As readers of OBG Management, you are very familiar with the name Janelle Yates. Janelle was an editor and writer for the journal for more than 15 years. Her byline has graced articles on, among other topics, obstetrics, liability, menopause, and tissue extraction. You may recall the 3-part series on endometriosis she authored beginning in April 2015.¹ She worked with several expert surgeons to deliver an in-depth look at diagnosis, treatment, and related infertility. She interviewed presidents of the American Congress of Obstetricians and Gynecologists (ACOG)² and worked with ACOG staff, including Lucia DiVenere, MA, on legislative articles for OBG Management, helping to bring new policies and practice changes to the forefront for readers.^3,4

One topic that was of particular, personal interest to Janelle was breast cancer. She lived on and off with, but always under the shadow of, breast cancer for more than 8 years. This past December, Janelle developed a rare and incurable cancer of the nervous system, which took her life in January.

Janelle’s contributions to OBG Management Janelle worked closely with Robert L. Barbieri, MD, and the OBG Management Board of Editors on writing and editing projects. In fact, Janelle began as Senior Associate Editor with the journal in 2000, only a few months after Dr. Barbieri was inaugurated as Editor in Chief.

“Janelle was exceptionally skillful in polishing a rough manuscript into a superbly crafted article,” says Dr. Barbieri. “The physician authors with whom she collaborated were in awe of her talent and recognized the value of her contributions to advancing women’s health care.”

“Janelle approached the craft of writing like an artist, always searching for an additional layer of deeper meaning and insight. Her strength of character and myriad life experiences gave her unique skills in exploring, questioning, and improving the content that was brought forth.”

“She and I had an ongoing conversation on the pros and cons of being concise,” says Dr. Barbieri. “I would ask her the hypothetical, ‘If an author could effectively deliver his or her core message in a 1-page article, why take 3 pages to do so?’ As a counterpoint, her perspective was that if you could concisely make your point in 3 pages, it might be even better for an author to expand their article to 9 pages to help the reader achieve a deeper level of understanding and insight.”

In May 2013, Barbara S. Levy, MD, after serving for 17 years as an OBG Management Board of Editors member, assumed the position of Vice President for Health Policy at ACOG, and resigned her position on the journal’s editorial board. Janelle collaborated with Dr. Levy on an article commemorating her lifetime of service to women.⁵ Dr. Levy recalls that article, and the numerous others she partnered on with Janelle:

“She was the quintessential professional. We are professional doctors, but Janelle was a professional writer and editor. She had an ability to, when speaking with us, get the best out of us, and take what we said and translate that into a cogent, crisp presentation that was really meaningful to readers. Having her perspective as a partner in writing helped me reach a core in readers that I believe I otherwise would not have been able to reach.”

Andrew M. Kaunitz, MD, Board of Editors member since 2006, describes Janelle as “a wonderful colleague and person.”

“My early perceptions of Janelle,” he says, “relate to her tremendous skills as a medical writer. Over time, however, I recognized that, in addition to her wonderful talents as a writer, she brought what I can only call a sense of grace to each interaction that I had with her. I continue to find it hard to imagine a world without her.”

“During my 15-year excursion as the Editor in Chief of OBG Management,” says Dr. Barbieri, “Janelle was the perfect guide and travel companion. She will always be in my thoughts and heart.”

Janelle’s memory enduresJanelle’s colleagues at the journal office and the Board of Editors honor her dedication to OBG Management, and truly to women’s health in general, in a permanent way in the pages of OBG Management. Janelle’s name has been added to the journal’s staff masthead with the title, “Editor Emeritus.” We feel this is a small but sincere gesture from those of us who have had the immense pleasure and incredible honor to work with Janelle over the years. 

John Baranowski, who served as Editor of OBG Management from 2008 until mid-2012, eloquently states: “As her supervisor for several years, I was the initial recipient of tens of thousands of her well-ordered, well-chosen, and insightful words. At this time, it is hard for me to find words to offer on her behalf. Her outsized skill, her easeful manner, and her certain success at improving the care that physicians provide—those are humbling, silencing remembrances; things of such great value that words just do not work as tribute.”

Dianne Reynolds, Publisher of OBG Management, has known Janelle since 2008 and says that she feels blessed and fortunate to have had Janelle in her life on more than just a professional level. “I will cherish her memory forever,” she says.

OBG Management Managing Editor Deborah Reale joined the journal staff in 2010. “Words connected Janelle and I not only in our editorial work but also personally, through our shared love of poetry,” she says. Unbeknownst to many, Janelle was a published poet. She also wrote two biographies, of Woodie Guthrie and Zora Neale Hurston, while working many years ago as an editor for Ward Hill Press.

Like so many others, I feel privileged to have worked with Janelle. Her work was fearless. Whether it was an audio interview with gynecologic oncologist Eva Chalas, MD, on preserving minimally invasive approaches to gynecologic surgery⁶ or a Q&A article on liability claims in obstetrics,⁷ Janelle did it brilliantly. She applied her years of knowledge and experience to each piece she wrote or edited, always bringing an expert’s best voice forward. In fact, Dianne Reynolds says, “Janelle once told me that she had dreamed of being a doctor, and she imagined herself pushing through hospital doors on her way to treat patients. Instead, Janelle used her acquired medical knowledge in women’s health and writing acumen to assist physicians in explaining their techniques for the benefit of their colleagues.”

Janelle’s siblings Diana and Kent Yates, and her daughter Adrienne Cano, say they have been aware of how supportive the OBG Management extended team has been to Janelle. In speaking with Board of Editors member, Cheryl B. Iglesia, MD, Diana says, “This was such a blessing in her life. It was a rare thing, the kind of relationship she had with all of you. We appreciate so very much your nurturing of her talents and of her as a person.”

Janelle meant a great deal to her colleagues, of course because of her superb work and wise perspective, but also because of her warmth and gentle ease. Simply put, Janelle was a wonderful person to be near.

