Mary Ann Moon

Clinicians should no longer defer initiating antiretroviral therapy in asymptomatic adults with newly diagnosed HIV infection until their CD4+ count descends to a low threshold, according to a report presented at the International AIDS Society Conference on HIV Pathogenesis, Treatment, and Prevention.

Instead, antiretroviral agents should be initiated immediately, regardless of CD4+ count.

©xrender/thinkstockphotos.com

This report was simultaneously presented at the conference and published online in the New England Journal of Medicine (2015 July 20 [doi:10.1056/NEJMoa1506816]).

General practice has been to defer antiretroviral therapy until CD4+ counts decline to a certain threshold level – a level that has changed over time and that varies across different treatment guidelines. Such deferral was prompted by concerns that early treatment would expose patients to more of the adverse effects of antiretrovirals – particularly that today’s aging HIV-positive population would have more exposure to the detrimental effects on cardiovascular and renal health. Moreover, evidence of the potential benefit of immediate treatment has been inconsistent, noted the study’s writing group cochair Dr. Jens D. Lundgren, University of Copenhagen, and his colleagues.

To address this knowledge gap, investigators in the International Network for Strategic Initiatives in Global HIV Trials (INSIGHT) designed and conducted the Strategic Timing of Antiretroviral Therapy (START) trial, which compared the benefits and risks of immediate initiation of antiretroviral therapy in patients with CD4+ counts above 500 cells/cc (2,326 patients) against deferring therapy until CD4+ counts declined to 350 cells/cc (2,359 patients).

The study participants were in generally good health and had a median age of 36 years. They were treated at 215 medical centers in 35 countries and followed for a mean of 3 years.

The primary endpoint was a composite of any serious AIDS-related event and any serious non–AIDS-related event, such as fatal or nonfatal cardiovascular disease, end-stage renal disease, liver disease, or non–AIDS-defining cancer. The endpoint was chosen because most complications and deaths that occur in patients with high CD4+ counts are attributed to non–AIDS-related events.

The study was halted early, and all patients were offered immediate antiretroviral therapy, when an interim analysis showed that only 42 patients in the immediate-initiation group reached the composite endpoint, compared with 96 in the deferred-initiation group (hazard ratio, 0.43; P < .001). This significant treatment benefit remained consistent across all subgroups of patients, regardless of demographic and clinical characteristics, and it persisted in sensitivity analyses.

With immediate antiretroviral therapy, there was a 72% relative reduction in serious AIDS-related events, primarily tuberculosis, Kaposi’s sarcoma, and malignant lymphoma. There also was a 39% relative reduction in serious non–AIDS-related events, primarily cancers. Rates of bacterial infections also were significantly decreased with immediate antiretroviral therapy.

Rates of other serious adverse events were identical in the two study groups, affecting 73 patients in each.

This study was supported by the National Institute of Allergy and Infectious Diseases, National Institutes of Health Clinical Center, National Cancer Institute, National Heart, Lung, and Blood Institute, and other members of the National Institutes of Health; the French Agence Nationale de Recherches sur le SIDA et les Hepatites Virales; the Australian National Health and Medical Research Council; the Danish National Research Foundation; the German Bundesministerium fur Bildung und Forschung; the European AIDS Treatment Network; the U.K. Medical Research Council, National Institute for Health Research, and National Health Service; and the University of Minnesota. Antiretroviral drugs were donated by AbbVie, Bristol-Myers Squibb, Gilead Sciences, GlaxoSmithKline/ViiV Healthcare, Janssen Scientific, and Merck.

Dr. Lundgren reported having no relevant financial disclosures; his associates reported numerous ties to industry sources.

Clinicians should no longer defer initiating antiretroviral therapy in asymptomatic adults with newly diagnosed HIV infection until their CD4+ count descends to a low threshold, according to a report presented at the International AIDS Society Conference on HIV Pathogenesis, Treatment, and Prevention.

Instead, antiretroviral agents should be initiated immediately, regardless of CD4+ count.

©xrender/thinkstockphotos.com

This report was simultaneously presented at the conference and published online in the New England Journal of Medicine (2015 July 20 [doi:10.1056/NEJMoa1506816]).

General practice has been to defer antiretroviral therapy until CD4+ counts decline to a certain threshold level – a level that has changed over time and that varies across different treatment guidelines. Such deferral was prompted by concerns that early treatment would expose patients to more of the adverse effects of antiretrovirals – particularly that today’s aging HIV-positive population would have more exposure to the detrimental effects on cardiovascular and renal health. Moreover, evidence of the potential benefit of immediate treatment has been inconsistent, noted the study’s writing group cochair Dr. Jens D. Lundgren, University of Copenhagen, and his colleagues.

To address this knowledge gap, investigators in the International Network for Strategic Initiatives in Global HIV Trials (INSIGHT) designed and conducted the Strategic Timing of Antiretroviral Therapy (START) trial, which compared the benefits and risks of immediate initiation of antiretroviral therapy in patients with CD4+ counts above 500 cells/cc (2,326 patients) against deferring therapy until CD4+ counts declined to 350 cells/cc (2,359 patients).

The study participants were in generally good health and had a median age of 36 years. They were treated at 215 medical centers in 35 countries and followed for a mean of 3 years.

The primary endpoint was a composite of any serious AIDS-related event and any serious non–AIDS-related event, such as fatal or nonfatal cardiovascular disease, end-stage renal disease, liver disease, or non–AIDS-defining cancer. The endpoint was chosen because most complications and deaths that occur in patients with high CD4+ counts are attributed to non–AIDS-related events.

The study was halted early, and all patients were offered immediate antiretroviral therapy, when an interim analysis showed that only 42 patients in the immediate-initiation group reached the composite endpoint, compared with 96 in the deferred-initiation group (hazard ratio, 0.43; P < .001). This significant treatment benefit remained consistent across all subgroups of patients, regardless of demographic and clinical characteristics, and it persisted in sensitivity analyses.

With immediate antiretroviral therapy, there was a 72% relative reduction in serious AIDS-related events, primarily tuberculosis, Kaposi’s sarcoma, and malignant lymphoma. There also was a 39% relative reduction in serious non–AIDS-related events, primarily cancers. Rates of bacterial infections also were significantly decreased with immediate antiretroviral therapy.

Rates of other serious adverse events were identical in the two study groups, affecting 73 patients in each.

This study was supported by the National Institute of Allergy and Infectious Diseases, National Institutes of Health Clinical Center, National Cancer Institute, National Heart, Lung, and Blood Institute, and other members of the National Institutes of Health; the French Agence Nationale de Recherches sur le SIDA et les Hepatites Virales; the Australian National Health and Medical Research Council; the Danish National Research Foundation; the German Bundesministerium fur Bildung und Forschung; the European AIDS Treatment Network; the U.K. Medical Research Council, National Institute for Health Research, and National Health Service; and the University of Minnesota. Antiretroviral drugs were donated by AbbVie, Bristol-Myers Squibb, Gilead Sciences, GlaxoSmithKline/ViiV Healthcare, Janssen Scientific, and Merck.

Dr. Lundgren reported having no relevant financial disclosures; his associates reported numerous ties to industry sources.

Clinicians should no longer defer initiating antiretroviral therapy in asymptomatic adults with newly diagnosed HIV infection until their CD4+ count descends to a low threshold, according to a report presented at the International AIDS Society Conference on HIV Pathogenesis, Treatment, and Prevention.

Instead, antiretroviral agents should be initiated immediately, regardless of CD4+ count.

©xrender/thinkstockphotos.com

This report was simultaneously presented at the conference and published online in the New England Journal of Medicine (2015 July 20 [doi:10.1056/NEJMoa1506816]).

General practice has been to defer antiretroviral therapy until CD4+ counts decline to a certain threshold level – a level that has changed over time and that varies across different treatment guidelines. Such deferral was prompted by concerns that early treatment would expose patients to more of the adverse effects of antiretrovirals – particularly that today’s aging HIV-positive population would have more exposure to the detrimental effects on cardiovascular and renal health. Moreover, evidence of the potential benefit of immediate treatment has been inconsistent, noted the study’s writing group cochair Dr. Jens D. Lundgren, University of Copenhagen, and his colleagues.

To address this knowledge gap, investigators in the International Network for Strategic Initiatives in Global HIV Trials (INSIGHT) designed and conducted the Strategic Timing of Antiretroviral Therapy (START) trial, which compared the benefits and risks of immediate initiation of antiretroviral therapy in patients with CD4+ counts above 500 cells/cc (2,326 patients) against deferring therapy until CD4+ counts declined to 350 cells/cc (2,359 patients).

