Key clinical point: The risk for uterine diseases was significantly increased in premenopausal women with breast cancer (BC) who received tamoxifen as an adjuvant hormone therapy.

Major finding: Compared with patients who did not receive adjuvant hormone therapy, those who received tamoxifen had a significantly higher risk for endometrial cancer (hazard ratio [HR] 3.77; 95% CI 3.04-4.66), endometrial polyps (HR 3.90; 95% CI 3.65-4.16), hyperplasia (HR 5.56; 95% CI 5.06-6.12), and other uterine cancers (HR 2.27; 95% CI 1.54-3.33).

Study details: Findings are from a nationwide, retrospective, longitudinal cohort study including 78,320 premenopausal women with BC who received (tamoxifen only; n = 34,637) or did not receive (n = 43,683) an adjuvant hormone treatment.

Disclosures: This study was supported by a National Research Foundation of Korea grant. The authors declared no conflicts of interest.

Source: Ryu KJ et al. Risk of endometrial polyps, hyperplasia, carcinoma, and uterine cancer after tamoxifen treatment in premenopausal women with breast cancer. JAMA Netw Open. 2022 5(11):e2243951 (Nov 28). Doi: 10.1001/jamanetworkopen.2022.43951

Key clinical point: The risk for uterine diseases was significantly increased in premenopausal women with breast cancer (BC) who received tamoxifen as an adjuvant hormone therapy.

Major finding: Compared with patients who did not receive adjuvant hormone therapy, those who received tamoxifen had a significantly higher risk for endometrial cancer (hazard ratio [HR] 3.77; 95% CI 3.04-4.66), endometrial polyps (HR 3.90; 95% CI 3.65-4.16), hyperplasia (HR 5.56; 95% CI 5.06-6.12), and other uterine cancers (HR 2.27; 95% CI 1.54-3.33).

Study details: Findings are from a nationwide, retrospective, longitudinal cohort study including 78,320 premenopausal women with BC who received (tamoxifen only; n = 34,637) or did not receive (n = 43,683) an adjuvant hormone treatment.

Disclosures: This study was supported by a National Research Foundation of Korea grant. The authors declared no conflicts of interest.

Source: Ryu KJ et al. Risk of endometrial polyps, hyperplasia, carcinoma, and uterine cancer after tamoxifen treatment in premenopausal women with breast cancer. JAMA Netw Open. 2022 5(11):e2243951 (Nov 28). Doi: 10.1001/jamanetworkopen.2022.43951

Key clinical point: The risk for uterine diseases was significantly increased in premenopausal women with breast cancer (BC) who received tamoxifen as an adjuvant hormone therapy.

Major finding: Compared with patients who did not receive adjuvant hormone therapy, those who received tamoxifen had a significantly higher risk for endometrial cancer (hazard ratio [HR] 3.77; 95% CI 3.04-4.66), endometrial polyps (HR 3.90; 95% CI 3.65-4.16), hyperplasia (HR 5.56; 95% CI 5.06-6.12), and other uterine cancers (HR 2.27; 95% CI 1.54-3.33).

Study details: Findings are from a nationwide, retrospective, longitudinal cohort study including 78,320 premenopausal women with BC who received (tamoxifen only; n = 34,637) or did not receive (n = 43,683) an adjuvant hormone treatment.

Disclosures: This study was supported by a National Research Foundation of Korea grant. The authors declared no conflicts of interest.

Source: Ryu KJ et al. Risk of endometrial polyps, hyperplasia, carcinoma, and uterine cancer after tamoxifen treatment in premenopausal women with breast cancer. JAMA Netw Open. 2022 5(11):e2243951 (Nov 28). Doi: 10.1001/jamanetworkopen.2022.43951

Key clinical point: The addition of weekly carboplatin to standard anthracycline-weekly paclitaxel-based neoadjuvant chemotherapy improved pathological complete response (pCR) rates in patients with triple-negative breast cancer (TNBC).

Major finding: The rate of pCR was significantly higher in the anthracycline-paclitaxel+carboplatin vs anthracycline-paclitaxel treatment group (51.9% vs 34.2%; odds ratio 2.40; P = .01); however, no significant differences were observed in grade ≥3 hematological toxicities between both groups.

Study details: Findings are from a multicenter study including 247 patients with TNBC who received sequential treatment with anthracycline and weekly paclitaxel with or without weekly carboplatin.

Disclosures: This study was supported by the Italian Ministry of Health. The authors declared receiving personal fees, grants, or non-financial support from several sources.

Source: Dieci MV et al. Incorporating weekly carboplatin in anthracycline and paclitaxel-containing neoadjuvant chemotherapy for triple-negative breast cancer: Propensity-score matching analysis and TIL evaluation. Br J Cancer. 2022 (Nov 17). Doi: 10.1038/s41416-022-02050-8

Key clinical point: The addition of weekly carboplatin to standard anthracycline-weekly paclitaxel-based neoadjuvant chemotherapy improved pathological complete response (pCR) rates in patients with triple-negative breast cancer (TNBC).

Major finding: The rate of pCR was significantly higher in the anthracycline-paclitaxel+carboplatin vs anthracycline-paclitaxel treatment group (51.9% vs 34.2%; odds ratio 2.40; P = .01); however, no significant differences were observed in grade ≥3 hematological toxicities between both groups.

Study details: Findings are from a multicenter study including 247 patients with TNBC who received sequential treatment with anthracycline and weekly paclitaxel with or without weekly carboplatin.

Disclosures: This study was supported by the Italian Ministry of Health. The authors declared receiving personal fees, grants, or non-financial support from several sources.

Source: Dieci MV et al. Incorporating weekly carboplatin in anthracycline and paclitaxel-containing neoadjuvant chemotherapy for triple-negative breast cancer: Propensity-score matching analysis and TIL evaluation. Br J Cancer. 2022 (Nov 17). Doi: 10.1038/s41416-022-02050-8

Key clinical point: The addition of weekly carboplatin to standard anthracycline-weekly paclitaxel-based neoadjuvant chemotherapy improved pathological complete response (pCR) rates in patients with triple-negative breast cancer (TNBC).

Major finding: The rate of pCR was significantly higher in the anthracycline-paclitaxel+carboplatin vs anthracycline-paclitaxel treatment group (51.9% vs 34.2%; odds ratio 2.40; P = .01); however, no significant differences were observed in grade ≥3 hematological toxicities between both groups.

Study details: Findings are from a multicenter study including 247 patients with TNBC who received sequential treatment with anthracycline and weekly paclitaxel with or without weekly carboplatin.

Disclosures: This study was supported by the Italian Ministry of Health. The authors declared receiving personal fees, grants, or non-financial support from several sources.

Source: Dieci MV et al. Incorporating weekly carboplatin in anthracycline and paclitaxel-containing neoadjuvant chemotherapy for triple-negative breast cancer: Propensity-score matching analysis and TIL evaluation. Br J Cancer. 2022 (Nov 17). Doi: 10.1038/s41416-022-02050-8

Key clinical point: Breast cancer (BC) survivors who were active or moderately active had an ~60% lower risk for mortality compared with those who were insufficiently active.

Major finding: Compared with insufficiently active participants, the risk for mortality was ~60% lower in active (hazard ratio [HR] 0.42; 95% CI 0.21-0.85) and moderately active (HR 0.40; 95% CI 0.17-0.95) participants.

Study details: Findings are from a cohort study including 315 postmenopausal BC survivors who were followed for a minimum of 2 years post-diagnosis.

Disclosures: This study was supported by the US National Cancer Institute. The authors declared no conflicts of interest.

Source: Chen LH et al. Association of physical activity with risk of mortality among breast cancer survivors. JAMA Netw Open. 2022;5(11):e2242660 (Nov 17). Doi: 10.1001/jamanetworkopen.2022.42660

Key clinical point: Breast cancer (BC) survivors who were active or moderately active had an ~60% lower risk for mortality compared with those who were insufficiently active.

Major finding: Compared with insufficiently active participants, the risk for mortality was ~60% lower in active (hazard ratio [HR] 0.42; 95% CI 0.21-0.85) and moderately active (HR 0.40; 95% CI 0.17-0.95) participants.

Study details: Findings are from a cohort study including 315 postmenopausal BC survivors who were followed for a minimum of 2 years post-diagnosis.

Disclosures: This study was supported by the US National Cancer Institute. The authors declared no conflicts of interest.

Source: Chen LH et al. Association of physical activity with risk of mortality among breast cancer survivors. JAMA Netw Open. 2022;5(11):e2242660 (Nov 17). Doi: 10.1001/jamanetworkopen.2022.42660

Key clinical point: Breast cancer (BC) survivors who were active or moderately active had an ~60% lower risk for mortality compared with those who were insufficiently active.

Major finding: Compared with insufficiently active participants, the risk for mortality was ~60% lower in active (hazard ratio [HR] 0.42; 95% CI 0.21-0.85) and moderately active (HR 0.40; 95% CI 0.17-0.95) participants.

Study details: Findings are from a cohort study including 315 postmenopausal BC survivors who were followed for a minimum of 2 years post-diagnosis.

Disclosures: This study was supported by the US National Cancer Institute. The authors declared no conflicts of interest.

Source: Chen LH et al. Association of physical activity with risk of mortality among breast cancer survivors. JAMA Netw Open. 2022;5(11):e2242660 (Nov 17). Doi: 10.1001/jamanetworkopen.2022.42660

Key clinical point: Trastuzumab deruxtecan demonstrated superior survival outcomes compared with trastuzumab emtansine in the second-line setting and also had a manageable safety profile in patients with human epidermal growth factor receptor 2-positive (HER2+) metastatic breast cancer (BC).

Major finding: Trastuzumab deruxtecan vs trastuzumab emtansine resulted in a ~36% reduction in the risk for death (hazard ratio 0.64; P = .0037) and the longest reported improvement in progression-free survival (28.8 months vs 6.8 months; nominal P < .0001). The rate of grade ≥3 adverse events was similar with trastuzumab deruxtecan vs trastuzumab emtansine (56% vs 52%).

Study details: Findings are from the phase 3, DESTINY-Breast03 trial including 524 patients with HER2+ metastatic BC who had progressed during or after treatment with trastuzumab and a taxane and were randomly assigned to receive trastuzumab deruxtecan or trastuzumab emtansine.

