Jennie Smith

Pregnant women taking antiepileptic drugs have higher odds for preeclampsia, bleeding, labor induction, caesarean section, and major malformations of the newborn, Norwegian researchers have learned.

The findings, published May 11 in BJOG: An International Journal of Obstetrics and Gynaecology, add to mounting evidence that pregnancy risks for epileptic women may be linked to antiepileptic drugs (AEDs) rather than epilepsy itself.

In the study, Dr. Ingrid Borthen of Haukeland University Hospital, in Bergen, Norway, and her associates retrospectively compared obstetric outcomes for 205 deliveries by 170 women with a past or present history of epilepsy (57% of whom were taking AEDs) and 205 matched, nonepileptic control patients. The women in both groups had a mean age of 28 years.

Epileptic women taking AEDs had higher odds of severe preeclampsia (odds ratio [OR], 5.0; 95% CI, 1.3-19.9), bleeding in early pregnancy (OR, 6.4; 95% CI, 2.7-15.2), labor induction (OR, 2.3; 95% CI, 1.2-4.3), cesarean section (OR, 2.5; 95% CI, 1.4-4.7), and malformations in the offspring (OR, 7.1; 95% CI, 1.4-36.6). The comparisons of outcomes between the two groups were controlled for confounding factors, including smoking during pregnancy, mother’s age, highest maternal education, parity, body mass index of 30 kg/m² or greater, diabetes and medical conditions, and previous caesarean section, bleeding, and preeclampsia on comparisons of birth outcomes.

Women with active epilepsy (defined as seizures within 5 years of conception) not using the drugs did not have increased odds for any of these outcomes; however, they did have higher odds for vaginal forceps delivery and preterm birth.

Which specific drugs may be implicated is still difficult to say, said Dr. Borthen, but the study showed that lamotrigine is associated with a higher risk (BJOG 2011 May 11 [doi: 10.1111/j.1471-0528.2011.03004.x]).

Two years ago, Dr. Borthen and her colleagues demonstrated that epileptic women taking AEDs had a significantly increased odds of experiencing preeclampsia and preterm delivery, compared with nonepileptic women, while epileptic women not using AEDs did not have higher odds for any outcomes (BJOG 2009;116:1736-42).

"In our study from 2009, carbamazepine was what was prescribed throughout Norway," Dr. Borthen said in an interview. In the current study, which enrolled women taking lamotrigine, carbamazepine, valproate, and polytherapies, women with lamotrigine monotherapy had an unadjusted OR of 7.5 (95% CI, 1.4-39.0) for severe preeclampsia. Women with polytherapy and with lamotrigine monotherapy had an increased risk of early bleeding (unadjusted OR, 8.6; 95% CI, 2.8-26.3 and OR, 6.2; 95% CI, 2.0-19.3, respectively).

"We use lamotrigine because it doesn’t harm the fetus. But maybe it harms the woman instead," Dr. Borthen said, adding that her team is now designing a new study that would enroll all women with epilepsy in Bergen, hoping for a finer picture of risk ascribable to individual drugs.

"It’s so interesting to see why the medication should have such an impact," Dr. Borthen said, adding that it was possible that interactions with folate could play a part. In this study, the vast majority of women with epilepsy and AED use were also taking folate.

Dr. Borthen and her colleagues noted that the proportion of women using AEDs during pregnancy may represent a larger group than epileptic women, as there is "growing use of AEDs for pain and psychiatric conditions."

One limitation of the study, Dr. Borthen and colleagues wrote in their analysis, was a lack of data on seizure type and severity. The study was funded by the Norwegian Research Council. Dr. Borthen and her colleagues declared that they had no conflicts of interest.

Pregnant women taking antiepileptic drugs have higher odds for preeclampsia, bleeding, labor induction, caesarean section, and major malformations of the newborn, Norwegian researchers have learned.

The findings, published May 11 in BJOG: An International Journal of Obstetrics and Gynaecology, add to mounting evidence that pregnancy risks for epileptic women may be linked to antiepileptic drugs (AEDs) rather than epilepsy itself.

In the study, Dr. Ingrid Borthen of Haukeland University Hospital, in Bergen, Norway, and her associates retrospectively compared obstetric outcomes for 205 deliveries by 170 women with a past or present history of epilepsy (57% of whom were taking AEDs) and 205 matched, nonepileptic control patients. The women in both groups had a mean age of 28 years.

Epileptic women taking AEDs had higher odds of severe preeclampsia (odds ratio [OR], 5.0; 95% CI, 1.3-19.9), bleeding in early pregnancy (OR, 6.4; 95% CI, 2.7-15.2), labor induction (OR, 2.3; 95% CI, 1.2-4.3), cesarean section (OR, 2.5; 95% CI, 1.4-4.7), and malformations in the offspring (OR, 7.1; 95% CI, 1.4-36.6). The comparisons of outcomes between the two groups were controlled for confounding factors, including smoking during pregnancy, mother’s age, highest maternal education, parity, body mass index of 30 kg/m² or greater, diabetes and medical conditions, and previous caesarean section, bleeding, and preeclampsia on comparisons of birth outcomes.

Women with active epilepsy (defined as seizures within 5 years of conception) not using the drugs did not have increased odds for any of these outcomes; however, they did have higher odds for vaginal forceps delivery and preterm birth.

Which specific drugs may be implicated is still difficult to say, said Dr. Borthen, but the study showed that lamotrigine is associated with a higher risk (BJOG 2011 May 11 [doi: 10.1111/j.1471-0528.2011.03004.x]).

Two years ago, Dr. Borthen and her colleagues demonstrated that epileptic women taking AEDs had a significantly increased odds of experiencing preeclampsia and preterm delivery, compared with nonepileptic women, while epileptic women not using AEDs did not have higher odds for any outcomes (BJOG 2009;116:1736-42).

"In our study from 2009, carbamazepine was what was prescribed throughout Norway," Dr. Borthen said in an interview. In the current study, which enrolled women taking lamotrigine, carbamazepine, valproate, and polytherapies, women with lamotrigine monotherapy had an unadjusted OR of 7.5 (95% CI, 1.4-39.0) for severe preeclampsia. Women with polytherapy and with lamotrigine monotherapy had an increased risk of early bleeding (unadjusted OR, 8.6; 95% CI, 2.8-26.3 and OR, 6.2; 95% CI, 2.0-19.3, respectively).

"We use lamotrigine because it doesn’t harm the fetus. But maybe it harms the woman instead," Dr. Borthen said, adding that her team is now designing a new study that would enroll all women with epilepsy in Bergen, hoping for a finer picture of risk ascribable to individual drugs.

"It’s so interesting to see why the medication should have such an impact," Dr. Borthen said, adding that it was possible that interactions with folate could play a part. In this study, the vast majority of women with epilepsy and AED use were also taking folate.

Dr. Borthen and her colleagues noted that the proportion of women using AEDs during pregnancy may represent a larger group than epileptic women, as there is "growing use of AEDs for pain and psychiatric conditions."

One limitation of the study, Dr. Borthen and colleagues wrote in their analysis, was a lack of data on seizure type and severity. The study was funded by the Norwegian Research Council. Dr. Borthen and her colleagues declared that they had no conflicts of interest.

Pregnant women taking antiepileptic drugs have higher odds for preeclampsia, bleeding, labor induction, caesarean section, and major malformations of the newborn, Norwegian researchers have learned.

The findings, published May 11 in BJOG: An International Journal of Obstetrics and Gynaecology, add to mounting evidence that pregnancy risks for epileptic women may be linked to antiepileptic drugs (AEDs) rather than epilepsy itself.

In the study, Dr. Ingrid Borthen of Haukeland University Hospital, in Bergen, Norway, and her associates retrospectively compared obstetric outcomes for 205 deliveries by 170 women with a past or present history of epilepsy (57% of whom were taking AEDs) and 205 matched, nonepileptic control patients. The women in both groups had a mean age of 28 years.

Epileptic women taking AEDs had higher odds of severe preeclampsia (odds ratio [OR], 5.0; 95% CI, 1.3-19.9), bleeding in early pregnancy (OR, 6.4; 95% CI, 2.7-15.2), labor induction (OR, 2.3; 95% CI, 1.2-4.3), cesarean section (OR, 2.5; 95% CI, 1.4-4.7), and malformations in the offspring (OR, 7.1; 95% CI, 1.4-36.6). The comparisons of outcomes between the two groups were controlled for confounding factors, including smoking during pregnancy, mother’s age, highest maternal education, parity, body mass index of 30 kg/m² or greater, diabetes and medical conditions, and previous caesarean section, bleeding, and preeclampsia on comparisons of birth outcomes.

Women with active epilepsy (defined as seizures within 5 years of conception) not using the drugs did not have increased odds for any of these outcomes; however, they did have higher odds for vaginal forceps delivery and preterm birth.

Which specific drugs may be implicated is still difficult to say, said Dr. Borthen, but the study showed that lamotrigine is associated with a higher risk (BJOG 2011 May 11 [doi: 10.1111/j.1471-0528.2011.03004.x]).

Two years ago, Dr. Borthen and her colleagues demonstrated that epileptic women taking AEDs had a significantly increased odds of experiencing preeclampsia and preterm delivery, compared with nonepileptic women, while epileptic women not using AEDs did not have higher odds for any outcomes (BJOG 2009;116:1736-42).

"In our study from 2009, carbamazepine was what was prescribed throughout Norway," Dr. Borthen said in an interview. In the current study, which enrolled women taking lamotrigine, carbamazepine, valproate, and polytherapies, women with lamotrigine monotherapy had an unadjusted OR of 7.5 (95% CI, 1.4-39.0) for severe preeclampsia. Women with polytherapy and with lamotrigine monotherapy had an increased risk of early bleeding (unadjusted OR, 8.6; 95% CI, 2.8-26.3 and OR, 6.2; 95% CI, 2.0-19.3, respectively).

"We use lamotrigine because it doesn’t harm the fetus. But maybe it harms the woman instead," Dr. Borthen said, adding that her team is now designing a new study that would enroll all women with epilepsy in Bergen, hoping for a finer picture of risk ascribable to individual drugs.

"It’s so interesting to see why the medication should have such an impact," Dr. Borthen said, adding that it was possible that interactions with folate could play a part. In this study, the vast majority of women with epilepsy and AED use were also taking folate.

Dr. Borthen and her colleagues noted that the proportion of women using AEDs during pregnancy may represent a larger group than epileptic women, as there is "growing use of AEDs for pain and psychiatric conditions."

One limitation of the study, Dr. Borthen and colleagues wrote in their analysis, was a lack of data on seizure type and severity. The study was funded by the Norwegian Research Council. Dr. Borthen and her colleagues declared that they had no conflicts of interest.

Pregnant women taking antiepileptic drugs have higher odds for preeclampsia, bleeding, labor induction, caesarean section, and major malformations of the newborn, Norwegian researchers have learned.

The findings, published May 11 in BJOG: An International Journal of Obstetrics and Gynaecology, add to mounting evidence that pregnancy risks for epileptic women may be linked to antiepileptic drugs (AEDs) rather than epilepsy itself.

In the study, Dr. Ingrid Borthen of Haukeland University Hospital, in Bergen, Norway, and her associates retrospectively compared obstetric outcomes for 205 deliveries by 170 women with a past or present history of epilepsy (57% of whom were taking AEDs) and 205 matched, nonepileptic control patients. The women in both groups had a mean age of 28 years.

Epileptic women taking AEDs had higher odds of severe preeclampsia (odds ratio [OR], 5.0; 95% CI, 1.3-19.9), bleeding in early pregnancy (OR, 6.4; 95% CI, 2.7-15.2), labor induction (OR, 2.3; 95% CI, 1.2-4.3), cesarean section (OR, 2.5; 95% CI, 1.4-4.7), and malformations in the offspring (OR, 7.1; 95% CI, 1.4-36.6). The comparisons of outcomes between the two groups were controlled for confounding factors, including smoking during pregnancy, mother’s age, highest maternal education, parity, body mass index of 30 kg/m² or greater, diabetes and medical conditions, and previous caesarean section, bleeding, and preeclampsia on comparisons of birth outcomes.

Women with active epilepsy (defined as seizures within 5 years of conception) not using the drugs did not have increased odds for any of these outcomes; however, they did have higher odds for vaginal forceps delivery and preterm birth.

Which specific drugs may be implicated is still difficult to say, said Dr. Borthen, but the study showed that lamotrigine is associated with a higher risk (BJOG 2011 May 11 [doi: 10.1111/j.1471-0528.2011.03004.x]).

Two years ago, Dr. Borthen and her colleagues demonstrated that epileptic women taking AEDs had a significantly increased odds of experiencing preeclampsia and preterm delivery, compared with nonepileptic women, while epileptic women not using AEDs did not have higher odds for any outcomes (BJOG 2009;116:1736-42).

"In our study from 2009, carbamazepine was what was prescribed throughout Norway," Dr. Borthen said in an interview. In the current study, which enrolled women taking lamotrigine, carbamazepine, valproate, and polytherapies, women with lamotrigine monotherapy had an unadjusted OR of 7.5 (95% CI, 1.4-39.0) for severe preeclampsia. Women with polytherapy and with lamotrigine monotherapy had an increased risk of early bleeding (unadjusted OR, 8.6; 95% CI, 2.8-26.3 and OR, 6.2; 95% CI, 2.0-19.3, respectively).

"We use lamotrigine because it doesn’t harm the fetus. But maybe it harms the woman instead," Dr. Borthen said, adding that her team is now designing a new study that would enroll all women with epilepsy in Bergen, hoping for a finer picture of risk ascribable to individual drugs.

"It’s so interesting to see why the medication should have such an impact," Dr. Borthen said, adding that it was possible that interactions with folate could play a part. In this study, the vast majority of women with epilepsy and AED use were also taking folate.

Dr. Borthen and her colleagues noted that the proportion of women using AEDs during pregnancy may represent a larger group than epileptic women, as there is "growing use of AEDs for pain and psychiatric conditions."

One limitation of the study, Dr. Borthen and colleagues wrote in their analysis, was a lack of data on seizure type and severity. The study was funded by the Norwegian Research Council. Dr. Borthen and her colleagues declared that they had no conflicts of interest.

Pregnant women taking antiepileptic drugs have higher odds for preeclampsia, bleeding, labor induction, caesarean section, and major malformations of the newborn, Norwegian researchers have learned.

The findings, published May 11 in BJOG: An International Journal of Obstetrics and Gynaecology, add to mounting evidence that pregnancy risks for epileptic women may be linked to antiepileptic drugs (AEDs) rather than epilepsy itself.