The study participants were in generally good health and had a median age of 36 years. They were treated at 215 medical centers in 35 countries and followed for a mean of 3 years.

The primary endpoint was a composite of any serious AIDS-related event and any serious non–AIDS-related event, such as fatal or nonfatal cardiovascular disease, end-stage renal disease, liver disease, or non–AIDS-defining cancer. The endpoint was chosen because most complications and deaths that occur in patients with high CD4+ counts are attributed to non–AIDS-related events.

The study was halted early, and all patients were offered immediate antiretroviral therapy, when an interim analysis showed that only 42 patients in the immediate-initiation group reached the composite endpoint, compared with 96 in the deferred-initiation group (hazard ratio, 0.43; P < .001). This significant treatment benefit remained consistent across all subgroups of patients, regardless of demographic and clinical characteristics, and it persisted in sensitivity analyses.

With immediate antiretroviral therapy, there was a 72% relative reduction in serious AIDS-related events, primarily tuberculosis, Kaposi’s sarcoma, and malignant lymphoma. There also was a 39% relative reduction in serious non–AIDS-related events, primarily cancers. Rates of bacterial infections also were significantly decreased with immediate antiretroviral therapy.

Rates of other serious adverse events were identical in the two study groups, affecting 73 patients in each.

This study was supported by the National Institute of Allergy and Infectious Diseases, National Institutes of Health Clinical Center, National Cancer Institute, National Heart, Lung, and Blood Institute, and other members of the National Institutes of Health; the French Agence Nationale de Recherches sur le SIDA et les Hepatites Virales; the Australian National Health and Medical Research Council; the Danish National Research Foundation; the German Bundesministerium fur Bildung und Forschung; the European AIDS Treatment Network; the U.K. Medical Research Council, National Institute for Health Research, and National Health Service; and the University of Minnesota. Antiretroviral drugs were donated by AbbVie, Bristol-Myers Squibb, Gilead Sciences, GlaxoSmithKline/ViiV Healthcare, Janssen Scientific, and Merck.

Dr. Lundgren reported having no relevant financial disclosures; his associates reported numerous ties to industry sources.

The ACC/AHA guideline for cholesterol management, updated in 2013 to address statin therapy for asymptomatic adults at risk for atherosclerotic cardiovascular diseases (primary prevention), proved more accurate and efficient than the NCEP 2004 guideline at identifying which patients will benefit most from statins because of their increased risk, according to two reports published online July 14 in JAMA.

The updated ACC/AHA guideline shifted the focus of primary prevention to absolute CV risk as estimated by the 10-year ASCVD (atherosclerotic cardiovascular disease) score, rather than by cholesterol levels. Critics voiced concern that applying the new guideline in clinical practice would increase the number of adults eligible for statin therapy by several million, increasing costs and exposing many people to possible harms of statins when their benefits were still uncertain.

Two groups of researchers have now examined the accuracy and cost-effectiveness of applying the new guideline in separate studies.

In one study, investigators compared the ACC/AHA eligibility criteria for statin therapy against those of the National Cholesterol Education Program (NCEP), using data from a large prospective community-based asymptomatic cohort of adults aged 35 years and older participating in the Framingham Health Study. They focused on 2,425 “overwhelmingly white” men and women (mean age, 51 years) who underwent CT imaging to identify coronary artery calcium as part of the study, said Dr. Amit Pursnani of the department of radiology at Massachusetts General Hospital and Harvard Medical School, both in Boston, and his associates.

As expected, many more participants were eligible for statins according to the ACC/AHA guideline (39%), compared with the NCEP guideline (14%).

The ACC/AHA guideline was much more accurate at matching statin eligibility with the presence and extent of subclinical atherosclerosis, as measured by coronary artery calcium (CAC) scores. Patients with high-risk CAC scores were much more likely to be allocated to statin therapy using the ACC/AHA guideline (85%) than the NCEP guideline (34%).

During a mean of 9.4 years of follow-up, there were 74 incident CVD events and 43 incident coronary heart disease events. The risk of incident events among statin-eligible vs. noneligible participants was significantly higher when applying the ACC/AHA eligibility guideline, compared with the NCEP guideline. Therefore, the newer guideline was more accurate and efficient at identifying patients at highest risk.

This finding held true across several subgroups of patients, including women and patients at intermediate CVD risk according to the Framingham Risk Score. The latter subgroup is particularly important because they are “the most challenging group in clinical practice for whom to decide to initiate statin therapy,” Dr. Pursnani and his associates wrote (JAMA 2015 July 14 [doi:10.1001/jama.2015.7515]).

“Extrapolating our findings to the approximately 10 million U.S. adults who are newly eligible for statins, we estimate that between 41,000 and 63,000 incident CVD events would be prevented over a 10-year period by adopting the ACC/AHA guidelines,” they said.

In the other study, Ankur Pandya, Ph.D. of the department of health policy and management, Harvard School of Public Health, Boston, and his associates constructed a microsimulation model of 1 million hypothetical U.S. adults aged 45-70 years to examine whether following the ACC/AHA guideline on statin eligibility is cost effective.

The guideline recommends statin therapy for patients who have a 7.5% or higher 10-year ASCVD risk. The model predicted that the health benefits of receiving statins at this risk threshold clearly are worth the additional costs of treating more patients, with an incremental cost-effectiveness ratio of $37,000/quality-adjusted life year (QALY) gained. This is well below the conservative $50,000/QALY threshold used in other health care cost-benefit analyses, Dr. Pandya and his associates said (JAMA 2015 July 14 [doi:10.1001/jama.2015.6822]).

Moreover, the model estimated that statin therapy would still be cost effective if even more lenient ASCVD risk thresholds – 3%-4% – were used. “Shifting from the 7.5% or higher threshold to 3.0% or higher ... was associated with an estimated additional 125,000-160,000 CVD events averted,” they noted.

However, these estimates were influenced by such variables as the price of the statins entered into the model (whether patients used generic or name-brand agents), patients’ level of adherence, and the risk of statin-induced diabetes, which has not yet been quantified for different groups of patients.

Dr. Pursnani’s study was supported by the National Heart, Lung, and Blood Institute’s Framingham Heart Study and the National Institutes of Health. Dr. Pursnani reported having no relevant financial disclosures; one of his associates reported ties to several imaging manufacturers. Dr. Pandya’s study was supported by the Harvard School of Public Health and the NHLBI. Dr. Pandya reported receiving grants from NIH and the AHA, and one of his associates reported receiving personal fees from OptumInsight.

The ACC/AHA guideline for cholesterol management, updated in 2013 to address statin therapy for asymptomatic adults at risk for atherosclerotic cardiovascular diseases (primary prevention), proved more accurate and efficient than the NCEP 2004 guideline at identifying which patients will benefit most from statins because of their increased risk, according to two reports published online July 14 in JAMA.

The updated ACC/AHA guideline shifted the focus of primary prevention to absolute CV risk as estimated by the 10-year ASCVD (atherosclerotic cardiovascular disease) score, rather than by cholesterol levels. Critics voiced concern that applying the new guideline in clinical practice would increase the number of adults eligible for statin therapy by several million, increasing costs and exposing many people to possible harms of statins when their benefits were still uncertain.

Two groups of researchers have now examined the accuracy and cost-effectiveness of applying the new guideline in separate studies.

In one study, investigators compared the ACC/AHA eligibility criteria for statin therapy against those of the National Cholesterol Education Program (NCEP), using data from a large prospective community-based asymptomatic cohort of adults aged 35 years and older participating in the Framingham Health Study. They focused on 2,425 “overwhelmingly white” men and women (mean age, 51 years) who underwent CT imaging to identify coronary artery calcium as part of the study, said Dr. Amit Pursnani of the department of radiology at Massachusetts General Hospital and Harvard Medical School, both in Boston, and his associates.

As expected, many more participants were eligible for statins according to the ACC/AHA guideline (39%), compared with the NCEP guideline (14%).

The ACC/AHA guideline was much more accurate at matching statin eligibility with the presence and extent of subclinical atherosclerosis, as measured by coronary artery calcium (CAC) scores. Patients with high-risk CAC scores were much more likely to be allocated to statin therapy using the ACC/AHA guideline (85%) than the NCEP guideline (34%).

During a mean of 9.4 years of follow-up, there were 74 incident CVD events and 43 incident coronary heart disease events. The risk of incident events among statin-eligible vs. noneligible participants was significantly higher when applying the ACC/AHA eligibility guideline, compared with the NCEP guideline. Therefore, the newer guideline was more accurate and efficient at identifying patients at highest risk.