“She was absolutely amazing and will be greatly missed both personally and professionally,” says 10-year OBG Management board member JoAnn V. Pinkerton, MD.

Dr. Iglesia asserts, “Janelle never will be forgotten. She truly has left a legacy of very important articles for many generations.”

Janelle, we can only hope that with your name on the masthead, readers of OBG Management in future generations will have the privilege of your touch. May that touch bring them the gift of journalistic accuracy, professional integrity, spot-on syntax and, above all, compelling reading. 

Share your thoughts! Send your Letter to the Editor to [email protected]. Please include your name and the city and state in which you practice.

As readers of OBG Management, you are very familiar with the name Janelle Yates. Janelle was an editor and writer for the journal for more than 15 years. Her byline has graced articles on, among other topics, obstetrics, liability, menopause, and tissue extraction. You may recall the 3-part series on endometriosis she authored beginning in April 2015.¹ She worked with several expert surgeons to deliver an in-depth look at diagnosis, treatment, and related infertility. She interviewed presidents of the American Congress of Obstetricians and Gynecologists (ACOG)² and worked with ACOG staff, including Lucia DiVenere, MA, on legislative articles for OBG Management, helping to bring new policies and practice changes to the forefront for readers.^3,4

One topic that was of particular, personal interest to Janelle was breast cancer. She lived on and off with, but always under the shadow of, breast cancer for more than 8 years. This past December, Janelle developed a rare and incurable cancer of the nervous system, which took her life in January.

Janelle’s contributions to OBG Management Janelle worked closely with Robert L. Barbieri, MD, and the OBG Management Board of Editors on writing and editing projects. In fact, Janelle began as Senior Associate Editor with the journal in 2000, only a few months after Dr. Barbieri was inaugurated as Editor in Chief.

“Janelle was exceptionally skillful in polishing a rough manuscript into a superbly crafted article,” says Dr. Barbieri. “The physician authors with whom she collaborated were in awe of her talent and recognized the value of her contributions to advancing women’s health care.”

“Janelle approached the craft of writing like an artist, always searching for an additional layer of deeper meaning and insight. Her strength of character and myriad life experiences gave her unique skills in exploring, questioning, and improving the content that was brought forth.”

“She and I had an ongoing conversation on the pros and cons of being concise,” says Dr. Barbieri. “I would ask her the hypothetical, ‘If an author could effectively deliver his or her core message in a 1-page article, why take 3 pages to do so?’ As a counterpoint, her perspective was that if you could concisely make your point in 3 pages, it might be even better for an author to expand their article to 9 pages to help the reader achieve a deeper level of understanding and insight.”

In May 2013, Barbara S. Levy, MD, after serving for 17 years as an OBG Management Board of Editors member, assumed the position of Vice President for Health Policy at ACOG, and resigned her position on the journal’s editorial board. Janelle collaborated with Dr. Levy on an article commemorating her lifetime of service to women.⁵ Dr. Levy recalls that article, and the numerous others she partnered on with Janelle:

“She was the quintessential professional. We are professional doctors, but Janelle was a professional writer and editor. She had an ability to, when speaking with us, get the best out of us, and take what we said and translate that into a cogent, crisp presentation that was really meaningful to readers. Having her perspective as a partner in writing helped me reach a core in readers that I believe I otherwise would not have been able to reach.”

Andrew M. Kaunitz, MD, Board of Editors member since 2006, describes Janelle as “a wonderful colleague and person.”

“My early perceptions of Janelle,” he says, “relate to her tremendous skills as a medical writer. Over time, however, I recognized that, in addition to her wonderful talents as a writer, she brought what I can only call a sense of grace to each interaction that I had with her. I continue to find it hard to imagine a world without her.”

“During my 15-year excursion as the Editor in Chief of OBG Management,” says Dr. Barbieri, “Janelle was the perfect guide and travel companion. She will always be in my thoughts and heart.”

Janelle’s memory enduresJanelle’s colleagues at the journal office and the Board of Editors honor her dedication to OBG Management, and truly to women’s health in general, in a permanent way in the pages of OBG Management. Janelle’s name has been added to the journal’s staff masthead with the title, “Editor Emeritus.” We feel this is a small but sincere gesture from those of us who have had the immense pleasure and incredible honor to work with Janelle over the years. 

John Baranowski, who served as Editor of OBG Management from 2008 until mid-2012, eloquently states: “As her supervisor for several years, I was the initial recipient of tens of thousands of her well-ordered, well-chosen, and insightful words. At this time, it is hard for me to find words to offer on her behalf. Her outsized skill, her easeful manner, and her certain success at improving the care that physicians provide—those are humbling, silencing remembrances; things of such great value that words just do not work as tribute.”

Dianne Reynolds, Publisher of OBG Management, has known Janelle since 2008 and says that she feels blessed and fortunate to have had Janelle in her life on more than just a professional level. “I will cherish her memory forever,” she says.

OBG Management Managing Editor Deborah Reale joined the journal staff in 2010. “Words connected Janelle and I not only in our editorial work but also personally, through our shared love of poetry,” she says. Unbeknownst to many, Janelle was a published poet. She also wrote two biographies, of Woodie Guthrie and Zora Neale Hurston, while working many years ago as an editor for Ward Hill Press.

Like so many others, I feel privileged to have worked with Janelle. Her work was fearless. Whether it was an audio interview with gynecologic oncologist Eva Chalas, MD, on preserving minimally invasive approaches to gynecologic surgery⁶ or a Q&A article on liability claims in obstetrics,⁷ Janelle did it brilliantly. She applied her years of knowledge and experience to each piece she wrote or edited, always bringing an expert’s best voice forward. In fact, Dianne Reynolds says, “Janelle once told me that she had dreamed of being a doctor, and she imagined herself pushing through hospital doors on her way to treat patients. Instead, Janelle used her acquired medical knowledge in women’s health and writing acumen to assist physicians in explaining their techniques for the benefit of their colleagues.”