In the study, Dr. Ingrid Borthen of Haukeland University Hospital, in Bergen, Norway, and her associates retrospectively compared obstetric outcomes for 205 deliveries by 170 women with a past or present history of epilepsy (57% of whom were taking AEDs) and 205 matched, nonepileptic control patients. The women in both groups had a mean age of 28 years.

Epileptic women taking AEDs had higher odds of severe preeclampsia (odds ratio [OR], 5.0; 95% CI, 1.3-19.9), bleeding in early pregnancy (OR, 6.4; 95% CI, 2.7-15.2), labor induction (OR, 2.3; 95% CI, 1.2-4.3), cesarean section (OR, 2.5; 95% CI, 1.4-4.7), and malformations in the offspring (OR, 7.1; 95% CI, 1.4-36.6). The comparisons of outcomes between the two groups were controlled for confounding factors, including smoking during pregnancy, mother’s age, highest maternal education, parity, body mass index of 30 kg/m² or greater, diabetes and medical conditions, and previous caesarean section, bleeding, and preeclampsia on comparisons of birth outcomes.

Women with active epilepsy (defined as seizures within 5 years of conception) not using the drugs did not have increased odds for any of these outcomes; however, they did have higher odds for vaginal forceps delivery and preterm birth.

Which specific drugs may be implicated is still difficult to say, said Dr. Borthen, but the study showed that lamotrigine is associated with a higher risk (BJOG 2011 May 11 [doi: 10.1111/j.1471-0528.2011.03004.x]).

Two years ago, Dr. Borthen and her colleagues demonstrated that epileptic women taking AEDs had a significantly increased odds of experiencing preeclampsia and preterm delivery, compared with nonepileptic women, while epileptic women not using AEDs did not have higher odds for any outcomes (BJOG 2009;116:1736-42).

"In our study from 2009, carbamazepine was what was prescribed throughout Norway," Dr. Borthen said in an interview. In the current study, which enrolled women taking lamotrigine, carbamazepine, valproate, and polytherapies, women with lamotrigine monotherapy had an unadjusted OR of 7.5 (95% CI, 1.4-39.0) for severe preeclampsia. Women with polytherapy and with lamotrigine monotherapy had an increased risk of early bleeding (unadjusted OR, 8.6; 95% CI, 2.8-26.3 and OR, 6.2; 95% CI, 2.0-19.3, respectively).

"We use lamotrigine because it doesn’t harm the fetus. But maybe it harms the woman instead," Dr. Borthen said, adding that her team is now designing a new study that would enroll all women with epilepsy in Bergen, hoping for a finer picture of risk ascribable to individual drugs.

"It’s so interesting to see why the medication should have such an impact," Dr. Borthen said, adding that it was possible that interactions with folate could play a part. In this study, the vast majority of women with epilepsy and AED use were also taking folate.

Dr. Borthen and her colleagues noted that the proportion of women using AEDs during pregnancy may represent a larger group than epileptic women, as there is "growing use of AEDs for pain and psychiatric conditions."

One limitation of the study, Dr. Borthen and colleagues wrote in their analysis, was a lack of data on seizure type and severity. The study was funded by the Norwegian Research Council. Dr. Borthen and her colleagues declared that they had no conflicts of interest.

Pregnant women taking antiepileptic drugs have higher odds for preeclampsia, bleeding, labor induction, caesarean section, and major malformations of the newborn, Norwegian researchers have learned.

The findings, published May 11 in BJOG: An International Journal of Obstetrics and Gynaecology, add to mounting evidence that pregnancy risks for epileptic women may be linked to antiepileptic drugs (AEDs) rather than epilepsy itself.

In the study, Dr. Ingrid Borthen of Haukeland University Hospital, in Bergen, Norway, and her associates retrospectively compared obstetric outcomes for 205 deliveries by 170 women with a past or present history of epilepsy (57% of whom were taking AEDs) and 205 matched, nonepileptic control patients. The women in both groups had a mean age of 28 years.

Epileptic women taking AEDs had higher odds of severe preeclampsia (odds ratio [OR], 5.0; 95% CI, 1.3-19.9), bleeding in early pregnancy (OR, 6.4; 95% CI, 2.7-15.2), labor induction (OR, 2.3; 95% CI, 1.2-4.3), cesarean section (OR, 2.5; 95% CI, 1.4-4.7), and malformations in the offspring (OR, 7.1; 95% CI, 1.4-36.6). The comparisons of outcomes between the two groups were controlled for confounding factors, including smoking during pregnancy, mother’s age, highest maternal education, parity, body mass index of 30 kg/m² or greater, diabetes and medical conditions, and previous caesarean section, bleeding, and preeclampsia on comparisons of birth outcomes.

Women with active epilepsy (defined as seizures within 5 years of conception) not using the drugs did not have increased odds for any of these outcomes; however, they did have higher odds for vaginal forceps delivery and preterm birth.

Which specific drugs may be implicated is still difficult to say, said Dr. Borthen, but the study showed that lamotrigine is associated with a higher risk (BJOG 2011 May 11 [doi: 10.1111/j.1471-0528.2011.03004.x]).

Two years ago, Dr. Borthen and her colleagues demonstrated that epileptic women taking AEDs had a significantly increased odds of experiencing preeclampsia and preterm delivery, compared with nonepileptic women, while epileptic women not using AEDs did not have higher odds for any outcomes (BJOG 2009;116:1736-42).

"In our study from 2009, carbamazepine was what was prescribed throughout Norway," Dr. Borthen said in an interview. In the current study, which enrolled women taking lamotrigine, carbamazepine, valproate, and polytherapies, women with lamotrigine monotherapy had an unadjusted OR of 7.5 (95% CI, 1.4-39.0) for severe preeclampsia. Women with polytherapy and with lamotrigine monotherapy had an increased risk of early bleeding (unadjusted OR, 8.6; 95% CI, 2.8-26.3 and OR, 6.2; 95% CI, 2.0-19.3, respectively).

"We use lamotrigine because it doesn’t harm the fetus. But maybe it harms the woman instead," Dr. Borthen said, adding that her team is now designing a new study that would enroll all women with epilepsy in Bergen, hoping for a finer picture of risk ascribable to individual drugs.

"It’s so interesting to see why the medication should have such an impact," Dr. Borthen said, adding that it was possible that interactions with folate could play a part. In this study, the vast majority of women with epilepsy and AED use were also taking folate.

Dr. Borthen and her colleagues noted that the proportion of women using AEDs during pregnancy may represent a larger group than epileptic women, as there is "growing use of AEDs for pain and psychiatric conditions."

One limitation of the study, Dr. Borthen and colleagues wrote in their analysis, was a lack of data on seizure type and severity. The study was funded by the Norwegian Research Council. Dr. Borthen and her colleagues declared that they had no conflicts of interest.

People with intracranial aneurysms are more likely to have them rupture after drinking a cup of coffee, said a team of researchers, who suggested that eliminating coffee and making other lifestyle changes might be helpful for people with known intracranial aneurysms.

The researchers also identified vigorous exercise, nose blowing, sexual intercourse, straining to defecate, drinking cola, and being startled or angry as contributing to the immediate risk of rupture – in that order. Among all the triggers, the one with the highest population-attributable risk, or proportion of hemorrhages attributable to the trigger, was 10.6% for coffee consumption, followed by exercise at 7.9%.

Photo credit: Lynda Banzi/Elsevier Global Medical News

Although chronic risk factors for rupture (such as age, female sex, smoking, and alcohol use) have been known to raise the risk of subarachnoid hemorrhage in people with an intracranial aneurysm (IA), only physical exercise had been identified as an immediate trigger. The new study, which was published online May 5 in the journal Stroke, expanded the known triggers for aneurysm rupture, with all eight, its authors noted, associated with short-term increases in blood pressure (Stroke 2011 May 5 [doi:10.1161/ STROKEAHA.110.606558]).

Dr. Monique H.M. Vlak of University Medical Center Utrecht (the Netherlands), the lead author of the study, said in an interview that her team expected to find cigarette smoking to be one of the triggers, based on findings from another study (Stroke 2003;34:1771-6), but they did not.

For their research, Dr. Vlak and colleagues received questionnaires from 250 people who had survived a subarachnoid hemorrhage. Subjects were asked about their exposure to 30 potential triggers in the hour before the hemorrhage, including consuming various caffeinated beverages, smoking, lifting something heavy, becoming angry or surprised, engaging in sexual activity, experiencing temperature change (such as using a sauna), and undertaking vigorous exercise.

Although sexual intercourse and coffee were both associated – independently – with elevated risk in the hour before a rupture, neither masturbation nor tea drinking seemed to matter. However, Dr. Vlak said, few of her study subjects confessed to the former.

"We were also interested to see if Red Bull was a trigger," Dr. Vlak said, referring to the popular energy drink that contains a large amount of caffeine. IA rupture, she noted, affects relatively young people, compared with other cardiovascular events, and the mean age of subjects in this study was 54 years. However, Dr. Vlak said, the number of study subjects who had consumed the drink in the trigger period was too small to matter.

The questionnaire covered the use of the drugs cocaine, marijuana, and sildenafil (Viagra) within 4 hours of the rupture, and any illness or alcohol use within the previous 24 hours. Dr. Vlak said that although cocaine remains a suspected trigger, too few subjects had used it to reach any conclusion.

Subjects were also asked to describe their exposure to all of the potential triggers in the previous year, along with their usual frequency of exposure. The design of the study examined the effect of transient exposure to the potential trigger factors on risk by comparing exposure in the period immediately before the event with the patient’s usual frequency of exposure.

In terms of relative risk, coffee consumption (RR, 1.7; 95% confidence interval, 1.2-2.4), cola consumption (RR, 3.4; 95% CI, 1.5-7.9), anger (RR, 6.3; 95% CI, 1.6-25), becoming startled (RR, 23.3; 95% CI, 4.2-128), straining for defecation (RR, 7.3; 95% CI, 2.9-19), sexual intercourse (RR, 11.2; 95% CI, 5.3-24), nose blowing (RR, 2.3; 95% CI, 1.3-4.5), and vigorous physical exercise (RR, 2.4; 95% CI, 1.2-4.2) were all identified as immediate triggers in the hour before a hemorrhage.

The largest contributors to population-attributable risk were coffee consumption and exercise, followed by nose blowing contributing 5.4%, sexual intercourse contributing 4.3%, straining to defecate contributing 3.6%, cola consumption contributing 3.5%, being startled contributing 2.7%, and being angry contributing 1.3%.

As several of these triggers can be avoided, Dr. Vlak and colleagues wrote in their analysis that "further studies should assess whether reduction of exposure to these factors or measures preventing sudden increase in blood pressure decrease the risk of rupture in patients known to have an intracranial aneurysm."

The authors noted as limitations of their study the relatively long period between the subarachnoid hemorrhage event and subjects’ completion of the questionnaire (about 2 weeks for most subjects), leading to a potential for recall bias.

Also, they noted, the analysis was limited to survivors – the researchers had identified 467 subjects initially, of whom 120 died, another 51 were too disabled afterward to participate, and others dropped out or were excluded for other reasons – allowing for the possibility of survival bias "if certain triggers affect prognosis" after subarachnoid hemorrhage.

A third limitation, Dr. Vlak and colleagues wrote, was the assumption of a 24-hour hazard period for alcohol: "Many patients who reported exposure in the hazard period had a daily intake of at least [one glass] per day and therefore did not contribute to the [relative risk] in the main analysis."

The study was funded by the University Medical Center Utrecht. The authors reported no relevant disclosures.

People with intracranial aneurysms are more likely to have them rupture after drinking a cup of coffee, said a team of researchers, who suggested that eliminating coffee and making other lifestyle changes might be helpful for people with known intracranial aneurysms.

The researchers also identified vigorous exercise, nose blowing, sexual intercourse, straining to defecate, drinking cola, and being startled or angry as contributing to the immediate risk of rupture – in that order. Among all the triggers, the one with the highest population-attributable risk, or proportion of hemorrhages attributable to the trigger, was 10.6% for coffee consumption, followed by exercise at 7.9%.

Photo credit: Lynda Banzi/Elsevier Global Medical News

Although chronic risk factors for rupture (such as age, female sex, smoking, and alcohol use) have been known to raise the risk of subarachnoid hemorrhage in people with an intracranial aneurysm (IA), only physical exercise had been identified as an immediate trigger. The new study, which was published online May 5 in the journal Stroke, expanded the known triggers for aneurysm rupture, with all eight, its authors noted, associated with short-term increases in blood pressure (Stroke 2011 May 5 [doi:10.1161/ STROKEAHA.110.606558]).

Dr. Monique H.M. Vlak of University Medical Center Utrecht (the Netherlands), the lead author of the study, said in an interview that her team expected to find cigarette smoking to be one of the triggers, based on findings from another study (Stroke 2003;34:1771-6), but they did not.

For their research, Dr. Vlak and colleagues received questionnaires from 250 people who had survived a subarachnoid hemorrhage. Subjects were asked about their exposure to 30 potential triggers in the hour before the hemorrhage, including consuming various caffeinated beverages, smoking, lifting something heavy, becoming angry or surprised, engaging in sexual activity, experiencing temperature change (such as using a sauna), and undertaking vigorous exercise.

Although sexual intercourse and coffee were both associated – independently – with elevated risk in the hour before a rupture, neither masturbation nor tea drinking seemed to matter. However, Dr. Vlak said, few of her study subjects confessed to the former.

"We were also interested to see if Red Bull was a trigger," Dr. Vlak said, referring to the popular energy drink that contains a large amount of caffeine. IA rupture, she noted, affects relatively young people, compared with other cardiovascular events, and the mean age of subjects in this study was 54 years. However, Dr. Vlak said, the number of study subjects who had consumed the drink in the trigger period was too small to matter.

The questionnaire covered the use of the drugs cocaine, marijuana, and sildenafil (Viagra) within 4 hours of the rupture, and any illness or alcohol use within the previous 24 hours. Dr. Vlak said that although cocaine remains a suspected trigger, too few subjects had used it to reach any conclusion.

Subjects were also asked to describe their exposure to all of the potential triggers in the previous year, along with their usual frequency of exposure. The design of the study examined the effect of transient exposure to the potential trigger factors on risk by comparing exposure in the period immediately before the event with the patient’s usual frequency of exposure.

In terms of relative risk, coffee consumption (RR, 1.7; 95% confidence interval, 1.2-2.4), cola consumption (RR, 3.4; 95% CI, 1.5-7.9), anger (RR, 6.3; 95% CI, 1.6-25), becoming startled (RR, 23.3; 95% CI, 4.2-128), straining for defecation (RR, 7.3; 95% CI, 2.9-19), sexual intercourse (RR, 11.2; 95% CI, 5.3-24), nose blowing (RR, 2.3; 95% CI, 1.3-4.5), and vigorous physical exercise (RR, 2.4; 95% CI, 1.2-4.2) were all identified as immediate triggers in the hour before a hemorrhage.