This finding held true across several subgroups of patients, including women and patients at intermediate CVD risk according to the Framingham Risk Score. The latter subgroup is particularly important because they are “the most challenging group in clinical practice for whom to decide to initiate statin therapy,” Dr. Pursnani and his associates wrote (JAMA 2015 July 14 [doi:10.1001/jama.2015.7515]).

“Extrapolating our findings to the approximately 10 million U.S. adults who are newly eligible for statins, we estimate that between 41,000 and 63,000 incident CVD events would be prevented over a 10-year period by adopting the ACC/AHA guidelines,” they said.

In the other study, Ankur Pandya, Ph.D. of the department of health policy and management, Harvard School of Public Health, Boston, and his associates constructed a microsimulation model of 1 million hypothetical U.S. adults aged 45-70 years to examine whether following the ACC/AHA guideline on statin eligibility is cost effective.

The guideline recommends statin therapy for patients who have a 7.5% or higher 10-year ASCVD risk. The model predicted that the health benefits of receiving statins at this risk threshold clearly are worth the additional costs of treating more patients, with an incremental cost-effectiveness ratio of $37,000/quality-adjusted life year (QALY) gained. This is well below the conservative $50,000/QALY threshold used in other health care cost-benefit analyses, Dr. Pandya and his associates said (JAMA 2015 July 14 [doi:10.1001/jama.2015.6822]).

Moreover, the model estimated that statin therapy would still be cost effective if even more lenient ASCVD risk thresholds – 3%-4% – were used. “Shifting from the 7.5% or higher threshold to 3.0% or higher ... was associated with an estimated additional 125,000-160,000 CVD events averted,” they noted.

However, these estimates were influenced by such variables as the price of the statins entered into the model (whether patients used generic or name-brand agents), patients’ level of adherence, and the risk of statin-induced diabetes, which has not yet been quantified for different groups of patients.

Dr. Pursnani’s study was supported by the National Heart, Lung, and Blood Institute’s Framingham Heart Study and the National Institutes of Health. Dr. Pursnani reported having no relevant financial disclosures; one of his associates reported ties to several imaging manufacturers. Dr. Pandya’s study was supported by the Harvard School of Public Health and the NHLBI. Dr. Pandya reported receiving grants from NIH and the AHA, and one of his associates reported receiving personal fees from OptumInsight.

The ACC/AHA guideline for cholesterol management, updated in 2013 to address statin therapy for asymptomatic adults at risk for atherosclerotic cardiovascular diseases (primary prevention), proved more accurate and efficient than the NCEP 2004 guideline at identifying which patients will benefit most from statins because of their increased risk, according to two reports published online July 14 in JAMA.

The updated ACC/AHA guideline shifted the focus of primary prevention to absolute CV risk as estimated by the 10-year ASCVD (atherosclerotic cardiovascular disease) score, rather than by cholesterol levels. Critics voiced concern that applying the new guideline in clinical practice would increase the number of adults eligible for statin therapy by several million, increasing costs and exposing many people to possible harms of statins when their benefits were still uncertain.

Two groups of researchers have now examined the accuracy and cost-effectiveness of applying the new guideline in separate studies.

In one study, investigators compared the ACC/AHA eligibility criteria for statin therapy against those of the National Cholesterol Education Program (NCEP), using data from a large prospective community-based asymptomatic cohort of adults aged 35 years and older participating in the Framingham Health Study. They focused on 2,425 “overwhelmingly white” men and women (mean age, 51 years) who underwent CT imaging to identify coronary artery calcium as part of the study, said Dr. Amit Pursnani of the department of radiology at Massachusetts General Hospital and Harvard Medical School, both in Boston, and his associates.

As expected, many more participants were eligible for statins according to the ACC/AHA guideline (39%), compared with the NCEP guideline (14%).

The ACC/AHA guideline was much more accurate at matching statin eligibility with the presence and extent of subclinical atherosclerosis, as measured by coronary artery calcium (CAC) scores. Patients with high-risk CAC scores were much more likely to be allocated to statin therapy using the ACC/AHA guideline (85%) than the NCEP guideline (34%).

During a mean of 9.4 years of follow-up, there were 74 incident CVD events and 43 incident coronary heart disease events. The risk of incident events among statin-eligible vs. noneligible participants was significantly higher when applying the ACC/AHA eligibility guideline, compared with the NCEP guideline. Therefore, the newer guideline was more accurate and efficient at identifying patients at highest risk.

This finding held true across several subgroups of patients, including women and patients at intermediate CVD risk according to the Framingham Risk Score. The latter subgroup is particularly important because they are “the most challenging group in clinical practice for whom to decide to initiate statin therapy,” Dr. Pursnani and his associates wrote (JAMA 2015 July 14 [doi:10.1001/jama.2015.7515]).

“Extrapolating our findings to the approximately 10 million U.S. adults who are newly eligible for statins, we estimate that between 41,000 and 63,000 incident CVD events would be prevented over a 10-year period by adopting the ACC/AHA guidelines,” they said.

In the other study, Ankur Pandya, Ph.D. of the department of health policy and management, Harvard School of Public Health, Boston, and his associates constructed a microsimulation model of 1 million hypothetical U.S. adults aged 45-70 years to examine whether following the ACC/AHA guideline on statin eligibility is cost effective.

The guideline recommends statin therapy for patients who have a 7.5% or higher 10-year ASCVD risk. The model predicted that the health benefits of receiving statins at this risk threshold clearly are worth the additional costs of treating more patients, with an incremental cost-effectiveness ratio of $37,000/quality-adjusted life year (QALY) gained. This is well below the conservative $50,000/QALY threshold used in other health care cost-benefit analyses, Dr. Pandya and his associates said (JAMA 2015 July 14 [doi:10.1001/jama.2015.6822]).

Moreover, the model estimated that statin therapy would still be cost effective if even more lenient ASCVD risk thresholds – 3%-4% – were used. “Shifting from the 7.5% or higher threshold to 3.0% or higher ... was associated with an estimated additional 125,000-160,000 CVD events averted,” they noted.

However, these estimates were influenced by such variables as the price of the statins entered into the model (whether patients used generic or name-brand agents), patients’ level of adherence, and the risk of statin-induced diabetes, which has not yet been quantified for different groups of patients.

Dr. Pursnani’s study was supported by the National Heart, Lung, and Blood Institute’s Framingham Heart Study and the National Institutes of Health. Dr. Pursnani reported having no relevant financial disclosures; one of his associates reported ties to several imaging manufacturers. Dr. Pandya’s study was supported by the Harvard School of Public Health and the NHLBI. Dr. Pandya reported receiving grants from NIH and the AHA, and one of his associates reported receiving personal fees from OptumInsight.

The ACC/AHA guideline for cholesterol management, updated in 2013 to address statin therapy for asymptomatic adults at risk for atherosclerotic cardiovascular diseases (primary prevention), proved more accurate and efficient than the NCEP 2004 guideline at identifying which patients will benefit most from statins because of their increased risk, according to two reports published online July 14 in JAMA.

The updated ACC/AHA guideline shifted the focus of primary prevention to absolute CV risk as estimated by the 10-year ASCVD (atherosclerotic cardiovascular disease) score, rather than by cholesterol levels. Critics voiced concern that applying the new guideline in clinical practice would increase the number of adults eligible for statin therapy by several million, increasing costs and exposing many people to possible harms of statins when their benefits were still uncertain.

Two groups of researchers have now examined the accuracy and cost-effectiveness of applying the new guideline in separate studies.

In one study, investigators compared the ACC/AHA eligibility criteria for statin therapy against those of the National Cholesterol Education Program (NCEP), using data from a large prospective community-based asymptomatic cohort of adults aged 35 years and older participating in the Framingham Health Study. They focused on 2,425 “overwhelmingly white” men and women (mean age, 51 years) who underwent CT imaging to identify coronary artery calcium as part of the study, said Dr. Amit Pursnani of the department of radiology at Massachusetts General Hospital and Harvard Medical School, both in Boston, and his associates.

As expected, many more participants were eligible for statins according to the ACC/AHA guideline (39%), compared with the NCEP guideline (14%).

The ACC/AHA guideline was much more accurate at matching statin eligibility with the presence and extent of subclinical atherosclerosis, as measured by coronary artery calcium (CAC) scores. Patients with high-risk CAC scores were much more likely to be allocated to statin therapy using the ACC/AHA guideline (85%) than the NCEP guideline (34%).

During a mean of 9.4 years of follow-up, there were 74 incident CVD events and 43 incident coronary heart disease events. The risk of incident events among statin-eligible vs. noneligible participants was significantly higher when applying the ACC/AHA eligibility guideline, compared with the NCEP guideline. Therefore, the newer guideline was more accurate and efficient at identifying patients at highest risk.

