocorticoid therapy due to the chronic inflammatory state seen in these patients. If a phase III trial in RA patients “confirms the findings of our smaller phase II study [Arthritis Rheum 2008;58;1299-309], in my opinion denosumab could be used as a therapy to treat both the [RA] and low bone mass seen in this population of patients,” she said.

“Our phase II study was too small to evaluate the efficacy of denosumab to reduce fractures in patients [with RA] but it was found to increase bone mineral density in patients [with RA] both with and without glucocorticoid treatment and with and without bisphosphonate treatment.”

Although a phase III study in RA patients (if performed) would be larger, “it still would not have the power to demonstrate fracture reduction in this population,” said Dr. Dore of the University of California, Los Angeles.

In osteoporotic postmenopausal women aged 60-90 years with a baseline bone mineral density T score of less than −2.5 but not less than −4.0 at the lumbar spine or total hip, the cumulative incidence of new vertebral fractures was 2.3% on denosumab and 7.2% on placebo, a relative decrease of 68%.

Reduction in new vertebral fracture was the primary end point of the FREEDOM (Fracture Reduction Evaluation of Denosumab in Osteoporosis Every 6 Months) trial. The primary outcomes of HALT (Hormone Ablation Bone Loss Trial) showed significantly improved lumbar density at 24 months in the denosumab group (an increase of 5.6%), compared with the placebo group, (which had a bone density loss of 1%,) in men receiving androgen deprivation therapy for prostate cancer. The age range of the denosumab group was 48-92 years and the age range of the placebo group was 50-97 years. The original 2-year study protocol was extended to 3 years for further evaluation. One of the secondary end points showed significantly decreased risk for new vertebral fractures at 36 months on denosumab (1.5%), compared with placebo (3.9%), a relative improvement of 62%.

Amgen, the company that is developing the drug for the United States, has applied for FDA approval for denosumab (to be marketed as Prolia) to treat postmenopausal osteoporosis and to prevent bone loss in patients undergoing hormone ablation for prostate or breast cancer. A previous study found that denosumab was associated with increased bone mineral density in women receiving aromatase-inhibitor therapy for breast cancer (J. Clin. Oncol. 2008;26:4875-82).

Dr. Steven R. Cummings of the University of California, San Francisco, and his associates in the FREEDOM trial noted that rare adverse effects associated with other osteoporosis therapies—necrosis of the jaw and fractures of the femoral shaft—were not seen with denosumab. However, theoretical concerns have been raised previously about a possible increase in the risk of cancer or infection with denosumab because of the drug's potential effects on the immune system.

Dr. Cummings reported no significant increase in the rate of serious infections, but did find significant increases in risks for eczema (3% vs. 1.7% on placebo), cellulitis (0.3% vs. less than 0.1%), and flatulence (2.2% vs. 1.4%).

Dr. Matthew R. Smith of Massachusetts General Hospital, Boston, and his associates in HALT reported that rates of adverse events were similar between groups. However, rates were higher in the denosumab group, compared with placebo, for serious adverse events (34.6% vs. 30.6%), serious adverse events related to infection (5.9% vs. 4.6%), and cataracts (4.7% vs. 1.2%), although none of the cataracts was considered to be related to the drug treatment.

In an accompanying editorial, Dr. Sundeep Khosla of the Mayo Clinic, Rochester, Minn., noted that a previous study of 314 women with low bone mineral density found that neoplasms developed in six patients randomized to denosumab therapy and in none on placebo, and serious infections developed in three patients on the drug and none on placebo (N. Engl. J. Med. 2006;354:821-31). “Although not statistically significant, such findings support ongoing surveillance of patients receiving denosumab,” Dr. Khosla suggested (N. Engl. J. Med. 2009 [doi:10.1056NEJMe0905480]).

The studies were funded by Amgen. Dr. Cummings has received fees and/or grant support from Amgen, Eli Lilly, GlaxoSmithKline, Organon, Pfizer, and Novartis. Dr. Smith has received fees from Amgen, Novartis, and GTx. Their study associates work for, are invested in, and/or receive support from Amgen and other companies. Dr. Khosla reported having no potential conflicts of interest related to these topics. Dr. Dore reported receiving funding from Amgen for clinical trials, is a consultant to Amgen, and participates on their speakers bureau.

Denosumab use was not associated with jaw osteonecrosis or femoral shaft fractures seen with other agents.

Source DR. CUMMINGS

Results of two separate pivotal trials of the investigational drug denosumab show significant decreases in the risk of fractures during 36 months of twice-yearly injections in 7,868 postmenopausal women with osteoporosis and in 1,468 men receiving androgen deprivation therapy for prostate cancer, compared with placebo injections.

The two randomized, double-blind, multicenter trials were published in the New England Journal of Medicine (2009 [doi:10.1056/NEJM0a0809493doi;10.1056/NEJM0a0809003

The FDA's Reproductive Health Drugs Advisory Committee has recommended approval of the drug for treating osteoporosis in postmenopausal women but not for preventing it. (See story, p. 8.)

The benefits of denosumab therapy have the potential to extend beyond osteoporosis to the management of rheumatoid arthritis.

Rheumatologist Robin Dore noted in an interview with Rheumatology News that patients with rheumatoid arthritis are at increased risk of fracture even if they have never received glucocorticoid therapy due to the chronic inflammatory state seen in these patients. If a phase III trial in RA patients “confirms the findings of our smaller phase II study [Arthritis Rheum 2008;58;1299-309], in my opinion denosumab could be used as a therapy to treat both the [RA] and low bone mass seen in this population of patients,” she said.

“Our phase II study was too small to evaluate the efficacy of denosumab to reduce fractures in patients [with RA] but it was found to increase bone mineral density in patients [with RA] both with and without glucocorticoid treatment and with and without bisphosphonate treatment.”

Although a phase III study in RA patients (if performed) would be larger, “it still would not have the power to demonstrate fracture reduction in this population,” said Dr. Dore of the University of California, Los Angeles.

In osteoporotic postmenopausal women aged 60-90 years with a baseline bone mineral density T score of less than −2.5 but not less than −4.0 at the lumbar spine or total hip, the cumulative incidence of new vertebral fractures was 2.3% on denosumab and 7.2% on placebo, a relative decrease of 68%.

Reduction in new vertebral fracture was the primary end point of the FREEDOM (Fracture Reduction Evaluation of Denosumab in Osteoporosis Every 6 Months) trial. The primary outcomes of HALT (Hormone Ablation Bone Loss Trial) showed significantly improved lumbar density at 24 months in the denosumab group (an increase of 5.6%), compared with the placebo group, (which had a bone density loss of 1%,) in men receiving androgen deprivation therapy for prostate cancer. The age range of the denosumab group was 48-92 years and the age range of the placebo group was 50-97 years. The original 2-year study protocol was extended to 3 years for further evaluation. One of the secondary end points showed significantly decreased risk for new vertebral fractures at 36 months on denosumab (1.5%), compared with placebo (3.9%), a relative improvement of 62%.

Amgen, the company that is developing the drug for the United States, has applied for FDA approval for denosumab (to be marketed as Prolia) to treat postmenopausal osteoporosis and to prevent bone loss in patients undergoing hormone ablation for prostate or breast cancer. A previous study found that denosumab was associated with increased bone mineral density in women receiving aromatase-inhibitor therapy for breast cancer (J. Clin. Oncol. 2008;26:4875-82).

Dr. Steven R. Cummings of the University of California, San Francisco, and his associates in the FREEDOM trial noted that rare adverse effects associated with other osteoporosis therapies—necrosis of the jaw and fractures of the femoral shaft—were not seen with denosumab. However, theoretical concerns have been raised previously about a possible increase in the risk of cancer or infection with denosumab because of the drug's potential effects on the immune system.

Dr. Cummings reported no significant increase in the rate of serious infections, but did find significant increases in risks for eczema (3% vs. 1.7% on placebo), cellulitis (0.3% vs. less than 0.1%), and flatulence (2.2% vs. 1.4%).