The largest contributors to population-attributable risk were coffee consumption and exercise, followed by nose blowing contributing 5.4%, sexual intercourse contributing 4.3%, straining to defecate contributing 3.6%, cola consumption contributing 3.5%, being startled contributing 2.7%, and being angry contributing 1.3%.

As several of these triggers can be avoided, Dr. Vlak and colleagues wrote in their analysis that "further studies should assess whether reduction of exposure to these factors or measures preventing sudden increase in blood pressure decrease the risk of rupture in patients known to have an intracranial aneurysm."

The authors noted as limitations of their study the relatively long period between the subarachnoid hemorrhage event and subjects’ completion of the questionnaire (about 2 weeks for most subjects), leading to a potential for recall bias.

Also, they noted, the analysis was limited to survivors – the researchers had identified 467 subjects initially, of whom 120 died, another 51 were too disabled afterward to participate, and others dropped out or were excluded for other reasons – allowing for the possibility of survival bias "if certain triggers affect prognosis" after subarachnoid hemorrhage.

A third limitation, Dr. Vlak and colleagues wrote, was the assumption of a 24-hour hazard period for alcohol: "Many patients who reported exposure in the hazard period had a daily intake of at least [one glass] per day and therefore did not contribute to the [relative risk] in the main analysis."

The study was funded by the University Medical Center Utrecht. The authors reported no relevant disclosures.

People with intracranial aneurysms are more likely to have them rupture after drinking a cup of coffee, said a team of researchers, who suggested that eliminating coffee and making other lifestyle changes might be helpful for people with known intracranial aneurysms.

The researchers also identified vigorous exercise, nose blowing, sexual intercourse, straining to defecate, drinking cola, and being startled or angry as contributing to the immediate risk of rupture – in that order. Among all the triggers, the one with the highest population-attributable risk, or proportion of hemorrhages attributable to the trigger, was 10.6% for coffee consumption, followed by exercise at 7.9%.

Photo credit: Lynda Banzi/Elsevier Global Medical News

Although chronic risk factors for rupture (such as age, female sex, smoking, and alcohol use) have been known to raise the risk of subarachnoid hemorrhage in people with an intracranial aneurysm (IA), only physical exercise had been identified as an immediate trigger. The new study, which was published online May 5 in the journal Stroke, expanded the known triggers for aneurysm rupture, with all eight, its authors noted, associated with short-term increases in blood pressure (Stroke 2011 May 5 [doi:10.1161/ STROKEAHA.110.606558]).

Dr. Monique H.M. Vlak of University Medical Center Utrecht (the Netherlands), the lead author of the study, said in an interview that her team expected to find cigarette smoking to be one of the triggers, based on findings from another study (Stroke 2003;34:1771-6), but they did not.

For their research, Dr. Vlak and colleagues received questionnaires from 250 people who had survived a subarachnoid hemorrhage. Subjects were asked about their exposure to 30 potential triggers in the hour before the hemorrhage, including consuming various caffeinated beverages, smoking, lifting something heavy, becoming angry or surprised, engaging in sexual activity, experiencing temperature change (such as using a sauna), and undertaking vigorous exercise.

Although sexual intercourse and coffee were both associated – independently – with elevated risk in the hour before a rupture, neither masturbation nor tea drinking seemed to matter. However, Dr. Vlak said, few of her study subjects confessed to the former.

"We were also interested to see if Red Bull was a trigger," Dr. Vlak said, referring to the popular energy drink that contains a large amount of caffeine. IA rupture, she noted, affects relatively young people, compared with other cardiovascular events, and the mean age of subjects in this study was 54 years. However, Dr. Vlak said, the number of study subjects who had consumed the drink in the trigger period was too small to matter.

The questionnaire covered the use of the drugs cocaine, marijuana, and sildenafil (Viagra) within 4 hours of the rupture, and any illness or alcohol use within the previous 24 hours. Dr. Vlak said that although cocaine remains a suspected trigger, too few subjects had used it to reach any conclusion.

Subjects were also asked to describe their exposure to all of the potential triggers in the previous year, along with their usual frequency of exposure. The design of the study examined the effect of transient exposure to the potential trigger factors on risk by comparing exposure in the period immediately before the event with the patient’s usual frequency of exposure.

In terms of relative risk, coffee consumption (RR, 1.7; 95% confidence interval, 1.2-2.4), cola consumption (RR, 3.4; 95% CI, 1.5-7.9), anger (RR, 6.3; 95% CI, 1.6-25), becoming startled (RR, 23.3; 95% CI, 4.2-128), straining for defecation (RR, 7.3; 95% CI, 2.9-19), sexual intercourse (RR, 11.2; 95% CI, 5.3-24), nose blowing (RR, 2.3; 95% CI, 1.3-4.5), and vigorous physical exercise (RR, 2.4; 95% CI, 1.2-4.2) were all identified as immediate triggers in the hour before a hemorrhage.

The largest contributors to population-attributable risk were coffee consumption and exercise, followed by nose blowing contributing 5.4%, sexual intercourse contributing 4.3%, straining to defecate contributing 3.6%, cola consumption contributing 3.5%, being startled contributing 2.7%, and being angry contributing 1.3%.

As several of these triggers can be avoided, Dr. Vlak and colleagues wrote in their analysis that "further studies should assess whether reduction of exposure to these factors or measures preventing sudden increase in blood pressure decrease the risk of rupture in patients known to have an intracranial aneurysm."

The authors noted as limitations of their study the relatively long period between the subarachnoid hemorrhage event and subjects’ completion of the questionnaire (about 2 weeks for most subjects), leading to a potential for recall bias.

Also, they noted, the analysis was limited to survivors – the researchers had identified 467 subjects initially, of whom 120 died, another 51 were too disabled afterward to participate, and others dropped out or were excluded for other reasons – allowing for the possibility of survival bias "if certain triggers affect prognosis" after subarachnoid hemorrhage.

A third limitation, Dr. Vlak and colleagues wrote, was the assumption of a 24-hour hazard period for alcohol: "Many patients who reported exposure in the hazard period had a daily intake of at least [one glass] per day and therefore did not contribute to the [relative risk] in the main analysis."

The study was funded by the University Medical Center Utrecht. The authors reported no relevant disclosures.

People with intracranial aneurysms are more likely to have them rupture after drinking a cup of coffee, said a team of researchers, who suggested that eliminating coffee and making other lifestyle changes might be helpful for people with known intracranial aneurysms.

The researchers also identified vigorous exercise, nose blowing, sexual intercourse, straining to defecate, drinking cola, and being startled or angry as contributing to the immediate risk of rupture – in that order. Among all the triggers, the one with the highest population-attributable risk, or proportion of hemorrhages attributable to the trigger, was 10.6% for coffee consumption, followed by exercise at 7.9%.

Photo credit: Lynda Banzi/Elsevier Global Medical News

Although chronic risk factors for rupture (such as age, female sex, smoking, and alcohol use) have been known to raise the risk of subarachnoid hemorrhage in people with an intracranial aneurysm (IA), only physical exercise had been identified as an immediate trigger. The new study, which was published online May 5 in the journal Stroke, expanded the known triggers for aneurysm rupture, with all eight, its authors noted, associated with short-term increases in blood pressure (Stroke 2011 May 5 [doi:10.1161/ STROKEAHA.110.606558]).

Dr. Monique H.M. Vlak of University Medical Center Utrecht (the Netherlands), the lead author of the study, said in an interview that her team expected to find cigarette smoking to be one of the triggers, based on findings from another study (Stroke 2003;34:1771-6), but they did not.

For their research, Dr. Vlak and colleagues received questionnaires from 250 people who had survived a subarachnoid hemorrhage. Subjects were asked about their exposure to 30 potential triggers in the hour before the hemorrhage, including consuming various caffeinated beverages, smoking, lifting something heavy, becoming angry or surprised, engaging in sexual activity, experiencing temperature change (such as using a sauna), and undertaking vigorous exercise.

Although sexual intercourse and coffee were both associated – independently – with elevated risk in the hour before a rupture, neither masturbation nor tea drinking seemed to matter. However, Dr. Vlak said, few of her study subjects confessed to the former.

"We were also interested to see if Red Bull was a trigger," Dr. Vlak said, referring to the popular energy drink that contains a large amount of caffeine. IA rupture, she noted, affects relatively young people, compared with other cardiovascular events, and the mean age of subjects in this study was 54 years. However, Dr. Vlak said, the number of study subjects who had consumed the drink in the trigger period was too small to matter.

The questionnaire covered the use of the drugs cocaine, marijuana, and sildenafil (Viagra) within 4 hours of the rupture, and any illness or alcohol use within the previous 24 hours. Dr. Vlak said that although cocaine remains a suspected trigger, too few subjects had used it to reach any conclusion.

Subjects were also asked to describe their exposure to all of the potential triggers in the previous year, along with their usual frequency of exposure. The design of the study examined the effect of transient exposure to the potential trigger factors on risk by comparing exposure in the period immediately before the event with the patient’s usual frequency of exposure.

In terms of relative risk, coffee consumption (RR, 1.7; 95% confidence interval, 1.2-2.4), cola consumption (RR, 3.4; 95% CI, 1.5-7.9), anger (RR, 6.3; 95% CI, 1.6-25), becoming startled (RR, 23.3; 95% CI, 4.2-128), straining for defecation (RR, 7.3; 95% CI, 2.9-19), sexual intercourse (RR, 11.2; 95% CI, 5.3-24), nose blowing (RR, 2.3; 95% CI, 1.3-4.5), and vigorous physical exercise (RR, 2.4; 95% CI, 1.2-4.2) were all identified as immediate triggers in the hour before a hemorrhage.

The largest contributors to population-attributable risk were coffee consumption and exercise, followed by nose blowing contributing 5.4%, sexual intercourse contributing 4.3%, straining to defecate contributing 3.6%, cola consumption contributing 3.5%, being startled contributing 2.7%, and being angry contributing 1.3%.

As several of these triggers can be avoided, Dr. Vlak and colleagues wrote in their analysis that "further studies should assess whether reduction of exposure to these factors or measures preventing sudden increase in blood pressure decrease the risk of rupture in patients known to have an intracranial aneurysm."

The authors noted as limitations of their study the relatively long period between the subarachnoid hemorrhage event and subjects’ completion of the questionnaire (about 2 weeks for most subjects), leading to a potential for recall bias.

Also, they noted, the analysis was limited to survivors – the researchers had identified 467 subjects initially, of whom 120 died, another 51 were too disabled afterward to participate, and others dropped out or were excluded for other reasons – allowing for the possibility of survival bias "if certain triggers affect prognosis" after subarachnoid hemorrhage.

A third limitation, Dr. Vlak and colleagues wrote, was the assumption of a 24-hour hazard period for alcohol: "Many patients who reported exposure in the hazard period had a daily intake of at least [one glass] per day and therefore did not contribute to the [relative risk] in the main analysis."

The study was funded by the University Medical Center Utrecht. The authors reported no relevant disclosures.

People with intracranial aneurysms are more likely to have them rupture after drinking a cup of coffee, said a team of researchers, who suggested that eliminating coffee and making other lifestyle changes might be helpful for people with known intracranial aneurysms.

The researchers also identified vigorous exercise, nose blowing, sexual intercourse, straining to defecate, drinking cola, and being startled or angry as contributing to the immediate risk of rupture – in that order. Among all the triggers, the one with the highest population-attributable risk, or proportion of hemorrhages attributable to the trigger, was 10.6% for coffee consumption, followed by exercise at 7.9%.

Photo credit: Lynda Banzi/Elsevier Global Medical News

Although chronic risk factors for rupture (such as age, female sex, smoking, and alcohol use) have been known to raise the risk of subarachnoid hemorrhage in people with an intracranial aneurysm (IA), only physical exercise had been identified as an immediate trigger. The new study, which was published online May 5 in the journal Stroke, expanded the known triggers for aneurysm rupture, with all eight, its authors noted, associated with short-term increases in blood pressure (Stroke 2011 May 5 [doi:10.1161/ STROKEAHA.110.606558]).

Dr. Monique H.M. Vlak of University Medical Center Utrecht (the Netherlands), the lead author of the study, said in an interview that her team expected to find cigarette smoking to be one of the triggers, based on findings from another study (Stroke 2003;34:1771-6), but they did not.

For their research, Dr. Vlak and colleagues received questionnaires from 250 people who had survived a subarachnoid hemorrhage. Subjects were asked about their exposure to 30 potential triggers in the hour before the hemorrhage, including consuming various caffeinated beverages, smoking, lifting something heavy, becoming angry or surprised, engaging in sexual activity, experiencing temperature change (such as using a sauna), and undertaking vigorous exercise.

Although sexual intercourse and coffee were both associated – independently – with elevated risk in the hour before a rupture, neither masturbation nor tea drinking seemed to matter. However, Dr. Vlak said, few of her study subjects confessed to the former.

"We were also interested to see if Red Bull was a trigger," Dr. Vlak said, referring to the popular energy drink that contains a large amount of caffeine. IA rupture, she noted, affects relatively young people, compared with other cardiovascular events, and the mean age of subjects in this study was 54 years. However, Dr. Vlak said, the number of study subjects who had consumed the drink in the trigger period was too small to matter.

The questionnaire covered the use of the drugs cocaine, marijuana, and sildenafil (Viagra) within 4 hours of the rupture, and any illness or alcohol use within the previous 24 hours. Dr. Vlak said that although cocaine remains a suspected trigger, too few subjects had used it to reach any conclusion.

Subjects were also asked to describe their exposure to all of the potential triggers in the previous year, along with their usual frequency of exposure. The design of the study examined the effect of transient exposure to the potential trigger factors on risk by comparing exposure in the period immediately before the event with the patient’s usual frequency of exposure.

In terms of relative risk, coffee consumption (RR, 1.7; 95% confidence interval, 1.2-2.4), cola consumption (RR, 3.4; 95% CI, 1.5-7.9), anger (RR, 6.3; 95% CI, 1.6-25), becoming startled (RR, 23.3; 95% CI, 4.2-128), straining for defecation (RR, 7.3; 95% CI, 2.9-19), sexual intercourse (RR, 11.2; 95% CI, 5.3-24), nose blowing (RR, 2.3; 95% CI, 1.3-4.5), and vigorous physical exercise (RR, 2.4; 95% CI, 1.2-4.2) were all identified as immediate triggers in the hour before a hemorrhage.