Disclosures: This study was funded by Daiichi Sankyo and AstraZeneca. Four authors declared being employees or stockholders of Daiichi Sankyo, and the other authors reported ties with various sources, including Daiichi Sankyo and AstraZeneca.

Source: Hurvitz SA et al. Trastuzumab deruxtecan versus trastuzumab emtansine in patients with HER2-positive metastatic breast cancer: Updated results from DESTINY-Breast03, a randomised, open-label, phase 3 trial. Lancet. 2022 (Dec 7). Doi: 10.1016/S0140-6736(22)02420-5

Key clinical point: Trastuzumab deruxtecan demonstrated superior survival outcomes compared with trastuzumab emtansine in the second-line setting and also had a manageable safety profile in patients with human epidermal growth factor receptor 2-positive (HER2+) metastatic breast cancer (BC).

Major finding: Trastuzumab deruxtecan vs trastuzumab emtansine resulted in a ~36% reduction in the risk for death (hazard ratio 0.64; P = .0037) and the longest reported improvement in progression-free survival (28.8 months vs 6.8 months; nominal P < .0001). The rate of grade ≥3 adverse events was similar with trastuzumab deruxtecan vs trastuzumab emtansine (56% vs 52%).

Study details: Findings are from the phase 3, DESTINY-Breast03 trial including 524 patients with HER2+ metastatic BC who had progressed during or after treatment with trastuzumab and a taxane and were randomly assigned to receive trastuzumab deruxtecan or trastuzumab emtansine.

Disclosures: This study was funded by Daiichi Sankyo and AstraZeneca. Four authors declared being employees or stockholders of Daiichi Sankyo, and the other authors reported ties with various sources, including Daiichi Sankyo and AstraZeneca.

Source: Hurvitz SA et al. Trastuzumab deruxtecan versus trastuzumab emtansine in patients with HER2-positive metastatic breast cancer: Updated results from DESTINY-Breast03, a randomised, open-label, phase 3 trial. Lancet. 2022 (Dec 7). Doi: 10.1016/S0140-6736(22)02420-5

Key clinical point: Trastuzumab deruxtecan demonstrated superior survival outcomes compared with trastuzumab emtansine in the second-line setting and also had a manageable safety profile in patients with human epidermal growth factor receptor 2-positive (HER2+) metastatic breast cancer (BC).

Major finding: Trastuzumab deruxtecan vs trastuzumab emtansine resulted in a ~36% reduction in the risk for death (hazard ratio 0.64; P = .0037) and the longest reported improvement in progression-free survival (28.8 months vs 6.8 months; nominal P < .0001). The rate of grade ≥3 adverse events was similar with trastuzumab deruxtecan vs trastuzumab emtansine (56% vs 52%).

Study details: Findings are from the phase 3, DESTINY-Breast03 trial including 524 patients with HER2+ metastatic BC who had progressed during or after treatment with trastuzumab and a taxane and were randomly assigned to receive trastuzumab deruxtecan or trastuzumab emtansine.

Disclosures: This study was funded by Daiichi Sankyo and AstraZeneca. Four authors declared being employees or stockholders of Daiichi Sankyo, and the other authors reported ties with various sources, including Daiichi Sankyo and AstraZeneca.

Source: Hurvitz SA et al. Trastuzumab deruxtecan versus trastuzumab emtansine in patients with HER2-positive metastatic breast cancer: Updated results from DESTINY-Breast03, a randomised, open-label, phase 3 trial. Lancet. 2022 (Dec 7). Doi: 10.1016/S0140-6736(22)02420-5

A systematic review of observational studies and clinical trials found dolutegravir and raltegravir to be safe and effective for treating teens and children living with HIV.

Effectiveness was higher across dolutegravir studies, the authors reported. After 12 months of treatment and observation, viral suppression levels were greater than 70% in most studies assessing dolutegravir. Viral suppression with raltegravir after 12 months varied between 42% and 83%.

“Our findings support the use of these two integrase inhibitors as part of WHO-recommended regimens for treating HIV,” said lead study author Claire Townsend, PhD, an epidemiologist and consultant to the World Health Organization HIV department in Geneva. “They were in line with what has been reported in adults and provide reassurance for the continued use of these two drugs in children and adolescents.”

The study was published in the Journal of the International AIDS Society.
 

Tracking outcomes for WHO guidelines

Integrase inhibitors, including dolutegravir and raltegravir, have become leading first- and second-line treatments in patients with HIV, largely owing to their effectiveness and fewer side effects, compared with other antiretroviral treatments.

Monitoring short- and long-term health outcomes of these widely used drugs is critical, the authors wrote. This is especially the case for dolutegravir, which has recently been approved in pediatric formulations. The review supported the development of the 2021 WHO consolidated HIV guidelines.

Dr. Townsend and colleagues searched the literature and screened trial registries for relevant studies conducted from January 2009 to March 2021. Among more than 4,000 published papers and abstracts, they identified 19 studies that met their review criteria relating to dolutegravir or raltegravir in children or adolescents aged 0-19 years who are living with HIV, including two studies that reported data on both agents.

Data on dolutegravir were extracted from 11 studies that included 2,330 children and adolescents in 1 randomized controlled trial, 1 single-arm trial, and 9 cohort studies. Data on raltegravir were extracted from 10 studies that included 649 children and adolescents in 1 randomized controlled trial, 1 single-arm trial, and 8 cohort studies.

The median follow-up in the dolutegravir studies was 6-36 months. Six studies recruited participants from Europe, three studies were based in sub-Saharan Africa, and two studies included persons from multiple geographic regions.

Across all studies, grade 3/4 adverse events were reported in 0%-50% of cases. Of these adverse events, very few were drug related, and no deaths were attributed to either dolutegravir or raltegravir.

However, Dr. Townsend cautioned that future research is needed to fill in evidence gaps “on longer-term safety and effectiveness of dolutegravir and raltegravir in children and adolescents,” including “research into adverse outcomes such as weight gain, potential metabolic changes, and neuropsychiatric adverse events, which have been reported in adults.”

The researchers noted that the small sample size of many of the studies contributed to variability in the findings and that most studies were observational, providing important real-world data but making their results less robust compared with data from randomized controlled studies with large sample sizes. They also noted that there was a high risk of bias (4 studies) and unclear risk of bias (5 studies) among the 15 observational studies included in their analysis.

“This research is particularly important because it supports the WHO recommendation that dolutegravir, which has a particularly high barrier of resistance to the HIV virus, be synchronized in adults and children as the preferred first-line and second-line treatment against HIV,” said Natella Rakhmanina, MD, PhD, director of HIV Services & Special Immunology at the Children’s National Hospital in Washington, D.C. Dr. Rakhmanina was not associated with the study.

Dr. Rakhmanina agreed that the safety profile of both drugs is “very good.” The lack of serious adverse events was meaningful, she highlighted, because “good tolerability is very important, particularly in children” as it means that drug compliance and viral suppression are achievable.

Two authors reported their authorship on two studies included in the review, as well as grant funding from ViiV Healthcare/GlaxoSmithKline, the marketing authorization holder for dolutegravir.

A version of this article first appeared on Medscape.com.

A systematic review of observational studies and clinical trials found dolutegravir and raltegravir to be safe and effective for treating teens and children living with HIV.

Effectiveness was higher across dolutegravir studies, the authors reported. After 12 months of treatment and observation, viral suppression levels were greater than 70% in most studies assessing dolutegravir. Viral suppression with raltegravir after 12 months varied between 42% and 83%.

“Our findings support the use of these two integrase inhibitors as part of WHO-recommended regimens for treating HIV,” said lead study author Claire Townsend, PhD, an epidemiologist and consultant to the World Health Organization HIV department in Geneva. “They were in line with what has been reported in adults and provide reassurance for the continued use of these two drugs in children and adolescents.”

The study was published in the Journal of the International AIDS Society.
 

Tracking outcomes for WHO guidelines

Integrase inhibitors, including dolutegravir and raltegravir, have become leading first- and second-line treatments in patients with HIV, largely owing to their effectiveness and fewer side effects, compared with other antiretroviral treatments.

Monitoring short- and long-term health outcomes of these widely used drugs is critical, the authors wrote. This is especially the case for dolutegravir, which has recently been approved in pediatric formulations. The review supported the development of the 2021 WHO consolidated HIV guidelines.

Dr. Townsend and colleagues searched the literature and screened trial registries for relevant studies conducted from January 2009 to March 2021. Among more than 4,000 published papers and abstracts, they identified 19 studies that met their review criteria relating to dolutegravir or raltegravir in children or adolescents aged 0-19 years who are living with HIV, including two studies that reported data on both agents.

Data on dolutegravir were extracted from 11 studies that included 2,330 children and adolescents in 1 randomized controlled trial, 1 single-arm trial, and 9 cohort studies. Data on raltegravir were extracted from 10 studies that included 649 children and adolescents in 1 randomized controlled trial, 1 single-arm trial, and 8 cohort studies.

The median follow-up in the dolutegravir studies was 6-36 months. Six studies recruited participants from Europe, three studies were based in sub-Saharan Africa, and two studies included persons from multiple geographic regions.

Across all studies, grade 3/4 adverse events were reported in 0%-50% of cases. Of these adverse events, very few were drug related, and no deaths were attributed to either dolutegravir or raltegravir.

However, Dr. Townsend cautioned that future research is needed to fill in evidence gaps “on longer-term safety and effectiveness of dolutegravir and raltegravir in children and adolescents,” including “research into adverse outcomes such as weight gain, potential metabolic changes, and neuropsychiatric adverse events, which have been reported in adults.”

The researchers noted that the small sample size of many of the studies contributed to variability in the findings and that most studies were observational, providing important real-world data but making their results less robust compared with data from randomized controlled studies with large sample sizes. They also noted that there was a high risk of bias (4 studies) and unclear risk of bias (5 studies) among the 15 observational studies included in their analysis.

“This research is particularly important because it supports the WHO recommendation that dolutegravir, which has a particularly high barrier of resistance to the HIV virus, be synchronized in adults and children as the preferred first-line and second-line treatment against HIV,” said Natella Rakhmanina, MD, PhD, director of HIV Services & Special Immunology at the Children’s National Hospital in Washington, D.C. Dr. Rakhmanina was not associated with the study.

Dr. Rakhmanina agreed that the safety profile of both drugs is “very good.” The lack of serious adverse events was meaningful, she highlighted, because “good tolerability is very important, particularly in children” as it means that drug compliance and viral suppression are achievable.