This finding held true across several subgroups of patients, including women and patients at intermediate CVD risk according to the Framingham Risk Score. The latter subgroup is particularly important because they are “the most challenging group in clinical practice for whom to decide to initiate statin therapy,” Dr. Pursnani and his associates wrote (JAMA 2015 July 14 [doi:10.1001/jama.2015.7515]).

“Extrapolating our findings to the approximately 10 million U.S. adults who are newly eligible for statins, we estimate that between 41,000 and 63,000 incident CVD events would be prevented over a 10-year period by adopting the ACC/AHA guidelines,” they said.

In the other study, Ankur Pandya, Ph.D. of the department of health policy and management, Harvard School of Public Health, Boston, and his associates constructed a microsimulation model of 1 million hypothetical U.S. adults aged 45-70 years to examine whether following the ACC/AHA guideline on statin eligibility is cost effective.

The guideline recommends statin therapy for patients who have a 7.5% or higher 10-year ASCVD risk. The model predicted that the health benefits of receiving statins at this risk threshold clearly are worth the additional costs of treating more patients, with an incremental cost-effectiveness ratio of $37,000/quality-adjusted life year (QALY) gained. This is well below the conservative $50,000/QALY threshold used in other health care cost-benefit analyses, Dr. Pandya and his associates said (JAMA 2015 July 14 [doi:10.1001/jama.2015.6822]).

Moreover, the model estimated that statin therapy would still be cost effective if even more lenient ASCVD risk thresholds – 3%-4% – were used. “Shifting from the 7.5% or higher threshold to 3.0% or higher ... was associated with an estimated additional 125,000-160,000 CVD events averted,” they noted.

However, these estimates were influenced by such variables as the price of the statins entered into the model (whether patients used generic or name-brand agents), patients’ level of adherence, and the risk of statin-induced diabetes, which has not yet been quantified for different groups of patients.

Dr. Pursnani’s study was supported by the National Heart, Lung, and Blood Institute’s Framingham Heart Study and the National Institutes of Health. Dr. Pursnani reported having no relevant financial disclosures; one of his associates reported ties to several imaging manufacturers. Dr. Pandya’s study was supported by the Harvard School of Public Health and the NHLBI. Dr. Pandya reported receiving grants from NIH and the AHA, and one of his associates reported receiving personal fees from OptumInsight.

The ACC/AHA guideline for cholesterol management, updated in 2013 to address statin therapy for asymptomatic adults at risk for atherosclerotic cardiovascular diseases (primary prevention), proved more accurate and efficient than the NCEP 2004 guideline at identifying which patients will benefit most from statins because of their increased risk, according to two reports published online July 14 in JAMA.

The updated ACC/AHA guideline shifted the focus of primary prevention to absolute CV risk as estimated by the 10-year ASCVD (atherosclerotic cardiovascular disease) score, rather than by cholesterol levels. Critics voiced concern that applying the new guideline in clinical practice would increase the number of adults eligible for statin therapy by several million, increasing costs and exposing many people to possible harms of statins when their benefits were still uncertain.

Two groups of researchers have now examined the accuracy and cost-effectiveness of applying the new guideline in separate studies.

In one study, investigators compared the ACC/AHA eligibility criteria for statin therapy against those of the National Cholesterol Education Program (NCEP), using data from a large prospective community-based asymptomatic cohort of adults aged 35 years and older participating in the Framingham Health Study. They focused on 2,425 “overwhelmingly white” men and women (mean age, 51 years) who underwent CT imaging to identify coronary artery calcium as part of the study, said Dr. Amit Pursnani of the department of radiology at Massachusetts General Hospital and Harvard Medical School, both in Boston, and his associates.

As expected, many more participants were eligible for statins according to the ACC/AHA guideline (39%), compared with the NCEP guideline (14%).

The ACC/AHA guideline was much more accurate at matching statin eligibility with the presence and extent of subclinical atherosclerosis, as measured by coronary artery calcium (CAC) scores. Patients with high-risk CAC scores were much more likely to be allocated to statin therapy using the ACC/AHA guideline (85%) than the NCEP guideline (34%).

During a mean of 9.4 years of follow-up, there were 74 incident CVD events and 43 incident coronary heart disease events. The risk of incident events among statin-eligible vs. noneligible participants was significantly higher when applying the ACC/AHA eligibility guideline, compared with the NCEP guideline. Therefore, the newer guideline was more accurate and efficient at identifying patients at highest risk.

This finding held true across several subgroups of patients, including women and patients at intermediate CVD risk according to the Framingham Risk Score. The latter subgroup is particularly important because they are “the most challenging group in clinical practice for whom to decide to initiate statin therapy,” Dr. Pursnani and his associates wrote (JAMA 2015 July 14 [doi:10.1001/jama.2015.7515]).

“Extrapolating our findings to the approximately 10 million U.S. adults who are newly eligible for statins, we estimate that between 41,000 and 63,000 incident CVD events would be prevented over a 10-year period by adopting the ACC/AHA guidelines,” they said.

In the other study, Ankur Pandya, Ph.D. of the department of health policy and management, Harvard School of Public Health, Boston, and his associates constructed a microsimulation model of 1 million hypothetical U.S. adults aged 45-70 years to examine whether following the ACC/AHA guideline on statin eligibility is cost effective.

The guideline recommends statin therapy for patients who have a 7.5% or higher 10-year ASCVD risk. The model predicted that the health benefits of receiving statins at this risk threshold clearly are worth the additional costs of treating more patients, with an incremental cost-effectiveness ratio of $37,000/quality-adjusted life year (QALY) gained. This is well below the conservative $50,000/QALY threshold used in other health care cost-benefit analyses, Dr. Pandya and his associates said (JAMA 2015 July 14 [doi:10.1001/jama.2015.6822]).

Moreover, the model estimated that statin therapy would still be cost effective if even more lenient ASCVD risk thresholds – 3%-4% – were used. “Shifting from the 7.5% or higher threshold to 3.0% or higher ... was associated with an estimated additional 125,000-160,000 CVD events averted,” they noted.

However, these estimates were influenced by such variables as the price of the statins entered into the model (whether patients used generic or name-brand agents), patients’ level of adherence, and the risk of statin-induced diabetes, which has not yet been quantified for different groups of patients.

Dr. Pursnani’s study was supported by the National Heart, Lung, and Blood Institute’s Framingham Heart Study and the National Institutes of Health. Dr. Pursnani reported having no relevant financial disclosures; one of his associates reported ties to several imaging manufacturers. Dr. Pandya’s study was supported by the Harvard School of Public Health and the NHLBI. Dr. Pandya reported receiving grants from NIH and the AHA, and one of his associates reported receiving personal fees from OptumInsight.

The ACC/AHA guideline for cholesterol management, updated in 2013 to address statin therapy for asymptomatic adults at risk for atherosclerotic cardiovascular diseases (primary prevention), proved more accurate and efficient than the NCEP 2004 guideline at identifying which patients will benefit most from statins because of their increased risk, according to two reports published online July 14 in JAMA.

The updated ACC/AHA guideline shifted the focus of primary prevention to absolute CV risk as estimated by the 10-year ASCVD (atherosclerotic cardiovascular disease) score, rather than by cholesterol levels. Critics voiced concern that applying the new guideline in clinical practice would increase the number of adults eligible for statin therapy by several million, increasing costs and exposing many people to possible harms of statins when their benefits were still uncertain.

Two groups of researchers have now examined the accuracy and cost-effectiveness of applying the new guideline in separate studies.

In one study, investigators compared the ACC/AHA eligibility criteria for statin therapy against those of the National Cholesterol Education Program (NCEP), using data from a large prospective community-based asymptomatic cohort of adults aged 35 years and older participating in the Framingham Health Study. They focused on 2,425 “overwhelmingly white” men and women (mean age, 51 years) who underwent CT imaging to identify coronary artery calcium as part of the study, said Dr. Amit Pursnani of the department of radiology at Massachusetts General Hospital and Harvard Medical School, both in Boston, and his associates.

As expected, many more participants were eligible for statins according to the ACC/AHA guideline (39%), compared with the NCEP guideline (14%).

The ACC/AHA guideline was much more accurate at matching statin eligibility with the presence and extent of subclinical atherosclerosis, as measured by coronary artery calcium (CAC) scores. Patients with high-risk CAC scores were much more likely to be allocated to statin therapy using the ACC/AHA guideline (85%) than the NCEP guideline (34%).