Janelle’s siblings Diana and Kent Yates, and her daughter Adrienne Cano, say they have been aware of how supportive the OBG Management extended team has been to Janelle. In speaking with Board of Editors member, Cheryl B. Iglesia, MD, Diana says, “This was such a blessing in her life. It was a rare thing, the kind of relationship she had with all of you. We appreciate so very much your nurturing of her talents and of her as a person.”

Janelle meant a great deal to her colleagues, of course because of her superb work and wise perspective, but also because of her warmth and gentle ease. Simply put, Janelle was a wonderful person to be near.

“She was absolutely amazing and will be greatly missed both personally and professionally,” says 10-year OBG Management board member JoAnn V. Pinkerton, MD.

Dr. Iglesia asserts, “Janelle never will be forgotten. She truly has left a legacy of very important articles for many generations.”

Janelle, we can only hope that with your name on the masthead, readers of OBG Management in future generations will have the privilege of your touch. May that touch bring them the gift of journalistic accuracy, professional integrity, spot-on syntax and, above all, compelling reading. 

Share your thoughts! Send your Letter to the Editor to [email protected]. Please include your name and the city and state in which you practice.

As readers of OBG Management, you are very familiar with the name Janelle Yates. Janelle was an editor and writer for the journal for more than 15 years. Her byline has graced articles on, among other topics, obstetrics, liability, menopause, and tissue extraction. You may recall the 3-part series on endometriosis she authored beginning in April 2015.¹ She worked with several expert surgeons to deliver an in-depth look at diagnosis, treatment, and related infertility. She interviewed presidents of the American Congress of Obstetricians and Gynecologists (ACOG)² and worked with ACOG staff, including Lucia DiVenere, MA, on legislative articles for OBG Management, helping to bring new policies and practice changes to the forefront for readers.^3,4

One topic that was of particular, personal interest to Janelle was breast cancer. She lived on and off with, but always under the shadow of, breast cancer for more than 8 years. This past December, Janelle developed a rare and incurable cancer of the nervous system, which took her life in January.

Janelle’s contributions to OBG Management Janelle worked closely with Robert L. Barbieri, MD, and the OBG Management Board of Editors on writing and editing projects. In fact, Janelle began as Senior Associate Editor with the journal in 2000, only a few months after Dr. Barbieri was inaugurated as Editor in Chief.

“Janelle was exceptionally skillful in polishing a rough manuscript into a superbly crafted article,” says Dr. Barbieri. “The physician authors with whom she collaborated were in awe of her talent and recognized the value of her contributions to advancing women’s health care.”

“Janelle approached the craft of writing like an artist, always searching for an additional layer of deeper meaning and insight. Her strength of character and myriad life experiences gave her unique skills in exploring, questioning, and improving the content that was brought forth.”

“She and I had an ongoing conversation on the pros and cons of being concise,” says Dr. Barbieri. “I would ask her the hypothetical, ‘If an author could effectively deliver his or her core message in a 1-page article, why take 3 pages to do so?’ As a counterpoint, her perspective was that if you could concisely make your point in 3 pages, it might be even better for an author to expand their article to 9 pages to help the reader achieve a deeper level of understanding and insight.”

In May 2013, Barbara S. Levy, MD, after serving for 17 years as an OBG Management Board of Editors member, assumed the position of Vice President for Health Policy at ACOG, and resigned her position on the journal’s editorial board. Janelle collaborated with Dr. Levy on an article commemorating her lifetime of service to women.⁵ Dr. Levy recalls that article, and the numerous others she partnered on with Janelle:

“She was the quintessential professional. We are professional doctors, but Janelle was a professional writer and editor. She had an ability to, when speaking with us, get the best out of us, and take what we said and translate that into a cogent, crisp presentation that was really meaningful to readers. Having her perspective as a partner in writing helped me reach a core in readers that I believe I otherwise would not have been able to reach.”

Andrew M. Kaunitz, MD, Board of Editors member since 2006, describes Janelle as “a wonderful colleague and person.”

“My early perceptions of Janelle,” he says, “relate to her tremendous skills as a medical writer. Over time, however, I recognized that, in addition to her wonderful talents as a writer, she brought what I can only call a sense of grace to each interaction that I had with her. I continue to find it hard to imagine a world without her.”

“During my 15-year excursion as the Editor in Chief of OBG Management,” says Dr. Barbieri, “Janelle was the perfect guide and travel companion. She will always be in my thoughts and heart.”

Janelle’s memory enduresJanelle’s colleagues at the journal office and the Board of Editors honor her dedication to OBG Management, and truly to women’s health in general, in a permanent way in the pages of OBG Management. Janelle’s name has been added to the journal’s staff masthead with the title, “Editor Emeritus.” We feel this is a small but sincere gesture from those of us who have had the immense pleasure and incredible honor to work with Janelle over the years. 

John Baranowski, who served as Editor of OBG Management from 2008 until mid-2012, eloquently states: “As her supervisor for several years, I was the initial recipient of tens of thousands of her well-ordered, well-chosen, and insightful words. At this time, it is hard for me to find words to offer on her behalf. Her outsized skill, her easeful manner, and her certain success at improving the care that physicians provide—those are humbling, silencing remembrances; things of such great value that words just do not work as tribute.”

Dianne Reynolds, Publisher of OBG Management, has known Janelle since 2008 and says that she feels blessed and fortunate to have had Janelle in her life on more than just a professional level. “I will cherish her memory forever,” she says.

OBG Management Managing Editor Deborah Reale joined the journal staff in 2010. “Words connected Janelle and I not only in our editorial work but also personally, through our shared love of poetry,” she says. Unbeknownst to many, Janelle was a published poet. She also wrote two biographies, of Woodie Guthrie and Zora Neale Hurston, while working many years ago as an editor for Ward Hill Press.