Two authors reported their authorship on two studies included in the review, as well as grant funding from ViiV Healthcare/GlaxoSmithKline, the marketing authorization holder for dolutegravir.

A version of this article first appeared on Medscape.com.

A systematic review of observational studies and clinical trials found dolutegravir and raltegravir to be safe and effective for treating teens and children living with HIV.

Effectiveness was higher across dolutegravir studies, the authors reported. After 12 months of treatment and observation, viral suppression levels were greater than 70% in most studies assessing dolutegravir. Viral suppression with raltegravir after 12 months varied between 42% and 83%.

“Our findings support the use of these two integrase inhibitors as part of WHO-recommended regimens for treating HIV,” said lead study author Claire Townsend, PhD, an epidemiologist and consultant to the World Health Organization HIV department in Geneva. “They were in line with what has been reported in adults and provide reassurance for the continued use of these two drugs in children and adolescents.”

The study was published in the Journal of the International AIDS Society.
 

Tracking outcomes for WHO guidelines

Integrase inhibitors, including dolutegravir and raltegravir, have become leading first- and second-line treatments in patients with HIV, largely owing to their effectiveness and fewer side effects, compared with other antiretroviral treatments.

Monitoring short- and long-term health outcomes of these widely used drugs is critical, the authors wrote. This is especially the case for dolutegravir, which has recently been approved in pediatric formulations. The review supported the development of the 2021 WHO consolidated HIV guidelines.

Dr. Townsend and colleagues searched the literature and screened trial registries for relevant studies conducted from January 2009 to March 2021. Among more than 4,000 published papers and abstracts, they identified 19 studies that met their review criteria relating to dolutegravir or raltegravir in children or adolescents aged 0-19 years who are living with HIV, including two studies that reported data on both agents.

Data on dolutegravir were extracted from 11 studies that included 2,330 children and adolescents in 1 randomized controlled trial, 1 single-arm trial, and 9 cohort studies. Data on raltegravir were extracted from 10 studies that included 649 children and adolescents in 1 randomized controlled trial, 1 single-arm trial, and 8 cohort studies.

The median follow-up in the dolutegravir studies was 6-36 months. Six studies recruited participants from Europe, three studies were based in sub-Saharan Africa, and two studies included persons from multiple geographic regions.

Across all studies, grade 3/4 adverse events were reported in 0%-50% of cases. Of these adverse events, very few were drug related, and no deaths were attributed to either dolutegravir or raltegravir.

However, Dr. Townsend cautioned that future research is needed to fill in evidence gaps “on longer-term safety and effectiveness of dolutegravir and raltegravir in children and adolescents,” including “research into adverse outcomes such as weight gain, potential metabolic changes, and neuropsychiatric adverse events, which have been reported in adults.”

The researchers noted that the small sample size of many of the studies contributed to variability in the findings and that most studies were observational, providing important real-world data but making their results less robust compared with data from randomized controlled studies with large sample sizes. They also noted that there was a high risk of bias (4 studies) and unclear risk of bias (5 studies) among the 15 observational studies included in their analysis.

“This research is particularly important because it supports the WHO recommendation that dolutegravir, which has a particularly high barrier of resistance to the HIV virus, be synchronized in adults and children as the preferred first-line and second-line treatment against HIV,” said Natella Rakhmanina, MD, PhD, director of HIV Services & Special Immunology at the Children’s National Hospital in Washington, D.C. Dr. Rakhmanina was not associated with the study.

Dr. Rakhmanina agreed that the safety profile of both drugs is “very good.” The lack of serious adverse events was meaningful, she highlighted, because “good tolerability is very important, particularly in children” as it means that drug compliance and viral suppression are achievable.

Two authors reported their authorship on two studies included in the review, as well as grant funding from ViiV Healthcare/GlaxoSmithKline, the marketing authorization holder for dolutegravir.

A version of this article first appeared on Medscape.com.

Dispatching trained volunteer responders via smartphones to retrieve automated external defibrillators for patients in out-of-hospital cardiac arrest (OHCA) did not significantly increase bystander AED use in a randomized clinical trial in Sweden.

Most patients in OHCA can be saved if cardiopulmonary resuscitation and defibrillation are initiated within minutes, but despite the “substantial” public availability of AEDs and widespread CPR training among the Swedish public, use rates of both are low, Mattias Ringh, MD, PhD, of Karolinska Institutet in Stockholm, and colleagues wrote.

A previous study by the team showed that dispatching volunteer responders via a smartphone app significantly increased bystander CPR. The current study, called the Swedish AED and Mobile Bystander Activation (SAMBA) trial, aimed to see whether dispatching volunteer responders to collect a nearby AED would increase bystander AED use. A control group of volunteer responders was instructed to go straight to the scene and start CPR.

“The results showed that the volunteer responders were first to provide treatment with both CPR and AEDs in a large proportion of cases in both groups, thereby creating a ‘statistical’ dilutional effect,” Dr. Ringh said in an interview. In effect, the control arm also became an active arm.

“But if we agree that treatment with AEDs and CPR is saving lives, then dispatching volunteer responders is doing just that, although we could not fully measure the effect in our study,” he added.

The study was published online in JAMA Cardiology.
 

No significant differences

The SAMBA trial assessed outcomes of the smartphone dispatch system (Heartrunner), which is triggered at emergency dispatch centers in response to suspected OHCAs at the same time that an ambulance with advanced life support equipment is dispatched.

The volunteer responder system locates a maximum of 30 volunteer responders within a 1.3-km radius from the suspected out-of-hospital cardiac arrest, the researchers explained in their report. Volunteer responders are requested via their smartphone application to accept or decline the alert. If they accept an alert, the volunteer responders receive map-aided route directions to the location of the suspected arrest.

In patients allocated to intervention in this study, four of five of all volunteer responders who accepted the alert received instructions to collect the nearest available AED and then go directly to the patient with suspected out-of-hospital cardiac arrest, the authors noted. Route directions to the scene of the cardiac arrest and the AED were displayed on their smartphones. One of the 5 volunteer responders, closest to the arrest, was dispatched to go directly to initiate CPR.

In patients allocated to the control group, all volunteer responders who accepted the alert were instructed to go directly to the patient with suspected out-of-hospital cardiac arrest to perform CPR. No route directions to or locations of AEDs were displayed.

The study was conducted in Stockholm and in Västra Götaland from 2018 to 2020. At the start of the study, there were 3,123 AEDs and 24,493 volunteer responders in Stockholm and 3,195 AEDs and 19,117 volunteer responders in Västra Götaland.

Post-randomization exclusions included patients without OHCA, those with OHCAs not treated by emergency medical services, and those with OHCAs witnessed by EMS.

The primary outcome was overall bystander AED attachment before the arrival of EMS, including those attached by the volunteer responders but also by lay volunteers who did not use the smartphone app.

Volunteer responders were activated for 947 individuals with OHCA; 461 patients were randomized to the intervention group and 486 to the control group. In both groups, the patients’ median age was 73 and about 65% were men.

Attachment of the AED before the arrival of EMS or first responders occurred in 61 patients (13.2%) in the intervention group versus 46 (9.5%) in the control group (P = .08). However, the majority of all AEDs were attached by lay volunteers who were not volunteer responders using the smartphone app (37 in the intervention arm vs. 28 in the control arm), the researchers noted.

No significant differences were seen in secondary outcomes, which included bystander CPR (69% vs. 71.6%, respectively) and defibrillation before EMS arrival (3.7% vs. 3.9%) between groups.

Among the volunteer responders using the app, crossover was 11% and compliance to instructions was 31%. Overall, volunteer responders attached 38% of all bystander-attached AEDs and provided 45% of all bystander defibrillations and 43% of all bystander CPR.

Going forward, Dr. Ringh and colleagues will be further analyzing the results to understand how to better optimize the logistical challenges involved with smartphone dispatch to OHCA patients. “In the longer term, investigating the impact on survival is also warranted,” he concluded.
 

U.S. in worse shape

In a comment, Christopher Calandrella, DO, chair of emergency medicine at Long Island Jewish Forest Hills,, New York, part of Northwell Health, said: “Significant data are available to support the importance of prompt initiation of CPR and defibrillation for OHCA, and although this study did not demonstrate a meaningful increase in use of AEDs with the trial system, layperson CPR was initiated in approximately 70% of cases in the cohort as a whole. Because of this, I believe it is evident that patients still benefit from a system that encourages bystanders to provide aid prior to the arrival of EMS.”

Nevertheless, he noted, “despite the training of volunteers in applying an AED, overall, only a small percentage of patients in either group had placement and use of the device. While the reasons likely are multifactorial, it may be in part due to the significant stress and anxiety associated with OHCA.”

Additional research would be helpful, he said. “Future studies focusing on more rural areas with lower population density and limited availability of AEDs may be beneficial. Expanding the research outside of Europe to other countries would be useful. Next-phase trials looking at 30-day survival in these patients would also be important.”

Currently in the United States, research is underway to evaluate the use of smartphones to improve in-hospital cardiac arrests, he added, “but no nationwide programs are in place for OHCA.”

Similarly, Kevin G. Volpp, MD, PhD, and Benjamin S. Abella, MD, MPhil, both of the University of Pennsylvania, Philadelphia, wrote in a related editorial: “It is sobering to recognize that, in the U.S., it may be nearly impossible to even test an idea like this, given the lack of a supporting data infrastructure.”

Although there is an app in the United States to link OHCA events to bystander response, they noted, less than half of eligible 911 centers have linked to it.

“Furthermore, the bystander CPR rate in the U.S. is less than 35%, only about half of the Swedish rate, indicating far fewer people are trained in CPR and comfortable performing it in the U.S.,” they wrote. “A wealthy country like the U.S. should be able to develop a far more effective approach to preventing millions of ... families from having a loved one die of OHCA in the decade to come.”

The study was funded by unrestricted grant from the Swedish Heart-Lung Foundation and Stockholm County. The authors, editorialists, and Dr. Calandrella disclosed no relevant financial relationships.

A version of this article first appeared on Medscape.com.

Dispatching trained volunteer responders via smartphones to retrieve automated external defibrillators for patients in out-of-hospital cardiac arrest (OHCA) did not significantly increase bystander AED use in a randomized clinical trial in Sweden.