During a mean of 9.4 years of follow-up, there were 74 incident CVD events and 43 incident coronary heart disease events. The risk of incident events among statin-eligible vs. noneligible participants was significantly higher when applying the ACC/AHA eligibility guideline, compared with the NCEP guideline. Therefore, the newer guideline was more accurate and efficient at identifying patients at highest risk.

This finding held true across several subgroups of patients, including women and patients at intermediate CVD risk according to the Framingham Risk Score. The latter subgroup is particularly important because they are “the most challenging group in clinical practice for whom to decide to initiate statin therapy,” Dr. Pursnani and his associates wrote (JAMA 2015 July 14 [doi:10.1001/jama.2015.7515]).

“Extrapolating our findings to the approximately 10 million U.S. adults who are newly eligible for statins, we estimate that between 41,000 and 63,000 incident CVD events would be prevented over a 10-year period by adopting the ACC/AHA guidelines,” they said.

In the other study, Ankur Pandya, Ph.D. of the department of health policy and management, Harvard School of Public Health, Boston, and his associates constructed a microsimulation model of 1 million hypothetical U.S. adults aged 45-70 years to examine whether following the ACC/AHA guideline on statin eligibility is cost effective.

The guideline recommends statin therapy for patients who have a 7.5% or higher 10-year ASCVD risk. The model predicted that the health benefits of receiving statins at this risk threshold clearly are worth the additional costs of treating more patients, with an incremental cost-effectiveness ratio of $37,000/quality-adjusted life year (QALY) gained. This is well below the conservative $50,000/QALY threshold used in other health care cost-benefit analyses, Dr. Pandya and his associates said (JAMA 2015 July 14 [doi:10.1001/jama.2015.6822]).

Moreover, the model estimated that statin therapy would still be cost effective if even more lenient ASCVD risk thresholds – 3%-4% – were used. “Shifting from the 7.5% or higher threshold to 3.0% or higher ... was associated with an estimated additional 125,000-160,000 CVD events averted,” they noted.

However, these estimates were influenced by such variables as the price of the statins entered into the model (whether patients used generic or name-brand agents), patients’ level of adherence, and the risk of statin-induced diabetes, which has not yet been quantified for different groups of patients.

Dr. Pursnani’s study was supported by the National Heart, Lung, and Blood Institute’s Framingham Heart Study and the National Institutes of Health. Dr. Pursnani reported having no relevant financial disclosures; one of his associates reported ties to several imaging manufacturers. Dr. Pandya’s study was supported by the Harvard School of Public Health and the NHLBI. Dr. Pandya reported receiving grants from NIH and the AHA, and one of his associates reported receiving personal fees from OptumInsight.

Patiromer, an orally administered potassium-binding polymer, significantly decreased serum potassium in adults who had diabetic kidney disease with hyperkalemia in a phase II study funded by and conducted with the manufacturer.

Patiromer consists of tiny, smooth beads in a liquid suspension and works by binding potassium throughout the GI tract, allowing it to be excreted in the feces. After preliminary studies demonstrated the agent’s usefulness in reducing hyperkalemia for up to 12 weeks in high-risk patients, researchers performed this open-label, uncontrolled trial to determine optimal dosing and to assess its longer-term safety. The findings were reported online July 14 in JAMA.

All four doses of patiromer studied significantly reduced serum potassium, beginning within 48 hours of the initial dose and continuing through all 52 weeks of treatment. The proportion of patients whose potassium levels reached target range at all scheduled visits ranged from 83% to 93% in those who had mild hyperkalemia at baseline and from 77% to 95% in those who had moderate hyperkalemia at baseline. Hyperkalemia quickly reappeared when patiromer treatment ended, reverting to baseline levels, wrote Dr. George L. Bakris of the ASH Comprehensive Hypertension Center, division of endocrinology, diabetes, and metabolism, University of Chicago, and his associates.

Study participants were 222 white patients with mild and 84 with moderate hyperkalemia (mean age, 66 years). All had type 2 diabetes and hypertension, and approximately one-third had heart failure; 65% had stage 3 and 22% had stage 4 chronic kidney disease (CKD), All were taking an ACE inhibitor, an angiotensin II receptor blocker, or both, with or without spironolactone. At 48 medical centers in five European countries, they were randomly assigned to receive one of four doses of patiromer that could be titrated up or down as needed for 4 weeks. Patients then entered an 8-week treatment phase, after which they continued maintenance therapy for a further 40 weeks (JAMA 2015 July 14 [doi:10.1001/jama.2015.7446]).

The optimal doses of patiromer were found to be the two lowest doses assessed in this study, 8.4 g daily and 16.8 g daily, which significantly decreased serum potassium without provoking hypokalemia. These doses will now be tested in a phase III study.

The most frequent treatment-related adverse events in the phase II study were nonsevere hypomagnesemia (7.2%), constipation (4.6%), and diarrhea (2.7%). A total of 28 patients (9.2%) developed at least one adverse event prompting them to discontinue patiromer, including worsening of CKD (which was considered unrelated to treatment), hypokalemia (5 patients), and one hypertensive crisis (also unrelated to treatment). No dose-related edema was noted, and there were no clinically relevant changes in serum calcium or phosphate levels.

Patiromer, an orally administered potassium-binding polymer, significantly decreased serum potassium in adults who had diabetic kidney disease with hyperkalemia in a phase II study funded by and conducted with the manufacturer.

Patiromer consists of tiny, smooth beads in a liquid suspension and works by binding potassium throughout the GI tract, allowing it to be excreted in the feces. After preliminary studies demonstrated the agent’s usefulness in reducing hyperkalemia for up to 12 weeks in high-risk patients, researchers performed this open-label, uncontrolled trial to determine optimal dosing and to assess its longer-term safety. The findings were reported online July 14 in JAMA.

All four doses of patiromer studied significantly reduced serum potassium, beginning within 48 hours of the initial dose and continuing through all 52 weeks of treatment. The proportion of patients whose potassium levels reached target range at all scheduled visits ranged from 83% to 93% in those who had mild hyperkalemia at baseline and from 77% to 95% in those who had moderate hyperkalemia at baseline. Hyperkalemia quickly reappeared when patiromer treatment ended, reverting to baseline levels, wrote Dr. George L. Bakris of the ASH Comprehensive Hypertension Center, division of endocrinology, diabetes, and metabolism, University of Chicago, and his associates.

Study participants were 222 white patients with mild and 84 with moderate hyperkalemia (mean age, 66 years). All had type 2 diabetes and hypertension, and approximately one-third had heart failure; 65% had stage 3 and 22% had stage 4 chronic kidney disease (CKD), All were taking an ACE inhibitor, an angiotensin II receptor blocker, or both, with or without spironolactone. At 48 medical centers in five European countries, they were randomly assigned to receive one of four doses of patiromer that could be titrated up or down as needed for 4 weeks. Patients then entered an 8-week treatment phase, after which they continued maintenance therapy for a further 40 weeks (JAMA 2015 July 14 [doi:10.1001/jama.2015.7446]).

The optimal doses of patiromer were found to be the two lowest doses assessed in this study, 8.4 g daily and 16.8 g daily, which significantly decreased serum potassium without provoking hypokalemia. These doses will now be tested in a phase III study.

The most frequent treatment-related adverse events in the phase II study were nonsevere hypomagnesemia (7.2%), constipation (4.6%), and diarrhea (2.7%). A total of 28 patients (9.2%) developed at least one adverse event prompting them to discontinue patiromer, including worsening of CKD (which was considered unrelated to treatment), hypokalemia (5 patients), and one hypertensive crisis (also unrelated to treatment). No dose-related edema was noted, and there were no clinically relevant changes in serum calcium or phosphate levels.

Patiromer, an orally administered potassium-binding polymer, significantly decreased serum potassium in adults who had diabetic kidney disease with hyperkalemia in a phase II study funded by and conducted with the manufacturer.

Patiromer consists of tiny, smooth beads in a liquid suspension and works by binding potassium throughout the GI tract, allowing it to be excreted in the feces. After preliminary studies demonstrated the agent’s usefulness in reducing hyperkalemia for up to 12 weeks in high-risk patients, researchers performed this open-label, uncontrolled trial to determine optimal dosing and to assess its longer-term safety. The findings were reported online July 14 in JAMA.

All four doses of patiromer studied significantly reduced serum potassium, beginning within 48 hours of the initial dose and continuing through all 52 weeks of treatment. The proportion of patients whose potassium levels reached target range at all scheduled visits ranged from 83% to 93% in those who had mild hyperkalemia at baseline and from 77% to 95% in those who had moderate hyperkalemia at baseline. Hyperkalemia quickly reappeared when patiromer treatment ended, reverting to baseline levels, wrote Dr. George L. Bakris of the ASH Comprehensive Hypertension Center, division of endocrinology, diabetes, and metabolism, University of Chicago, and his associates.