The largest contributors to population-attributable risk were coffee consumption and exercise, followed by nose blowing contributing 5.4%, sexual intercourse contributing 4.3%, straining to defecate contributing 3.6%, cola consumption contributing 3.5%, being startled contributing 2.7%, and being angry contributing 1.3%.

As several of these triggers can be avoided, Dr. Vlak and colleagues wrote in their analysis that "further studies should assess whether reduction of exposure to these factors or measures preventing sudden increase in blood pressure decrease the risk of rupture in patients known to have an intracranial aneurysm."

The authors noted as limitations of their study the relatively long period between the subarachnoid hemorrhage event and subjects’ completion of the questionnaire (about 2 weeks for most subjects), leading to a potential for recall bias.

Also, they noted, the analysis was limited to survivors – the researchers had identified 467 subjects initially, of whom 120 died, another 51 were too disabled afterward to participate, and others dropped out or were excluded for other reasons – allowing for the possibility of survival bias "if certain triggers affect prognosis" after subarachnoid hemorrhage.

A third limitation, Dr. Vlak and colleagues wrote, was the assumption of a 24-hour hazard period for alcohol: "Many patients who reported exposure in the hazard period had a daily intake of at least [one glass] per day and therefore did not contribute to the [relative risk] in the main analysis."

The study was funded by the University Medical Center Utrecht. The authors reported no relevant disclosures.

People with intracranial aneurysms are more likely to have them rupture after drinking a cup of coffee, said a team of researchers, who suggested that eliminating coffee and making other lifestyle changes might be helpful for people with known intracranial aneurysms.

The researchers also identified vigorous exercise, nose blowing, sexual intercourse, straining to defecate, drinking cola, and being startled or angry as contributing to the immediate risk of rupture – in that order. Among all the triggers, the one with the highest population-attributable risk, or proportion of hemorrhages attributable to the trigger, was 10.6% for coffee consumption, followed by exercise at 7.9%.

Photo credit: Lynda Banzi/Elsevier Global Medical News

Although chronic risk factors for rupture (such as age, female sex, smoking, and alcohol use) have been known to raise the risk of subarachnoid hemorrhage in people with an intracranial aneurysm (IA), only physical exercise had been identified as an immediate trigger. The new study, which was published online May 5 in the journal Stroke, expanded the known triggers for aneurysm rupture, with all eight, its authors noted, associated with short-term increases in blood pressure (Stroke 2011 May 5 [doi:10.1161/ STROKEAHA.110.606558]).

Dr. Monique H.M. Vlak of University Medical Center Utrecht (the Netherlands), the lead author of the study, said in an interview that her team expected to find cigarette smoking to be one of the triggers, based on findings from another study (Stroke 2003;34:1771-6), but they did not.

For their research, Dr. Vlak and colleagues received questionnaires from 250 people who had survived a subarachnoid hemorrhage. Subjects were asked about their exposure to 30 potential triggers in the hour before the hemorrhage, including consuming various caffeinated beverages, smoking, lifting something heavy, becoming angry or surprised, engaging in sexual activity, experiencing temperature change (such as using a sauna), and undertaking vigorous exercise.

Although sexual intercourse and coffee were both associated – independently – with elevated risk in the hour before a rupture, neither masturbation nor tea drinking seemed to matter. However, Dr. Vlak said, few of her study subjects confessed to the former.

"We were also interested to see if Red Bull was a trigger," Dr. Vlak said, referring to the popular energy drink that contains a large amount of caffeine. IA rupture, she noted, affects relatively young people, compared with other cardiovascular events, and the mean age of subjects in this study was 54 years. However, Dr. Vlak said, the number of study subjects who had consumed the drink in the trigger period was too small to matter.

The questionnaire covered the use of the drugs cocaine, marijuana, and sildenafil (Viagra) within 4 hours of the rupture, and any illness or alcohol use within the previous 24 hours. Dr. Vlak said that although cocaine remains a suspected trigger, too few subjects had used it to reach any conclusion.

Subjects were also asked to describe their exposure to all of the potential triggers in the previous year, along with their usual frequency of exposure. The design of the study examined the effect of transient exposure to the potential trigger factors on risk by comparing exposure in the period immediately before the event with the patient’s usual frequency of exposure.

In terms of relative risk, coffee consumption (RR, 1.7; 95% confidence interval, 1.2-2.4), cola consumption (RR, 3.4; 95% CI, 1.5-7.9), anger (RR, 6.3; 95% CI, 1.6-25), becoming startled (RR, 23.3; 95% CI, 4.2-128), straining for defecation (RR, 7.3; 95% CI, 2.9-19), sexual intercourse (RR, 11.2; 95% CI, 5.3-24), nose blowing (RR, 2.3; 95% CI, 1.3-4.5), and vigorous physical exercise (RR, 2.4; 95% CI, 1.2-4.2) were all identified as immediate triggers in the hour before a hemorrhage.

The largest contributors to population-attributable risk were coffee consumption and exercise, followed by nose blowing contributing 5.4%, sexual intercourse contributing 4.3%, straining to defecate contributing 3.6%, cola consumption contributing 3.5%, being startled contributing 2.7%, and being angry contributing 1.3%.

As several of these triggers can be avoided, Dr. Vlak and colleagues wrote in their analysis that "further studies should assess whether reduction of exposure to these factors or measures preventing sudden increase in blood pressure decrease the risk of rupture in patients known to have an intracranial aneurysm."

The authors noted as limitations of their study the relatively long period between the subarachnoid hemorrhage event and subjects’ completion of the questionnaire (about 2 weeks for most subjects), leading to a potential for recall bias.

Also, they noted, the analysis was limited to survivors – the researchers had identified 467 subjects initially, of whom 120 died, another 51 were too disabled afterward to participate, and others dropped out or were excluded for other reasons – allowing for the possibility of survival bias "if certain triggers affect prognosis" after subarachnoid hemorrhage.

A third limitation, Dr. Vlak and colleagues wrote, was the assumption of a 24-hour hazard period for alcohol: "Many patients who reported exposure in the hazard period had a daily intake of at least [one glass] per day and therefore did not contribute to the [relative risk] in the main analysis."

The study was funded by the University Medical Center Utrecht. The authors reported no relevant disclosures.

People with intracranial aneurysms are more likely to have them rupture after drinking a cup of coffee, said a team of researchers, who suggested that eliminating coffee and making other lifestyle changes might be helpful for people with known intracranial aneurysms.

The researchers also identified vigorous exercise, nose blowing, sexual intercourse, straining to defecate, drinking cola, and being startled or angry as contributing to the immediate risk of rupture – in that order. Among all the triggers, the one with the highest population-attributable risk, or proportion of hemorrhages attributable to the trigger, was 10.6% for coffee consumption, followed by exercise at 7.9%.

Photo credit: Lynda Banzi/Elsevier Global Medical News

Although chronic risk factors for rupture (such as age, female sex, smoking, and alcohol use) have been known to raise the risk of subarachnoid hemorrhage in people with an intracranial aneurysm (IA), only physical exercise had been identified as an immediate trigger. The new study, which was published online May 5 in the journal Stroke, expanded the known triggers for aneurysm rupture, with all eight, its authors noted, associated with short-term increases in blood pressure (Stroke 2011 May 5 [doi:10.1161/ STROKEAHA.110.606558]).

Dr. Monique H.M. Vlak of University Medical Center Utrecht (the Netherlands), the lead author of the study, said in an interview that her team expected to find cigarette smoking to be one of the triggers, based on findings from another study (Stroke 2003;34:1771-6), but they did not.

For their research, Dr. Vlak and colleagues received questionnaires from 250 people who had survived a subarachnoid hemorrhage. Subjects were asked about their exposure to 30 potential triggers in the hour before the hemorrhage, including consuming various caffeinated beverages, smoking, lifting something heavy, becoming angry or surprised, engaging in sexual activity, experiencing temperature change (such as using a sauna), and undertaking vigorous exercise.

Although sexual intercourse and coffee were both associated – independently – with elevated risk in the hour before a rupture, neither masturbation nor tea drinking seemed to matter. However, Dr. Vlak said, few of her study subjects confessed to the former.

"We were also interested to see if Red Bull was a trigger," Dr. Vlak said, referring to the popular energy drink that contains a large amount of caffeine. IA rupture, she noted, affects relatively young people, compared with other cardiovascular events, and the mean age of subjects in this study was 54 years. However, Dr. Vlak said, the number of study subjects who had consumed the drink in the trigger period was too small to matter.

The questionnaire covered the use of the drugs cocaine, marijuana, and sildenafil (Viagra) within 4 hours of the rupture, and any illness or alcohol use within the previous 24 hours. Dr. Vlak said that although cocaine remains a suspected trigger, too few subjects had used it to reach any conclusion.

Subjects were also asked to describe their exposure to all of the potential triggers in the previous year, along with their usual frequency of exposure. The design of the study examined the effect of transient exposure to the potential trigger factors on risk by comparing exposure in the period immediately before the event with the patient’s usual frequency of exposure.

In terms of relative risk, coffee consumption (RR, 1.7; 95% confidence interval, 1.2-2.4), cola consumption (RR, 3.4; 95% CI, 1.5-7.9), anger (RR, 6.3; 95% CI, 1.6-25), becoming startled (RR, 23.3; 95% CI, 4.2-128), straining for defecation (RR, 7.3; 95% CI, 2.9-19), sexual intercourse (RR, 11.2; 95% CI, 5.3-24), nose blowing (RR, 2.3; 95% CI, 1.3-4.5), and vigorous physical exercise (RR, 2.4; 95% CI, 1.2-4.2) were all identified as immediate triggers in the hour before a hemorrhage.

The largest contributors to population-attributable risk were coffee consumption and exercise, followed by nose blowing contributing 5.4%, sexual intercourse contributing 4.3%, straining to defecate contributing 3.6%, cola consumption contributing 3.5%, being startled contributing 2.7%, and being angry contributing 1.3%.

As several of these triggers can be avoided, Dr. Vlak and colleagues wrote in their analysis that "further studies should assess whether reduction of exposure to these factors or measures preventing sudden increase in blood pressure decrease the risk of rupture in patients known to have an intracranial aneurysm."

The authors noted as limitations of their study the relatively long period between the subarachnoid hemorrhage event and subjects’ completion of the questionnaire (about 2 weeks for most subjects), leading to a potential for recall bias.

Also, they noted, the analysis was limited to survivors – the researchers had identified 467 subjects initially, of whom 120 died, another 51 were too disabled afterward to participate, and others dropped out or were excluded for other reasons – allowing for the possibility of survival bias "if certain triggers affect prognosis" after subarachnoid hemorrhage.

A third limitation, Dr. Vlak and colleagues wrote, was the assumption of a 24-hour hazard period for alcohol: "Many patients who reported exposure in the hazard period had a daily intake of at least [one glass] per day and therefore did not contribute to the [relative risk] in the main analysis."

The study was funded by the University Medical Center Utrecht. The authors reported no relevant disclosures.

People with intracranial aneurysms are more likely to have them rupture after drinking a cup of coffee, said a team of researchers, who suggested that eliminating coffee and making other lifestyle changes might be helpful for people with known intracranial aneurysms.

The researchers also identified vigorous exercise, nose blowing, sexual intercourse, straining to defecate, drinking cola, and being startled or angry as contributing to the immediate risk of rupture – in that order. Among all the triggers, the one with the highest population-attributable risk, or proportion of hemorrhages attributable to the trigger, was 10.6% for coffee consumption, followed by exercise at 7.9%.

Photo credit: Lynda Banzi/Elsevier Global Medical News

Although chronic risk factors for rupture (such as age, female sex, smoking, and alcohol use) have been known to raise the risk of subarachnoid hemorrhage in people with an intracranial aneurysm (IA), only physical exercise had been identified as an immediate trigger. The new study, which was published online May 5 in the journal Stroke, expanded the known triggers for aneurysm rupture, with all eight, its authors noted, associated with short-term increases in blood pressure (Stroke 2011 May 5 [doi:10.1161/ STROKEAHA.110.606558]).

Dr. Monique H.M. Vlak of University Medical Center Utrecht (the Netherlands), the lead author of the study, said in an interview that her team expected to find cigarette smoking to be one of the triggers, based on findings from another study (Stroke 2003;34:1771-6), but they did not.

For their research, Dr. Vlak and colleagues received questionnaires from 250 people who had survived a subarachnoid hemorrhage. Subjects were asked about their exposure to 30 potential triggers in the hour before the hemorrhage, including consuming various caffeinated beverages, smoking, lifting something heavy, becoming angry or surprised, engaging in sexual activity, experiencing temperature change (such as using a sauna), and undertaking vigorous exercise.

Although sexual intercourse and coffee were both associated – independently – with elevated risk in the hour before a rupture, neither masturbation nor tea drinking seemed to matter. However, Dr. Vlak said, few of her study subjects confessed to the former.

"We were also interested to see if Red Bull was a trigger," Dr. Vlak said, referring to the popular energy drink that contains a large amount of caffeine. IA rupture, she noted, affects relatively young people, compared with other cardiovascular events, and the mean age of subjects in this study was 54 years. However, Dr. Vlak said, the number of study subjects who had consumed the drink in the trigger period was too small to matter.

The questionnaire covered the use of the drugs cocaine, marijuana, and sildenafil (Viagra) within 4 hours of the rupture, and any illness or alcohol use within the previous 24 hours. Dr. Vlak said that although cocaine remains a suspected trigger, too few subjects had used it to reach any conclusion.

Subjects were also asked to describe their exposure to all of the potential triggers in the previous year, along with their usual frequency of exposure. The design of the study examined the effect of transient exposure to the potential trigger factors on risk by comparing exposure in the period immediately before the event with the patient’s usual frequency of exposure.

In terms of relative risk, coffee consumption (RR, 1.7; 95% confidence interval, 1.2-2.4), cola consumption (RR, 3.4; 95% CI, 1.5-7.9), anger (RR, 6.3; 95% CI, 1.6-25), becoming startled (RR, 23.3; 95% CI, 4.2-128), straining for defecation (RR, 7.3; 95% CI, 2.9-19), sexual intercourse (RR, 11.2; 95% CI, 5.3-24), nose blowing (RR, 2.3; 95% CI, 1.3-4.5), and vigorous physical exercise (RR, 2.4; 95% CI, 1.2-4.2) were all identified as immediate triggers in the hour before a hemorrhage.

The largest contributors to population-attributable risk were coffee consumption and exercise, followed by nose blowing contributing 5.4%, sexual intercourse contributing 4.3%, straining to defecate contributing 3.6%, cola consumption contributing 3.5%, being startled contributing 2.7%, and being angry contributing 1.3%.