Like so many others, I feel privileged to have worked with Janelle. Her work was fearless. Whether it was an audio interview with gynecologic oncologist Eva Chalas, MD, on preserving minimally invasive approaches to gynecologic surgery⁶ or a Q&A article on liability claims in obstetrics,⁷ Janelle did it brilliantly. She applied her years of knowledge and experience to each piece she wrote or edited, always bringing an expert’s best voice forward. In fact, Dianne Reynolds says, “Janelle once told me that she had dreamed of being a doctor, and she imagined herself pushing through hospital doors on her way to treat patients. Instead, Janelle used her acquired medical knowledge in women’s health and writing acumen to assist physicians in explaining their techniques for the benefit of their colleagues.”

Janelle’s siblings Diana and Kent Yates, and her daughter Adrienne Cano, say they have been aware of how supportive the OBG Management extended team has been to Janelle. In speaking with Board of Editors member, Cheryl B. Iglesia, MD, Diana says, “This was such a blessing in her life. It was a rare thing, the kind of relationship she had with all of you. We appreciate so very much your nurturing of her talents and of her as a person.”

Janelle meant a great deal to her colleagues, of course because of her superb work and wise perspective, but also because of her warmth and gentle ease. Simply put, Janelle was a wonderful person to be near.

“She was absolutely amazing and will be greatly missed both personally and professionally,” says 10-year OBG Management board member JoAnn V. Pinkerton, MD.

Dr. Iglesia asserts, “Janelle never will be forgotten. She truly has left a legacy of very important articles for many generations.”

Janelle, we can only hope that with your name on the masthead, readers of OBG Management in future generations will have the privilege of your touch. May that touch bring them the gift of journalistic accuracy, professional integrity, spot-on syntax and, above all, compelling reading. 

Share your thoughts! Send your Letter to the Editor to [email protected]. Please include your name and the city and state in which you practice.

“CAN WE SOLVE THE PROBLEM OF INADEQUATE CONTRACEPTION FOR WOMEN AT HIGH RISK FOR ADVERSE PREGNANCY OUTCOMES?”
ROBERT L. BARBIERI, MD (EDITORIAL; FEBRUARY 2016)

“Contraception as a vital sign”
In his recent Editorial Dr. Barbieri asked for ideas to improve contraception counseling for women with medical problems that put them at risk for adverse pregnancy outcomes. His idea of “contraception status as a vital sign” is applied in our very large group practice in Northern California using the electronic health record (EHR).

Over 10 years ago, I attempted to put a hard stop in the EHR to require documentation that women of reproductive age be evaluated for contraception. This scheme seemed to be too cumbersome and was rejected at the time.

The idea was not abandoned, however. Medical assistants must now document a means of contraception for each woman of reproductive age. This does not guarantee that a physician will look at the information, but it is a step in the right direction.

My hope is that someday we will have automatic contraception as a vital sign documentation for all reproductive-age women, including “children” who are documented as menstruating. In the meantime, thank you for highlighting this critical issue.

Tia Will, MD
Sacramento, California

Reduce reimbursement when standard of care is not met
When I read Dr. Barbieri’s Editorial, I was surprised that he avoided the elephant in the room: the current political climate of denying contraception to women, including the defunding of Planned Parenthood and the Supreme Court decision to allow corporations to deny contraceptive coverage for religious issues.

Although I am not currently involved in women’s health, I do work under the auspices of a large Catholic health care system in the United States. Here, all employees are prohibited from providing contraceptive procedures, prescriptions, or even counseling unless it is a Natural Family Planning/ Fertility Awareness Method. These employees also are not provided individual contraceptive health coverage by their employer; this coverage is provided by the federal government thanks to the Affordable Care Act.

Contraception is part of the standard of care for women. However, many women are denied this standard of care due to “religious” reasons, which I suspect may be partially financial and/or political in nature. 

This issue must therefore be addressed by political and financial means. My recommendation is for legislation that mandates lower reimbursement rates for health care systems and providers that refuse to offer full contraceptive options to women. If they do not provide full care, they do not get full payment for services. The money saved by reduced reimbursements could then fund federal women’s health clinics in areas dominated by “religious” health care systems that would guarantee full reproductive health options to all.

Name and practice location withheld

Remove Medicaid barriers to postpartum sterilization
An issue not addressed in Dr. Barbieri’s Editorial is that of women who, after appropriate and extensive counseling by a physician and with a full understanding of the reproductive implications and the possible adverse effect of additional pregnancies on their health and life, decide for permanent contraception. A woman’s opportunity to obtain postpartum or interval contraceptive procedure varies by her insurance coverage, which is indirectly associated with her ethnicity or race.

In 1979, Medicaid Title XIX imposed a 30-day interval between the signing of the sterilization informed consent by the patient and the performance of the procedure. These regulations are still in effect today. What was instituted to protect vulnerable populations from coerced methods in the 1970s represents an anachronistic and archaic approach in the 21st Century. This regulation discriminates against low-income and minority women whose health care is covered by public insurance yet who are frequently at highest risk for unintended and possible risky pregnancy or abortion. In simple words, this imposition violates the standards of justice, beneficence, and nonmaleficence as it treats publicly insured women differently from privately insured women.

The American Medical Association and the American College of Obstetricians and Gynecologists¹ state that this regulation must be revised and charged practitioners to develop policies and procedures to ensure all women who desire postpartum sterilization can receive it. It is incumbent upon all women’s health care physicians to see that this barrier is removed.

Federico G. Mariona, MD, MHSA
Dearborn, Michigan

Reference

Educate the sexual partners of at-risk women
It always strikes me how little emphasis is placed on including the sexual partners of women with serious medical problems in the dialogue about responsibility for at-risk pregnancy. As advocates for women’s health, we should educate the couple about vasectomy and liberally provide referrals. Community outreach to help men understand how they can protect their partner from potentially dangerous unwanted pregnancy is extremely important and not stressed enough. Vasectomy is a quick, safe procedure performed in a physician’s office under local anesthesia. Why should any woman who has already risked her life carrying and delivering a baby be required to bear the contraceptive burden when there is a safe and convenient alternative?