Study participants were 222 white patients with mild and 84 with moderate hyperkalemia (mean age, 66 years). All had type 2 diabetes and hypertension, and approximately one-third had heart failure; 65% had stage 3 and 22% had stage 4 chronic kidney disease (CKD), All were taking an ACE inhibitor, an angiotensin II receptor blocker, or both, with or without spironolactone. At 48 medical centers in five European countries, they were randomly assigned to receive one of four doses of patiromer that could be titrated up or down as needed for 4 weeks. Patients then entered an 8-week treatment phase, after which they continued maintenance therapy for a further 40 weeks (JAMA 2015 July 14 [doi:10.1001/jama.2015.7446]).

The optimal doses of patiromer were found to be the two lowest doses assessed in this study, 8.4 g daily and 16.8 g daily, which significantly decreased serum potassium without provoking hypokalemia. These doses will now be tested in a phase III study.

The most frequent treatment-related adverse events in the phase II study were nonsevere hypomagnesemia (7.2%), constipation (4.6%), and diarrhea (2.7%). A total of 28 patients (9.2%) developed at least one adverse event prompting them to discontinue patiromer, including worsening of CKD (which was considered unrelated to treatment), hypokalemia (5 patients), and one hypertensive crisis (also unrelated to treatment). No dose-related edema was noted, and there were no clinically relevant changes in serum calcium or phosphate levels.

Head contact with other players, not with the ball, is the main source of concussions among high-school soccer players of both sexes, according to a report published online July 13 in JAMA Pediatrics.

Several studies have shown that “heading” the ball during soccer practices and games is responsible for many soccer-related concussions, and some have called for banning such heading, especially among children and adolescents, to make the sport safer. But until now, no large study has examined the exact mechanism of head injuries among school-aged soccer players, so such prevention efforts cannot be considered evidence based, said R. Dawn Comstock, Ph.D., an epidemiologist at the University of Colorado Denver, Aurora, and her associates.

©James Boulette/iStockphoto.com

The investigators performed a retrospective analysis of data from a large, Internet-based sports injury surveillance study, focusing on concussions sustained during soccer practices or games which required medical attention and restricted the athlete’s participation for 1 or more days. They assessed nationally representative samples of 100 high schools every year for a 9-year period. There were 627 concussions during 1,393,753 athletic exposures among girls (4.50 per 10,000 exposures) and 442 concussions during 1,592,238 athletic exposures among boys (2.78 per 10,000 exposures).

The most common mechanism of concussion was player-to-player contact among both boys (68.8% of concussions) and girls (51.3% of concussions). In contrast, contact with the ball accounted for 17% of concussions among boys and 29% among girls.

The number and types of concussion symptoms were the same, regardless of whether the concussion was caused by player-to-player contact or player-to-ball contact. However, symptom resolution time was slightly but significantly longer for both boys and girls when the concussion was caused by collision with a ball or goal post (JAMA Pediatr. 2015 July 13 [doi:10.1001/jamapediatrics.2015.1062]).

“We postulate that banning heading from soccer will have limited effectiveness as a primary prevention mechanism (i.e., in preventing concussion injuries) unless such a ban is combined with concurrent efforts to reduce athlete-athlete contact throughout the game,” Dr. Comstock and her associates said.

Moreover, “it may be culturally more tolerable to the soccer community to attempt to reduce athlete-athlete contact across all phases of play through better enforcement of existing rules, enhanced education of athletes on the rules of the game, and improved coaching of activities such as heading,” rather than simply banning heading, they added.

Head contact with other players, not with the ball, is the main source of concussions among high-school soccer players of both sexes, according to a report published online July 13 in JAMA Pediatrics.

Several studies have shown that “heading” the ball during soccer practices and games is responsible for many soccer-related concussions, and some have called for banning such heading, especially among children and adolescents, to make the sport safer. But until now, no large study has examined the exact mechanism of head injuries among school-aged soccer players, so such prevention efforts cannot be considered evidence based, said R. Dawn Comstock, Ph.D., an epidemiologist at the University of Colorado Denver, Aurora, and her associates.

©James Boulette/iStockphoto.com

The investigators performed a retrospective analysis of data from a large, Internet-based sports injury surveillance study, focusing on concussions sustained during soccer practices or games which required medical attention and restricted the athlete’s participation for 1 or more days. They assessed nationally representative samples of 100 high schools every year for a 9-year period. There were 627 concussions during 1,393,753 athletic exposures among girls (4.50 per 10,000 exposures) and 442 concussions during 1,592,238 athletic exposures among boys (2.78 per 10,000 exposures).

The most common mechanism of concussion was player-to-player contact among both boys (68.8% of concussions) and girls (51.3% of concussions). In contrast, contact with the ball accounted for 17% of concussions among boys and 29% among girls.

The number and types of concussion symptoms were the same, regardless of whether the concussion was caused by player-to-player contact or player-to-ball contact. However, symptom resolution time was slightly but significantly longer for both boys and girls when the concussion was caused by collision with a ball or goal post (JAMA Pediatr. 2015 July 13 [doi:10.1001/jamapediatrics.2015.1062]).

“We postulate that banning heading from soccer will have limited effectiveness as a primary prevention mechanism (i.e., in preventing concussion injuries) unless such a ban is combined with concurrent efforts to reduce athlete-athlete contact throughout the game,” Dr. Comstock and her associates said.

Moreover, “it may be culturally more tolerable to the soccer community to attempt to reduce athlete-athlete contact across all phases of play through better enforcement of existing rules, enhanced education of athletes on the rules of the game, and improved coaching of activities such as heading,” rather than simply banning heading, they added.

Head contact with other players, not with the ball, is the main source of concussions among high-school soccer players of both sexes, according to a report published online July 13 in JAMA Pediatrics.

Several studies have shown that “heading” the ball during soccer practices and games is responsible for many soccer-related concussions, and some have called for banning such heading, especially among children and adolescents, to make the sport safer. But until now, no large study has examined the exact mechanism of head injuries among school-aged soccer players, so such prevention efforts cannot be considered evidence based, said R. Dawn Comstock, Ph.D., an epidemiologist at the University of Colorado Denver, Aurora, and her associates.

©James Boulette/iStockphoto.com

The investigators performed a retrospective analysis of data from a large, Internet-based sports injury surveillance study, focusing on concussions sustained during soccer practices or games which required medical attention and restricted the athlete’s participation for 1 or more days. They assessed nationally representative samples of 100 high schools every year for a 9-year period. There were 627 concussions during 1,393,753 athletic exposures among girls (4.50 per 10,000 exposures) and 442 concussions during 1,592,238 athletic exposures among boys (2.78 per 10,000 exposures).

The most common mechanism of concussion was player-to-player contact among both boys (68.8% of concussions) and girls (51.3% of concussions). In contrast, contact with the ball accounted for 17% of concussions among boys and 29% among girls.

The number and types of concussion symptoms were the same, regardless of whether the concussion was caused by player-to-player contact or player-to-ball contact. However, symptom resolution time was slightly but significantly longer for both boys and girls when the concussion was caused by collision with a ball or goal post (JAMA Pediatr. 2015 July 13 [doi:10.1001/jamapediatrics.2015.1062]).

“We postulate that banning heading from soccer will have limited effectiveness as a primary prevention mechanism (i.e., in preventing concussion injuries) unless such a ban is combined with concurrent efforts to reduce athlete-athlete contact throughout the game,” Dr. Comstock and her associates said.

Moreover, “it may be culturally more tolerable to the soccer community to attempt to reduce athlete-athlete contact across all phases of play through better enforcement of existing rules, enhanced education of athletes on the rules of the game, and improved coaching of activities such as heading,” rather than simply banning heading, they added.

Approximately half of cases of COPD in older adults appear to stem from low forced expiratory volume in 1 second in early adulthood that declines at a normal rate, rather than the accelerated decline in normal FEV₁ that has been considered “an obligate feature” of the disease, according to a report published online July 9 in the New England Journal of Medicine.

“Even though we cannot precisely estimate the contribution of the trajectory of low maximally attained lung function to COPD using our study design, our results suggest that this contribution may be substantial and that populations of patients with COPD comprise persons with different rates of decline in FEV₁,” said Dr. Peter Lange of the Institute of Public Health, Copenhagen University, and his associates.

©designer491/Thinkstockphotos.com

“This observation is in accord with previous studies and suggests that a substantial proportion of patients with COPD may not have had a rapid decline in FEV₁, which for decades has been regarded as the hallmark of COPD,” the researchers added.