As several of these triggers can be avoided, Dr. Vlak and colleagues wrote in their analysis that "further studies should assess whether reduction of exposure to these factors or measures preventing sudden increase in blood pressure decrease the risk of rupture in patients known to have an intracranial aneurysm."

The authors noted as limitations of their study the relatively long period between the subarachnoid hemorrhage event and subjects’ completion of the questionnaire (about 2 weeks for most subjects), leading to a potential for recall bias.

Also, they noted, the analysis was limited to survivors – the researchers had identified 467 subjects initially, of whom 120 died, another 51 were too disabled afterward to participate, and others dropped out or were excluded for other reasons – allowing for the possibility of survival bias "if certain triggers affect prognosis" after subarachnoid hemorrhage.

A third limitation, Dr. Vlak and colleagues wrote, was the assumption of a 24-hour hazard period for alcohol: "Many patients who reported exposure in the hazard period had a daily intake of at least [one glass] per day and therefore did not contribute to the [relative risk] in the main analysis."

The study was funded by the University Medical Center Utrecht. The authors reported no relevant disclosures.

People with intracranial aneurysms are more likely to have them rupture after drinking a cup of coffee, said a team of researchers, who suggested that eliminating coffee and making other lifestyle changes might be helpful for people with known intracranial aneurysms.

The researchers also identified vigorous exercise, nose blowing, sexual intercourse, straining to defecate, drinking cola, and being startled or angry as contributing to the immediate risk of rupture – in that order. Among all the triggers, the one with the highest population-attributable risk, or proportion of hemorrhages attributable to the trigger, was 10.6% for coffee consumption, followed by exercise at 7.9%.

Photo credit: Lynda Banzi/Elsevier Global Medical News

Although chronic risk factors for rupture (such as age, female sex, smoking, and alcohol use) have been known to raise the risk of subarachnoid hemorrhage in people with an intracranial aneurysm (IA), only physical exercise had been identified as an immediate trigger. The new study, which was published online May 5 in the journal Stroke, expanded the known triggers for aneurysm rupture, with all eight, its authors noted, associated with short-term increases in blood pressure (Stroke 2011 May 5 [doi:10.1161/ STROKEAHA.110.606558]).

Dr. Monique H.M. Vlak of University Medical Center Utrecht (the Netherlands), the lead author of the study, said in an interview that her team expected to find cigarette smoking to be one of the triggers, based on findings from another study (Stroke 2003;34:1771-6), but they did not.

For their research, Dr. Vlak and colleagues received questionnaires from 250 people who had survived a subarachnoid hemorrhage. Subjects were asked about their exposure to 30 potential triggers in the hour before the hemorrhage, including consuming various caffeinated beverages, smoking, lifting something heavy, becoming angry or surprised, engaging in sexual activity, experiencing temperature change (such as using a sauna), and undertaking vigorous exercise.

Although sexual intercourse and coffee were both associated – independently – with elevated risk in the hour before a rupture, neither masturbation nor tea drinking seemed to matter. However, Dr. Vlak said, few of her study subjects confessed to the former.

"We were also interested to see if Red Bull was a trigger," Dr. Vlak said, referring to the popular energy drink that contains a large amount of caffeine. IA rupture, she noted, affects relatively young people, compared with other cardiovascular events, and the mean age of subjects in this study was 54 years. However, Dr. Vlak said, the number of study subjects who had consumed the drink in the trigger period was too small to matter.

The questionnaire covered the use of the drugs cocaine, marijuana, and sildenafil (Viagra) within 4 hours of the rupture, and any illness or alcohol use within the previous 24 hours. Dr. Vlak said that although cocaine remains a suspected trigger, too few subjects had used it to reach any conclusion.

Subjects were also asked to describe their exposure to all of the potential triggers in the previous year, along with their usual frequency of exposure. The design of the study examined the effect of transient exposure to the potential trigger factors on risk by comparing exposure in the period immediately before the event with the patient’s usual frequency of exposure.

In terms of relative risk, coffee consumption (RR, 1.7; 95% confidence interval, 1.2-2.4), cola consumption (RR, 3.4; 95% CI, 1.5-7.9), anger (RR, 6.3; 95% CI, 1.6-25), becoming startled (RR, 23.3; 95% CI, 4.2-128), straining for defecation (RR, 7.3; 95% CI, 2.9-19), sexual intercourse (RR, 11.2; 95% CI, 5.3-24), nose blowing (RR, 2.3; 95% CI, 1.3-4.5), and vigorous physical exercise (RR, 2.4; 95% CI, 1.2-4.2) were all identified as immediate triggers in the hour before a hemorrhage.

The largest contributors to population-attributable risk were coffee consumption and exercise, followed by nose blowing contributing 5.4%, sexual intercourse contributing 4.3%, straining to defecate contributing 3.6%, cola consumption contributing 3.5%, being startled contributing 2.7%, and being angry contributing 1.3%.

As several of these triggers can be avoided, Dr. Vlak and colleagues wrote in their analysis that "further studies should assess whether reduction of exposure to these factors or measures preventing sudden increase in blood pressure decrease the risk of rupture in patients known to have an intracranial aneurysm."

The authors noted as limitations of their study the relatively long period between the subarachnoid hemorrhage event and subjects’ completion of the questionnaire (about 2 weeks for most subjects), leading to a potential for recall bias.

Also, they noted, the analysis was limited to survivors – the researchers had identified 467 subjects initially, of whom 120 died, another 51 were too disabled afterward to participate, and others dropped out or were excluded for other reasons – allowing for the possibility of survival bias "if certain triggers affect prognosis" after subarachnoid hemorrhage.

A third limitation, Dr. Vlak and colleagues wrote, was the assumption of a 24-hour hazard period for alcohol: "Many patients who reported exposure in the hazard period had a daily intake of at least [one glass] per day and therefore did not contribute to the [relative risk] in the main analysis."

The study was funded by the University Medical Center Utrecht. The authors reported no relevant disclosures.

The American College of Cardiolo­gy Foundation and the American Heart Association have published updated guidelines for managing pa­tients with unstable angina/non–ST el­evation myocardial infarction, taking into consideration the use of a newer agent, prasugrel, as an alternative to clopidogrel, and recommending diag­nostic angiography sooner for patients at high risk, among other changes.

The guidelines, published March 28in the Journal of the American College of Cardiology  (Am. J. Cardiol. 2011 March 28 [doi:10.1016/j.jacc.2011.02.009]) and based on the most recent clinical trial ev­idence available, update recommenda­tions from 2007, and include several changes clinicians should be aware of, the guidelines’ lead author, Dr. R. Scott Wright of the Mayo Clinic in Rochester, Minn., said in an e-mail interview. These are, in order of importance:

• The timing of invasive therapy in medium- and high-risk patients.
• The role of triple- vs. dual-antiplatelet therapy in patients at medium and high risk.
• The role of invasive therapy in pa­tients with chronic kidney disease.
• The importance of participating in quality improvement processes.
• The role of prasugrel in non–ST ele­vation acute coronary syndrome.

Clinicians face tough decisions about when to perform an invasive strategy such as diagnostic coronary angiography – whether within hours of presentation or days, Dr. Wright and his colleagues wrote in their analysis.

Immediate catheterization with revas­cularization of unstable coronary lesions may prevent ischemic events that would otherwise occur during medical therapy – but pretreatment with antithrombotics “may diminish thrombus burden and ‘passivate’ unstable plaques,” improving the safety of the procedure and reducing the risk of ischemic complications.

<[stk 2]>The new guidelines, based on findings from three randomized controlled trials evaluating the timing of angiography, recommend an early invasive strategy (12-24 hours after presentation) over a delayed invasive strategy (more than 24 hours after presentation) for initially stabilized high-risk patients with UA/NSTEMI. <[etk]>

“For patients not at high risk, a delayed invasive approach is also reasonable,” Dr. Wright and his colleagues wrote.

Several changes to earlier recommen­dations for antiplatelet therapy are con­tained in the new guidelines, including altered loading doses for clopidogrel to counter the potential for the drug to be less effective in some patient groups, and the addition of prasugrel, which was approved by the Food and Drug Ad­ministration after the last guidelines were published.

Prasugrel, in a randomized controlled trial comparing it with clopidogrel, was shown to be superior in reducing clinical events but at the expense of an increased risk of bleeding, the guideline writers noted.

In March 2010 the FDA issued a warn­ing that in some patient groups clopido­grel is less effective than it should be because of a genetic variant that inhibits the body’s conversion of the prodrug to the drug.

However, Dr. Wright and his col­leagues stopped short of endorsing pra­sugrel as a first choice over clopidogrel because of the higher bleeding risk and other considerations. People aged 75 years or older, those with a history of transient ischemic attack or stroke or with active pathological bleeding, and people weighing less than 60 kg saw no benefit and/or net harm from prasugrel, they noted.

Dr. Wright and his colleagues also changed recommendations involving glycoprotein IIB/IIIa inhibitors, noting that recent studies “more strongly sup­port a strategy of selective rather than provisional use of GP IIb/IIIa inhibitor
therapy as part of triple-antiplatelet ther­apy,” due to concerns about the poten­tial bleeding risks. Therefore, according to the new guidelines, for UA/NSTEMI patients who are at low risk of ischemic events or at high risk of bleeding and who are already receiving aspirin and clopidogrel, upstream GP IIb/IIIa in­hibitors are not recommended.

People with kidney disease should re­ceive adequate preparatory hydration before catheterization, say the new guidelines, which also tweak earlier recommendations about the contrast agents used in angiography.

Finally, the guidelines recommend that clinicians and hospitals “participate in a standardized quality-of-care data registry designed to track and measure outcomes, complications, and adherence to evidence-based processes of care and quality improvement for UA/NSTEMI.” No such recommendation had been included in the 2007 guidelines.

I have checked the following facts in my story: (Please initial each.)

<[stk 1]>Dr. Wright declared no conflicts of in­terest. Several of Dr. Wright’s coau­thors, including Dr. Jeffrey L. Anderson, the writing committee’s vice chair, dis­closed consultant relationships with pharmaceutical firms Sanofi-Aventis, Bristol Myers-Squibb, Lilly, and Daiichi. Members with conflicts were not per­mitted to vote on recommended drug therapies.

The American College of Cardiolo­gy Foundation and the American Heart Association have published updated guidelines for managing pa­tients with unstable angina/non–ST el­evation myocardial infarction, taking into consideration the use of a newer agent, prasugrel, as an alternative to clopidogrel, and recommending diag­nostic angiography sooner for patients at high risk, among other changes.

The guidelines, published March 28in the Journal of the American College of Cardiology  (Am. J. Cardiol. 2011 March 28 [doi:10.1016/j.jacc.2011.02.009]) and based on the most recent clinical trial ev­idence available, update recommenda­tions from 2007, and include several changes clinicians should be aware of, the guidelines’ lead author, Dr. R. Scott Wright of the Mayo Clinic in Rochester, Minn., said in an e-mail interview. These are, in order of importance:

• The timing of invasive therapy in medium- and high-risk patients.
• The role of triple- vs. dual-antiplatelet therapy in patients at medium and high risk.
• The role of invasive therapy in pa­tients with chronic kidney disease.
• The importance of participating in quality improvement processes.
• The role of prasugrel in non–ST ele­vation acute coronary syndrome.

Clinicians face tough decisions about when to perform an invasive strategy such as diagnostic coronary angiography – whether within hours of presentation or days, Dr. Wright and his colleagues wrote in their analysis.

Immediate catheterization with revas­cularization of unstable coronary lesions may prevent ischemic events that would otherwise occur during medical therapy – but pretreatment with antithrombotics “may diminish thrombus burden and ‘passivate’ unstable plaques,” improving the safety of the procedure and reducing the risk of ischemic complications.

<[stk 2]>The new guidelines, based on findings from three randomized controlled trials evaluating the timing of angiography, recommend an early invasive strategy (12-24 hours after presentation) over a delayed invasive strategy (more than 24 hours after presentation) for initially stabilized high-risk patients with UA/NSTEMI. <[etk]>

“For patients not at high risk, a delayed invasive approach is also reasonable,” Dr. Wright and his colleagues wrote.

Several changes to earlier recommen­dations for antiplatelet therapy are con­tained in the new guidelines, including altered loading doses for clopidogrel to counter the potential for the drug to be less effective in some patient groups, and the addition of prasugrel, which was approved by the Food and Drug Ad­ministration after the last guidelines were published.

Prasugrel, in a randomized controlled trial comparing it with clopidogrel, was shown to be superior in reducing clinical events but at the expense of an increased risk of bleeding, the guideline writers noted.

In March 2010 the FDA issued a warn­ing that in some patient groups clopido­grel is less effective than it should be because of a genetic variant that inhibits the body’s conversion of the prodrug to the drug.

However, Dr. Wright and his col­leagues stopped short of endorsing pra­sugrel as a first choice over clopidogrel because of the higher bleeding risk and other considerations. People aged 75 years or older, those with a history of transient ischemic attack or stroke or with active pathological bleeding, and people weighing less than 60 kg saw no benefit and/or net harm from prasugrel, they noted.

Dr. Wright and his colleagues also changed recommendations involving glycoprotein IIB/IIIa inhibitors, noting that recent studies “more strongly sup­port a strategy of selective rather than provisional use of GP IIb/IIIa inhibitor
therapy as part of triple-antiplatelet ther­apy,” due to concerns about the poten­tial bleeding risks. Therefore, according to the new guidelines, for UA/NSTEMI patients who are at low risk of ischemic events or at high risk of bleeding and who are already receiving aspirin and clopidogrel, upstream GP IIb/IIIa in­hibitors are not recommended.

People with kidney disease should re­ceive adequate preparatory hydration before catheterization, say the new guidelines, which also tweak earlier recommendations about the contrast agents used in angiography.

Finally, the guidelines recommend that clinicians and hospitals “participate in a standardized quality-of-care data registry designed to track and measure outcomes, complications, and adherence to evidence-based processes of care and quality improvement for UA/NSTEMI.” No such recommendation had been included in the 2007 guidelines.

I have checked the following facts in my story: (Please initial each.)

<[stk 1]>Dr. Wright declared no conflicts of in­terest. Several of Dr. Wright’s coau­thors, including Dr. Jeffrey L. Anderson, the writing committee’s vice chair, dis­closed consultant relationships with pharmaceutical firms Sanofi-Aventis, Bristol Myers-Squibb, Lilly, and Daiichi. Members with conflicts were not per­mitted to vote on recommended drug therapies.