Dr. Matthew R. Smith of Massachusetts General Hospital, Boston, and his associates in HALT reported that rates of adverse events were similar between groups. However, rates were higher in the denosumab group, compared with placebo, for serious adverse events (34.6% vs. 30.6%), serious adverse events related to infection (5.9% vs. 4.6%), and cataracts (4.7% vs. 1.2%), although none of the cataracts was considered to be related to the drug treatment.

In an accompanying editorial, Dr. Sundeep Khosla of the Mayo Clinic, Rochester, Minn., noted that a previous study of 314 women with low bone mineral density found that neoplasms developed in six patients randomized to denosumab therapy and in none on placebo, and serious infections developed in three patients on the drug and none on placebo (N. Engl. J. Med. 2006;354:821-31). “Although not statistically significant, such findings support ongoing surveillance of patients receiving denosumab,” Dr. Khosla suggested (N. Engl. J. Med. 2009 [doi:10.1056NEJMe0905480]).

The studies were funded by Amgen. Dr. Cummings has received fees and/or grant support from Amgen, Eli Lilly, GlaxoSmithKline, Organon, Pfizer, and Novartis. Dr. Smith has received fees from Amgen, Novartis, and GTx. Their study associates work for, are invested in, and/or receive support from Amgen and other companies. Dr. Khosla reported having no potential conflicts of interest related to these topics. Dr. Dore reported receiving funding from Amgen for clinical trials, is a consultant to Amgen, and participates on their speakers bureau.

Denosumab use was not associated with jaw osteonecrosis or femoral shaft fractures seen with other agents.

Source DR. CUMMINGS

SAN FRANCISCO — Increased levels of fitness attenuated a higher risk of death in women with impaired renal function in a 16-year study of 5,716 participants who were asymptomatic at baseline.

Estimates of glomerular filtration rate (GFR) and fitness should be added to use of traditional cardiovascular risk assessments to help stratify risk and prioritize intervention in selected patients, Dr. Martha Gulati said at the annual meeting of the American Society of Hypertension.

The study recruited community women in 1992 who had no known renal or heart disease and compared baseline urinalyses, estimated GFR, and estimated fitness as measured by metabolic equivalent units (METs) with all-cause mortality in 2008.

At baseline, 79% of the women had a GFR of less than 60 mL/minute per 1.73 m2, putting them at higher risk for chronic kidney disease and cardiovascular disease than women with a higher GFR. The mostly white cohort had a mean age of 53 years and a mean waist circumference of 33 inches. Fifteen percent were smokers, 45% had hypertension, and 5% had diabetes. Overall, at baseline “this was a relatively healthy cohort with a really good level of fitness,” based on a mean of 8 METs, said Dr. Gulati of Northwestern University, Chicago.

In an analysis that adjusted for the effects of traditional cardiovascular risk factors using the Framingham risk score, a creatinine level greater than 1.4 mg/dL increased the risk of mortality by 80%, compared with lower creatinine levels. Every unit increase in GFR decreased mortality by 3%, Dr. Gulati reported.

When exercise capacity was added to the analysis, these variables remained significant predictors of risk. Compared with those who had a GFR below 45 mL/minute per 1.73 m2, the mortality risk was 37% lower in the 66% of the cohort who had a GFR of 45-59, and 46% lower in the 21% of the cohort with a GFR of at least 60. About 75% of the lowest-GFR group was alive 16 years later, compared with 91% in the intermediate-GFR group and 94% in the highest GFR group.

In each of the GFR subgroups, women with better baseline fitness were less likely to die. Mortality rates (per 1,000 person-years) in the lowest GFR group were 3.18 at the highest fitness levels (greater than 8 METs), 3.81 with intermediate fitness (5-8 METs), and 7.62 among the least fit (less than 5 METs).

In the intermediate GFR group, mortality rates were 0.98, 1.76, and 3.16 per 1,000 person-years in the highest, intermediate, and lowest fitness subgroups.

In the highest GFR group, mortality rates were 0.56, 1.18, and 1.68 per 1,000 person-years in the highest, intermediate, and lowest fitness subgroups.

Dr. Gulati disclosed that she has been a speaker for AstraZeneca and Fujisawa Healthcare and has received research funds from the latter.

SAN FRANCISCO — Increased levels of fitness attenuated a higher risk of death in women with impaired renal function in a 16-year study of 5,716 participants who were asymptomatic at baseline.

Estimates of glomerular filtration rate (GFR) and fitness should be added to use of traditional cardiovascular risk assessments to help stratify risk and prioritize intervention in selected patients, Dr. Martha Gulati said at the annual meeting of the American Society of Hypertension.

The study recruited community women in 1992 who had no known renal or heart disease and compared baseline urinalyses, estimated GFR, and estimated fitness as measured by metabolic equivalent units (METs) with all-cause mortality in 2008.

At baseline, 79% of the women had a GFR of less than 60 mL/minute per 1.73 m2, putting them at higher risk for chronic kidney disease and cardiovascular disease than women with a higher GFR. The mostly white cohort had a mean age of 53 years and a mean waist circumference of 33 inches. Fifteen percent were smokers, 45% had hypertension, and 5% had diabetes. Overall, at baseline “this was a relatively healthy cohort with a really good level of fitness,” based on a mean of 8 METs, said Dr. Gulati of Northwestern University, Chicago.

In an analysis that adjusted for the effects of traditional cardiovascular risk factors using the Framingham risk score, a creatinine level greater than 1.4 mg/dL increased the risk of mortality by 80%, compared with lower creatinine levels. Every unit increase in GFR decreased mortality by 3%, Dr. Gulati reported.

When exercise capacity was added to the analysis, these variables remained significant predictors of risk. Compared with those who had a GFR below 45 mL/minute per 1.73 m2, the mortality risk was 37% lower in the 66% of the cohort who had a GFR of 45-59, and 46% lower in the 21% of the cohort with a GFR of at least 60. About 75% of the lowest-GFR group was alive 16 years later, compared with 91% in the intermediate-GFR group and 94% in the highest GFR group.

In each of the GFR subgroups, women with better baseline fitness were less likely to die. Mortality rates (per 1,000 person-years) in the lowest GFR group were 3.18 at the highest fitness levels (greater than 8 METs), 3.81 with intermediate fitness (5-8 METs), and 7.62 among the least fit (less than 5 METs).

In the intermediate GFR group, mortality rates were 0.98, 1.76, and 3.16 per 1,000 person-years in the highest, intermediate, and lowest fitness subgroups.

In the highest GFR group, mortality rates were 0.56, 1.18, and 1.68 per 1,000 person-years in the highest, intermediate, and lowest fitness subgroups.

Dr. Gulati disclosed that she has been a speaker for AstraZeneca and Fujisawa Healthcare and has received research funds from the latter.

SAN FRANCISCO — Increased levels of fitness attenuated a higher risk of death in women with impaired renal function in a 16-year study of 5,716 participants who were asymptomatic at baseline.

Estimates of glomerular filtration rate (GFR) and fitness should be added to use of traditional cardiovascular risk assessments to help stratify risk and prioritize intervention in selected patients, Dr. Martha Gulati said at the annual meeting of the American Society of Hypertension.

The study recruited community women in 1992 who had no known renal or heart disease and compared baseline urinalyses, estimated GFR, and estimated fitness as measured by metabolic equivalent units (METs) with all-cause mortality in 2008.

At baseline, 79% of the women had a GFR of less than 60 mL/minute per 1.73 m2, putting them at higher risk for chronic kidney disease and cardiovascular disease than women with a higher GFR. The mostly white cohort had a mean age of 53 years and a mean waist circumference of 33 inches. Fifteen percent were smokers, 45% had hypertension, and 5% had diabetes. Overall, at baseline “this was a relatively healthy cohort with a really good level of fitness,” based on a mean of 8 METs, said Dr. Gulati of Northwestern University, Chicago.

In an analysis that adjusted for the effects of traditional cardiovascular risk factors using the Framingham risk score, a creatinine level greater than 1.4 mg/dL increased the risk of mortality by 80%, compared with lower creatinine levels. Every unit increase in GFR decreased mortality by 3%, Dr. Gulati reported.