Emily Gubert, MD
East Islip, New York

Dr. Barbieri responds
I thank Drs. Will, Mariona, and Gubert and the anonymous author for their wonderful recommendations on approaches to help improve contraceptive care for women. I agree with Dr. Will that the EHR is a valuable tool to advance contraceptive care. The anonymous author and Dr. Mariona make the critically important point that all women should have access to desired contraception without any barriers based on institutional beliefs or government regulations. The patient’s needs should be prioritized in all medical decision making. I agree with Dr. Gubert that including the male partner in the care process is an important part of effective contraception for women. I enthusiastically agree with her that the best permanent contraceptive for a stable couple is vasectomy.

Share your thoughts! Send your Letter to the Editor to [email protected]. Please include your name and the city and state in which you practice.

“CAN WE SOLVE THE PROBLEM OF INADEQUATE CONTRACEPTION FOR WOMEN AT HIGH RISK FOR ADVERSE PREGNANCY OUTCOMES?”
ROBERT L. BARBIERI, MD (EDITORIAL; FEBRUARY 2016)

“Contraception as a vital sign”
In his recent Editorial Dr. Barbieri asked for ideas to improve contraception counseling for women with medical problems that put them at risk for adverse pregnancy outcomes. His idea of “contraception status as a vital sign” is applied in our very large group practice in Northern California using the electronic health record (EHR).

Over 10 years ago, I attempted to put a hard stop in the EHR to require documentation that women of reproductive age be evaluated for contraception. This scheme seemed to be too cumbersome and was rejected at the time.

The idea was not abandoned, however. Medical assistants must now document a means of contraception for each woman of reproductive age. This does not guarantee that a physician will look at the information, but it is a step in the right direction.

My hope is that someday we will have automatic contraception as a vital sign documentation for all reproductive-age women, including “children” who are documented as menstruating. In the meantime, thank you for highlighting this critical issue.

Tia Will, MD
Sacramento, California

Reduce reimbursement when standard of care is not met
When I read Dr. Barbieri’s Editorial, I was surprised that he avoided the elephant in the room: the current political climate of denying contraception to women, including the defunding of Planned Parenthood and the Supreme Court decision to allow corporations to deny contraceptive coverage for religious issues.

Although I am not currently involved in women’s health, I do work under the auspices of a large Catholic health care system in the United States. Here, all employees are prohibited from providing contraceptive procedures, prescriptions, or even counseling unless it is a Natural Family Planning/ Fertility Awareness Method. These employees also are not provided individual contraceptive health coverage by their employer; this coverage is provided by the federal government thanks to the Affordable Care Act.

Contraception is part of the standard of care for women. However, many women are denied this standard of care due to “religious” reasons, which I suspect may be partially financial and/or political in nature. 

This issue must therefore be addressed by political and financial means. My recommendation is for legislation that mandates lower reimbursement rates for health care systems and providers that refuse to offer full contraceptive options to women. If they do not provide full care, they do not get full payment for services. The money saved by reduced reimbursements could then fund federal women’s health clinics in areas dominated by “religious” health care systems that would guarantee full reproductive health options to all.

Name and practice location withheld

Remove Medicaid barriers to postpartum sterilization
An issue not addressed in Dr. Barbieri’s Editorial is that of women who, after appropriate and extensive counseling by a physician and with a full understanding of the reproductive implications and the possible adverse effect of additional pregnancies on their health and life, decide for permanent contraception. A woman’s opportunity to obtain postpartum or interval contraceptive procedure varies by her insurance coverage, which is indirectly associated with her ethnicity or race.

In 1979, Medicaid Title XIX imposed a 30-day interval between the signing of the sterilization informed consent by the patient and the performance of the procedure. These regulations are still in effect today. What was instituted to protect vulnerable populations from coerced methods in the 1970s represents an anachronistic and archaic approach in the 21st Century. This regulation discriminates against low-income and minority women whose health care is covered by public insurance yet who are frequently at highest risk for unintended and possible risky pregnancy or abortion. In simple words, this imposition violates the standards of justice, beneficence, and nonmaleficence as it treats publicly insured women differently from privately insured women.

The American Medical Association and the American College of Obstetricians and Gynecologists¹ state that this regulation must be revised and charged practitioners to develop policies and procedures to ensure all women who desire postpartum sterilization can receive it. It is incumbent upon all women’s health care physicians to see that this barrier is removed.

Federico G. Mariona, MD, MHSA
Dearborn, Michigan

Reference

Educate the sexual partners of at-risk women
It always strikes me how little emphasis is placed on including the sexual partners of women with serious medical problems in the dialogue about responsibility for at-risk pregnancy. As advocates for women’s health, we should educate the couple about vasectomy and liberally provide referrals. Community outreach to help men understand how they can protect their partner from potentially dangerous unwanted pregnancy is extremely important and not stressed enough. Vasectomy is a quick, safe procedure performed in a physician’s office under local anesthesia. Why should any woman who has already risked her life carrying and delivering a baby be required to bear the contraceptive burden when there is a safe and convenient alternative?

Emily Gubert, MD
East Islip, New York

Dr. Barbieri responds
I thank Drs. Will, Mariona, and Gubert and the anonymous author for their wonderful recommendations on approaches to help improve contraceptive care for women. I agree with Dr. Will that the EHR is a valuable tool to advance contraceptive care. The anonymous author and Dr. Mariona make the critically important point that all women should have access to desired contraception without any barriers based on institutional beliefs or government regulations. The patient’s needs should be prioritized in all medical decision making. I agree with Dr. Gubert that including the male partner in the care process is an important part of effective contraception for women. I enthusiastically agree with her that the best permanent contraceptive for a stable couple is vasectomy.

Share your thoughts! Send your Letter to the Editor to [email protected]. Please include your name and the city and state in which you practice.