Most patients in OHCA can be saved if cardiopulmonary resuscitation and defibrillation are initiated within minutes, but despite the “substantial” public availability of AEDs and widespread CPR training among the Swedish public, use rates of both are low, Mattias Ringh, MD, PhD, of Karolinska Institutet in Stockholm, and colleagues wrote.

A previous study by the team showed that dispatching volunteer responders via a smartphone app significantly increased bystander CPR. The current study, called the Swedish AED and Mobile Bystander Activation (SAMBA) trial, aimed to see whether dispatching volunteer responders to collect a nearby AED would increase bystander AED use. A control group of volunteer responders was instructed to go straight to the scene and start CPR.

“The results showed that the volunteer responders were first to provide treatment with both CPR and AEDs in a large proportion of cases in both groups, thereby creating a ‘statistical’ dilutional effect,” Dr. Ringh said in an interview. In effect, the control arm also became an active arm.

“But if we agree that treatment with AEDs and CPR is saving lives, then dispatching volunteer responders is doing just that, although we could not fully measure the effect in our study,” he added.

The study was published online in JAMA Cardiology.
 

No significant differences

The SAMBA trial assessed outcomes of the smartphone dispatch system (Heartrunner), which is triggered at emergency dispatch centers in response to suspected OHCAs at the same time that an ambulance with advanced life support equipment is dispatched.

The volunteer responder system locates a maximum of 30 volunteer responders within a 1.3-km radius from the suspected out-of-hospital cardiac arrest, the researchers explained in their report. Volunteer responders are requested via their smartphone application to accept or decline the alert. If they accept an alert, the volunteer responders receive map-aided route directions to the location of the suspected arrest.

In patients allocated to intervention in this study, four of five of all volunteer responders who accepted the alert received instructions to collect the nearest available AED and then go directly to the patient with suspected out-of-hospital cardiac arrest, the authors noted. Route directions to the scene of the cardiac arrest and the AED were displayed on their smartphones. One of the 5 volunteer responders, closest to the arrest, was dispatched to go directly to initiate CPR.

In patients allocated to the control group, all volunteer responders who accepted the alert were instructed to go directly to the patient with suspected out-of-hospital cardiac arrest to perform CPR. No route directions to or locations of AEDs were displayed.

The study was conducted in Stockholm and in Västra Götaland from 2018 to 2020. At the start of the study, there were 3,123 AEDs and 24,493 volunteer responders in Stockholm and 3,195 AEDs and 19,117 volunteer responders in Västra Götaland.

Post-randomization exclusions included patients without OHCA, those with OHCAs not treated by emergency medical services, and those with OHCAs witnessed by EMS.

The primary outcome was overall bystander AED attachment before the arrival of EMS, including those attached by the volunteer responders but also by lay volunteers who did not use the smartphone app.

Volunteer responders were activated for 947 individuals with OHCA; 461 patients were randomized to the intervention group and 486 to the control group. In both groups, the patients’ median age was 73 and about 65% were men.

Attachment of the AED before the arrival of EMS or first responders occurred in 61 patients (13.2%) in the intervention group versus 46 (9.5%) in the control group (P = .08). However, the majority of all AEDs were attached by lay volunteers who were not volunteer responders using the smartphone app (37 in the intervention arm vs. 28 in the control arm), the researchers noted.

No significant differences were seen in secondary outcomes, which included bystander CPR (69% vs. 71.6%, respectively) and defibrillation before EMS arrival (3.7% vs. 3.9%) between groups.

Among the volunteer responders using the app, crossover was 11% and compliance to instructions was 31%. Overall, volunteer responders attached 38% of all bystander-attached AEDs and provided 45% of all bystander defibrillations and 43% of all bystander CPR.

Going forward, Dr. Ringh and colleagues will be further analyzing the results to understand how to better optimize the logistical challenges involved with smartphone dispatch to OHCA patients. “In the longer term, investigating the impact on survival is also warranted,” he concluded.
 

U.S. in worse shape

In a comment, Christopher Calandrella, DO, chair of emergency medicine at Long Island Jewish Forest Hills,, New York, part of Northwell Health, said: “Significant data are available to support the importance of prompt initiation of CPR and defibrillation for OHCA, and although this study did not demonstrate a meaningful increase in use of AEDs with the trial system, layperson CPR was initiated in approximately 70% of cases in the cohort as a whole. Because of this, I believe it is evident that patients still benefit from a system that encourages bystanders to provide aid prior to the arrival of EMS.”

Nevertheless, he noted, “despite the training of volunteers in applying an AED, overall, only a small percentage of patients in either group had placement and use of the device. While the reasons likely are multifactorial, it may be in part due to the significant stress and anxiety associated with OHCA.”

Additional research would be helpful, he said. “Future studies focusing on more rural areas with lower population density and limited availability of AEDs may be beneficial. Expanding the research outside of Europe to other countries would be useful. Next-phase trials looking at 30-day survival in these patients would also be important.”

Currently in the United States, research is underway to evaluate the use of smartphones to improve in-hospital cardiac arrests, he added, “but no nationwide programs are in place for OHCA.”

Similarly, Kevin G. Volpp, MD, PhD, and Benjamin S. Abella, MD, MPhil, both of the University of Pennsylvania, Philadelphia, wrote in a related editorial: “It is sobering to recognize that, in the U.S., it may be nearly impossible to even test an idea like this, given the lack of a supporting data infrastructure.”

Although there is an app in the United States to link OHCA events to bystander response, they noted, less than half of eligible 911 centers have linked to it.

“Furthermore, the bystander CPR rate in the U.S. is less than 35%, only about half of the Swedish rate, indicating far fewer people are trained in CPR and comfortable performing it in the U.S.,” they wrote. “A wealthy country like the U.S. should be able to develop a far more effective approach to preventing millions of ... families from having a loved one die of OHCA in the decade to come.”

The study was funded by unrestricted grant from the Swedish Heart-Lung Foundation and Stockholm County. The authors, editorialists, and Dr. Calandrella disclosed no relevant financial relationships.

A version of this article first appeared on Medscape.com.

Dispatching trained volunteer responders via smartphones to retrieve automated external defibrillators for patients in out-of-hospital cardiac arrest (OHCA) did not significantly increase bystander AED use in a randomized clinical trial in Sweden.

Most patients in OHCA can be saved if cardiopulmonary resuscitation and defibrillation are initiated within minutes, but despite the “substantial” public availability of AEDs and widespread CPR training among the Swedish public, use rates of both are low, Mattias Ringh, MD, PhD, of Karolinska Institutet in Stockholm, and colleagues wrote.

A previous study by the team showed that dispatching volunteer responders via a smartphone app significantly increased bystander CPR. The current study, called the Swedish AED and Mobile Bystander Activation (SAMBA) trial, aimed to see whether dispatching volunteer responders to collect a nearby AED would increase bystander AED use. A control group of volunteer responders was instructed to go straight to the scene and start CPR.

“The results showed that the volunteer responders were first to provide treatment with both CPR and AEDs in a large proportion of cases in both groups, thereby creating a ‘statistical’ dilutional effect,” Dr. Ringh said in an interview. In effect, the control arm also became an active arm.

“But if we agree that treatment with AEDs and CPR is saving lives, then dispatching volunteer responders is doing just that, although we could not fully measure the effect in our study,” he added.

The study was published online in JAMA Cardiology.
 

No significant differences

The SAMBA trial assessed outcomes of the smartphone dispatch system (Heartrunner), which is triggered at emergency dispatch centers in response to suspected OHCAs at the same time that an ambulance with advanced life support equipment is dispatched.

The volunteer responder system locates a maximum of 30 volunteer responders within a 1.3-km radius from the suspected out-of-hospital cardiac arrest, the researchers explained in their report. Volunteer responders are requested via their smartphone application to accept or decline the alert. If they accept an alert, the volunteer responders receive map-aided route directions to the location of the suspected arrest.

In patients allocated to intervention in this study, four of five of all volunteer responders who accepted the alert received instructions to collect the nearest available AED and then go directly to the patient with suspected out-of-hospital cardiac arrest, the authors noted. Route directions to the scene of the cardiac arrest and the AED were displayed on their smartphones. One of the 5 volunteer responders, closest to the arrest, was dispatched to go directly to initiate CPR.

In patients allocated to the control group, all volunteer responders who accepted the alert were instructed to go directly to the patient with suspected out-of-hospital cardiac arrest to perform CPR. No route directions to or locations of AEDs were displayed.

The study was conducted in Stockholm and in Västra Götaland from 2018 to 2020. At the start of the study, there were 3,123 AEDs and 24,493 volunteer responders in Stockholm and 3,195 AEDs and 19,117 volunteer responders in Västra Götaland.

Post-randomization exclusions included patients without OHCA, those with OHCAs not treated by emergency medical services, and those with OHCAs witnessed by EMS.

The primary outcome was overall bystander AED attachment before the arrival of EMS, including those attached by the volunteer responders but also by lay volunteers who did not use the smartphone app.

Volunteer responders were activated for 947 individuals with OHCA; 461 patients were randomized to the intervention group and 486 to the control group. In both groups, the patients’ median age was 73 and about 65% were men.

Attachment of the AED before the arrival of EMS or first responders occurred in 61 patients (13.2%) in the intervention group versus 46 (9.5%) in the control group (P = .08). However, the majority of all AEDs were attached by lay volunteers who were not volunteer responders using the smartphone app (37 in the intervention arm vs. 28 in the control arm), the researchers noted.

No significant differences were seen in secondary outcomes, which included bystander CPR (69% vs. 71.6%, respectively) and defibrillation before EMS arrival (3.7% vs. 3.9%) between groups.

Among the volunteer responders using the app, crossover was 11% and compliance to instructions was 31%. Overall, volunteer responders attached 38% of all bystander-attached AEDs and provided 45% of all bystander defibrillations and 43% of all bystander CPR.

Going forward, Dr. Ringh and colleagues will be further analyzing the results to understand how to better optimize the logistical challenges involved with smartphone dispatch to OHCA patients. “In the longer term, investigating the impact on survival is also warranted,” he concluded.
 

U.S. in worse shape

In a comment, Christopher Calandrella, DO, chair of emergency medicine at Long Island Jewish Forest Hills,, New York, part of Northwell Health, said: “Significant data are available to support the importance of prompt initiation of CPR and defibrillation for OHCA, and although this study did not demonstrate a meaningful increase in use of AEDs with the trial system, layperson CPR was initiated in approximately 70% of cases in the cohort as a whole. Because of this, I believe it is evident that patients still benefit from a system that encourages bystanders to provide aid prior to the arrival of EMS.”