Previous authors have questioned the prevailing paradigm of COPD pathogenesis, but the possibility that low lung function in early adulthood can lead to later COPD has never been examined in a long-term, prospective study.

Dr. Lange and his colleagues explored that question using data from three large, independent longitudinal cohort studies: the Framingham Offspring Cohort, the Copenhagen City Heart Study, and the Lovelace Smokers Cohort. A total of 2,864 participants in the studies underwent serial spirometry beginning in early adulthood and continuing through approximately 22 years of follow-up. That allowed Dr. Lange and his associates to track their decline in lung function over time.

Overall, 332 participants (12% of the entire study population) had grade 2 or higher COPD at final follow-up when they were age 55 years or older, according to the Global Initiative for Chronic Obstructive Lung Disease (GOLD) grading system.

A total of 48% of the COPD patients followed the typical trajectory of a normal FEV₁ at baseline that declined an average of 53 mL per year. However, 52% followed a different trajectory, with a low FEV₁ at baseline that declined only 27 mL per year, the investigators said (N. Engl. J. Med. 2015;373:111-22).

Compared with participants who had normal FEV₁ at baseline, those with initially low FEV₁ were significantly more likely to be hospitalized with respiratory disease (25% vs. 18%), to be admitted for COPD (9% vs. 4%), and to die (32% vs. 25%) during follow-up.

People with a low FEV₁ at baseline “had a risk of COPD at midlife that was more than three times as high as the risk among those with a higher baseline FEV₁ (26% vs 7%),” Dr. Lange and his associates added.

The three cohort studies that contributed data to this analysis were funded by the National Heart, Lung, and Blood Institute, GlaxoSmithKline, the Capital Region of Copenhagen, the Danish Heart Foundation, the Danish Lung Foundation, the Velux Foundation, the state of New Mexico, and the National Institutes of Health. Dr. Lange reported receiving grants and personal fees from Almirall, AstraZeneca, Boehringer Ingelheim, Chiesi, GlaxoSmithKline, Norpharma, Novartis, Pfizer, Takeda, and TEVA. His associates reported ties to numerous industry sources.

Approximately half of cases of COPD in older adults appear to stem from low forced expiratory volume in 1 second in early adulthood that declines at a normal rate, rather than the accelerated decline in normal FEV₁ that has been considered “an obligate feature” of the disease, according to a report published online July 9 in the New England Journal of Medicine.

“Even though we cannot precisely estimate the contribution of the trajectory of low maximally attained lung function to COPD using our study design, our results suggest that this contribution may be substantial and that populations of patients with COPD comprise persons with different rates of decline in FEV₁,” said Dr. Peter Lange of the Institute of Public Health, Copenhagen University, and his associates.

©designer491/Thinkstockphotos.com

“This observation is in accord with previous studies and suggests that a substantial proportion of patients with COPD may not have had a rapid decline in FEV₁, which for decades has been regarded as the hallmark of COPD,” the researchers added.

Previous authors have questioned the prevailing paradigm of COPD pathogenesis, but the possibility that low lung function in early adulthood can lead to later COPD has never been examined in a long-term, prospective study.

Dr. Lange and his colleagues explored that question using data from three large, independent longitudinal cohort studies: the Framingham Offspring Cohort, the Copenhagen City Heart Study, and the Lovelace Smokers Cohort. A total of 2,864 participants in the studies underwent serial spirometry beginning in early adulthood and continuing through approximately 22 years of follow-up. That allowed Dr. Lange and his associates to track their decline in lung function over time.

Overall, 332 participants (12% of the entire study population) had grade 2 or higher COPD at final follow-up when they were age 55 years or older, according to the Global Initiative for Chronic Obstructive Lung Disease (GOLD) grading system.

A total of 48% of the COPD patients followed the typical trajectory of a normal FEV₁ at baseline that declined an average of 53 mL per year. However, 52% followed a different trajectory, with a low FEV₁ at baseline that declined only 27 mL per year, the investigators said (N. Engl. J. Med. 2015;373:111-22).

Compared with participants who had normal FEV₁ at baseline, those with initially low FEV₁ were significantly more likely to be hospitalized with respiratory disease (25% vs. 18%), to be admitted for COPD (9% vs. 4%), and to die (32% vs. 25%) during follow-up.

People with a low FEV₁ at baseline “had a risk of COPD at midlife that was more than three times as high as the risk among those with a higher baseline FEV₁ (26% vs 7%),” Dr. Lange and his associates added.

The three cohort studies that contributed data to this analysis were funded by the National Heart, Lung, and Blood Institute, GlaxoSmithKline, the Capital Region of Copenhagen, the Danish Heart Foundation, the Danish Lung Foundation, the Velux Foundation, the state of New Mexico, and the National Institutes of Health. Dr. Lange reported receiving grants and personal fees from Almirall, AstraZeneca, Boehringer Ingelheim, Chiesi, GlaxoSmithKline, Norpharma, Novartis, Pfizer, Takeda, and TEVA. His associates reported ties to numerous industry sources.

Approximately half of cases of COPD in older adults appear to stem from low forced expiratory volume in 1 second in early adulthood that declines at a normal rate, rather than the accelerated decline in normal FEV₁ that has been considered “an obligate feature” of the disease, according to a report published online July 9 in the New England Journal of Medicine.

“Even though we cannot precisely estimate the contribution of the trajectory of low maximally attained lung function to COPD using our study design, our results suggest that this contribution may be substantial and that populations of patients with COPD comprise persons with different rates of decline in FEV₁,” said Dr. Peter Lange of the Institute of Public Health, Copenhagen University, and his associates.

©designer491/Thinkstockphotos.com

“This observation is in accord with previous studies and suggests that a substantial proportion of patients with COPD may not have had a rapid decline in FEV₁, which for decades has been regarded as the hallmark of COPD,” the researchers added.

Previous authors have questioned the prevailing paradigm of COPD pathogenesis, but the possibility that low lung function in early adulthood can lead to later COPD has never been examined in a long-term, prospective study.

Dr. Lange and his colleagues explored that question using data from three large, independent longitudinal cohort studies: the Framingham Offspring Cohort, the Copenhagen City Heart Study, and the Lovelace Smokers Cohort. A total of 2,864 participants in the studies underwent serial spirometry beginning in early adulthood and continuing through approximately 22 years of follow-up. That allowed Dr. Lange and his associates to track their decline in lung function over time.

Overall, 332 participants (12% of the entire study population) had grade 2 or higher COPD at final follow-up when they were age 55 years or older, according to the Global Initiative for Chronic Obstructive Lung Disease (GOLD) grading system.

A total of 48% of the COPD patients followed the typical trajectory of a normal FEV₁ at baseline that declined an average of 53 mL per year. However, 52% followed a different trajectory, with a low FEV₁ at baseline that declined only 27 mL per year, the investigators said (N. Engl. J. Med. 2015;373:111-22).

Compared with participants who had normal FEV₁ at baseline, those with initially low FEV₁ were significantly more likely to be hospitalized with respiratory disease (25% vs. 18%), to be admitted for COPD (9% vs. 4%), and to die (32% vs. 25%) during follow-up.

People with a low FEV₁ at baseline “had a risk of COPD at midlife that was more than three times as high as the risk among those with a higher baseline FEV₁ (26% vs 7%),” Dr. Lange and his associates added.

The three cohort studies that contributed data to this analysis were funded by the National Heart, Lung, and Blood Institute, GlaxoSmithKline, the Capital Region of Copenhagen, the Danish Heart Foundation, the Danish Lung Foundation, the Velux Foundation, the state of New Mexico, and the National Institutes of Health. Dr. Lange reported receiving grants and personal fees from Almirall, AstraZeneca, Boehringer Ingelheim, Chiesi, GlaxoSmithKline, Norpharma, Novartis, Pfizer, Takeda, and TEVA. His associates reported ties to numerous industry sources.

Guselkumab, a monoclonal antibody that specifically inhibits interleukin-23 signaling, was safe and more effective than placebo or adalimumab against plaque psoriasis in a phase II clinical trial, according to a report published online July 9 in the New England Journal of Medicine.

The 1-year randomized double-blind study, funded and administered by the maker of guselkumab, involved 293 adult patients treated at 31 sites in North America and 12 in Europe. The median duration of disease was 19 years. Study participants were randomly assigned to receive one of five subcutaneous doses of the agent (5 mg, 15 mg, 50 mg, 100 mg, or 200 mg) at two different dosing intervals (208 patients), matching placebo (42 patients), or adalimumab (43 patients) for 40 weeks and were followed for an additional 12 weeks. At 16 weeks, patients in the placebo group crossed over to receive 100 mg of guselkumab every 8 weeks, said Dr. Kenneth B. Gordon of Northwestern University, Chicago, and his associates.