“CAN WE SOLVE THE PROBLEM OF INADEQUATE CONTRACEPTION FOR WOMEN AT HIGH RISK FOR ADVERSE PREGNANCY OUTCOMES?”
ROBERT L. BARBIERI, MD (EDITORIAL; FEBRUARY 2016)

“Contraception as a vital sign”
In his recent Editorial Dr. Barbieri asked for ideas to improve contraception counseling for women with medical problems that put them at risk for adverse pregnancy outcomes. His idea of “contraception status as a vital sign” is applied in our very large group practice in Northern California using the electronic health record (EHR).

Over 10 years ago, I attempted to put a hard stop in the EHR to require documentation that women of reproductive age be evaluated for contraception. This scheme seemed to be too cumbersome and was rejected at the time.

The idea was not abandoned, however. Medical assistants must now document a means of contraception for each woman of reproductive age. This does not guarantee that a physician will look at the information, but it is a step in the right direction.

My hope is that someday we will have automatic contraception as a vital sign documentation for all reproductive-age women, including “children” who are documented as menstruating. In the meantime, thank you for highlighting this critical issue.

Tia Will, MD
Sacramento, California

Reduce reimbursement when standard of care is not met
When I read Dr. Barbieri’s Editorial, I was surprised that he avoided the elephant in the room: the current political climate of denying contraception to women, including the defunding of Planned Parenthood and the Supreme Court decision to allow corporations to deny contraceptive coverage for religious issues.

Although I am not currently involved in women’s health, I do work under the auspices of a large Catholic health care system in the United States. Here, all employees are prohibited from providing contraceptive procedures, prescriptions, or even counseling unless it is a Natural Family Planning/ Fertility Awareness Method. These employees also are not provided individual contraceptive health coverage by their employer; this coverage is provided by the federal government thanks to the Affordable Care Act.

Contraception is part of the standard of care for women. However, many women are denied this standard of care due to “religious” reasons, which I suspect may be partially financial and/or political in nature. 

This issue must therefore be addressed by political and financial means. My recommendation is for legislation that mandates lower reimbursement rates for health care systems and providers that refuse to offer full contraceptive options to women. If they do not provide full care, they do not get full payment for services. The money saved by reduced reimbursements could then fund federal women’s health clinics in areas dominated by “religious” health care systems that would guarantee full reproductive health options to all.

Name and practice location withheld

Remove Medicaid barriers to postpartum sterilization
An issue not addressed in Dr. Barbieri’s Editorial is that of women who, after appropriate and extensive counseling by a physician and with a full understanding of the reproductive implications and the possible adverse effect of additional pregnancies on their health and life, decide for permanent contraception. A woman’s opportunity to obtain postpartum or interval contraceptive procedure varies by her insurance coverage, which is indirectly associated with her ethnicity or race.

In 1979, Medicaid Title XIX imposed a 30-day interval between the signing of the sterilization informed consent by the patient and the performance of the procedure. These regulations are still in effect today. What was instituted to protect vulnerable populations from coerced methods in the 1970s represents an anachronistic and archaic approach in the 21st Century. This regulation discriminates against low-income and minority women whose health care is covered by public insurance yet who are frequently at highest risk for unintended and possible risky pregnancy or abortion. In simple words, this imposition violates the standards of justice, beneficence, and nonmaleficence as it treats publicly insured women differently from privately insured women.

The American Medical Association and the American College of Obstetricians and Gynecologists¹ state that this regulation must be revised and charged practitioners to develop policies and procedures to ensure all women who desire postpartum sterilization can receive it. It is incumbent upon all women’s health care physicians to see that this barrier is removed.

Federico G. Mariona, MD, MHSA
Dearborn, Michigan

Reference

Educate the sexual partners of at-risk women
It always strikes me how little emphasis is placed on including the sexual partners of women with serious medical problems in the dialogue about responsibility for at-risk pregnancy. As advocates for women’s health, we should educate the couple about vasectomy and liberally provide referrals. Community outreach to help men understand how they can protect their partner from potentially dangerous unwanted pregnancy is extremely important and not stressed enough. Vasectomy is a quick, safe procedure performed in a physician’s office under local anesthesia. Why should any woman who has already risked her life carrying and delivering a baby be required to bear the contraceptive burden when there is a safe and convenient alternative?

Emily Gubert, MD
East Islip, New York

Dr. Barbieri responds
I thank Drs. Will, Mariona, and Gubert and the anonymous author for their wonderful recommendations on approaches to help improve contraceptive care for women. I agree with Dr. Will that the EHR is a valuable tool to advance contraceptive care. The anonymous author and Dr. Mariona make the critically important point that all women should have access to desired contraception without any barriers based on institutional beliefs or government regulations. The patient’s needs should be prioritized in all medical decision making. I agree with Dr. Gubert that including the male partner in the care process is an important part of effective contraception for women. I enthusiastically agree with her that the best permanent contraceptive for a stable couple is vasectomy.

Share your thoughts! Send your Letter to the Editor to [email protected]. Please include your name and the city and state in which you practice.

Presently it seems that anything a pregnant woman ingests can be correlated with a teratology or an unfortunate neurobehavioral outcome. In an era when up to 15% of pregnant women are taking antidepressant therapy, antidepressants are obvious drugs to be correlated with an untoward fetal outcome, despite the fact that untreated maternal depression itself is significantly worse.1

A recent retrospective secondary end point study by Boukhris and colleagues on antidepressant use in pregnancy and the risk of autism spectrum disorder (ASD) in children is an example of correlation without substantive evidence of causation. Although this study received media attention,² it is a “data-dredge” study. While the authors correctly note that the database is derived from a prospective registry-based population-based cohort study (the Quebec Pregnancy/Children Cohort), their study’s design more closely resembles a post hoc nested case-control study.

Details of the study
Researchers evaluated data from 145,456 singleton full-term infants born alive between January 1, 1998, and December 31, 2009, with antidepressant exposure during pregnancy defined according to trimester and specific antidepressant classes. Children were considered as having autism if they had received at least 1 autism diagnosis between their date of birth and the last date of follow-up.