Nevertheless, he noted, “despite the training of volunteers in applying an AED, overall, only a small percentage of patients in either group had placement and use of the device. While the reasons likely are multifactorial, it may be in part due to the significant stress and anxiety associated with OHCA.”

Additional research would be helpful, he said. “Future studies focusing on more rural areas with lower population density and limited availability of AEDs may be beneficial. Expanding the research outside of Europe to other countries would be useful. Next-phase trials looking at 30-day survival in these patients would also be important.”

Currently in the United States, research is underway to evaluate the use of smartphones to improve in-hospital cardiac arrests, he added, “but no nationwide programs are in place for OHCA.”

Similarly, Kevin G. Volpp, MD, PhD, and Benjamin S. Abella, MD, MPhil, both of the University of Pennsylvania, Philadelphia, wrote in a related editorial: “It is sobering to recognize that, in the U.S., it may be nearly impossible to even test an idea like this, given the lack of a supporting data infrastructure.”

Although there is an app in the United States to link OHCA events to bystander response, they noted, less than half of eligible 911 centers have linked to it.

“Furthermore, the bystander CPR rate in the U.S. is less than 35%, only about half of the Swedish rate, indicating far fewer people are trained in CPR and comfortable performing it in the U.S.,” they wrote. “A wealthy country like the U.S. should be able to develop a far more effective approach to preventing millions of ... families from having a loved one die of OHCA in the decade to come.”

The study was funded by unrestricted grant from the Swedish Heart-Lung Foundation and Stockholm County. The authors, editorialists, and Dr. Calandrella disclosed no relevant financial relationships.

A version of this article first appeared on Medscape.com.

Women with preexisting ischemic heart disease without another cardiac diagnosis have a higher risk of severe maternal morbidity and mortality than women with no cardiac disease, a new study suggests.

However, after adjustment for other comorbidities, the risk associated with isolated preexisting ischemic heart disease without additional evidence of cardiomyopathy was relatively similar to that of other low-risk cardiac diseases.

“These are reassuring findings,” lead author of the study, Anna E. Denoble, MD, Yale University, New Haven, Conn., told this news organization. “The risk is not zero. Women with preexisting ischemic heart disease are at a small increased risk compared to women without preexisting cardiac disease. But with good control of cardiovascular risk factors, these women have a good chance of a positive outcome.”

The study was published online in JACC: Advances.

“To our knowledge, this study provides the largest analysis to date examining the risk of severe morbidity and mortality among pregnant people with pre-existing ischemic heart disease,” the authors noted.

Dr. Denoble, a maternal and fetal medicine specialist, explained that in recent years, there has been an increase in the number of patients with preexisting ischemic heart disease who are considering pregnancy or who are pregnant when they present, but there is little information on outcomes for these patients.

The diagnosis of ischemic heart disease is not included in the main classification used for heart disease in pregnancy – the modified World Health Organization classification, Dr. Denoble noted. “This classification includes information on pregnancy outcomes in women with many cardiac conditions, including arrhythmias, congenital heart disease, heart failure, and aortic aneurysm, but ischemic heart disease is missing.”

She suggested this is probably because ischemic heart disease is regarded as a condition that occurs mainly in older people. “But we are seeing more and more women with ischemic heart disease who are pregnant or considering pregnancy. This could be because women are now often older when considering pregnancy, and also risk factors for ischemic heart disease, such as obesity and diabetes, are becoming more frequent in younger women.”

The researchers conducted the current study to investigate pregnancy outcomes for these women.

The retrospective cohort study analyzed data from the Nationwide Readmissions Database on women who had experienced a delivery hospitalization from Oct. 1, 2015, to Dec. 31, 2018. They compared outcomes for women with isolated preexisting ischemic heart disease with those of women who had no apparent cardiac condition and to those with mild or more severe cardiac conditions included in the mWHO classification after controlling for other comorbidities.

The primary outcome was severe maternal morbidity or death. Dr. Denoble explained that severe maternal morbidity includes mechanical ventilation, blood transfusion, and hysterectomy – the more severe maternal adverse outcomes of pregnancy.

Results showed that, of 11,556,136 delivery hospitalizations, 65,331 patients had another cardiac diagnosis, and 3,009 had ischemic heart disease alone. Patients with ischemic heart disease were older, and rates of diabetes and hypertension were higher.

In unadjusted analyses, adverse outcomes were more common among patients with ischemic heart disease alone than among patients with no cardiac disease and mild cardiac conditions (mWHO class I-II cardiac disease).

Of those with preexisting ischemic heart disease, 6.6% experienced severe maternal morbidity or death, compared with 1.5% of those without a cardiac disease (unadjusted relative risk vs. no cardiac disease, 4.3; 95% confidence interval, 3.5-5.2).

In comparison, 4.2% of women with mWHO I-II cardiac diseases and 23.1% of those with more severe mWHO II/III-IV cardiac diseases experienced severe maternal morbidity or death.

Similar differences were noted for nontransfusion severe maternal morbidity and mortality, as well as cardiac severe maternal morbidity and mortality.

After adjustment, ischemic heart disease alone was associated with a higher risk of severe maternal morbidity or death compared to no cardiac disease (adjusted RR, 1.51; 95% CI, 1.19-1.92).

In comparison, the aRR was 1.90 for WHO class I-II diseases and 5.87 (95% CI, 5.49-6.27) for more severe cardiac conditions defined as WHO II/III-IV diseases.

Risk for nontransfusion severe maternal morbidity or death (aRR, 1.60) and cardiac severe maternal morbidity or death (aRR, 2.98) were also higher for those with ischemic heart disease than for women without any cardiac disease.

There were no significant differences in preterm birth for those with preexisting ischemic heart disease compared to those with no cardiac disease after adjustment.

The risk of severe maternal morbidity and mortality, nontransfusion severe maternal morbidity and mortality, and cardiac severe maternal morbidity and mortality for ischemic heart disease alone most closely approximated that of mWHO class I or II cardiac diseases, the researchers said.

“We found that individuals with preexisting ischemic heart disease had a rate of severe maternal morbidity/mortality in the same range as those with other cardiac diagnoses in the mild cardiac disease classification (class I or II),” Dr. Denoble commented.

“This prognosis suggests it is very reasonable for these women to consider pregnancy. The risk of adverse outcomes is not so high that pregnancy is contraindicated,” she added.

Dr. Denoble said this information will be very helpful when counseling women with preexisting ischemic heart disease who are considering pregnancy. “These patients may need some extra monitoring, but in general, they have a high chance of a good outcome,” she noted.

“I would still advise these women to register with a high-risk obstetrics provider to have a baseline cardiovascular pregnancy evaluation. As long as that is reassuring, then further frequent intensive supervision may not be necessary,” she said.

However, the authors pointed out, “it is important to communicate to patients that while pregnancy may be considered low risk in the setting of pre-existing ischemic heart disease, 6.6% of patients with pre-existing ischemic heart disease alone did experience severe maternal morbidity or death during the delivery hospitalization.”

They added that other medical comorbidities should be factored into discussions regarding the risks of pregnancy.

The researchers also noted that the study was limited to evaluation of maternal outcomes occurring during the delivery hospitalization and that additional research that assesses rates of maternal adverse cardiac events and maternal morbidity occurring prior to or after the delivery hospitalization would be beneficial.

Future studies examining the potential gradation in risk associated with additional cardiac comorbidities in individuals with preexisting ischemic heart disease would also be worthwhile, they added.

The study was supported by funding from the National Institutes of Health and the Foundation for Women and Girls with Blood Disorders. The authors disclosed no relevant financial relationships.

A version of this article first appeared on Medscape.com.

Women with preexisting ischemic heart disease without another cardiac diagnosis have a higher risk of severe maternal morbidity and mortality than women with no cardiac disease, a new study suggests.

However, after adjustment for other comorbidities, the risk associated with isolated preexisting ischemic heart disease without additional evidence of cardiomyopathy was relatively similar to that of other low-risk cardiac diseases.

“These are reassuring findings,” lead author of the study, Anna E. Denoble, MD, Yale University, New Haven, Conn., told this news organization. “The risk is not zero. Women with preexisting ischemic heart disease are at a small increased risk compared to women without preexisting cardiac disease. But with good control of cardiovascular risk factors, these women have a good chance of a positive outcome.”

The study was published online in JACC: Advances.

“To our knowledge, this study provides the largest analysis to date examining the risk of severe morbidity and mortality among pregnant people with pre-existing ischemic heart disease,” the authors noted.

Dr. Denoble, a maternal and fetal medicine specialist, explained that in recent years, there has been an increase in the number of patients with preexisting ischemic heart disease who are considering pregnancy or who are pregnant when they present, but there is little information on outcomes for these patients.

The diagnosis of ischemic heart disease is not included in the main classification used for heart disease in pregnancy – the modified World Health Organization classification, Dr. Denoble noted. “This classification includes information on pregnancy outcomes in women with many cardiac conditions, including arrhythmias, congenital heart disease, heart failure, and aortic aneurysm, but ischemic heart disease is missing.”

She suggested this is probably because ischemic heart disease is regarded as a condition that occurs mainly in older people. “But we are seeing more and more women with ischemic heart disease who are pregnant or considering pregnancy. This could be because women are now often older when considering pregnancy, and also risk factors for ischemic heart disease, such as obesity and diabetes, are becoming more frequent in younger women.”

The researchers conducted the current study to investigate pregnancy outcomes for these women.

The retrospective cohort study analyzed data from the Nationwide Readmissions Database on women who had experienced a delivery hospitalization from Oct. 1, 2015, to Dec. 31, 2018. They compared outcomes for women with isolated preexisting ischemic heart disease with those of women who had no apparent cardiac condition and to those with mild or more severe cardiac conditions included in the mWHO classification after controlling for other comorbidities.

The primary outcome was severe maternal morbidity or death. Dr. Denoble explained that severe maternal morbidity includes mechanical ventilation, blood transfusion, and hysterectomy – the more severe maternal adverse outcomes of pregnancy.

Results showed that, of 11,556,136 delivery hospitalizations, 65,331 patients had another cardiac diagnosis, and 3,009 had ischemic heart disease alone. Patients with ischemic heart disease were older, and rates of diabetes and hypertension were higher.