When exercise capacity was added to the analysis, these variables remained significant predictors of risk. Compared with those who had a GFR below 45 mL/minute per 1.73 m2, the mortality risk was 37% lower in the 66% of the cohort who had a GFR of 45-59, and 46% lower in the 21% of the cohort with a GFR of at least 60. About 75% of the lowest-GFR group was alive 16 years later, compared with 91% in the intermediate-GFR group and 94% in the highest GFR group.

In each of the GFR subgroups, women with better baseline fitness were less likely to die. Mortality rates (per 1,000 person-years) in the lowest GFR group were 3.18 at the highest fitness levels (greater than 8 METs), 3.81 with intermediate fitness (5-8 METs), and 7.62 among the least fit (less than 5 METs).

In the intermediate GFR group, mortality rates were 0.98, 1.76, and 3.16 per 1,000 person-years in the highest, intermediate, and lowest fitness subgroups.

In the highest GFR group, mortality rates were 0.56, 1.18, and 1.68 per 1,000 person-years in the highest, intermediate, and lowest fitness subgroups.

Dr. Gulati disclosed that she has been a speaker for AstraZeneca and Fujisawa Healthcare and has received research funds from the latter.

SAN FRANCISCO – There may be ethnic-specific risk factors in youth suicidality that could inform the design of culturally influenced suicide prevention, a study of 648 Mexican and European American adolescents suggests.

The study found high rates of suicidality (ideation and behavior) and associations between friendship problems and suicidality. However, the associations were found to differ by ethnicity, Erin Winterrowd reported in a poster presentation at the annual conference of the American Society of Suicidology.

For Mexican American girls, having friends who were disconnected from school was associated with suicidal ideation. For European American girls and boys, friends' delinquency was related to suicidal behavior, said Ms. Winterrowd of Colorado State University, Fort Collins, and her associates.

The cohort of youths aged 14-20 years came from two midsized, urban Southwestern communities and was 52% Mexican American and 51% female. The subgroups of Mexican American and European American youths were matched by sex, age, and grade.

Overall, 32% reported suicidal ideation, and 11% reported nonfatal suicidal behavior. Suicidality rates were higher among Mexican Americans (32%) than among the European Americans (12%).

For both ethnic subgroups, other risk factors for suicidality included youth, depression, and low family support. Physical abuse or low self-esteem were risk factors for Mexican American teens, delinquency or sexual abuse were risk factors for suicidality in European Americans.

SAN FRANCISCO – There may be ethnic-specific risk factors in youth suicidality that could inform the design of culturally influenced suicide prevention, a study of 648 Mexican and European American adolescents suggests.

The study found high rates of suicidality (ideation and behavior) and associations between friendship problems and suicidality. However, the associations were found to differ by ethnicity, Erin Winterrowd reported in a poster presentation at the annual conference of the American Society of Suicidology.

For Mexican American girls, having friends who were disconnected from school was associated with suicidal ideation. For European American girls and boys, friends' delinquency was related to suicidal behavior, said Ms. Winterrowd of Colorado State University, Fort Collins, and her associates.

The cohort of youths aged 14-20 years came from two midsized, urban Southwestern communities and was 52% Mexican American and 51% female. The subgroups of Mexican American and European American youths were matched by sex, age, and grade.

Overall, 32% reported suicidal ideation, and 11% reported nonfatal suicidal behavior. Suicidality rates were higher among Mexican Americans (32%) than among the European Americans (12%).

For both ethnic subgroups, other risk factors for suicidality included youth, depression, and low family support. Physical abuse or low self-esteem were risk factors for Mexican American teens, delinquency or sexual abuse were risk factors for suicidality in European Americans.

SAN FRANCISCO – There may be ethnic-specific risk factors in youth suicidality that could inform the design of culturally influenced suicide prevention, a study of 648 Mexican and European American adolescents suggests.

The study found high rates of suicidality (ideation and behavior) and associations between friendship problems and suicidality. However, the associations were found to differ by ethnicity, Erin Winterrowd reported in a poster presentation at the annual conference of the American Society of Suicidology.

For Mexican American girls, having friends who were disconnected from school was associated with suicidal ideation. For European American girls and boys, friends' delinquency was related to suicidal behavior, said Ms. Winterrowd of Colorado State University, Fort Collins, and her associates.

The cohort of youths aged 14-20 years came from two midsized, urban Southwestern communities and was 52% Mexican American and 51% female. The subgroups of Mexican American and European American youths were matched by sex, age, and grade.

Overall, 32% reported suicidal ideation, and 11% reported nonfatal suicidal behavior. Suicidality rates were higher among Mexican Americans (32%) than among the European Americans (12%).

For both ethnic subgroups, other risk factors for suicidality included youth, depression, and low family support. Physical abuse or low self-esteem were risk factors for Mexican American teens, delinquency or sexual abuse were risk factors for suicidality in European Americans.

SAN FRANCISCO — Approximately 16% of 264,697 patients in a community-based practice network had treatment-resistant hypertension in 2007.

The true prevalence may be 8%-11% after adjustment for pseudoresistance, which previous studies suggest accounts for 30%-50% of suspected treatment-resistant hypertension, Dr. Brent M. Egan said at the annual meeting of the American Society of Hypertension.

At the same time, many of these patients are undertreated. Only two or fewer antihypertensive medications were prescribed for 60% of 49,043 patients who had diabetes or chronic kidney disease plus uncontrolled hypertension and for 78% of 66,337 patients who had uncontrolled hypertension without the other two cardiovascular risk factors. If those subgroups were more aggressively treated with three or more antihypertensives, the prevalence of truly treatment-resistant hypertension might be closer to 20%-30%, estimated Dr. Egan, professor of medicine and director of the Hypertension Initiative at the Medical University of South Carolina, Charleston.

The findings have significant implications as the U.S. population becomes older and more obese with more complex medical histories and more kidney disease. Practical clinical trials are needed to address the contributors to uncontrolled hypertension, such as therapeutic inertia and the limited effectiveness of current antihypertensive drug regimens, Dr. Egan suggested.

He and his associates analyzed observational data collected from the electronic medical records of more than 150 community-based practices in the multistate Hypertension Initiative.

Resistant hypertension is defined as having a blood pressure above goal while on a regimen of three or more antihypertensive medications, or having controlled blood pressure while on four or more antihypertensives. Pseudoresistance to treatment can result from patients not taking prescribed medications, inaccurate blood pressure measurement, white-coat hypertension, or inadequate therapy. The current study could assess only the medications prescribed, not whether patients adhered to therapy.

Blood pressure goals for hypertensive patients without diabetes or chronic kidney disease were less than 140/90 mm Hg. Blood pressure goals for hypertensive patients with diabetes or chronic kidney disease were less than 130/80 mm Hg.

Blood pressure was uncontrolled in 36% of patients without diabetes or kidney disease and in 60% of patients with those diseases. African Americans were more likely than were whites to have uncontrolled hypertension.

Physicians were more aggressive in treating hypertension in patients with diabetes or kidney disease, prescribing three or more antihypertensives in 35% of patients who achieved goal and 39% of those who did not. Among patients without diabetes or kidney disease, 17% who achieved goal and 22% who did not reach goal received three or more drugs.

Still, that left large numbers of patients who were given two or fewer medications, Dr. Egan noted. No antihypertensives at all were prescribed for 13%-15% of hypertensive patients with diabetes or kidney disease and for 26%-32% without diabetes or kidney disease.

Dr. Egan has had financial relationships with several makers of antihypertensive medications.

No medications were prescribed for 26%-32% of hypertensive patients without diabetes or kidney disease.

Source DR. EGAN

SAN FRANCISCO — Approximately 16% of 264,697 patients in a community-based practice network had treatment-resistant hypertension in 2007.

The true prevalence may be 8%-11% after adjustment for pseudoresistance, which previous studies suggest accounts for 30%-50% of suspected treatment-resistant hypertension, Dr. Brent M. Egan said at the annual meeting of the American Society of Hypertension.