The American College of Cardiolo­gy Foundation and the American Heart Association have published updated guidelines for managing pa­tients with unstable angina/non–ST el­evation myocardial infarction, taking into consideration the use of a newer agent, prasugrel, as an alternative to clopidogrel, and recommending diag­nostic angiography sooner for patients at high risk, among other changes.

The guidelines, published March 28in the Journal of the American College of Cardiology  (Am. J. Cardiol. 2011 March 28 [doi:10.1016/j.jacc.2011.02.009]) and based on the most recent clinical trial ev­idence available, update recommenda­tions from 2007, and include several changes clinicians should be aware of, the guidelines’ lead author, Dr. R. Scott Wright of the Mayo Clinic in Rochester, Minn., said in an e-mail interview. These are, in order of importance:

• The timing of invasive therapy in medium- and high-risk patients.
• The role of triple- vs. dual-antiplatelet therapy in patients at medium and high risk.
• The role of invasive therapy in pa­tients with chronic kidney disease.
• The importance of participating in quality improvement processes.
• The role of prasugrel in non–ST ele­vation acute coronary syndrome.

Clinicians face tough decisions about when to perform an invasive strategy such as diagnostic coronary angiography – whether within hours of presentation or days, Dr. Wright and his colleagues wrote in their analysis.

Immediate catheterization with revas­cularization of unstable coronary lesions may prevent ischemic events that would otherwise occur during medical therapy – but pretreatment with antithrombotics “may diminish thrombus burden and ‘passivate’ unstable plaques,” improving the safety of the procedure and reducing the risk of ischemic complications.

<[stk 2]>The new guidelines, based on findings from three randomized controlled trials evaluating the timing of angiography, recommend an early invasive strategy (12-24 hours after presentation) over a delayed invasive strategy (more than 24 hours after presentation) for initially stabilized high-risk patients with UA/NSTEMI. <[etk]>

“For patients not at high risk, a delayed invasive approach is also reasonable,” Dr. Wright and his colleagues wrote.

Several changes to earlier recommen­dations for antiplatelet therapy are con­tained in the new guidelines, including altered loading doses for clopidogrel to counter the potential for the drug to be less effective in some patient groups, and the addition of prasugrel, which was approved by the Food and Drug Ad­ministration after the last guidelines were published.

Prasugrel, in a randomized controlled trial comparing it with clopidogrel, was shown to be superior in reducing clinical events but at the expense of an increased risk of bleeding, the guideline writers noted.

In March 2010 the FDA issued a warn­ing that in some patient groups clopido­grel is less effective than it should be because of a genetic variant that inhibits the body’s conversion of the prodrug to the drug.

However, Dr. Wright and his col­leagues stopped short of endorsing pra­sugrel as a first choice over clopidogrel because of the higher bleeding risk and other considerations. People aged 75 years or older, those with a history of transient ischemic attack or stroke or with active pathological bleeding, and people weighing less than 60 kg saw no benefit and/or net harm from prasugrel, they noted.

Dr. Wright and his colleagues also changed recommendations involving glycoprotein IIB/IIIa inhibitors, noting that recent studies “more strongly sup­port a strategy of selective rather than provisional use of GP IIb/IIIa inhibitor
therapy as part of triple-antiplatelet ther­apy,” due to concerns about the poten­tial bleeding risks. Therefore, according to the new guidelines, for UA/NSTEMI patients who are at low risk of ischemic events or at high risk of bleeding and who are already receiving aspirin and clopidogrel, upstream GP IIb/IIIa in­hibitors are not recommended.

People with kidney disease should re­ceive adequate preparatory hydration before catheterization, say the new guidelines, which also tweak earlier recommendations about the contrast agents used in angiography.

Finally, the guidelines recommend that clinicians and hospitals “participate in a standardized quality-of-care data registry designed to track and measure outcomes, complications, and adherence to evidence-based processes of care and quality improvement for UA/NSTEMI.” No such recommendation had been included in the 2007 guidelines.

I have checked the following facts in my story: (Please initial each.)

<[stk 1]>Dr. Wright declared no conflicts of in­terest. Several of Dr. Wright’s coau­thors, including Dr. Jeffrey L. Anderson, the writing committee’s vice chair, dis­closed consultant relationships with pharmaceutical firms Sanofi-Aventis, Bristol Myers-Squibb, Lilly, and Daiichi. Members with conflicts were not per­mitted to vote on recommended drug therapies.

Triglyceride levels, which play a large role in both atherosclerotic risk and metabolic health, are highly responsive to decreases in dietary sugar intake and saturated and trans fat intake, along with increases in omega-3 acid intake and exercise, according to a scientific statement from the American Heart Association.

“What's new is that we point out that triglycerides might be considered a marker for metabolic health,” Dr. Neil J. Stone of Northwestern University, Chicago, vice chair of the statement's writing group, said in an interview. “If you have a country where you're seeing more obesity and more diabetes, it becomes important for people to start asking themselves 'are there signs that I should be doing something different?' and this is one,” he said.

The scientific advisory, citing some 528 sources, was not presented as a clinical guideline so much as a distillation of 30 years worth of evidence on the complex relationship among lifestyle factors, triglycerides, and cardiovascular and metabolic health (Circulation 2011 [doi:10.1161/CIR.0b013e3182160726]).

However, the authors, led by Dr. Michael Miller, director of the Center for Preventive Cardiology at the University of Maryland, Baltimore, included a number of recommendations on diagnosing and treating hypertriglyceridemia, focusing on dietary and lifestyle changes.

The statement emphasizes the “increasingly crucial role” of triglycerides in the evaluation and management of cardiovascular disease, and the importance of diet – including consumption of sugars common in beverages – in contributing to unhealthy triglyceride levels.

Reductions of 50% or more are achievable without the use of medication – indeed medication is not a widely accepted strategy for reducing triglycerides except among people with values of greater than 500 mg/dL. “The subject of medication and triglycerides is still lacking crucial clinical trial evidence,” Dr. Miller and colleagues wrote in their analysis, noting that certain medications, including hormonal treatments, can also contribute to elevated triglycerides.

About a third of American adults have elevated triglyceride levels, which are defined as fasting triglyceride of 150 mg/dL or higher. The authors recommended that optimal fasting triglyceride levels now be defined as 100 mg/dL – and that clinicians screen initially for nonfasting triglyceride, defining normal at below 200 mg/dL. People with higher nonfasting levels may then be further screened for fasting triglyceride.

The new dietary recommendations include restricting added dietary sugar to 5%-10% percent of calories consumed. In support of this, the authors cited a study of 6,113 U.S. adults showing that the lowest triglyceride levels were observed when added sugar represented less than 10% of total energy, and that higher triglyceride levels corresponded with added sugar accounting for a greater proportion of energy intake (JAMA 2010;303:1490-7).

The authors singled out fructose as particularly problematic. Fructose in excess of 100 g/day, and possibly in excess of 50 g/day, has been associated with raised triglyceride levels. A typical can of cola or lemon-lime soda contains more than 20 g of fructose, the authors noted.

Dr. Miller and his colleagues advocated weight loss of 5%-10% of body weight, which is associated with a 20% reduction in triglycerides, and regular aerobic exercise, to reduce triglyceride levels closer to optimal. They also promoted increasing dietary fiber, keeping saturated fat below 7% of calories, eliminating trans fat from the diet, and increasing omega-3 polyunsaturated fatty acid consumption in the form of marine fish.

Funding for the statement was provided by the American Heart Association. Dr. Miller declared no conflicts affecting the drafting of the statement. Dr. Stone and the report's third author, Dr. Christie Ballantyne of Baylor College of Medicine in Houston, disclosed support from pharmaceutical industry sources. Other coauthors and some reviewers disclosed additional support from pharmaceutical and agricultural firms.

View on the News

Link to Cardiovascular Risk Is Weak

While epidemiological studies have shown triglycerides to be an independent risk factor for cardiovascular disease, most of the residual risk associated with hypertriglyceridemia tends to disappear after controlling for HDL cholesterol. Current National Cholesterol Education Program guidelines do not identify triglycerides as a specific target, except when levels are extremely elevated. Drugs that reduce triglycerides may also affect other lipoprotein concentrations, and clinical trial evidence demonstrating that triglyceride reduction decreases cardiovascular risk is lacking.

For example, analysis of the VA-HIT trial showed that coronary event reduction was due to increases in HDL cholesterol achieved with the study drug and was not associated with reductions in triglycerides (JAMA 2001;285:1585-91).

Thus, while the AHA statement's stringent dietary and lifestyle recommendations should have healthful effects, the evidence linking the expected decrease in triglycerides to cardiovascular benefit is weak.

Perhaps the high prevalence of hypertriglyceridemia in patients with the metabolic syndrome accounts for the intensity of these recommendations, in which case I applaud this attempt.

ANTONIO M. GOTTO JR., M.D., is the dean of Weill Cornell Medical College, New York. He is a consultant for AstraZeneca, KOWA, and Merck; is on the Board of Directors for Aegerion Pharmaceuticals and Arisaph Pharmaceuticals; and is on advisory boards for DuPont and Vatera Capital.

Vitals

Triglyceride levels, which play a large role in both atherosclerotic risk and metabolic health, are highly responsive to decreases in dietary sugar intake and saturated and trans fat intake, along with increases in omega-3 acid intake and exercise, according to a scientific statement from the American Heart Association.

“What's new is that we point out that triglycerides might be considered a marker for metabolic health,” Dr. Neil J. Stone of Northwestern University, Chicago, vice chair of the statement's writing group, said in an interview. “If you have a country where you're seeing more obesity and more diabetes, it becomes important for people to start asking themselves 'are there signs that I should be doing something different?' and this is one,” he said.

The scientific advisory, citing some 528 sources, was not presented as a clinical guideline so much as a distillation of 30 years worth of evidence on the complex relationship among lifestyle factors, triglycerides, and cardiovascular and metabolic health (Circulation 2011 [doi:10.1161/CIR.0b013e3182160726]).

However, the authors, led by Dr. Michael Miller, director of the Center for Preventive Cardiology at the University of Maryland, Baltimore, included a number of recommendations on diagnosing and treating hypertriglyceridemia, focusing on dietary and lifestyle changes.

The statement emphasizes the “increasingly crucial role” of triglycerides in the evaluation and management of cardiovascular disease, and the importance of diet – including consumption of sugars common in beverages – in contributing to unhealthy triglyceride levels.

Reductions of 50% or more are achievable without the use of medication – indeed medication is not a widely accepted strategy for reducing triglycerides except among people with values of greater than 500 mg/dL. “The subject of medication and triglycerides is still lacking crucial clinical trial evidence,” Dr. Miller and colleagues wrote in their analysis, noting that certain medications, including hormonal treatments, can also contribute to elevated triglycerides.

About a third of American adults have elevated triglyceride levels, which are defined as fasting triglyceride of 150 mg/dL or higher. The authors recommended that optimal fasting triglyceride levels now be defined as 100 mg/dL – and that clinicians screen initially for nonfasting triglyceride, defining normal at below 200 mg/dL. People with higher nonfasting levels may then be further screened for fasting triglyceride.

The new dietary recommendations include restricting added dietary sugar to 5%-10% percent of calories consumed. In support of this, the authors cited a study of 6,113 U.S. adults showing that the lowest triglyceride levels were observed when added sugar represented less than 10% of total energy, and that higher triglyceride levels corresponded with added sugar accounting for a greater proportion of energy intake (JAMA 2010;303:1490-7).

The authors singled out fructose as particularly problematic. Fructose in excess of 100 g/day, and possibly in excess of 50 g/day, has been associated with raised triglyceride levels. A typical can of cola or lemon-lime soda contains more than 20 g of fructose, the authors noted.

Dr. Miller and his colleagues advocated weight loss of 5%-10% of body weight, which is associated with a 20% reduction in triglycerides, and regular aerobic exercise, to reduce triglyceride levels closer to optimal. They also promoted increasing dietary fiber, keeping saturated fat below 7% of calories, eliminating trans fat from the diet, and increasing omega-3 polyunsaturated fatty acid consumption in the form of marine fish.

Funding for the statement was provided by the American Heart Association. Dr. Miller declared no conflicts affecting the drafting of the statement. Dr. Stone and the report's third author, Dr. Christie Ballantyne of Baylor College of Medicine in Houston, disclosed support from pharmaceutical industry sources. Other coauthors and some reviewers disclosed additional support from pharmaceutical and agricultural firms.

View on the News

Link to Cardiovascular Risk Is Weak

While epidemiological studies have shown triglycerides to be an independent risk factor for cardiovascular disease, most of the residual risk associated with hypertriglyceridemia tends to disappear after controlling for HDL cholesterol. Current National Cholesterol Education Program guidelines do not identify triglycerides as a specific target, except when levels are extremely elevated. Drugs that reduce triglycerides may also affect other lipoprotein concentrations, and clinical trial evidence demonstrating that triglyceride reduction decreases cardiovascular risk is lacking.

For example, analysis of the VA-HIT trial showed that coronary event reduction was due to increases in HDL cholesterol achieved with the study drug and was not associated with reductions in triglycerides (JAMA 2001;285:1585-91).

Thus, while the AHA statement's stringent dietary and lifestyle recommendations should have healthful effects, the evidence linking the expected decrease in triglycerides to cardiovascular benefit is weak.

Perhaps the high prevalence of hypertriglyceridemia in patients with the metabolic syndrome accounts for the intensity of these recommendations, in which case I applaud this attempt.

ANTONIO M. GOTTO JR., M.D., is the dean of Weill Cornell Medical College, New York. He is a consultant for AstraZeneca, KOWA, and Merck; is on the Board of Directors for Aegerion Pharmaceuticals and Arisaph Pharmaceuticals; and is on advisory boards for DuPont and Vatera Capital.

Vitals

Triglyceride levels, which play a large role in both atherosclerotic risk and metabolic health, are highly responsive to decreases in dietary sugar intake and saturated and trans fat intake, along with increases in omega-3 acid intake and exercise, according to a scientific statement from the American Heart Association.

“What's new is that we point out that triglycerides might be considered a marker for metabolic health,” Dr. Neil J. Stone of Northwestern University, Chicago, vice chair of the statement's writing group, said in an interview. “If you have a country where you're seeing more obesity and more diabetes, it becomes important for people to start asking themselves 'are there signs that I should be doing something different?' and this is one,” he said.

The scientific advisory, citing some 528 sources, was not presented as a clinical guideline so much as a distillation of 30 years worth of evidence on the complex relationship among lifestyle factors, triglycerides, and cardiovascular and metabolic health (Circulation 2011 [doi:10.1161/CIR.0b013e3182160726]).

