Antipsychotics boosted CVD events in elderly

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Antipsychotics boosted CVD events in elderly

DALLAS – Elderly patients who started treatment with an antipsychotic drug had a substantially increased risk for a major adverse cardiovascular disease event, especially during the first month on treatment, according to Danish national records from more than 1 million people.

The risk remained elevated even when the analysis focused on elderly people who were aged 70 years or older and were without cardiovascular disease or dementia at the time of their first use of an antipsychotic medication, Dr. Charlotte Andersson and her associates reported in a poster at the American Heart Association scientific sessions.

Treatment was linked with a significantly increased rate of major adverse cardiovascular events (MACE) at some time during follow-up for all eight antipsychotic drugs studied in detail: haloperidol (Haldol), flupentixol (Fluanxol), chlorprothixene, levomepromazine (Nozinan), quetiapine (Seroquel), risperidone (Risperdal), olanzapine, and ziprasidone (Geodon), reported Dr. Andersson, a researcher at Gentofte Hospital in Copenhagen. The MACE association was relatively weak for ziprasidone, but it was robust for the other seven agents.

The study included 1,235,869 Danes aged 70 years or older during 1997-2009 who had not previously been treated with an antipsychotic drug. During the period studied, 100,140 (8%) of these people started treatment with an antipsychotic drug. During follow-up the researchers tallied the incidence of MACE (the combined rate of nonfatal myocardial infarction, nonfatal stroke, and cardiovascular death).

Overall, use of an antipsychotic drug for more than 1 year was linked with a roughly doubled rate of MACE after adjustment for several demographic and clinical factors, including age, gender, diabetes, renal disease, dementia, and schizophrenia. The adjusted relative increase in MACE was even higher during the first 30 days of treatment for most of the eight drugs.

For example, during the first 30 days following the start of treatment, patients treated with any haloperidol dosage had a roughly fivefold increased adjusted MACE rate compared with people not receiving an antipsychotic. The relative risk was highest during the first 30 days in patients on the highest haloperidol dosages, 2 mg/day or more, who had a 10-fold increased MACE rate.

Similar increases in adjusted MACE rates were seen in patients treated with haloperidol for 1-12 months, as well as in those treated for more than a year, although with longer follow-up the adjusted relative risk was about two- to threefold above background. Similar risk patterns also existed in the subgroup of patients who were treated with haloperidol and were free from cardiovascular disease at baseline, as well as in those free from dementia at baseline.

Dr. Andersson and her associates said that they had no disclosures.

mzoler@frontlinemedcom.com

On Twitter @mitchelzoler

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DALLAS – Elderly patients who started treatment with an antipsychotic drug had a substantially increased risk for a major adverse cardiovascular disease event, especially during the first month on treatment, according to Danish national records from more than 1 million people.

The risk remained elevated even when the analysis focused on elderly people who were aged 70 years or older and were without cardiovascular disease or dementia at the time of their first use of an antipsychotic medication, Dr. Charlotte Andersson and her associates reported in a poster at the American Heart Association scientific sessions.

Treatment was linked with a significantly increased rate of major adverse cardiovascular events (MACE) at some time during follow-up for all eight antipsychotic drugs studied in detail: haloperidol (Haldol), flupentixol (Fluanxol), chlorprothixene, levomepromazine (Nozinan), quetiapine (Seroquel), risperidone (Risperdal), olanzapine, and ziprasidone (Geodon), reported Dr. Andersson, a researcher at Gentofte Hospital in Copenhagen. The MACE association was relatively weak for ziprasidone, but it was robust for the other seven agents.

The study included 1,235,869 Danes aged 70 years or older during 1997-2009 who had not previously been treated with an antipsychotic drug. During the period studied, 100,140 (8%) of these people started treatment with an antipsychotic drug. During follow-up the researchers tallied the incidence of MACE (the combined rate of nonfatal myocardial infarction, nonfatal stroke, and cardiovascular death).