In unadjusted analyses, adverse outcomes were more common among patients with ischemic heart disease alone than among patients with no cardiac disease and mild cardiac conditions (mWHO class I-II cardiac disease).

Of those with preexisting ischemic heart disease, 6.6% experienced severe maternal morbidity or death, compared with 1.5% of those without a cardiac disease (unadjusted relative risk vs. no cardiac disease, 4.3; 95% confidence interval, 3.5-5.2).

In comparison, 4.2% of women with mWHO I-II cardiac diseases and 23.1% of those with more severe mWHO II/III-IV cardiac diseases experienced severe maternal morbidity or death.

Similar differences were noted for nontransfusion severe maternal morbidity and mortality, as well as cardiac severe maternal morbidity and mortality.

After adjustment, ischemic heart disease alone was associated with a higher risk of severe maternal morbidity or death compared to no cardiac disease (adjusted RR, 1.51; 95% CI, 1.19-1.92).

In comparison, the aRR was 1.90 for WHO class I-II diseases and 5.87 (95% CI, 5.49-6.27) for more severe cardiac conditions defined as WHO II/III-IV diseases.

Risk for nontransfusion severe maternal morbidity or death (aRR, 1.60) and cardiac severe maternal morbidity or death (aRR, 2.98) were also higher for those with ischemic heart disease than for women without any cardiac disease.

There were no significant differences in preterm birth for those with preexisting ischemic heart disease compared to those with no cardiac disease after adjustment.

The risk of severe maternal morbidity and mortality, nontransfusion severe maternal morbidity and mortality, and cardiac severe maternal morbidity and mortality for ischemic heart disease alone most closely approximated that of mWHO class I or II cardiac diseases, the researchers said.

“We found that individuals with preexisting ischemic heart disease had a rate of severe maternal morbidity/mortality in the same range as those with other cardiac diagnoses in the mild cardiac disease classification (class I or II),” Dr. Denoble commented.

“This prognosis suggests it is very reasonable for these women to consider pregnancy. The risk of adverse outcomes is not so high that pregnancy is contraindicated,” she added.

Dr. Denoble said this information will be very helpful when counseling women with preexisting ischemic heart disease who are considering pregnancy. “These patients may need some extra monitoring, but in general, they have a high chance of a good outcome,” she noted.

“I would still advise these women to register with a high-risk obstetrics provider to have a baseline cardiovascular pregnancy evaluation. As long as that is reassuring, then further frequent intensive supervision may not be necessary,” she said.

However, the authors pointed out, “it is important to communicate to patients that while pregnancy may be considered low risk in the setting of pre-existing ischemic heart disease, 6.6% of patients with pre-existing ischemic heart disease alone did experience severe maternal morbidity or death during the delivery hospitalization.”

They added that other medical comorbidities should be factored into discussions regarding the risks of pregnancy.

The researchers also noted that the study was limited to evaluation of maternal outcomes occurring during the delivery hospitalization and that additional research that assesses rates of maternal adverse cardiac events and maternal morbidity occurring prior to or after the delivery hospitalization would be beneficial.

Future studies examining the potential gradation in risk associated with additional cardiac comorbidities in individuals with preexisting ischemic heart disease would also be worthwhile, they added.

The study was supported by funding from the National Institutes of Health and the Foundation for Women and Girls with Blood Disorders. The authors disclosed no relevant financial relationships.

A version of this article first appeared on Medscape.com.

Women with preexisting ischemic heart disease without another cardiac diagnosis have a higher risk of severe maternal morbidity and mortality than women with no cardiac disease, a new study suggests.

However, after adjustment for other comorbidities, the risk associated with isolated preexisting ischemic heart disease without additional evidence of cardiomyopathy was relatively similar to that of other low-risk cardiac diseases.

“These are reassuring findings,” lead author of the study, Anna E. Denoble, MD, Yale University, New Haven, Conn., told this news organization. “The risk is not zero. Women with preexisting ischemic heart disease are at a small increased risk compared to women without preexisting cardiac disease. But with good control of cardiovascular risk factors, these women have a good chance of a positive outcome.”

The study was published online in JACC: Advances.

“To our knowledge, this study provides the largest analysis to date examining the risk of severe morbidity and mortality among pregnant people with pre-existing ischemic heart disease,” the authors noted.

Dr. Denoble, a maternal and fetal medicine specialist, explained that in recent years, there has been an increase in the number of patients with preexisting ischemic heart disease who are considering pregnancy or who are pregnant when they present, but there is little information on outcomes for these patients.

The diagnosis of ischemic heart disease is not included in the main classification used for heart disease in pregnancy – the modified World Health Organization classification, Dr. Denoble noted. “This classification includes information on pregnancy outcomes in women with many cardiac conditions, including arrhythmias, congenital heart disease, heart failure, and aortic aneurysm, but ischemic heart disease is missing.”

She suggested this is probably because ischemic heart disease is regarded as a condition that occurs mainly in older people. “But we are seeing more and more women with ischemic heart disease who are pregnant or considering pregnancy. This could be because women are now often older when considering pregnancy, and also risk factors for ischemic heart disease, such as obesity and diabetes, are becoming more frequent in younger women.”

The researchers conducted the current study to investigate pregnancy outcomes for these women.

The retrospective cohort study analyzed data from the Nationwide Readmissions Database on women who had experienced a delivery hospitalization from Oct. 1, 2015, to Dec. 31, 2018. They compared outcomes for women with isolated preexisting ischemic heart disease with those of women who had no apparent cardiac condition and to those with mild or more severe cardiac conditions included in the mWHO classification after controlling for other comorbidities.

The primary outcome was severe maternal morbidity or death. Dr. Denoble explained that severe maternal morbidity includes mechanical ventilation, blood transfusion, and hysterectomy – the more severe maternal adverse outcomes of pregnancy.

Results showed that, of 11,556,136 delivery hospitalizations, 65,331 patients had another cardiac diagnosis, and 3,009 had ischemic heart disease alone. Patients with ischemic heart disease were older, and rates of diabetes and hypertension were higher.

In unadjusted analyses, adverse outcomes were more common among patients with ischemic heart disease alone than among patients with no cardiac disease and mild cardiac conditions (mWHO class I-II cardiac disease).

Of those with preexisting ischemic heart disease, 6.6% experienced severe maternal morbidity or death, compared with 1.5% of those without a cardiac disease (unadjusted relative risk vs. no cardiac disease, 4.3; 95% confidence interval, 3.5-5.2).

In comparison, 4.2% of women with mWHO I-II cardiac diseases and 23.1% of those with more severe mWHO II/III-IV cardiac diseases experienced severe maternal morbidity or death.

Similar differences were noted for nontransfusion severe maternal morbidity and mortality, as well as cardiac severe maternal morbidity and mortality.

After adjustment, ischemic heart disease alone was associated with a higher risk of severe maternal morbidity or death compared to no cardiac disease (adjusted RR, 1.51; 95% CI, 1.19-1.92).

In comparison, the aRR was 1.90 for WHO class I-II diseases and 5.87 (95% CI, 5.49-6.27) for more severe cardiac conditions defined as WHO II/III-IV diseases.

Risk for nontransfusion severe maternal morbidity or death (aRR, 1.60) and cardiac severe maternal morbidity or death (aRR, 2.98) were also higher for those with ischemic heart disease than for women without any cardiac disease.

There were no significant differences in preterm birth for those with preexisting ischemic heart disease compared to those with no cardiac disease after adjustment.

The risk of severe maternal morbidity and mortality, nontransfusion severe maternal morbidity and mortality, and cardiac severe maternal morbidity and mortality for ischemic heart disease alone most closely approximated that of mWHO class I or II cardiac diseases, the researchers said.

“We found that individuals with preexisting ischemic heart disease had a rate of severe maternal morbidity/mortality in the same range as those with other cardiac diagnoses in the mild cardiac disease classification (class I or II),” Dr. Denoble commented.

“This prognosis suggests it is very reasonable for these women to consider pregnancy. The risk of adverse outcomes is not so high that pregnancy is contraindicated,” she added.

Dr. Denoble said this information will be very helpful when counseling women with preexisting ischemic heart disease who are considering pregnancy. “These patients may need some extra monitoring, but in general, they have a high chance of a good outcome,” she noted.

“I would still advise these women to register with a high-risk obstetrics provider to have a baseline cardiovascular pregnancy evaluation. As long as that is reassuring, then further frequent intensive supervision may not be necessary,” she said.

However, the authors pointed out, “it is important to communicate to patients that while pregnancy may be considered low risk in the setting of pre-existing ischemic heart disease, 6.6% of patients with pre-existing ischemic heart disease alone did experience severe maternal morbidity or death during the delivery hospitalization.”

They added that other medical comorbidities should be factored into discussions regarding the risks of pregnancy.

The researchers also noted that the study was limited to evaluation of maternal outcomes occurring during the delivery hospitalization and that additional research that assesses rates of maternal adverse cardiac events and maternal morbidity occurring prior to or after the delivery hospitalization would be beneficial.

Future studies examining the potential gradation in risk associated with additional cardiac comorbidities in individuals with preexisting ischemic heart disease would also be worthwhile, they added.

The study was supported by funding from the National Institutes of Health and the Foundation for Women and Girls with Blood Disorders. The authors disclosed no relevant financial relationships.

A version of this article first appeared on Medscape.com.

LISBON – Efforts are underway to better identify which individuals with so-called “prediabetes” are at greatest risk for developing type 2 diabetes and subsequent complications, and therefore merit more intensive intervention.

“Prediabetes” is the term coined to refer to either “impaired fasting glucose (IFG)” or “impaired glucose tolerance (IGT),” both denoting levels of elevated glycemia that don’t meet the thresholds for diabetes. It’s a heterogeneous group overall, and despite its name, not everyone with prediabetes will progress to develop type 2 diabetes.

There have been major increases in prediabetes in the United States and globally over the past 2 decades, epidemiologist Elizabeth Selvin, PhD, said at the recent IDF World Diabetes Congress 2022.

She noted that the concept of “prediabetes” has been controversial, previously dubbed a “dubious diagnosis” and a “boon for Pharma” in a 2019 Science article.

Others have said it’s “not a medical condition” and that it’s “an artificial category with virtually zero clinical relevance” in a press statement issued for a 2014 BMJ article.

“I don’t agree with these statements entirely but I think they speak to the confusion and tremendous controversy around the concept of prediabetes ... I think instead of calling prediabetes a ‘dubious diagnosis’ we should think of it as an opportunity,” said Dr. Selvin, of Johns Hopkins University Bloomberg School of Public Health, Baltimore.