However, the authors, led by Dr. Michael Miller, director of the Center for Preventive Cardiology at the University of Maryland, Baltimore, included a number of recommendations on diagnosing and treating hypertriglyceridemia, focusing on dietary and lifestyle changes.

The statement emphasizes the “increasingly crucial role” of triglycerides in the evaluation and management of cardiovascular disease, and the importance of diet – including consumption of sugars common in beverages – in contributing to unhealthy triglyceride levels.

Reductions of 50% or more are achievable without the use of medication – indeed medication is not a widely accepted strategy for reducing triglycerides except among people with values of greater than 500 mg/dL. “The subject of medication and triglycerides is still lacking crucial clinical trial evidence,” Dr. Miller and colleagues wrote in their analysis, noting that certain medications, including hormonal treatments, can also contribute to elevated triglycerides.

About a third of American adults have elevated triglyceride levels, which are defined as fasting triglyceride of 150 mg/dL or higher. The authors recommended that optimal fasting triglyceride levels now be defined as 100 mg/dL – and that clinicians screen initially for nonfasting triglyceride, defining normal at below 200 mg/dL. People with higher nonfasting levels may then be further screened for fasting triglyceride.

The new dietary recommendations include restricting added dietary sugar to 5%-10% percent of calories consumed. In support of this, the authors cited a study of 6,113 U.S. adults showing that the lowest triglyceride levels were observed when added sugar represented less than 10% of total energy, and that higher triglyceride levels corresponded with added sugar accounting for a greater proportion of energy intake (JAMA 2010;303:1490-7).

The authors singled out fructose as particularly problematic. Fructose in excess of 100 g/day, and possibly in excess of 50 g/day, has been associated with raised triglyceride levels. A typical can of cola or lemon-lime soda contains more than 20 g of fructose, the authors noted.

Dr. Miller and his colleagues advocated weight loss of 5%-10% of body weight, which is associated with a 20% reduction in triglycerides, and regular aerobic exercise, to reduce triglyceride levels closer to optimal. They also promoted increasing dietary fiber, keeping saturated fat below 7% of calories, eliminating trans fat from the diet, and increasing omega-3 polyunsaturated fatty acid consumption in the form of marine fish.

Funding for the statement was provided by the American Heart Association. Dr. Miller declared no conflicts affecting the drafting of the statement. Dr. Stone and the report's third author, Dr. Christie Ballantyne of Baylor College of Medicine in Houston, disclosed support from pharmaceutical industry sources. Other coauthors and some reviewers disclosed additional support from pharmaceutical and agricultural firms.

View on the News

Link to Cardiovascular Risk Is Weak

While epidemiological studies have shown triglycerides to be an independent risk factor for cardiovascular disease, most of the residual risk associated with hypertriglyceridemia tends to disappear after controlling for HDL cholesterol. Current National Cholesterol Education Program guidelines do not identify triglycerides as a specific target, except when levels are extremely elevated. Drugs that reduce triglycerides may also affect other lipoprotein concentrations, and clinical trial evidence demonstrating that triglyceride reduction decreases cardiovascular risk is lacking.

For example, analysis of the VA-HIT trial showed that coronary event reduction was due to increases in HDL cholesterol achieved with the study drug and was not associated with reductions in triglycerides (JAMA 2001;285:1585-91).

Thus, while the AHA statement's stringent dietary and lifestyle recommendations should have healthful effects, the evidence linking the expected decrease in triglycerides to cardiovascular benefit is weak.

Perhaps the high prevalence of hypertriglyceridemia in patients with the metabolic syndrome accounts for the intensity of these recommendations, in which case I applaud this attempt.

ANTONIO M. GOTTO JR., M.D., is the dean of Weill Cornell Medical College, New York. He is a consultant for AstraZeneca, KOWA, and Merck; is on the Board of Directors for Aegerion Pharmaceuticals and Arisaph Pharmaceuticals; and is on advisory boards for DuPont and Vatera Capital.

Vitals

The American College of Cardiology Foundation and the American Heart Association have published updated guidelines for managing patients with unstable angina/non–ST elevation myocardial infarction, taking into consideration the use of a newer agent, prasugrel, as an alternative to clopidogrel, and recommending diagnostic angiography sooner for patients at high risk, among other changes.

The guidelines (Am. J. Cardiol. 2011 March 28 [doi:10.1016/j.jacc.2011.02.009]) are based on the most recent clinical trial evidence available., They update recommendations from 2007, and include several changes clinicians should be aware of, the guidelines' lead author, Dr. R. Scott Wright of the Mayo Clinic in Rochester, Minn., said in an e-mail interview. These are, in order of importance:

▸ The timing of invasive therapy in medium- and high-risk patients.

▸ The role of triple- vs. dual-antiplatelet therapy in patients at medium and high risk.

▸ The role of invasive therapy in patients with chronic kidney disease.

▸ The importance of participating in quality improvement processes.

▸ The role of prasugrel in non–ST elevation acute coronary syndrome.

Clinicians face tough decisions about when to use an invasive strategy such as diagnostic coronary angiography – whether within hours of presentation or days, Dr. Wright and his colleagues wrote in their analysis. Immediate catheterization with revascularization of unstable coronary lesions may prevent ischemic events that would otherwise occur during medical therapy – but pretreatment with antithrombotics “may diminish thrombus burden and 'passivate' unstable plaques,” improving the safety of the procedure and reducing the risk of ischemic complications.

The new guidelines, based on three randomized controlled trials evaluating the timing of angiography, recommend an early invasive strategy (12-24 hours after presentation) over a delayed invasive strategy (more than 24 hours after presentation) for initially stabilized high-risk patients with UA/NSTEMI.

“For patients not at high risk, a delayed invasive approach is also reasonable,” Dr. Wright and his colleagues wrote.

Several changes to earlier recommendations for antiplatelet therapy are contained in the new guidelines, including altered loading doses for clopidogrel to counter the potential for the drug to be less effective in some patient groups, and the addition of prasugrel, which was approved by the Food and Drug Administration after the last guidelines were published.

Prasugrel, in a randomized controlled trial comparing it with clopidogrel, was shown to be superior in reducing clinical events but at the expense of an increased risk of bleeding, the guideline writers noted. In March 2010 the FDA issued a warning that in some patient groups clopidogrel is less effective than it should be because of a genetic variant that inhibits the body's conversion of the prodrug to the drug.

However, Dr. Wright and his colleagues stopped short of endorsing prasugrel as a first choice over clopidogrel because of the higher bleeding risk and other considerations. People aged 75 years or older, those with a history of transient ischemic attack or stroke or with active pathological bleeding, and people weighing less than 60 kg saw no benefit and/or net harm from prasugrel, they noted.

Dr. Wright and his colleagues also changed recommendations involving glycoprotein IIB/IIIa inhibitors, noting that recent studies “more strongly support a strategy of selective rather than provisional use of GP IIb/IIIa inhibitor therapy as part of triple-antiplatelet therapy,” due to concerns about the potential bleeding risks.

Dr. Wright declared no conflicts of interest. Several of Dr. Wright's coauthors, including Dr. Jeffrey L. Anderson, the writing committee's vice chair, disclosed consultant relationships with pharmaceutical firms Sanofi-Aventis, Bristol Myers-Squibb, Lilly, and Daiichi. Members with conflicts were not permitted to vote on recommended drug therapies.

The American College of Cardiology Foundation and the American Heart Association have published updated guidelines for managing patients with unstable angina/non–ST elevation myocardial infarction, taking into consideration the use of a newer agent, prasugrel, as an alternative to clopidogrel, and recommending diagnostic angiography sooner for patients at high risk, among other changes.

The guidelines (Am. J. Cardiol. 2011 March 28 [doi:10.1016/j.jacc.2011.02.009]) are based on the most recent clinical trial evidence available., They update recommendations from 2007, and include several changes clinicians should be aware of, the guidelines' lead author, Dr. R. Scott Wright of the Mayo Clinic in Rochester, Minn., said in an e-mail interview. These are, in order of importance:

▸ The timing of invasive therapy in medium- and high-risk patients.

▸ The role of triple- vs. dual-antiplatelet therapy in patients at medium and high risk.

▸ The role of invasive therapy in patients with chronic kidney disease.

▸ The importance of participating in quality improvement processes.

▸ The role of prasugrel in non–ST elevation acute coronary syndrome.

Clinicians face tough decisions about when to use an invasive strategy such as diagnostic coronary angiography – whether within hours of presentation or days, Dr. Wright and his colleagues wrote in their analysis. Immediate catheterization with revascularization of unstable coronary lesions may prevent ischemic events that would otherwise occur during medical therapy – but pretreatment with antithrombotics “may diminish thrombus burden and 'passivate' unstable plaques,” improving the safety of the procedure and reducing the risk of ischemic complications.

The new guidelines, based on three randomized controlled trials evaluating the timing of angiography, recommend an early invasive strategy (12-24 hours after presentation) over a delayed invasive strategy (more than 24 hours after presentation) for initially stabilized high-risk patients with UA/NSTEMI.

“For patients not at high risk, a delayed invasive approach is also reasonable,” Dr. Wright and his colleagues wrote.

Several changes to earlier recommendations for antiplatelet therapy are contained in the new guidelines, including altered loading doses for clopidogrel to counter the potential for the drug to be less effective in some patient groups, and the addition of prasugrel, which was approved by the Food and Drug Administration after the last guidelines were published.

Prasugrel, in a randomized controlled trial comparing it with clopidogrel, was shown to be superior in reducing clinical events but at the expense of an increased risk of bleeding, the guideline writers noted. In March 2010 the FDA issued a warning that in some patient groups clopidogrel is less effective than it should be because of a genetic variant that inhibits the body's conversion of the prodrug to the drug.

However, Dr. Wright and his colleagues stopped short of endorsing prasugrel as a first choice over clopidogrel because of the higher bleeding risk and other considerations. People aged 75 years or older, those with a history of transient ischemic attack or stroke or with active pathological bleeding, and people weighing less than 60 kg saw no benefit and/or net harm from prasugrel, they noted.

Dr. Wright and his colleagues also changed recommendations involving glycoprotein IIB/IIIa inhibitors, noting that recent studies “more strongly support a strategy of selective rather than provisional use of GP IIb/IIIa inhibitor therapy as part of triple-antiplatelet therapy,” due to concerns about the potential bleeding risks.

Dr. Wright declared no conflicts of interest. Several of Dr. Wright's coauthors, including Dr. Jeffrey L. Anderson, the writing committee's vice chair, disclosed consultant relationships with pharmaceutical firms Sanofi-Aventis, Bristol Myers-Squibb, Lilly, and Daiichi. Members with conflicts were not permitted to vote on recommended drug therapies.

The American College of Cardiology Foundation and the American Heart Association have published updated guidelines for managing patients with unstable angina/non–ST elevation myocardial infarction, taking into consideration the use of a newer agent, prasugrel, as an alternative to clopidogrel, and recommending diagnostic angiography sooner for patients at high risk, among other changes.

The guidelines (Am. J. Cardiol. 2011 March 28 [doi:10.1016/j.jacc.2011.02.009]) are based on the most recent clinical trial evidence available., They update recommendations from 2007, and include several changes clinicians should be aware of, the guidelines' lead author, Dr. R. Scott Wright of the Mayo Clinic in Rochester, Minn., said in an e-mail interview. These are, in order of importance:

▸ The timing of invasive therapy in medium- and high-risk patients.

▸ The role of triple- vs. dual-antiplatelet therapy in patients at medium and high risk.

▸ The role of invasive therapy in patients with chronic kidney disease.

▸ The importance of participating in quality improvement processes.

▸ The role of prasugrel in non–ST elevation acute coronary syndrome.

Clinicians face tough decisions about when to use an invasive strategy such as diagnostic coronary angiography – whether within hours of presentation or days, Dr. Wright and his colleagues wrote in their analysis. Immediate catheterization with revascularization of unstable coronary lesions may prevent ischemic events that would otherwise occur during medical therapy – but pretreatment with antithrombotics “may diminish thrombus burden and 'passivate' unstable plaques,” improving the safety of the procedure and reducing the risk of ischemic complications.

The new guidelines, based on three randomized controlled trials evaluating the timing of angiography, recommend an early invasive strategy (12-24 hours after presentation) over a delayed invasive strategy (more than 24 hours after presentation) for initially stabilized high-risk patients with UA/NSTEMI.

“For patients not at high risk, a delayed invasive approach is also reasonable,” Dr. Wright and his colleagues wrote.

Several changes to earlier recommendations for antiplatelet therapy are contained in the new guidelines, including altered loading doses for clopidogrel to counter the potential for the drug to be less effective in some patient groups, and the addition of prasugrel, which was approved by the Food and Drug Administration after the last guidelines were published.

Prasugrel, in a randomized controlled trial comparing it with clopidogrel, was shown to be superior in reducing clinical events but at the expense of an increased risk of bleeding, the guideline writers noted. In March 2010 the FDA issued a warning that in some patient groups clopidogrel is less effective than it should be because of a genetic variant that inhibits the body's conversion of the prodrug to the drug.

However, Dr. Wright and his colleagues stopped short of endorsing prasugrel as a first choice over clopidogrel because of the higher bleeding risk and other considerations. People aged 75 years or older, those with a history of transient ischemic attack or stroke or with active pathological bleeding, and people weighing less than 60 kg saw no benefit and/or net harm from prasugrel, they noted.

Dr. Wright and his colleagues also changed recommendations involving glycoprotein IIB/IIIa inhibitors, noting that recent studies “more strongly support a strategy of selective rather than provisional use of GP IIb/IIIa inhibitor therapy as part of triple-antiplatelet therapy,” due to concerns about the potential bleeding risks.

Dr. Wright declared no conflicts of interest. Several of Dr. Wright's coauthors, including Dr. Jeffrey L. Anderson, the writing committee's vice chair, disclosed consultant relationships with pharmaceutical firms Sanofi-Aventis, Bristol Myers-Squibb, Lilly, and Daiichi. Members with conflicts were not permitted to vote on recommended drug therapies.

Older adults currently taking thyroxine replacement are at increased risk of bone fracture, compared with people who have not taken levothyroxine for 6 months or longer, Canadian researchers have found, with people currently taking more than 0.093 mg/day at the highest risk.

Excess levothyroxine and hyperthyroidism are associated with lower bone density as well as other risk factors for falls and fractures; however, the study is the first to examine the effect of levothyroxine dose on fractures in older adults.

The findings, published April 29 in BMJ (doi:10.1136/bmj.d2238), suggest that people over age 70 years would benefit from ongoing monitoring of their levothyroxine dose to avoid overtreatment and reduce fracture risk. More than a fifth of older people receive levothyroxine replacement long term, most of them women.