We perceive several problems in the study’s design and the authors’ conclusions.

Shortcomings of study design
The study results are based on a post hoc analysis. Autism spectrum disorder was not the primary end point of interest in this database. Accordingly, in a secondary end point study, the risk for bias and confounding is substantial. This study design cannot prove causation.^3–5

Exposure is defined by number of antidepressant prescriptions filled. No data regarding adherence (true exposure) are provided. Many women will not take antidepressant drugs as prescribed during pregnancy. It has been reported that antidepressants dispensed to pregnant women during the last 2 trimesters of pregnancy were taken by only 55% of the women.⁶

The specific antidepressant agents and dosages used were not identified, and the study provided no good sense of duration of use. Is it biologically plausible, therefore, to suggest that all antidepressants—with their disparate structures and mechanisms, in all doses, and for various durations of use—have a uniform effect on fetal neurodevelopment?

Notably, in another prescription drug study of 668,468 pregnancies in 2013, investigators found no significant association between prenatal exposure to antidepressants and ASD.⁷

Some data suggest that ASD and depression may share preexisting risk factors.⁸ The increased risk for ASD proposed by Boukhris and colleagues’ study cannot likely be separated from the well-described genetic risk of ASD that might be shared with that of depression.^9,10

The stated hazard ratios (HRs) are all <2.2. Given this study’s design, it is plausible that various biases and confounders account for these findings. True significance of these HRs are suspect unless they exceed 3.0, and there is a greater probability of avoiding a type I error when the risk ratios are greater than 4 to 5.^3,4

What this evidence means for practice
In this registry-based study of an ongoing population-based cohort, the authors suggest a sensational 87% increased risk of ASD with use of antidepressants during pregnancy. While technically correct, the absolute risk (if real) is really less than 1%. Using sound epidemiologic principles, we would advise against speculating on a number needed to harm based on this study design. Such a projection would require a prospective randomized trial.
—Robert P. Kauffman, MD; Teresa Baker, MD; and Thomas W. Hale, PhD

Share your thoughts! Send your Letter to the Editor to [email protected]. Please include your name and the city and state in which you practice.

Presently it seems that anything a pregnant woman ingests can be correlated with a teratology or an unfortunate neurobehavioral outcome. In an era when up to 15% of pregnant women are taking antidepressant therapy, antidepressants are obvious drugs to be correlated with an untoward fetal outcome, despite the fact that untreated maternal depression itself is significantly worse.1

A recent retrospective secondary end point study by Boukhris and colleagues on antidepressant use in pregnancy and the risk of autism spectrum disorder (ASD) in children is an example of correlation without substantive evidence of causation. Although this study received media attention,² it is a “data-dredge” study. While the authors correctly note that the database is derived from a prospective registry-based population-based cohort study (the Quebec Pregnancy/Children Cohort), their study’s design more closely resembles a post hoc nested case-control study.

Details of the study
Researchers evaluated data from 145,456 singleton full-term infants born alive between January 1, 1998, and December 31, 2009, with antidepressant exposure during pregnancy defined according to trimester and specific antidepressant classes. Children were considered as having autism if they had received at least 1 autism diagnosis between their date of birth and the last date of follow-up.

We perceive several problems in the study’s design and the authors’ conclusions.

Shortcomings of study design
The study results are based on a post hoc analysis. Autism spectrum disorder was not the primary end point of interest in this database. Accordingly, in a secondary end point study, the risk for bias and confounding is substantial. This study design cannot prove causation.^3–5

Exposure is defined by number of antidepressant prescriptions filled. No data regarding adherence (true exposure) are provided. Many women will not take antidepressant drugs as prescribed during pregnancy. It has been reported that antidepressants dispensed to pregnant women during the last 2 trimesters of pregnancy were taken by only 55% of the women.⁶

The specific antidepressant agents and dosages used were not identified, and the study provided no good sense of duration of use. Is it biologically plausible, therefore, to suggest that all antidepressants—with their disparate structures and mechanisms, in all doses, and for various durations of use—have a uniform effect on fetal neurodevelopment?

Notably, in another prescription drug study of 668,468 pregnancies in 2013, investigators found no significant association between prenatal exposure to antidepressants and ASD.⁷

Some data suggest that ASD and depression may share preexisting risk factors.⁸ The increased risk for ASD proposed by Boukhris and colleagues’ study cannot likely be separated from the well-described genetic risk of ASD that might be shared with that of depression.^9,10

The stated hazard ratios (HRs) are all <2.2. Given this study’s design, it is plausible that various biases and confounders account for these findings. True significance of these HRs are suspect unless they exceed 3.0, and there is a greater probability of avoiding a type I error when the risk ratios are greater than 4 to 5.^3,4

What this evidence means for practice
In this registry-based study of an ongoing population-based cohort, the authors suggest a sensational 87% increased risk of ASD with use of antidepressants during pregnancy. While technically correct, the absolute risk (if real) is really less than 1%. Using sound epidemiologic principles, we would advise against speculating on a number needed to harm based on this study design. Such a projection would require a prospective randomized trial.
—Robert P. Kauffman, MD; Teresa Baker, MD; and Thomas W. Hale, PhD

Share your thoughts! Send your Letter to the Editor to [email protected]. Please include your name and the city and state in which you practice.

Presently it seems that anything a pregnant woman ingests can be correlated with a teratology or an unfortunate neurobehavioral outcome. In an era when up to 15% of pregnant women are taking antidepressant therapy, antidepressants are obvious drugs to be correlated with an untoward fetal outcome, despite the fact that untreated maternal depression itself is significantly worse.1

A recent retrospective secondary end point study by Boukhris and colleagues on antidepressant use in pregnancy and the risk of autism spectrum disorder (ASD) in children is an example of correlation without substantive evidence of causation. Although this study received media attention,² it is a “data-dredge” study. While the authors correctly note that the database is derived from a prospective registry-based population-based cohort study (the Quebec Pregnancy/Children Cohort), their study’s design more closely resembles a post hoc nested case-control study.