Overall, use of an antipsychotic drug for more than 1 year was linked with a roughly doubled rate of MACE after adjustment for several demographic and clinical factors, including age, gender, diabetes, renal disease, dementia, and schizophrenia. The adjusted relative increase in MACE was even higher during the first 30 days of treatment for most of the eight drugs.

For example, during the first 30 days following the start of treatment, patients treated with any haloperidol dosage had a roughly fivefold increased adjusted MACE rate compared with people not receiving an antipsychotic. The relative risk was highest during the first 30 days in patients on the highest haloperidol dosages, 2 mg/day or more, who had a 10-fold increased MACE rate.

Similar increases in adjusted MACE rates were seen in patients treated with haloperidol for 1-12 months, as well as in those treated for more than a year, although with longer follow-up the adjusted relative risk was about two- to threefold above background. Similar risk patterns also existed in the subgroup of patients who were treated with haloperidol and were free from cardiovascular disease at baseline, as well as in those free from dementia at baseline.

Dr. Andersson and her associates said that they had no disclosures.

mzoler@frontlinemedcom.com

On Twitter @mitchelzoler

DALLAS – Elderly patients who started treatment with an antipsychotic drug had a substantially increased risk for a major adverse cardiovascular disease event, especially during the first month on treatment, according to Danish national records from more than 1 million people.

The risk remained elevated even when the analysis focused on elderly people who were aged 70 years or older and were without cardiovascular disease or dementia at the time of their first use of an antipsychotic medication, Dr. Charlotte Andersson and her associates reported in a poster at the American Heart Association scientific sessions.

Treatment was linked with a significantly increased rate of major adverse cardiovascular events (MACE) at some time during follow-up for all eight antipsychotic drugs studied in detail: haloperidol (Haldol), flupentixol (Fluanxol), chlorprothixene, levomepromazine (Nozinan), quetiapine (Seroquel), risperidone (Risperdal), olanzapine, and ziprasidone (Geodon), reported Dr. Andersson, a researcher at Gentofte Hospital in Copenhagen. The MACE association was relatively weak for ziprasidone, but it was robust for the other seven agents.

The study included 1,235,869 Danes aged 70 years or older during 1997-2009 who had not previously been treated with an antipsychotic drug. During the period studied, 100,140 (8%) of these people started treatment with an antipsychotic drug. During follow-up the researchers tallied the incidence of MACE (the combined rate of nonfatal myocardial infarction, nonfatal stroke, and cardiovascular death).

Overall, use of an antipsychotic drug for more than 1 year was linked with a roughly doubled rate of MACE after adjustment for several demographic and clinical factors, including age, gender, diabetes, renal disease, dementia, and schizophrenia. The adjusted relative increase in MACE was even higher during the first 30 days of treatment for most of the eight drugs.

For example, during the first 30 days following the start of treatment, patients treated with any haloperidol dosage had a roughly fivefold increased adjusted MACE rate compared with people not receiving an antipsychotic. The relative risk was highest during the first 30 days in patients on the highest haloperidol dosages, 2 mg/day or more, who had a 10-fold increased MACE rate.

Similar increases in adjusted MACE rates were seen in patients treated with haloperidol for 1-12 months, as well as in those treated for more than a year, although with longer follow-up the adjusted relative risk was about two- to threefold above background. Similar risk patterns also existed in the subgroup of patients who were treated with haloperidol and were free from cardiovascular disease at baseline, as well as in those free from dementia at baseline.

Dr. Andersson and her associates said that they had no disclosures.

mzoler@frontlinemedcom.com

On Twitter @mitchelzoler

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Major finding: Long-term use of an antipsychotic drug by elderly Danes doubled their rate of major cardiovascular adverse events.

Data source: A review of 1,235,869 Danes aged 70 years or older during 1997-2009 who were not receiving an antipsychotic drug at the time they entered the database.

Disclosures: Dr. Andersson and her associates said that they had no disclosures.

LDL Cholesterol, Systolic Blood Pressure Predict Different CV Events

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LDL Cholesterol, Systolic Blood Pressure Predict Different CV Events

ORLANDO – Although higher systolic blood pressure and LDL cholesterol are traditional risk factors for cardiovascular disease, each may have a different effect on the cerebrovascular and coronary systems.