At the same time, many of these patients are undertreated. Only two or fewer antihypertensive medications were prescribed for 60% of 49,043 patients who had diabetes or chronic kidney disease plus uncontrolled hypertension and for 78% of 66,337 patients who had uncontrolled hypertension without the other two cardiovascular risk factors. If those subgroups were more aggressively treated with three or more antihypertensives, the prevalence of truly treatment-resistant hypertension might be closer to 20%-30%, estimated Dr. Egan, professor of medicine and director of the Hypertension Initiative at the Medical University of South Carolina, Charleston.

The findings have significant implications as the U.S. population becomes older and more obese with more complex medical histories and more kidney disease. Practical clinical trials are needed to address the contributors to uncontrolled hypertension, such as therapeutic inertia and the limited effectiveness of current antihypertensive drug regimens, Dr. Egan suggested.

He and his associates analyzed observational data collected from the electronic medical records of more than 150 community-based practices in the multistate Hypertension Initiative.

Resistant hypertension is defined as having a blood pressure above goal while on a regimen of three or more antihypertensive medications, or having controlled blood pressure while on four or more antihypertensives. Pseudoresistance to treatment can result from patients not taking prescribed medications, inaccurate blood pressure measurement, white-coat hypertension, or inadequate therapy. The current study could assess only the medications prescribed, not whether patients adhered to therapy.

Blood pressure goals for hypertensive patients without diabetes or chronic kidney disease were less than 140/90 mm Hg. Blood pressure goals for hypertensive patients with diabetes or chronic kidney disease were less than 130/80 mm Hg.

Blood pressure was uncontrolled in 36% of patients without diabetes or kidney disease and in 60% of patients with those diseases. African Americans were more likely than were whites to have uncontrolled hypertension.

Physicians were more aggressive in treating hypertension in patients with diabetes or kidney disease, prescribing three or more antihypertensives in 35% of patients who achieved goal and 39% of those who did not. Among patients without diabetes or kidney disease, 17% who achieved goal and 22% who did not reach goal received three or more drugs.

Still, that left large numbers of patients who were given two or fewer medications, Dr. Egan noted. No antihypertensives at all were prescribed for 13%-15% of hypertensive patients with diabetes or kidney disease and for 26%-32% without diabetes or kidney disease.

Dr. Egan has had financial relationships with several makers of antihypertensive medications.

No medications were prescribed for 26%-32% of hypertensive patients without diabetes or kidney disease.

Source DR. EGAN

SAN FRANCISCO — Approximately 16% of 264,697 patients in a community-based practice network had treatment-resistant hypertension in 2007.

The true prevalence may be 8%-11% after adjustment for pseudoresistance, which previous studies suggest accounts for 30%-50% of suspected treatment-resistant hypertension, Dr. Brent M. Egan said at the annual meeting of the American Society of Hypertension.

At the same time, many of these patients are undertreated. Only two or fewer antihypertensive medications were prescribed for 60% of 49,043 patients who had diabetes or chronic kidney disease plus uncontrolled hypertension and for 78% of 66,337 patients who had uncontrolled hypertension without the other two cardiovascular risk factors. If those subgroups were more aggressively treated with three or more antihypertensives, the prevalence of truly treatment-resistant hypertension might be closer to 20%-30%, estimated Dr. Egan, professor of medicine and director of the Hypertension Initiative at the Medical University of South Carolina, Charleston.

The findings have significant implications as the U.S. population becomes older and more obese with more complex medical histories and more kidney disease. Practical clinical trials are needed to address the contributors to uncontrolled hypertension, such as therapeutic inertia and the limited effectiveness of current antihypertensive drug regimens, Dr. Egan suggested.

He and his associates analyzed observational data collected from the electronic medical records of more than 150 community-based practices in the multistate Hypertension Initiative.

Resistant hypertension is defined as having a blood pressure above goal while on a regimen of three or more antihypertensive medications, or having controlled blood pressure while on four or more antihypertensives. Pseudoresistance to treatment can result from patients not taking prescribed medications, inaccurate blood pressure measurement, white-coat hypertension, or inadequate therapy. The current study could assess only the medications prescribed, not whether patients adhered to therapy.

Blood pressure goals for hypertensive patients without diabetes or chronic kidney disease were less than 140/90 mm Hg. Blood pressure goals for hypertensive patients with diabetes or chronic kidney disease were less than 130/80 mm Hg.

Blood pressure was uncontrolled in 36% of patients without diabetes or kidney disease and in 60% of patients with those diseases. African Americans were more likely than were whites to have uncontrolled hypertension.

Physicians were more aggressive in treating hypertension in patients with diabetes or kidney disease, prescribing three or more antihypertensives in 35% of patients who achieved goal and 39% of those who did not. Among patients without diabetes or kidney disease, 17% who achieved goal and 22% who did not reach goal received three or more drugs.

Still, that left large numbers of patients who were given two or fewer medications, Dr. Egan noted. No antihypertensives at all were prescribed for 13%-15% of hypertensive patients with diabetes or kidney disease and for 26%-32% without diabetes or kidney disease.

Dr. Egan has had financial relationships with several makers of antihypertensive medications.

No medications were prescribed for 26%-32% of hypertensive patients without diabetes or kidney disease.

Source DR. EGAN

Prophylactic budesonide did not significantly decrease the risk of grade 2 or higher diarrhea that is common in patients who have unresectable melanoma treated with the investigational drug ipilimumab, a phase II trial found.

Ipilimumab is a human monoclonal antibody directed against CTL antigen-4, which is a key negative regulator of the T-cell immune response. In clinical studies, immune-related adverse events associated with ipilimumab most commonly have involved the gastrointestinal tract or the skin.

Dr. Jeffrey Weber and his associates hypothesized that oral budesonide, which is used to treat grade 2 diarrhea when it accompanies ipilimumab therapy, might work as prophylaxis to prevent diarrhea without affecting any antitumor activity from ipilimumab.

They randomized 115 patients with unresectable stage III or IV melanoma to treatment with open-label IV ipilimumab (10 mg/kg every 3 weeks for four doses), plus blinded oral budesonide or placebo. The once-daily budesonide dose was 9 mg through week 12, then tapered until discontinuation at week 16.

Grade 2 or higher diarrhea occurred in 19 (33%) of the 58 patients in the budesonide group and 20 (35%) of the 57 patients in the placebo group, Dr. Weber and colleagues reported in an online article to appear in the Sept. 1, 2009, issue of Clinical Cancer Research (doi:10.1158/1078-0432.CCR-09-1024

Budesonide should not be used prophylactically for grade 2 or higher diarrhea associated with ipilimumab therapy, concluded Dr. Weber of the Moffitt Cancer Center and Research Institute, Tampa. Prompt treatment of diarrhea or colitis, however, seemed to be effective in preventing serious complications such as gastrointestinal perforations, he added.

Patients who developed grade 2 or higher diarrhea or other immune-related adverse events discontinued the blinded drug and started open-label therapy with budesonide or other steroids. If the diarrhea lasted 2 weeks or there was grade 3 or 4 diarrhea, they stopped ipilimumab. None of the patients developed gastrointestinal or colonic perforations.

Bristol-Myers Squibb, which is developing ipilimumab with Medarex, sponsored the study and funded editorial and writing assistance for the investigators. Dr. Weber and three of his associates have received funds for speaking, advising, and research for Bristol-Myers Squibb. Dr. Weber owns part of a patent with Medarex on CT2A-4 antibodies. The journal marked the article as an advertisement because page charges were levied to defray the costs of publication.

Grade 3–4 immune-related adverse events occurred in 46 (40%) of all patients, compared with rates of 25% and 22% in other studies that used the same dosing regimens of ipilimumab, the investigators noted. Unlike some of the earlier studies, the current trial included many patients with poor prognostic markers.

Immune-related adverse events affecting the skin, gastrointestinal system, liver, endocrine system, or other area were seen in 47 patients (81%) in the budesonide group and 48 patients (84%) in the placebo group.