For their research, Dr. Marci Turner of the University of Toronto and her colleagues used a population-based health database to identify cohort of 213,511 adults aged 70 years or older who were prescribed levothyroxine during 2002-2007; follow-up lasted until 2008.

The study used a nested case-control design: Cases were cohort members admitted to the hospital for any bone fracture, matched with up to five controls from within the cohort who had not yet had a fracture for age, sex, and levothyroxine use. Of all the subjects with fractures over a mean 3.8 years of follow-up, 22,236, or 10.4%, women accounted for 88% of the fractures.

Dr. Turner and her colleagues looked at the risks associated with current levothyroxine use, compared with use that had terminated before a fracture. They found a significant increased risk (odds ratio, 1.88) for current users, compared with those who had terminated treatment more than 6 months before.

In addition to finding that current users were more likely to have a fracture than were those who had stopped levothyroxine more than 6 months before, high (mean greater than 0.093mg/day) and medium (0.044-0.093 mg/day) cumulative doses of levothyroxine were associated with a significantly increased risk of fracture among current users, compared with doses of less than 0.044 mg/day. High doses were associated with a 3.5-fold increased risk and medium doses with 2.6-fold higher risk of fracture, compared with low doses, the investigators found.

"Dosages commonly used in clinical practice, especially over 0.093 mg a day, may be excessive for this population," Dr. Turner and colleagues wrote in their analysis. "While further work is needed ... our study raises concerns that levothyroxine treatment targets may need to be modified in elderly people and that dose monitoring remains essential even into older age."

The authors cited as limitations of their study its observational design, the fact that prescribing information might have been incomplete, and that laboratory and radiology reports were not available. Other potentially confounding information, such as body mass index, family history of fractures, smoking, caffeine or alcohol use, or nonprescription drug use, was not available to the researchers.

The study was funded by the Canadian Institutes of Health Research, and Dr. Turner and her colleagues declared that they had no conflicts of interest.

Older adults currently taking thyroxine replacement are at increased risk of bone fracture, compared with people who have not taken levothyroxine for 6 months or longer, Canadian researchers have found, with people currently taking more than 0.093 mg/day at the highest risk.

Excess levothyroxine and hyperthyroidism are associated with lower bone density as well as other risk factors for falls and fractures; however, the study is the first to examine the effect of levothyroxine dose on fractures in older adults.

The findings, published April 29 in BMJ (doi:10.1136/bmj.d2238), suggest that people over age 70 years would benefit from ongoing monitoring of their levothyroxine dose to avoid overtreatment and reduce fracture risk. More than a fifth of older people receive levothyroxine replacement long term, most of them women.

For their research, Dr. Marci Turner of the University of Toronto and her colleagues used a population-based health database to identify cohort of 213,511 adults aged 70 years or older who were prescribed levothyroxine during 2002-2007; follow-up lasted until 2008.

The study used a nested case-control design: Cases were cohort members admitted to the hospital for any bone fracture, matched with up to five controls from within the cohort who had not yet had a fracture for age, sex, and levothyroxine use. Of all the subjects with fractures over a mean 3.8 years of follow-up, 22,236, or 10.4%, women accounted for 88% of the fractures.

Dr. Turner and her colleagues looked at the risks associated with current levothyroxine use, compared with use that had terminated before a fracture. They found a significant increased risk (odds ratio, 1.88) for current users, compared with those who had terminated treatment more than 6 months before.

In addition to finding that current users were more likely to have a fracture than were those who had stopped levothyroxine more than 6 months before, high (mean greater than 0.093mg/day) and medium (0.044-0.093 mg/day) cumulative doses of levothyroxine were associated with a significantly increased risk of fracture among current users, compared with doses of less than 0.044 mg/day. High doses were associated with a 3.5-fold increased risk and medium doses with 2.6-fold higher risk of fracture, compared with low doses, the investigators found.

"Dosages commonly used in clinical practice, especially over 0.093 mg a day, may be excessive for this population," Dr. Turner and colleagues wrote in their analysis. "While further work is needed ... our study raises concerns that levothyroxine treatment targets may need to be modified in elderly people and that dose monitoring remains essential even into older age."

The authors cited as limitations of their study its observational design, the fact that prescribing information might have been incomplete, and that laboratory and radiology reports were not available. Other potentially confounding information, such as body mass index, family history of fractures, smoking, caffeine or alcohol use, or nonprescription drug use, was not available to the researchers.

The study was funded by the Canadian Institutes of Health Research, and Dr. Turner and her colleagues declared that they had no conflicts of interest.

Older adults currently taking thyroxine replacement are at increased risk of bone fracture, compared with people who have not taken levothyroxine for 6 months or longer, Canadian researchers have found, with people currently taking more than 0.093 mg/day at the highest risk.

Excess levothyroxine and hyperthyroidism are associated with lower bone density as well as other risk factors for falls and fractures; however, the study is the first to examine the effect of levothyroxine dose on fractures in older adults.

The findings, published April 29 in BMJ (doi:10.1136/bmj.d2238), suggest that people over age 70 years would benefit from ongoing monitoring of their levothyroxine dose to avoid overtreatment and reduce fracture risk. More than a fifth of older people receive levothyroxine replacement long term, most of them women.

For their research, Dr. Marci Turner of the University of Toronto and her colleagues used a population-based health database to identify cohort of 213,511 adults aged 70 years or older who were prescribed levothyroxine during 2002-2007; follow-up lasted until 2008.

The study used a nested case-control design: Cases were cohort members admitted to the hospital for any bone fracture, matched with up to five controls from within the cohort who had not yet had a fracture for age, sex, and levothyroxine use. Of all the subjects with fractures over a mean 3.8 years of follow-up, 22,236, or 10.4%, women accounted for 88% of the fractures.

Dr. Turner and her colleagues looked at the risks associated with current levothyroxine use, compared with use that had terminated before a fracture. They found a significant increased risk (odds ratio, 1.88) for current users, compared with those who had terminated treatment more than 6 months before.

In addition to finding that current users were more likely to have a fracture than were those who had stopped levothyroxine more than 6 months before, high (mean greater than 0.093mg/day) and medium (0.044-0.093 mg/day) cumulative doses of levothyroxine were associated with a significantly increased risk of fracture among current users, compared with doses of less than 0.044 mg/day. High doses were associated with a 3.5-fold increased risk and medium doses with 2.6-fold higher risk of fracture, compared with low doses, the investigators found.

"Dosages commonly used in clinical practice, especially over 0.093 mg a day, may be excessive for this population," Dr. Turner and colleagues wrote in their analysis. "While further work is needed ... our study raises concerns that levothyroxine treatment targets may need to be modified in elderly people and that dose monitoring remains essential even into older age."

The authors cited as limitations of their study its observational design, the fact that prescribing information might have been incomplete, and that laboratory and radiology reports were not available. Other potentially confounding information, such as body mass index, family history of fractures, smoking, caffeine or alcohol use, or nonprescription drug use, was not available to the researchers.

The study was funded by the Canadian Institutes of Health Research, and Dr. Turner and her colleagues declared that they had no conflicts of interest.

Older adults currently taking thyroxine replacement are at increased risk of bone fracture, compared with people who have not taken levothyroxine for 6 months or longer, Canadian researchers have found, with people currently taking more than 0.093 mg/day at the highest risk.

Excess levothyroxine and hyperthyroidism are associated with lower bone density as well as other risk factors for falls and fractures; however, the study is the first to examine the effect of levothyroxine dose on fractures in older adults.

The findings, published April 29 in BMJ (doi:10.1136/bmj.d2238), suggest that people over age 70 years would benefit from ongoing monitoring of their levothyroxine dose to avoid overtreatment and reduce fracture risk. More than a fifth of older people receive levothyroxine replacement long term, most of them women.

For their research, Dr. Marci Turner of the University of Toronto and her colleagues used a population-based health database to identify cohort of 213,511 adults aged 70 years or older who were prescribed levothyroxine during 2002-2007; follow-up lasted until 2008.

The study used a nested case-control design: Cases were cohort members admitted to the hospital for any bone fracture, matched with up to five controls from within the cohort who had not yet had a fracture for age, sex, and levothyroxine use. Of all the subjects with fractures over a mean 3.8 years of follow-up, 22,236, or 10.4%, women accounted for 88% of the fractures.

Dr. Turner and her colleagues looked at the risks associated with current levothyroxine use, compared with use that had terminated before a fracture. They found a significant increased risk (odds ratio, 1.88) for current users, compared with those who had terminated treatment more than 6 months before.

In addition to finding that current users were more likely to have a fracture than were those who had stopped levothyroxine more than 6 months before, high (mean greater than 0.093mg/day) and medium (0.044-0.093 mg/day) cumulative doses of levothyroxine were associated with a significantly increased risk of fracture among current users, compared with doses of less than 0.044 mg/day. High doses were associated with a 3.5-fold increased risk and medium doses with 2.6-fold higher risk of fracture, compared with low doses, the investigators found.

"Dosages commonly used in clinical practice, especially over 0.093 mg a day, may be excessive for this population," Dr. Turner and colleagues wrote in their analysis. "While further work is needed ... our study raises concerns that levothyroxine treatment targets may need to be modified in elderly people and that dose monitoring remains essential even into older age."

The authors cited as limitations of their study its observational design, the fact that prescribing information might have been incomplete, and that laboratory and radiology reports were not available. Other potentially confounding information, such as body mass index, family history of fractures, smoking, caffeine or alcohol use, or nonprescription drug use, was not available to the researchers.

The study was funded by the Canadian Institutes of Health Research, and Dr. Turner and her colleagues declared that they had no conflicts of interest.

Older adults currently taking thyroxine replacement are at increased risk of bone fracture, compared with people who have not taken levothyroxine for 6 months or longer, Canadian researchers have found, with people currently taking more than 0.093 mg/day at the highest risk.

Excess levothyroxine and hyperthyroidism are associated with lower bone density as well as other risk factors for falls and fractures; however, the study is the first to examine the effect of levothyroxine dose on fractures in older adults.

The findings, published April 29 in BMJ (doi:10.1136/bmj.d2238), suggest that people over age 70 years would benefit from ongoing monitoring of their levothyroxine dose to avoid overtreatment and reduce fracture risk. More than a fifth of older people receive levothyroxine replacement long term, most of them women.

For their research, Dr. Marci Turner of the University of Toronto and her colleagues used a population-based health database to identify cohort of 213,511 adults aged 70 years or older who were prescribed levothyroxine during 2002-2007; follow-up lasted until 2008.

The study used a nested case-control design: Cases were cohort members admitted to the hospital for any bone fracture, matched with up to five controls from within the cohort who had not yet had a fracture for age, sex, and levothyroxine use. Of all the subjects with fractures over a mean 3.8 years of follow-up, 22,236, or 10.4%, women accounted for 88% of the fractures.

Dr. Turner and her colleagues looked at the risks associated with current levothyroxine use, compared with use that had terminated before a fracture. They found a significant increased risk (odds ratio, 1.88) for current users, compared with those who had terminated treatment more than 6 months before.

In addition to finding that current users were more likely to have a fracture than were those who had stopped levothyroxine more than 6 months before, high (mean greater than 0.093mg/day) and medium (0.044-0.093 mg/day) cumulative doses of levothyroxine were associated with a significantly increased risk of fracture among current users, compared with doses of less than 0.044 mg/day. High doses were associated with a 3.5-fold increased risk and medium doses with 2.6-fold higher risk of fracture, compared with low doses, the investigators found.

"Dosages commonly used in clinical practice, especially over 0.093 mg a day, may be excessive for this population," Dr. Turner and colleagues wrote in their analysis. "While further work is needed ... our study raises concerns that levothyroxine treatment targets may need to be modified in elderly people and that dose monitoring remains essential even into older age."

The authors cited as limitations of their study its observational design, the fact that prescribing information might have been incomplete, and that laboratory and radiology reports were not available. Other potentially confounding information, such as body mass index, family history of fractures, smoking, caffeine or alcohol use, or nonprescription drug use, was not available to the researchers.

The study was funded by the Canadian Institutes of Health Research, and Dr. Turner and her colleagues declared that they had no conflicts of interest.

Older adults currently taking thyroxine replacement are at increased risk of bone fracture, compared with people who have not taken levothyroxine for 6 months or longer, Canadian researchers have found, with people currently taking more than 0.093 mg/day at the highest risk.

Excess levothyroxine and hyperthyroidism are associated with lower bone density as well as other risk factors for falls and fractures; however, the study is the first to examine the effect of levothyroxine dose on fractures in older adults.

The findings, published April 29 in BMJ (doi:10.1136/bmj.d2238), suggest that people over age 70 years would benefit from ongoing monitoring of their levothyroxine dose to avoid overtreatment and reduce fracture risk. More than a fifth of older people receive levothyroxine replacement long term, most of them women.

For their research, Dr. Marci Turner of the University of Toronto and her colleagues used a population-based health database to identify cohort of 213,511 adults aged 70 years or older who were prescribed levothyroxine during 2002-2007; follow-up lasted until 2008.

The study used a nested case-control design: Cases were cohort members admitted to the hospital for any bone fracture, matched with up to five controls from within the cohort who had not yet had a fracture for age, sex, and levothyroxine use. Of all the subjects with fractures over a mean 3.8 years of follow-up, 22,236, or 10.4%, women accounted for 88% of the fractures.

Dr. Turner and her colleagues looked at the risks associated with current levothyroxine use, compared with use that had terminated before a fracture. They found a significant increased risk (odds ratio, 1.88) for current users, compared with those who had terminated treatment more than 6 months before.

In addition to finding that current users were more likely to have a fracture than were those who had stopped levothyroxine more than 6 months before, high (mean greater than 0.093mg/day) and medium (0.044-0.093 mg/day) cumulative doses of levothyroxine were associated with a significantly increased risk of fracture among current users, compared with doses of less than 0.044 mg/day. High doses were associated with a 3.5-fold increased risk and medium doses with 2.6-fold higher risk of fracture, compared with low doses, the investigators found.

"Dosages commonly used in clinical practice, especially over 0.093 mg a day, may be excessive for this population," Dr. Turner and colleagues wrote in their analysis. "While further work is needed ... our study raises concerns that levothyroxine treatment targets may need to be modified in elderly people and that dose monitoring remains essential even into older age."

The authors cited as limitations of their study its observational design, the fact that prescribing information might have been incomplete, and that laboratory and radiology reports were not available. Other potentially confounding information, such as body mass index, family history of fractures, smoking, caffeine or alcohol use, or nonprescription drug use, was not available to the researchers.

The study was funded by the Canadian Institutes of Health Research, and Dr. Turner and her colleagues declared that they had no conflicts of interest.