Pooled analysis of three landmark studies done on the cholesterol-lowering agent atorvastatin in high-risk patients showed that higher baseline systolic blood pressure is predictive of a significantly higher risk of stroke. Meanwhile, higher baseline LDL cholesterol is predictive of a significantly higher risk of coronary events, the analysis showed.

The findings have implications on both research design and clinical practice, Dr. Prakash C. Deedwania, the study’s lead author, said at the annual scientific sessions of the American Heart Association.

Patients who might be at risk of both stroke and coronary events should be treated aggressively to reduce systolic blood pressure and LDL cholesterol, he said.

Dr. Deedwania and his colleagues pooled data on 21,727 patients from three trials: Treating to New Targets (TNT), which compared 10 mg with 80 mg atorvastatin in patients with stable coronary heart disease and LDL levels below 130 mg/dL (N. Engl. J. Med. 2005;352:1425-35), Incremental Decrease in End Points Through Aggressive Lipid Lowering (IDEAL), which compared high-dose (80 mg) atorvastatin with normal-dose (20-40 mg) simvastatin in post-MI patients (JAMA 2005;294:2437-45), and the Collaborative Atorvastatin Diabetes Study (CARDS), which compared 20 mg atorvastatin with placebo in patients with type 2 diabetes and without established coronary heart disease (Lancet 2004;364:685-96).

Results showed that with each 10-mm Hg increase in baseline systolic blood pressure, the risk of a fatal or nonfatal stroke increased by 16%. Meanwhile, each 10-mg/dL increase in baseline LDL cholesterol increased the risk of coronary events by 5%. Both differences were significantly different.

Dr. Deedwania said that the reduction in LDL cholesterol has been associated with a decrease in the risk of stroke, "but perhaps by a different mechanism."

The authors also looked at a subgroup of patients with type 2 diabetes (5,408 patients from the three trials), and found results consistent with the larger cohort.

Although systolic blood pressure is known to be a powerful predictor of stroke, many clinicians may not be aware that LDL cholesterol is not associated with an increased risk of stroke, said Dr. Deedwania. "What predicts baseline risk is different than what happens in treatment, so there are yet many lessons to be learned from these trials."

Dr. Deedwania has received research grants from Pfizer. He has been a consultant to and on the advisory boards of Pfizer and Novartis.

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ORLANDO – Although higher systolic blood pressure and LDL cholesterol are traditional risk factors for cardiovascular disease, each may have a different effect on the cerebrovascular and coronary systems.

Pooled analysis of three landmark studies done on the cholesterol-lowering agent atorvastatin in high-risk patients showed that higher baseline systolic blood pressure is predictive of a significantly higher risk of stroke. Meanwhile, higher baseline LDL cholesterol is predictive of a significantly higher risk of coronary events, the analysis showed.

The findings have implications on both research design and clinical practice, Dr. Prakash C. Deedwania, the study’s lead author, said at the annual scientific sessions of the American Heart Association.

Patients who might be at risk of both stroke and coronary events should be treated aggressively to reduce systolic blood pressure and LDL cholesterol, he said.

Dr. Deedwania and his colleagues pooled data on 21,727 patients from three trials: Treating to New Targets (TNT), which compared 10 mg with 80 mg atorvastatin in patients with stable coronary heart disease and LDL levels below 130 mg/dL (N. Engl. J. Med. 2005;352:1425-35), Incremental Decrease in End Points Through Aggressive Lipid Lowering (IDEAL), which compared high-dose (80 mg) atorvastatin with normal-dose (20-40 mg) simvastatin in post-MI patients (JAMA 2005;294:2437-45), and the Collaborative Atorvastatin Diabetes Study (CARDS), which compared 20 mg atorvastatin with placebo in patients with type 2 diabetes and without established coronary heart disease (Lancet 2004;364:685-96).