Secondary end points in the study included multiple measures of the efficacy of ipilimumab in treating melanoma. A complete response or partial response was seen in seven patients (12%) in the budesonide group and in nine patients (16%) in the placebo group. In addition, the disease stabilized in 11 patients (19%) in each group.

With a median follow-up of over 12 months, the median overall survival rate was 18 months in the budesonide group and 19 months on placebo.

Prophylactic budesonide did not significantly decrease the risk of grade 2 or higher diarrhea that is common in patients who have unresectable melanoma treated with the investigational drug ipilimumab, a phase II trial found.

Ipilimumab is a human monoclonal antibody directed against CTL antigen-4, which is a key negative regulator of the T-cell immune response. In clinical studies, immune-related adverse events associated with ipilimumab most commonly have involved the gastrointestinal tract or the skin.

Dr. Jeffrey Weber and his associates hypothesized that oral budesonide, which is used to treat grade 2 diarrhea when it accompanies ipilimumab therapy, might work as prophylaxis to prevent diarrhea without affecting any antitumor activity from ipilimumab.

They randomized 115 patients with unresectable stage III or IV melanoma to treatment with open-label IV ipilimumab (10 mg/kg every 3 weeks for four doses), plus blinded oral budesonide or placebo. The once-daily budesonide dose was 9 mg through week 12, then tapered until discontinuation at week 16.

Grade 2 or higher diarrhea occurred in 19 (33%) of the 58 patients in the budesonide group and 20 (35%) of the 57 patients in the placebo group, Dr. Weber and colleagues reported in an online article to appear in the Sept. 1, 2009, issue of Clinical Cancer Research (doi:10.1158/1078-0432.CCR-09-1024

Budesonide should not be used prophylactically for grade 2 or higher diarrhea associated with ipilimumab therapy, concluded Dr. Weber of the Moffitt Cancer Center and Research Institute, Tampa. Prompt treatment of diarrhea or colitis, however, seemed to be effective in preventing serious complications such as gastrointestinal perforations, he added.

Patients who developed grade 2 or higher diarrhea or other immune-related adverse events discontinued the blinded drug and started open-label therapy with budesonide or other steroids. If the diarrhea lasted 2 weeks or there was grade 3 or 4 diarrhea, they stopped ipilimumab. None of the patients developed gastrointestinal or colonic perforations.

Bristol-Myers Squibb, which is developing ipilimumab with Medarex, sponsored the study and funded editorial and writing assistance for the investigators. Dr. Weber and three of his associates have received funds for speaking, advising, and research for Bristol-Myers Squibb. Dr. Weber owns part of a patent with Medarex on CT2A-4 antibodies. The journal marked the article as an advertisement because page charges were levied to defray the costs of publication.

Grade 3–4 immune-related adverse events occurred in 46 (40%) of all patients, compared with rates of 25% and 22% in other studies that used the same dosing regimens of ipilimumab, the investigators noted. Unlike some of the earlier studies, the current trial included many patients with poor prognostic markers.

Immune-related adverse events affecting the skin, gastrointestinal system, liver, endocrine system, or other area were seen in 47 patients (81%) in the budesonide group and 48 patients (84%) in the placebo group.

Secondary end points in the study included multiple measures of the efficacy of ipilimumab in treating melanoma. A complete response or partial response was seen in seven patients (12%) in the budesonide group and in nine patients (16%) in the placebo group. In addition, the disease stabilized in 11 patients (19%) in each group.

With a median follow-up of over 12 months, the median overall survival rate was 18 months in the budesonide group and 19 months on placebo.

Prophylactic budesonide did not significantly decrease the risk of grade 2 or higher diarrhea that is common in patients who have unresectable melanoma treated with the investigational drug ipilimumab, a phase II trial found.

Ipilimumab is a human monoclonal antibody directed against CTL antigen-4, which is a key negative regulator of the T-cell immune response. In clinical studies, immune-related adverse events associated with ipilimumab most commonly have involved the gastrointestinal tract or the skin.

Dr. Jeffrey Weber and his associates hypothesized that oral budesonide, which is used to treat grade 2 diarrhea when it accompanies ipilimumab therapy, might work as prophylaxis to prevent diarrhea without affecting any antitumor activity from ipilimumab.

They randomized 115 patients with unresectable stage III or IV melanoma to treatment with open-label IV ipilimumab (10 mg/kg every 3 weeks for four doses), plus blinded oral budesonide or placebo. The once-daily budesonide dose was 9 mg through week 12, then tapered until discontinuation at week 16.

Grade 2 or higher diarrhea occurred in 19 (33%) of the 58 patients in the budesonide group and 20 (35%) of the 57 patients in the placebo group, Dr. Weber and colleagues reported in an online article to appear in the Sept. 1, 2009, issue of Clinical Cancer Research (doi:10.1158/1078-0432.CCR-09-1024

Budesonide should not be used prophylactically for grade 2 or higher diarrhea associated with ipilimumab therapy, concluded Dr. Weber of the Moffitt Cancer Center and Research Institute, Tampa. Prompt treatment of diarrhea or colitis, however, seemed to be effective in preventing serious complications such as gastrointestinal perforations, he added.

Patients who developed grade 2 or higher diarrhea or other immune-related adverse events discontinued the blinded drug and started open-label therapy with budesonide or other steroids. If the diarrhea lasted 2 weeks or there was grade 3 or 4 diarrhea, they stopped ipilimumab. None of the patients developed gastrointestinal or colonic perforations.

Bristol-Myers Squibb, which is developing ipilimumab with Medarex, sponsored the study and funded editorial and writing assistance for the investigators. Dr. Weber and three of his associates have received funds for speaking, advising, and research for Bristol-Myers Squibb. Dr. Weber owns part of a patent with Medarex on CT2A-4 antibodies. The journal marked the article as an advertisement because page charges were levied to defray the costs of publication.

Grade 3–4 immune-related adverse events occurred in 46 (40%) of all patients, compared with rates of 25% and 22% in other studies that used the same dosing regimens of ipilimumab, the investigators noted. Unlike some of the earlier studies, the current trial included many patients with poor prognostic markers.

Immune-related adverse events affecting the skin, gastrointestinal system, liver, endocrine system, or other area were seen in 47 patients (81%) in the budesonide group and 48 patients (84%) in the placebo group.

Secondary end points in the study included multiple measures of the efficacy of ipilimumab in treating melanoma. A complete response or partial response was seen in seven patients (12%) in the budesonide group and in nine patients (16%) in the placebo group. In addition, the disease stabilized in 11 patients (19%) in each group.

With a median follow-up of over 12 months, the median overall survival rate was 18 months in the budesonide group and 19 months on placebo.

SAN FRANCISCO — The first pediatric study of isradipine therapy for acute hypertension suggests that it effectively lowers blood pressure and that a lower starting dose may be appropriate for children younger than 2 years.

The retrospective, single-center, observational study looked at the effects of a first-time dose of isradipine in the hospital or emergency department to treat acute hypertension in 391 children over a 2-year period. Mean blood pressures fell significantly from 147/92 mm Hg before treatment to 122/69 mm Hg, reaching a nadir 2.7 hours after treatment, Dr. Yosuke Miyashita and associates reported in a poster presentation at the annual meeting of the American Society of Hypertension.

Treatment also decreased mean arterial pressure significantly from 110 mm Hg to 86 mm Hg, said Dr. Miyashita of the University of Washington, Seattle.

Mean arterial pressure decreased by a median 24% in the 34 patients (9%) aged younger than 2 years, by 22% in 127 patients (32%) aged 2–11 years, by 18% in 167 patients (43%) aged 12–16 years, and by 20% in 63 patients (16%) aged 17 years or older.

Greater than 25% declines in mean arterial pressure—and adverse effects—were significantly more likely with dosages of 0.09 mg/kg compared with dosages of 0.08 mg/kg or lower. By age groups, a greater than 25% decrease in mean arterial pressure was seen in 47% of patients younger than 2 years of age, 43% of those aged 2–11 years, 29% of patients aged 12–16 years, and 27% of those 17 years or older.