She proposes trying to home in on those with highest risk of developing type 2 diabetes, which she suggests could be achieved by using a combination of elevated fasting glucose and an elevated A1c, although she stresses that this isn’t in any official guidance.

With the appropriate definition, people who are truly at risk for progression to type 2 diabetes can be identified so that lifestyle factors and cardiovascular risk can be addressed, and weight loss efforts implemented.

“Prevention of weight gain is ... important. That message often gets lost. Even if we can’t get people to lose weight, preventing [further] weight gain is important,” she noted.

Asked to comment, Sue Kirkman, MD, told this news organization, “The term prediabetes – or IFG or IGT or any of the ‘intermediate’ terms – is pragmatic in a way. It helps clinicians and patients understand that they are in a higher-risk category and might need intervention and likely need ongoing monitoring. But like many other risk factors [such as] blood pressure, [high] BMI, etc., the risk is not dichotomous but a continuum.

“People at the low end of the ‘intermediate’ range are not going to have much more risk compared to people who are ‘normal,’ while those at the high end of the range have very high risk,” said Dr. Kirkman, of the University of North Carolina, Chapel Hill, and a coauthor of the American Diabetes Association’s diabetes and prediabetes classifications.

“So we lose information if we just lump everyone into a single category. For individual patients, we definitely need better ways to estimate and communicate their potential risk.”


 

Currently five definitions for prediabetes: Home in on risk

The problem, Dr. Selvin explained, is that currently there are five official definitions for “prediabetes” using cutoffs for hemoglobin A1c, fasting glucose, or an oral glucose tolerance test.

Each one identifies different numbers of people with differing risk levels, ranging from a prevalence of 4.3% of the middle-aged adult population with the International Expert Committee’s definition of A1c 6.0%-6.4% to 43.5% with the American Diabetes Association’s 100-125 mg/dL fasting glucose.

“That’s an enormous difference. No wonder people are confused about who has prediabetes and what we should do about it,” Dr. Selvin said, adding that the concern about overdiagnosing “prediabetes” is even greater for older populations, in whom “it’s incredibly common to have mildly elevated glucose.”  

Hence her proposal of what she sees as an evidence-based, “really easy solution” that clinicians can use now to better identify which patients with “intermediate hyperglycemia” to be most concerned about: Use a combination of fasting glucose above 100 mg/dL and an A1c greater than 5.7%.

“If you have both fasting glucose and hemoglobin A1c, you can use them together ... This is not codified in any guidelines. You won’t see this mentioned anywhere. The guidelines are silent on what to do when some people have an elevated fasting glucose but not an elevated A1c ... but I think a simple message is that if people have both an elevated fasting glucose and an elevated A1c, that’s a very high-risk group,” she said.

On the other hand, Dr. Kirkman pointed out, “most discrepancies are near the margins, as in one test is slightly elevated and one isn’t, so those people probably are at low risk.

“It may be that both being elevated means higher risk because they have more hyperglycemia ... so it seems reasonable, but only if it changes what you tell people.”

For example, Dr. Kirkman said, “I’d tell someone with A1c of 5.8% and fasting glucose of 99 mg/dL the same thing I’d tell someone with that A1c and a glucose of 104 mg/dL – that their risk is still pretty low – and I’d recommend healthy lifestyle and weight loss if overweight either way.”

However, she also said, “Certainly people with higher glucose or A1c are at much higher risk, and same for those with both.”
 

Tie “prediabetes” definition to risk, as cardiology scores do?

Dr. Selvin also believes that risk-based definitions of prediabetes are needed. Ideally, these would incorporate demographics and clinical factors such as age and body mass index. Other biomarkers could potentially be developed and validated for inclusion in the definition, such as C-reactive protein (CRP), lipids, or even genetic/proteomic information.  

Moreover, she thinks that the definition should be tied to clinical decision-making, as is the pooled cohort equation in cardiology.

“I think we could do something very similar in prediabetes,” she suggested, adding that even simply incorporating age and BMI into the definition could help further stratify the risk level until other predictors are validated.

Dr. Kirkman said, “The concept of risk scores a la cardiology is interesting, although we’d have to make them simple and also validate them against some outcome.”

Regarding the age issue, Dr. Kirkman noted that although age wasn’t a predictor of progression to type 2 diabetes in the placebo arm of the landmark Diabetes Prevention Program (DPP) trial, “I do agree that it’s a problem that many older folks have the label of prediabetes because of a mildly elevated A1c and we know that most will never get diabetes.”

And, she noted, in the DPP people with prediabetes who had a BMI over 35 kg/m² did have significantly higher progression rates than those with lower BMI, while women with a history of gestational diabetes mellitus are also known to be at particularly high risk.
 

Whom should we throw the kitchen sink at?

Some of this discussion, Dr. Kirkman said, “is really a philosophical one, especially when you consider that lifestyle intervention has benefits for almost everyone on many short- and long-term outcomes.”

“The question is probably whom we should ‘throw the kitchen sink at,’ who should get more scalable advice that might apply to everyone regardless of glycemic levels, and whether there’s some more intermediate group that needs more of a [National Diabetes Prevention Program] approach.”

Dr. Selvin’s group is now working on gathering data to inform development of a risk-based prediabetes definition. “We have a whole research effort in this area. I hope that with some really strong data on risk in prediabetes, that can help to solve the heterogeneity issue. I’m focused on bringing evidence to bear to change the guidelines.”

In the meantime, she told this news organization, “I think there are things we can do now to provide more guidance. I get a lot of feedback from people saying things like ‘my physician told me I have prediabetes but now I don’t’ or ‘I saw in my labs that my blood sugar is elevated but my doctor never said anything.’  That’s a communications issue where we can do a better job.”

The meeting was sponsored by the International Diabetes Federation.

Dr. Selvin is deputy editor of Diabetes Care and on the editorial board of Diabetologia. She receives funding from the NIH and the Foundation for the NIH, and royalties from UpToDate for sections related to screening, diagnosis, and laboratory testing for diabetes. Dr. Kirkman reports no relevant financial relationships.

A version of this article first appeared on Medscape.com.

LISBON – Efforts are underway to better identify which individuals with so-called “prediabetes” are at greatest risk for developing type 2 diabetes and subsequent complications, and therefore merit more intensive intervention.

“Prediabetes” is the term coined to refer to either “impaired fasting glucose (IFG)” or “impaired glucose tolerance (IGT),” both denoting levels of elevated glycemia that don’t meet the thresholds for diabetes. It’s a heterogeneous group overall, and despite its name, not everyone with prediabetes will progress to develop type 2 diabetes.

There have been major increases in prediabetes in the United States and globally over the past 2 decades, epidemiologist Elizabeth Selvin, PhD, said at the recent IDF World Diabetes Congress 2022.

She noted that the concept of “prediabetes” has been controversial, previously dubbed a “dubious diagnosis” and a “boon for Pharma” in a 2019 Science article.

Others have said it’s “not a medical condition” and that it’s “an artificial category with virtually zero clinical relevance” in a press statement issued for a 2014 BMJ article.

“I don’t agree with these statements entirely but I think they speak to the confusion and tremendous controversy around the concept of prediabetes ... I think instead of calling prediabetes a ‘dubious diagnosis’ we should think of it as an opportunity,” said Dr. Selvin, of Johns Hopkins University Bloomberg School of Public Health, Baltimore.

She proposes trying to home in on those with highest risk of developing type 2 diabetes, which she suggests could be achieved by using a combination of elevated fasting glucose and an elevated A1c, although she stresses that this isn’t in any official guidance.

With the appropriate definition, people who are truly at risk for progression to type 2 diabetes can be identified so that lifestyle factors and cardiovascular risk can be addressed, and weight loss efforts implemented.

“Prevention of weight gain is ... important. That message often gets lost. Even if we can’t get people to lose weight, preventing [further] weight gain is important,” she noted.

Asked to comment, Sue Kirkman, MD, told this news organization, “The term prediabetes – or IFG or IGT or any of the ‘intermediate’ terms – is pragmatic in a way. It helps clinicians and patients understand that they are in a higher-risk category and might need intervention and likely need ongoing monitoring. But like many other risk factors [such as] blood pressure, [high] BMI, etc., the risk is not dichotomous but a continuum.

“People at the low end of the ‘intermediate’ range are not going to have much more risk compared to people who are ‘normal,’ while those at the high end of the range have very high risk,” said Dr. Kirkman, of the University of North Carolina, Chapel Hill, and a coauthor of the American Diabetes Association’s diabetes and prediabetes classifications.

“So we lose information if we just lump everyone into a single category. For individual patients, we definitely need better ways to estimate and communicate their potential risk.”


 

Currently five definitions for prediabetes: Home in on risk

The problem, Dr. Selvin explained, is that currently there are five official definitions for “prediabetes” using cutoffs for hemoglobin A1c, fasting glucose, or an oral glucose tolerance test.

Each one identifies different numbers of people with differing risk levels, ranging from a prevalence of 4.3% of the middle-aged adult population with the International Expert Committee’s definition of A1c 6.0%-6.4% to 43.5% with the American Diabetes Association’s 100-125 mg/dL fasting glucose.

“That’s an enormous difference. No wonder people are confused about who has prediabetes and what we should do about it,” Dr. Selvin said, adding that the concern about overdiagnosing “prediabetes” is even greater for older populations, in whom “it’s incredibly common to have mildly elevated glucose.”  

Hence her proposal of what she sees as an evidence-based, “really easy solution” that clinicians can use now to better identify which patients with “intermediate hyperglycemia” to be most concerned about: Use a combination of fasting glucose above 100 mg/dL and an A1c greater than 5.7%.

“If you have both fasting glucose and hemoglobin A1c, you can use them together ... This is not codified in any guidelines. You won’t see this mentioned anywhere. The guidelines are silent on what to do when some people have an elevated fasting glucose but not an elevated A1c ... but I think a simple message is that if people have both an elevated fasting glucose and an elevated A1c, that’s a very high-risk group,” she said.

On the other hand, Dr. Kirkman pointed out, “most discrepancies are near the margins, as in one test is slightly elevated and one isn’t, so those people probably are at low risk.

“It may be that both being elevated means higher risk because they have more hyperglycemia ... so it seems reasonable, but only if it changes what you tell people.”