Results showed that with each 10-mm Hg increase in baseline systolic blood pressure, the risk of a fatal or nonfatal stroke increased by 16%. Meanwhile, each 10-mg/dL increase in baseline LDL cholesterol increased the risk of coronary events by 5%. Both differences were significantly different.

Dr. Deedwania said that the reduction in LDL cholesterol has been associated with a decrease in the risk of stroke, "but perhaps by a different mechanism."

The authors also looked at a subgroup of patients with type 2 diabetes (5,408 patients from the three trials), and found results consistent with the larger cohort.

Although systolic blood pressure is known to be a powerful predictor of stroke, many clinicians may not be aware that LDL cholesterol is not associated with an increased risk of stroke, said Dr. Deedwania. "What predicts baseline risk is different than what happens in treatment, so there are yet many lessons to be learned from these trials."

Dr. Deedwania has received research grants from Pfizer. He has been a consultant to and on the advisory boards of Pfizer and Novartis.

ORLANDO – Although higher systolic blood pressure and LDL cholesterol are traditional risk factors for cardiovascular disease, each may have a different effect on the cerebrovascular and coronary systems.

Pooled analysis of three landmark studies done on the cholesterol-lowering agent atorvastatin in high-risk patients showed that higher baseline systolic blood pressure is predictive of a significantly higher risk of stroke. Meanwhile, higher baseline LDL cholesterol is predictive of a significantly higher risk of coronary events, the analysis showed.

The findings have implications on both research design and clinical practice, Dr. Prakash C. Deedwania, the study’s lead author, said at the annual scientific sessions of the American Heart Association.

Patients who might be at risk of both stroke and coronary events should be treated aggressively to reduce systolic blood pressure and LDL cholesterol, he said.

Dr. Deedwania and his colleagues pooled data on 21,727 patients from three trials: Treating to New Targets (TNT), which compared 10 mg with 80 mg atorvastatin in patients with stable coronary heart disease and LDL levels below 130 mg/dL (N. Engl. J. Med. 2005;352:1425-35), Incremental Decrease in End Points Through Aggressive Lipid Lowering (IDEAL), which compared high-dose (80 mg) atorvastatin with normal-dose (20-40 mg) simvastatin in post-MI patients (JAMA 2005;294:2437-45), and the Collaborative Atorvastatin Diabetes Study (CARDS), which compared 20 mg atorvastatin with placebo in patients with type 2 diabetes and without established coronary heart disease (Lancet 2004;364:685-96).

Results showed that with each 10-mm Hg increase in baseline systolic blood pressure, the risk of a fatal or nonfatal stroke increased by 16%. Meanwhile, each 10-mg/dL increase in baseline LDL cholesterol increased the risk of coronary events by 5%. Both differences were significantly different.

Dr. Deedwania said that the reduction in LDL cholesterol has been associated with a decrease in the risk of stroke, "but perhaps by a different mechanism."

The authors also looked at a subgroup of patients with type 2 diabetes (5,408 patients from the three trials), and found results consistent with the larger cohort.

Although systolic blood pressure is known to be a powerful predictor of stroke, many clinicians may not be aware that LDL cholesterol is not associated with an increased risk of stroke, said Dr. Deedwania. "What predicts baseline risk is different than what happens in treatment, so there are yet many lessons to be learned from these trials."

Dr. Deedwania has received research grants from Pfizer. He has been a consultant to and on the advisory boards of Pfizer and Novartis.

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FROM THE ANNUAL SCIENTIFIC SESSIONS OF THE AMERICAN HEART ASSOCIATION

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Major Finding: For each 10-mm Hg increase on baseline systolic blood pressure, the risk of a fatal or nonfatal stroke increased by 16%, and each 10-mg/dL increase in baseline LDL cholesterol increased the risk of coronary events by 5%.

Data Source: Pooled analysis of data from 21,727 patients in TNT, IDEAL, and CARDS trials.

Disclosures: Dr. Deedwania has received research grants from Pfizer. He has been a consultant to and on the advisory boards of Pfizer and Novartis.