A lower starting dose of 0.05 mg/kg may be needed for the youngest patients, the investigators suggested.

Fourteen percent of patients received dosages up to 0.05 mg/kg, 60% received 0.05–0.1 mg/kg, and 26% got more than 0.1 mg/kg. Most patients (63%) received isradipine capsules; the rest got a suspension formulation.

Among the diagnoses that contributed to the acute hypertension, four were predictive of significant decreases in blood pressure with isradipine therapy: renal disease, nonrenal transplant, oncologic disease, and neurologic disease.

Treatment produced another adverse effect—a significant pulse increase of seven pulses per minute among the whole cohort. By dosage category, however, the changes in pulse were not significant with dosages of 0.05 mg/kg or less (an extra three pulses per minute), but were significant at higher doses (an extra seven or eight pulses per minute).

Forty adverse events in 33 patients included emesis, headache, nausea, hypotension, flushing, feeling hot, dizziness, and lightheadedness. Adverse events were not necessarily dose dependent, Dr. Miyashita said.

The investigators did not disclose relevant conflicts of interest.

Study limitations include its retrospective, uncontrolled design, incomplete documentation of adverse events, and misclassification of diagnoses.

SAN FRANCISCO — The first pediatric study of isradipine therapy for acute hypertension suggests that it effectively lowers blood pressure and that a lower starting dose may be appropriate for children younger than 2 years.

The retrospective, single-center, observational study looked at the effects of a first-time dose of isradipine in the hospital or emergency department to treat acute hypertension in 391 children over a 2-year period. Mean blood pressures fell significantly from 147/92 mm Hg before treatment to 122/69 mm Hg, reaching a nadir 2.7 hours after treatment, Dr. Yosuke Miyashita and associates reported in a poster presentation at the annual meeting of the American Society of Hypertension.

Treatment also decreased mean arterial pressure significantly from 110 mm Hg to 86 mm Hg, said Dr. Miyashita of the University of Washington, Seattle.

Mean arterial pressure decreased by a median 24% in the 34 patients (9%) aged younger than 2 years, by 22% in 127 patients (32%) aged 2–11 years, by 18% in 167 patients (43%) aged 12–16 years, and by 20% in 63 patients (16%) aged 17 years or older.

Greater than 25% declines in mean arterial pressure—and adverse effects—were significantly more likely with dosages of 0.09 mg/kg compared with dosages of 0.08 mg/kg or lower. By age groups, a greater than 25% decrease in mean arterial pressure was seen in 47% of patients younger than 2 years of age, 43% of those aged 2–11 years, 29% of patients aged 12–16 years, and 27% of those 17 years or older.

A lower starting dose of 0.05 mg/kg may be needed for the youngest patients, the investigators suggested.

Fourteen percent of patients received dosages up to 0.05 mg/kg, 60% received 0.05–0.1 mg/kg, and 26% got more than 0.1 mg/kg. Most patients (63%) received isradipine capsules; the rest got a suspension formulation.

Among the diagnoses that contributed to the acute hypertension, four were predictive of significant decreases in blood pressure with isradipine therapy: renal disease, nonrenal transplant, oncologic disease, and neurologic disease.

Treatment produced another adverse effect—a significant pulse increase of seven pulses per minute among the whole cohort. By dosage category, however, the changes in pulse were not significant with dosages of 0.05 mg/kg or less (an extra three pulses per minute), but were significant at higher doses (an extra seven or eight pulses per minute).

Forty adverse events in 33 patients included emesis, headache, nausea, hypotension, flushing, feeling hot, dizziness, and lightheadedness. Adverse events were not necessarily dose dependent, Dr. Miyashita said.

The investigators did not disclose relevant conflicts of interest.

Study limitations include its retrospective, uncontrolled design, incomplete documentation of adverse events, and misclassification of diagnoses.

SAN FRANCISCO — The first pediatric study of isradipine therapy for acute hypertension suggests that it effectively lowers blood pressure and that a lower starting dose may be appropriate for children younger than 2 years.

The retrospective, single-center, observational study looked at the effects of a first-time dose of isradipine in the hospital or emergency department to treat acute hypertension in 391 children over a 2-year period. Mean blood pressures fell significantly from 147/92 mm Hg before treatment to 122/69 mm Hg, reaching a nadir 2.7 hours after treatment, Dr. Yosuke Miyashita and associates reported in a poster presentation at the annual meeting of the American Society of Hypertension.

Treatment also decreased mean arterial pressure significantly from 110 mm Hg to 86 mm Hg, said Dr. Miyashita of the University of Washington, Seattle.

Mean arterial pressure decreased by a median 24% in the 34 patients (9%) aged younger than 2 years, by 22% in 127 patients (32%) aged 2–11 years, by 18% in 167 patients (43%) aged 12–16 years, and by 20% in 63 patients (16%) aged 17 years or older.

Greater than 25% declines in mean arterial pressure—and adverse effects—were significantly more likely with dosages of 0.09 mg/kg compared with dosages of 0.08 mg/kg or lower. By age groups, a greater than 25% decrease in mean arterial pressure was seen in 47% of patients younger than 2 years of age, 43% of those aged 2–11 years, 29% of patients aged 12–16 years, and 27% of those 17 years or older.

A lower starting dose of 0.05 mg/kg may be needed for the youngest patients, the investigators suggested.

Fourteen percent of patients received dosages up to 0.05 mg/kg, 60% received 0.05–0.1 mg/kg, and 26% got more than 0.1 mg/kg. Most patients (63%) received isradipine capsules; the rest got a suspension formulation.

Among the diagnoses that contributed to the acute hypertension, four were predictive of significant decreases in blood pressure with isradipine therapy: renal disease, nonrenal transplant, oncologic disease, and neurologic disease.

Treatment produced another adverse effect—a significant pulse increase of seven pulses per minute among the whole cohort. By dosage category, however, the changes in pulse were not significant with dosages of 0.05 mg/kg or less (an extra three pulses per minute), but were significant at higher doses (an extra seven or eight pulses per minute).

Forty adverse events in 33 patients included emesis, headache, nausea, hypotension, flushing, feeling hot, dizziness, and lightheadedness. Adverse events were not necessarily dose dependent, Dr. Miyashita said.

The investigators did not disclose relevant conflicts of interest.

Study limitations include its retrospective, uncontrolled design, incomplete documentation of adverse events, and misclassification of diagnoses.

SAN FRANCISCO — Patients on three or more medications for resistant hypertension were more likely to have blood pressure under control and less likely to have a nondipper blood pressure pattern at night if they took at least one of the drugs at bedtime, according to ambulatory blood pressure monitoring study involving 1,306 patients.

For 48 consecutive hours, a device automatically measured blood pressure and heart rate every 20 minutes from 7 a.m. to 11 p.m. and every 30 minutes during the night. Simultaneous wrist actigraphy was used to monitor physical activity every minute. A comparison of data from the two devices allowed investigators to determine blood pressure means during waking and sleep time according to each individual's rest-activity cycle.

Among 573 patients who took at least one of their antihypertensives at bedtime and the remainder in the morning, 32% had blood pressure under control, which was significantly better compared with 23% of the 733 patients who took no antihypertensive medications at bedtime and all of them on awakening, Dr. Ramon C. Hermida and his associates reported at the annual meeting of the American Society of Hypertension.

The bedtime-dose group also had significantly lower blood pressures at nighttime and morning, and lower ambulatory pulse pressure compared with the morning-only group. The bedtime group patients had a higher awake/asleep blood pressure ratio, and thus were significantly less likely to have a nighttime nondipper blood pressure pattern that has been associated with a higher risk of cardiovascular and cerebrovascular events. A nondipper blood pressure pattern is defined as less than a 10% decline in mean blood pressure during sleep compared with awake blood pressure.

In the bedtime group, 40% had a nondipper pattern, compared with 83% in the morning-only group, said Dr. Hermida of the University of Vigo, Spain.