Courtesy Wikimedia Commons/James Heilman, MD/Creative Commons License

The primary efficacy endpoint – the proportion of patients at week 16 with a Physician’s Global Assessment score of 0 or 1 – was significantly higher in every guselkumab dosing group (34%, 61%, 79%, 86%, and 83%, respectively) than in the placebo group (7%). In addition, the proportion of patients showing a 75%, 90%, or 100% improvement in Psoriasis Area and Severity Index score was significantly higher in each guselkumab group than in the placebo group. Scores on the Dermatology Life Quality Index also showed significantly greater improvement from baseline to week 16 in the guselkumab groups.

The findings were similar when patients taking the higher doses of guselkumab were compared with those taking adalimumab. At week 16, the proportion of patients with a PGA score of 0 or 1 was 58% with adalimumab, compared with 79%, 86%, and 83% at the highest doses of guselkumab (50 mg, 100 mg, or 200 mg). And at week 40, the proportion of patients with a PGA score of 0 or 1 was significantly higher in those taking 50 mg (71%), 100 mg (77%), or 200 mg (81%) guselkumab than in patients taking adalimumab (49%). The response to guselkumab was noted at the earliest patient assessment at week 4, peaked at week 20, and was maintained through week 40, Dr. Gordon and his associates said (N. Engl. J. Med. 2015 July 9 [doi:10.1056/NEJMoa1501646]).

The rates of adverse events, serious adverse events, and infections were similar across all the treatment groups. At week 16, infections were reported in 20% of patients taking guselkumab, 14% of those taking placebo, and 12% of those taking adalimumab. At final follow-up, infections were reported in 30% of patients taking guselkumab and 35% taking adalimumab. This study had a limited ability to assess uncommon adverse events; three patients taking guselkumab had major cardiovascular events during treatment, but “it is difficult to interpret the significance” of such events, the investigators said.

They added that larger and longer-term phase III trials are now underway to further assess the efficacy and safety of guselkumab for this indication. Moreover, their study results “validate the use of interleukin-23 as a therapeutic target by showing that therapy involving selective antagonism of this single cytokine in patients with moderate to severe plaque psoriasis is highly efficacious, as compared with adalimumab therapy,” Dr. Gordon and his associates said.

Guselkumab, a monoclonal antibody that specifically inhibits interleukin-23 signaling, was safe and more effective than placebo or adalimumab against plaque psoriasis in a phase II clinical trial, according to a report published online July 9 in the New England Journal of Medicine.

The 1-year randomized double-blind study, funded and administered by the maker of guselkumab, involved 293 adult patients treated at 31 sites in North America and 12 in Europe. The median duration of disease was 19 years. Study participants were randomly assigned to receive one of five subcutaneous doses of the agent (5 mg, 15 mg, 50 mg, 100 mg, or 200 mg) at two different dosing intervals (208 patients), matching placebo (42 patients), or adalimumab (43 patients) for 40 weeks and were followed for an additional 12 weeks. At 16 weeks, patients in the placebo group crossed over to receive 100 mg of guselkumab every 8 weeks, said Dr. Kenneth B. Gordon of Northwestern University, Chicago, and his associates.

Courtesy Wikimedia Commons/James Heilman, MD/Creative Commons License

The primary efficacy endpoint – the proportion of patients at week 16 with a Physician’s Global Assessment score of 0 or 1 – was significantly higher in every guselkumab dosing group (34%, 61%, 79%, 86%, and 83%, respectively) than in the placebo group (7%). In addition, the proportion of patients showing a 75%, 90%, or 100% improvement in Psoriasis Area and Severity Index score was significantly higher in each guselkumab group than in the placebo group. Scores on the Dermatology Life Quality Index also showed significantly greater improvement from baseline to week 16 in the guselkumab groups.

The findings were similar when patients taking the higher doses of guselkumab were compared with those taking adalimumab. At week 16, the proportion of patients with a PGA score of 0 or 1 was 58% with adalimumab, compared with 79%, 86%, and 83% at the highest doses of guselkumab (50 mg, 100 mg, or 200 mg). And at week 40, the proportion of patients with a PGA score of 0 or 1 was significantly higher in those taking 50 mg (71%), 100 mg (77%), or 200 mg (81%) guselkumab than in patients taking adalimumab (49%). The response to guselkumab was noted at the earliest patient assessment at week 4, peaked at week 20, and was maintained through week 40, Dr. Gordon and his associates said (N. Engl. J. Med. 2015 July 9 [doi:10.1056/NEJMoa1501646]).

The rates of adverse events, serious adverse events, and infections were similar across all the treatment groups. At week 16, infections were reported in 20% of patients taking guselkumab, 14% of those taking placebo, and 12% of those taking adalimumab. At final follow-up, infections were reported in 30% of patients taking guselkumab and 35% taking adalimumab. This study had a limited ability to assess uncommon adverse events; three patients taking guselkumab had major cardiovascular events during treatment, but “it is difficult to interpret the significance” of such events, the investigators said.

They added that larger and longer-term phase III trials are now underway to further assess the efficacy and safety of guselkumab for this indication. Moreover, their study results “validate the use of interleukin-23 as a therapeutic target by showing that therapy involving selective antagonism of this single cytokine in patients with moderate to severe plaque psoriasis is highly efficacious, as compared with adalimumab therapy,” Dr. Gordon and his associates said.

Guselkumab, a monoclonal antibody that specifically inhibits interleukin-23 signaling, was safe and more effective than placebo or adalimumab against plaque psoriasis in a phase II clinical trial, according to a report published online July 9 in the New England Journal of Medicine.

The 1-year randomized double-blind study, funded and administered by the maker of guselkumab, involved 293 adult patients treated at 31 sites in North America and 12 in Europe. The median duration of disease was 19 years. Study participants were randomly assigned to receive one of five subcutaneous doses of the agent (5 mg, 15 mg, 50 mg, 100 mg, or 200 mg) at two different dosing intervals (208 patients), matching placebo (42 patients), or adalimumab (43 patients) for 40 weeks and were followed for an additional 12 weeks. At 16 weeks, patients in the placebo group crossed over to receive 100 mg of guselkumab every 8 weeks, said Dr. Kenneth B. Gordon of Northwestern University, Chicago, and his associates.

Courtesy Wikimedia Commons/James Heilman, MD/Creative Commons License

The primary efficacy endpoint – the proportion of patients at week 16 with a Physician’s Global Assessment score of 0 or 1 – was significantly higher in every guselkumab dosing group (34%, 61%, 79%, 86%, and 83%, respectively) than in the placebo group (7%). In addition, the proportion of patients showing a 75%, 90%, or 100% improvement in Psoriasis Area and Severity Index score was significantly higher in each guselkumab group than in the placebo group. Scores on the Dermatology Life Quality Index also showed significantly greater improvement from baseline to week 16 in the guselkumab groups.

The findings were similar when patients taking the higher doses of guselkumab were compared with those taking adalimumab. At week 16, the proportion of patients with a PGA score of 0 or 1 was 58% with adalimumab, compared with 79%, 86%, and 83% at the highest doses of guselkumab (50 mg, 100 mg, or 200 mg). And at week 40, the proportion of patients with a PGA score of 0 or 1 was significantly higher in those taking 50 mg (71%), 100 mg (77%), or 200 mg (81%) guselkumab than in patients taking adalimumab (49%). The response to guselkumab was noted at the earliest patient assessment at week 4, peaked at week 20, and was maintained through week 40, Dr. Gordon and his associates said (N. Engl. J. Med. 2015 July 9 [doi:10.1056/NEJMoa1501646]).

The rates of adverse events, serious adverse events, and infections were similar across all the treatment groups. At week 16, infections were reported in 20% of patients taking guselkumab, 14% of those taking placebo, and 12% of those taking adalimumab. At final follow-up, infections were reported in 30% of patients taking guselkumab and 35% taking adalimumab. This study had a limited ability to assess uncommon adverse events; three patients taking guselkumab had major cardiovascular events during treatment, but “it is difficult to interpret the significance” of such events, the investigators said.

They added that larger and longer-term phase III trials are now underway to further assess the efficacy and safety of guselkumab for this indication. Moreover, their study results “validate the use of interleukin-23 as a therapeutic target by showing that therapy involving selective antagonism of this single cytokine in patients with moderate to severe plaque psoriasis is highly efficacious, as compared with adalimumab therapy,” Dr. Gordon and his associates said.