For example, Dr. Kirkman said, “I’d tell someone with A1c of 5.8% and fasting glucose of 99 mg/dL the same thing I’d tell someone with that A1c and a glucose of 104 mg/dL – that their risk is still pretty low – and I’d recommend healthy lifestyle and weight loss if overweight either way.”

However, she also said, “Certainly people with higher glucose or A1c are at much higher risk, and same for those with both.”
 

Tie “prediabetes” definition to risk, as cardiology scores do?

Dr. Selvin also believes that risk-based definitions of prediabetes are needed. Ideally, these would incorporate demographics and clinical factors such as age and body mass index. Other biomarkers could potentially be developed and validated for inclusion in the definition, such as C-reactive protein (CRP), lipids, or even genetic/proteomic information.  

Moreover, she thinks that the definition should be tied to clinical decision-making, as is the pooled cohort equation in cardiology.

“I think we could do something very similar in prediabetes,” she suggested, adding that even simply incorporating age and BMI into the definition could help further stratify the risk level until other predictors are validated.

Dr. Kirkman said, “The concept of risk scores a la cardiology is interesting, although we’d have to make them simple and also validate them against some outcome.”

Regarding the age issue, Dr. Kirkman noted that although age wasn’t a predictor of progression to type 2 diabetes in the placebo arm of the landmark Diabetes Prevention Program (DPP) trial, “I do agree that it’s a problem that many older folks have the label of prediabetes because of a mildly elevated A1c and we know that most will never get diabetes.”

And, she noted, in the DPP people with prediabetes who had a BMI over 35 kg/m² did have significantly higher progression rates than those with lower BMI, while women with a history of gestational diabetes mellitus are also known to be at particularly high risk.
 

Whom should we throw the kitchen sink at?

Some of this discussion, Dr. Kirkman said, “is really a philosophical one, especially when you consider that lifestyle intervention has benefits for almost everyone on many short- and long-term outcomes.”

“The question is probably whom we should ‘throw the kitchen sink at,’ who should get more scalable advice that might apply to everyone regardless of glycemic levels, and whether there’s some more intermediate group that needs more of a [National Diabetes Prevention Program] approach.”

Dr. Selvin’s group is now working on gathering data to inform development of a risk-based prediabetes definition. “We have a whole research effort in this area. I hope that with some really strong data on risk in prediabetes, that can help to solve the heterogeneity issue. I’m focused on bringing evidence to bear to change the guidelines.”

In the meantime, she told this news organization, “I think there are things we can do now to provide more guidance. I get a lot of feedback from people saying things like ‘my physician told me I have prediabetes but now I don’t’ or ‘I saw in my labs that my blood sugar is elevated but my doctor never said anything.’  That’s a communications issue where we can do a better job.”

The meeting was sponsored by the International Diabetes Federation.

Dr. Selvin is deputy editor of Diabetes Care and on the editorial board of Diabetologia. She receives funding from the NIH and the Foundation for the NIH, and royalties from UpToDate for sections related to screening, diagnosis, and laboratory testing for diabetes. Dr. Kirkman reports no relevant financial relationships.

A version of this article first appeared on Medscape.com.

LISBON – Efforts are underway to better identify which individuals with so-called “prediabetes” are at greatest risk for developing type 2 diabetes and subsequent complications, and therefore merit more intensive intervention.

“Prediabetes” is the term coined to refer to either “impaired fasting glucose (IFG)” or “impaired glucose tolerance (IGT),” both denoting levels of elevated glycemia that don’t meet the thresholds for diabetes. It’s a heterogeneous group overall, and despite its name, not everyone with prediabetes will progress to develop type 2 diabetes.

There have been major increases in prediabetes in the United States and globally over the past 2 decades, epidemiologist Elizabeth Selvin, PhD, said at the recent IDF World Diabetes Congress 2022.

She noted that the concept of “prediabetes” has been controversial, previously dubbed a “dubious diagnosis” and a “boon for Pharma” in a 2019 Science article.

Others have said it’s “not a medical condition” and that it’s “an artificial category with virtually zero clinical relevance” in a press statement issued for a 2014 BMJ article.

“I don’t agree with these statements entirely but I think they speak to the confusion and tremendous controversy around the concept of prediabetes ... I think instead of calling prediabetes a ‘dubious diagnosis’ we should think of it as an opportunity,” said Dr. Selvin, of Johns Hopkins University Bloomberg School of Public Health, Baltimore.

She proposes trying to home in on those with highest risk of developing type 2 diabetes, which she suggests could be achieved by using a combination of elevated fasting glucose and an elevated A1c, although she stresses that this isn’t in any official guidance.

With the appropriate definition, people who are truly at risk for progression to type 2 diabetes can be identified so that lifestyle factors and cardiovascular risk can be addressed, and weight loss efforts implemented.

“Prevention of weight gain is ... important. That message often gets lost. Even if we can’t get people to lose weight, preventing [further] weight gain is important,” she noted.

Asked to comment, Sue Kirkman, MD, told this news organization, “The term prediabetes – or IFG or IGT or any of the ‘intermediate’ terms – is pragmatic in a way. It helps clinicians and patients understand that they are in a higher-risk category and might need intervention and likely need ongoing monitoring. But like many other risk factors [such as] blood pressure, [high] BMI, etc., the risk is not dichotomous but a continuum.

“People at the low end of the ‘intermediate’ range are not going to have much more risk compared to people who are ‘normal,’ while those at the high end of the range have very high risk,” said Dr. Kirkman, of the University of North Carolina, Chapel Hill, and a coauthor of the American Diabetes Association’s diabetes and prediabetes classifications.

“So we lose information if we just lump everyone into a single category. For individual patients, we definitely need better ways to estimate and communicate their potential risk.”


 

Currently five definitions for prediabetes: Home in on risk

The problem, Dr. Selvin explained, is that currently there are five official definitions for “prediabetes” using cutoffs for hemoglobin A1c, fasting glucose, or an oral glucose tolerance test.

Each one identifies different numbers of people with differing risk levels, ranging from a prevalence of 4.3% of the middle-aged adult population with the International Expert Committee’s definition of A1c 6.0%-6.4% to 43.5% with the American Diabetes Association’s 100-125 mg/dL fasting glucose.

“That’s an enormous difference. No wonder people are confused about who has prediabetes and what we should do about it,” Dr. Selvin said, adding that the concern about overdiagnosing “prediabetes” is even greater for older populations, in whom “it’s incredibly common to have mildly elevated glucose.”  

Hence her proposal of what she sees as an evidence-based, “really easy solution” that clinicians can use now to better identify which patients with “intermediate hyperglycemia” to be most concerned about: Use a combination of fasting glucose above 100 mg/dL and an A1c greater than 5.7%.

“If you have both fasting glucose and hemoglobin A1c, you can use them together ... This is not codified in any guidelines. You won’t see this mentioned anywhere. The guidelines are silent on what to do when some people have an elevated fasting glucose but not an elevated A1c ... but I think a simple message is that if people have both an elevated fasting glucose and an elevated A1c, that’s a very high-risk group,” she said.

On the other hand, Dr. Kirkman pointed out, “most discrepancies are near the margins, as in one test is slightly elevated and one isn’t, so those people probably are at low risk.

“It may be that both being elevated means higher risk because they have more hyperglycemia ... so it seems reasonable, but only if it changes what you tell people.”

For example, Dr. Kirkman said, “I’d tell someone with A1c of 5.8% and fasting glucose of 99 mg/dL the same thing I’d tell someone with that A1c and a glucose of 104 mg/dL – that their risk is still pretty low – and I’d recommend healthy lifestyle and weight loss if overweight either way.”

However, she also said, “Certainly people with higher glucose or A1c are at much higher risk, and same for those with both.”
 

Tie “prediabetes” definition to risk, as cardiology scores do?

Dr. Selvin also believes that risk-based definitions of prediabetes are needed. Ideally, these would incorporate demographics and clinical factors such as age and body mass index. Other biomarkers could potentially be developed and validated for inclusion in the definition, such as C-reactive protein (CRP), lipids, or even genetic/proteomic information.  

Moreover, she thinks that the definition should be tied to clinical decision-making, as is the pooled cohort equation in cardiology.

“I think we could do something very similar in prediabetes,” she suggested, adding that even simply incorporating age and BMI into the definition could help further stratify the risk level until other predictors are validated.

Dr. Kirkman said, “The concept of risk scores a la cardiology is interesting, although we’d have to make them simple and also validate them against some outcome.”

Regarding the age issue, Dr. Kirkman noted that although age wasn’t a predictor of progression to type 2 diabetes in the placebo arm of the landmark Diabetes Prevention Program (DPP) trial, “I do agree that it’s a problem that many older folks have the label of prediabetes because of a mildly elevated A1c and we know that most will never get diabetes.”

And, she noted, in the DPP people with prediabetes who had a BMI over 35 kg/m² did have significantly higher progression rates than those with lower BMI, while women with a history of gestational diabetes mellitus are also known to be at particularly high risk.
 

Whom should we throw the kitchen sink at?

Some of this discussion, Dr. Kirkman said, “is really a philosophical one, especially when you consider that lifestyle intervention has benefits for almost everyone on many short- and long-term outcomes.”

“The question is probably whom we should ‘throw the kitchen sink at,’ who should get more scalable advice that might apply to everyone regardless of glycemic levels, and whether there’s some more intermediate group that needs more of a [National Diabetes Prevention Program] approach.”

Dr. Selvin’s group is now working on gathering data to inform development of a risk-based prediabetes definition. “We have a whole research effort in this area. I hope that with some really strong data on risk in prediabetes, that can help to solve the heterogeneity issue. I’m focused on bringing evidence to bear to change the guidelines.”

In the meantime, she told this news organization, “I think there are things we can do now to provide more guidance. I get a lot of feedback from people saying things like ‘my physician told me I have prediabetes but now I don’t’ or ‘I saw in my labs that my blood sugar is elevated but my doctor never said anything.’  That’s a communications issue where we can do a better job.”

The meeting was sponsored by the International Diabetes Federation.

Dr. Selvin is deputy editor of Diabetes Care and on the editorial board of Diabetologia. She receives funding from the NIH and the Foundation for the NIH, and royalties from UpToDate for sections related to screening, diagnosis, and laboratory testing for diabetes. Dr. Kirkman reports no relevant financial relationships.

A version of this article first appeared on Medscape.com.