In addition, the bedtime group had significantly lower mean levels of glucose, total cholesterol, LDL cholesterol, fibrinogen, and urinary albumin excretion.

In general, patients with resistant hypertension have a high prevalence of the nondipper blood pressure pattern. Conventional strategies for managing resistant hypertension focus on adding another drug or changing a drug to see if that improves the combination therapy.

Research findings suggest that up to 89% of patients who take antihypertensives ingest them all in the morning, including patients with resistant hypertension.

With better timing of medication administration, blood pressure control could be improved and the number of patients with the nondipper pattern reduced, Dr. Hermida proposed.

The investigators are studying whether this normalization of the blood pressure pattern might reduce cardiovascular risk beyond the benefits conferred by reducing mean blood pressure values.

In the current study, the cohort had a mean age of 61 years; 52% of the participants were male.

Mean morning blood pressures were 136/79 mm Hg in the bedtime group and 142/82 mm Hg in the morning group.

Mean glucose values were 116 mg/dL in the bedtime group and 121 mg/dL in the morning group. Mean values for total cholesterol and LDL cholesterol were 201 mg/dL and 129 mg/dL in the bedtime group, respectively, and 206 mg/dL and 134 mg/dL in the morning group, respectively.

Fibrinogen levels were 339 mg/dL in the bedtime group and 351 mg/dL in the morning group. In the bedtime group, the urinary albumin excretion rate was 29 mg/day, compared with 39 mg/day in the morning group.

There were no significant differences in heart rates between the groups.

An audience member pointed out that the researchers did not indicate which antihypertensives were being taken in the a.m. or the p.m., an observation that was relevant since not all medications are effective for a 24-hour period.

The investigators reported having no relevant conflicts of interest.

In the bedtime-dose group, 40% had a nondipper pattern, compared with 83% in the morning-only group.

Source DR. HERMIDA

SAN FRANCISCO — Patients on three or more medications for resistant hypertension were more likely to have blood pressure under control and less likely to have a nondipper blood pressure pattern at night if they took at least one of the drugs at bedtime, according to ambulatory blood pressure monitoring study involving 1,306 patients.

For 48 consecutive hours, a device automatically measured blood pressure and heart rate every 20 minutes from 7 a.m. to 11 p.m. and every 30 minutes during the night. Simultaneous wrist actigraphy was used to monitor physical activity every minute. A comparison of data from the two devices allowed investigators to determine blood pressure means during waking and sleep time according to each individual's rest-activity cycle.

Among 573 patients who took at least one of their antihypertensives at bedtime and the remainder in the morning, 32% had blood pressure under control, which was significantly better compared with 23% of the 733 patients who took no antihypertensive medications at bedtime and all of them on awakening, Dr. Ramon C. Hermida and his associates reported at the annual meeting of the American Society of Hypertension.

The bedtime-dose group also had significantly lower blood pressures at nighttime and morning, and lower ambulatory pulse pressure compared with the morning-only group. The bedtime group patients had a higher awake/asleep blood pressure ratio, and thus were significantly less likely to have a nighttime nondipper blood pressure pattern that has been associated with a higher risk of cardiovascular and cerebrovascular events. A nondipper blood pressure pattern is defined as less than a 10% decline in mean blood pressure during sleep compared with awake blood pressure.

In the bedtime group, 40% had a nondipper pattern, compared with 83% in the morning-only group, said Dr. Hermida of the University of Vigo, Spain.

In addition, the bedtime group had significantly lower mean levels of glucose, total cholesterol, LDL cholesterol, fibrinogen, and urinary albumin excretion.

In general, patients with resistant hypertension have a high prevalence of the nondipper blood pressure pattern. Conventional strategies for managing resistant hypertension focus on adding another drug or changing a drug to see if that improves the combination therapy.

Research findings suggest that up to 89% of patients who take antihypertensives ingest them all in the morning, including patients with resistant hypertension.

With better timing of medication administration, blood pressure control could be improved and the number of patients with the nondipper pattern reduced, Dr. Hermida proposed.

The investigators are studying whether this normalization of the blood pressure pattern might reduce cardiovascular risk beyond the benefits conferred by reducing mean blood pressure values.

In the current study, the cohort had a mean age of 61 years; 52% of the participants were male.

Mean morning blood pressures were 136/79 mm Hg in the bedtime group and 142/82 mm Hg in the morning group.

Mean glucose values were 116 mg/dL in the bedtime group and 121 mg/dL in the morning group. Mean values for total cholesterol and LDL cholesterol were 201 mg/dL and 129 mg/dL in the bedtime group, respectively, and 206 mg/dL and 134 mg/dL in the morning group, respectively.

Fibrinogen levels were 339 mg/dL in the bedtime group and 351 mg/dL in the morning group. In the bedtime group, the urinary albumin excretion rate was 29 mg/day, compared with 39 mg/day in the morning group.

There were no significant differences in heart rates between the groups.

An audience member pointed out that the researchers did not indicate which antihypertensives were being taken in the a.m. or the p.m., an observation that was relevant since not all medications are effective for a 24-hour period.

The investigators reported having no relevant conflicts of interest.

In the bedtime-dose group, 40% had a nondipper pattern, compared with 83% in the morning-only group.

Source DR. HERMIDA

SAN FRANCISCO — Patients on three or more medications for resistant hypertension were more likely to have blood pressure under control and less likely to have a nondipper blood pressure pattern at night if they took at least one of the drugs at bedtime, according to ambulatory blood pressure monitoring study involving 1,306 patients.

For 48 consecutive hours, a device automatically measured blood pressure and heart rate every 20 minutes from 7 a.m. to 11 p.m. and every 30 minutes during the night. Simultaneous wrist actigraphy was used to monitor physical activity every minute. A comparison of data from the two devices allowed investigators to determine blood pressure means during waking and sleep time according to each individual's rest-activity cycle.

Among 573 patients who took at least one of their antihypertensives at bedtime and the remainder in the morning, 32% had blood pressure under control, which was significantly better compared with 23% of the 733 patients who took no antihypertensive medications at bedtime and all of them on awakening, Dr. Ramon C. Hermida and his associates reported at the annual meeting of the American Society of Hypertension.

The bedtime-dose group also had significantly lower blood pressures at nighttime and morning, and lower ambulatory pulse pressure compared with the morning-only group. The bedtime group patients had a higher awake/asleep blood pressure ratio, and thus were significantly less likely to have a nighttime nondipper blood pressure pattern that has been associated with a higher risk of cardiovascular and cerebrovascular events. A nondipper blood pressure pattern is defined as less than a 10% decline in mean blood pressure during sleep compared with awake blood pressure.

In the bedtime group, 40% had a nondipper pattern, compared with 83% in the morning-only group, said Dr. Hermida of the University of Vigo, Spain.

In addition, the bedtime group had significantly lower mean levels of glucose, total cholesterol, LDL cholesterol, fibrinogen, and urinary albumin excretion.

In general, patients with resistant hypertension have a high prevalence of the nondipper blood pressure pattern. Conventional strategies for managing resistant hypertension focus on adding another drug or changing a drug to see if that improves the combination therapy.

Research findings suggest that up to 89% of patients who take antihypertensives ingest them all in the morning, including patients with resistant hypertension.

With better timing of medication administration, blood pressure control could be improved and the number of patients with the nondipper pattern reduced, Dr. Hermida proposed.

The investigators are studying whether this normalization of the blood pressure pattern might reduce cardiovascular risk beyond the benefits conferred by reducing mean blood pressure values.

In the current study, the cohort had a mean age of 61 years; 52% of the participants were male.

Mean morning blood pressures were 136/79 mm Hg in the bedtime group and 142/82 mm Hg in the morning group.

Mean glucose values were 116 mg/dL in the bedtime group and 121 mg/dL in the morning group. Mean values for total cholesterol and LDL cholesterol were 201 mg/dL and 129 mg/dL in the bedtime group, respectively, and 206 mg/dL and 134 mg/dL in the morning group, respectively.

Fibrinogen levels were 339 mg/dL in the bedtime group and 351 mg/dL in the morning group. In the bedtime group, the urinary albumin excretion rate was 29 mg/day, compared with 39 mg/day in the morning group.

There were no significant differences in heart rates between the groups.

An audience member pointed out that the researchers did not indicate which antihypertensives were being taken in the a.m. or the p.m., an observation that was relevant since not all medications are effective for a 24-hour period.

The investigators reported having no relevant conflicts of interest.

In the bedtime-dose group, 40% had a nondipper pattern, compared with 83% in the morning-only group.

Source DR. HERMIDA

SAN FRANCISCO — Patients on three or more medications for resistant hypertension were more likely to have blood pressure under control and less likely to have a non-dipper BP pattern at night if they took at least one of the drugs at bedtime, according to ambulatory BP monitoring study involving 1,306 patients.

For 48 consecutive hours, a device automatically measured blood pressure and heart rate every 20 minutes from 7 a.m. to 11 p.m. and every 30 minutes during the night. Simultaneous wrist actigraphy was used to monitor physical activity every minute. A comparison of data from the two devices allowed investigators to determine blood pressure means during waking and sleep time according to each individual's rest-activity cycle.

Among 573 patients who took at least one of their antihypertensives at bedtime and the remainder in the morning, 32% had blood pressure under control, which was significantly better compared with 23% of the 733 patients who took no antihypertensive medications at bedtime and all of them on awakening, Dr. Ramon C. Hermida and his associates reported at the annual meeting of the American Society of Hypertension.

The bedtime-dose group also had significantly lower blood pressures at nighttime and morning, and lower ambulatory pulse pressure compared with the morning-only group. The bedtime group patients had a higher awake/asleep blood pressure ratio, and thus were significantly less likely to have a nighttime non-dipper blood pressure pattern that has been associated with a higher risk of cardiovascular and cerebrovascular events. A non-dipper blood pressure pattern is defined as less than a 10% decline in mean blood pressure during sleep compared with awake blood pressure.

In the bedtime group, 40% had a non-dipper pattern, compared with 83% in the morning-only group, said Dr. Hermida of the University of Vigo, Spain.

In addition, the bedtime group had significantly lower mean levels of glucose, total cholesterol, LDL cholesterol, fibrinogen, and urinary albumin excretion.

In general, patients with resistant hypertension have a high prevalence of the non-dipper blood pressure pattern. Conventional strategies for managing resistant hypertension focus on adding another drug or changing a drug to see if that improves the combination therapy.

Research findings suggest that up to 89% of patients who take antihypertensives ingest them all in the morning, including patients with resistant hypertension. With better timing of medication administration, blood pressure control could be improved and the number of patients with the non-dipper pattern reduced, Dr. Hermida proposed.

In the current study, the cohort had a mean age of 61 years; 52% of the participants were male. Mean morning blood pressures were 136/79 mm Hg in the bedtime group and 142/82 mm Hg in the morning group.

The investigators reported having no conflicts related to the study.

In the bedtime group, 40% hada non-dipper pattern, compared with 83% in the morning-only group.

Source DR. HERMIDA

SAN FRANCISCO — Patients on three or more medications for resistant hypertension were more likely to have blood pressure under control and less likely to have a non-dipper BP pattern at night if they took at least one of the drugs at bedtime, according to ambulatory BP monitoring study involving 1,306 patients.

For 48 consecutive hours, a device automatically measured blood pressure and heart rate every 20 minutes from 7 a.m. to 11 p.m. and every 30 minutes during the night. Simultaneous wrist actigraphy was used to monitor physical activity every minute. A comparison of data from the two devices allowed investigators to determine blood pressure means during waking and sleep time according to each individual's rest-activity cycle.

Among 573 patients who took at least one of their antihypertensives at bedtime and the remainder in the morning, 32% had blood pressure under control, which was significantly better compared with 23% of the 733 patients who took no antihypertensive medications at bedtime and all of them on awakening, Dr. Ramon C. Hermida and his associates reported at the annual meeting of the American Society of Hypertension.

The bedtime-dose group also had significantly lower blood pressures at nighttime and morning, and lower ambulatory pulse pressure compared with the morning-only group. The bedtime group patients had a higher awake/asleep blood pressure ratio, and thus were significantly less likely to have a nighttime non-dipper blood pressure pattern that has been associated with a higher risk of cardiovascular and cerebrovascular events. A non-dipper blood pressure pattern is defined as less than a 10% decline in mean blood pressure during sleep compared with awake blood pressure.

In the bedtime group, 40% had a non-dipper pattern, compared with 83% in the morning-only group, said Dr. Hermida of the University of Vigo, Spain.

In addition, the bedtime group had significantly lower mean levels of glucose, total cholesterol, LDL cholesterol, fibrinogen, and urinary albumin excretion.

In general, patients with resistant hypertension have a high prevalence of the non-dipper blood pressure pattern. Conventional strategies for managing resistant hypertension focus on adding another drug or changing a drug to see if that improves the combination therapy.

Research findings suggest that up to 89% of patients who take antihypertensives ingest them all in the morning, including patients with resistant hypertension. With better timing of medication administration, blood pressure control could be improved and the number of patients with the non-dipper pattern reduced, Dr. Hermida proposed.

In the current study, the cohort had a mean age of 61 years; 52% of the participants were male. Mean morning blood pressures were 136/79 mm Hg in the bedtime group and 142/82 mm Hg in the morning group.

The investigators reported having no conflicts related to the study.

In the bedtime group, 40% hada non-dipper pattern, compared with 83% in the morning-only group.

Source DR. HERMIDA

SAN FRANCISCO — Patients on three or more medications for resistant hypertension were more likely to have blood pressure under control and less likely to have a non-dipper BP pattern at night if they took at least one of the drugs at bedtime, according to ambulatory BP monitoring study involving 1,306 patients.

For 48 consecutive hours, a device automatically measured blood pressure and heart rate every 20 minutes from 7 a.m. to 11 p.m. and every 30 minutes during the night. Simultaneous wrist actigraphy was used to monitor physical activity every minute. A comparison of data from the two devices allowed investigators to determine blood pressure means during waking and sleep time according to each individual's rest-activity cycle.

Among 573 patients who took at least one of their antihypertensives at bedtime and the remainder in the morning, 32% had blood pressure under control, which was significantly better compared with 23% of the 733 patients who took no antihypertensive medications at bedtime and all of them on awakening, Dr. Ramon C. Hermida and his associates reported at the annual meeting of the American Society of Hypertension.

The bedtime-dose group also had significantly lower blood pressures at nighttime and morning, and lower ambulatory pulse pressure compared with the morning-only group. The bedtime group patients had a higher awake/asleep blood pressure ratio, and thus were significantly less likely to have a nighttime non-dipper blood pressure pattern that has been associated with a higher risk of cardiovascular and cerebrovascular events. A non-dipper blood pressure pattern is defined as less than a 10% decline in mean blood pressure during sleep compared with awake blood pressure.

In the bedtime group, 40% had a non-dipper pattern, compared with 83% in the morning-only group, said Dr. Hermida of the University of Vigo, Spain.

In addition, the bedtime group had significantly lower mean levels of glucose, total cholesterol, LDL cholesterol, fibrinogen, and urinary albumin excretion.

In general, patients with resistant hypertension have a high prevalence of the non-dipper blood pressure pattern. Conventional strategies for managing resistant hypertension focus on adding another drug or changing a drug to see if that improves the combination therapy.

Research findings suggest that up to 89% of patients who take antihypertensives ingest them all in the morning, including patients with resistant hypertension. With better timing of medication administration, blood pressure control could be improved and the number of patients with the non-dipper pattern reduced, Dr. Hermida proposed.

In the current study, the cohort had a mean age of 61 years; 52% of the participants were male. Mean morning blood pressures were 136/79 mm Hg in the bedtime group and 142/82 mm Hg in the morning group.

The investigators reported having no conflicts related to the study.

In the bedtime group, 40% hada non-dipper pattern, compared with 83% in the morning-only group.

Source DR. HERMIDA