Details of the study
Researchers evaluated data from 145,456 singleton full-term infants born alive between January 1, 1998, and December 31, 2009, with antidepressant exposure during pregnancy defined according to trimester and specific antidepressant classes. Children were considered as having autism if they had received at least 1 autism diagnosis between their date of birth and the last date of follow-up.

We perceive several problems in the study’s design and the authors’ conclusions.

Shortcomings of study design
The study results are based on a post hoc analysis. Autism spectrum disorder was not the primary end point of interest in this database. Accordingly, in a secondary end point study, the risk for bias and confounding is substantial. This study design cannot prove causation.^3–5

Exposure is defined by number of antidepressant prescriptions filled. No data regarding adherence (true exposure) are provided. Many women will not take antidepressant drugs as prescribed during pregnancy. It has been reported that antidepressants dispensed to pregnant women during the last 2 trimesters of pregnancy were taken by only 55% of the women.⁶

The specific antidepressant agents and dosages used were not identified, and the study provided no good sense of duration of use. Is it biologically plausible, therefore, to suggest that all antidepressants—with their disparate structures and mechanisms, in all doses, and for various durations of use—have a uniform effect on fetal neurodevelopment?

Notably, in another prescription drug study of 668,468 pregnancies in 2013, investigators found no significant association between prenatal exposure to antidepressants and ASD.⁷

Some data suggest that ASD and depression may share preexisting risk factors.⁸ The increased risk for ASD proposed by Boukhris and colleagues’ study cannot likely be separated from the well-described genetic risk of ASD that might be shared with that of depression.^9,10

The stated hazard ratios (HRs) are all <2.2. Given this study’s design, it is plausible that various biases and confounders account for these findings. True significance of these HRs are suspect unless they exceed 3.0, and there is a greater probability of avoiding a type I error when the risk ratios are greater than 4 to 5.^3,4

What this evidence means for practice
In this registry-based study of an ongoing population-based cohort, the authors suggest a sensational 87% increased risk of ASD with use of antidepressants during pregnancy. While technically correct, the absolute risk (if real) is really less than 1%. Using sound epidemiologic principles, we would advise against speculating on a number needed to harm based on this study design. Such a projection would require a prospective randomized trial.
—Robert P. Kauffman, MD; Teresa Baker, MD; and Thomas W. Hale, PhD

Share your thoughts! Send your Letter to the Editor to [email protected]. Please include your name and the city and state in which you practice.

CHICAGO – The results of the Surgical Treatment for Ischemic Heart Failure Extension Study (STICHES) presented at the annual meeting of the American College of Cardiology ought to change the clinical management of patients with coronary artery disease and heart failure with severe left ventricular dysfunction, according to Dr. Robert O. Bonow.

STICHES is the 10-year follow-up of 1,212 such patients who were randomized to coronary artery bypass graft surgery plus optimal guideline-directed medical therapy or to the medical therapy alone. At 10 years, the CABG group showed a significant survival advantage: an all-cause mortality rate of 58.9%, a significant 16% relative risk reduction compared with the 66.1% rate in the medically managed group. Secondary endpoints were also strongly in favor of the CABG group.

These findings indicate CABG is beneficial in patients with ischemic cardiomyopathy, and patients deserve to be so informed, according to Dr. Bonow, a member of the STICHES publication committee and professor of cardiology and director of the Center for Cardiovascular Innovation at Northwestern University in Chicago, who discussed the findings in this video interview.

He reported having no financial conflicts regarding this National Institutes of Health–funded study.

[email protected]

CHICAGO – The results of the Surgical Treatment for Ischemic Heart Failure Extension Study (STICHES) presented at the annual meeting of the American College of Cardiology ought to change the clinical management of patients with coronary artery disease and heart failure with severe left ventricular dysfunction, according to Dr. Robert O. Bonow.

STICHES is the 10-year follow-up of 1,212 such patients who were randomized to coronary artery bypass graft surgery plus optimal guideline-directed medical therapy or to the medical therapy alone. At 10 years, the CABG group showed a significant survival advantage: an all-cause mortality rate of 58.9%, a significant 16% relative risk reduction compared with the 66.1% rate in the medically managed group. Secondary endpoints were also strongly in favor of the CABG group.

These findings indicate CABG is beneficial in patients with ischemic cardiomyopathy, and patients deserve to be so informed, according to Dr. Bonow, a member of the STICHES publication committee and professor of cardiology and director of the Center for Cardiovascular Innovation at Northwestern University in Chicago, who discussed the findings in this video interview.

He reported having no financial conflicts regarding this National Institutes of Health–funded study.

[email protected]

CHICAGO – The results of the Surgical Treatment for Ischemic Heart Failure Extension Study (STICHES) presented at the annual meeting of the American College of Cardiology ought to change the clinical management of patients with coronary artery disease and heart failure with severe left ventricular dysfunction, according to Dr. Robert O. Bonow.

STICHES is the 10-year follow-up of 1,212 such patients who were randomized to coronary artery bypass graft surgery plus optimal guideline-directed medical therapy or to the medical therapy alone. At 10 years, the CABG group showed a significant survival advantage: an all-cause mortality rate of 58.9%, a significant 16% relative risk reduction compared with the 66.1% rate in the medically managed group. Secondary endpoints were also strongly in favor of the CABG group.

These findings indicate CABG is beneficial in patients with ischemic cardiomyopathy, and patients deserve to be so informed, according to Dr. Bonow, a member of the STICHES publication committee and professor of cardiology and director of the Center for Cardiovascular Innovation at Northwestern University in Chicago, who discussed the findings in this video interview.

He reported having no financial conflicts regarding this National Institutes of Health–funded study.

[email protected]

CHICAGO – The results of the Surgical Treatment for Ischemic Heart Failure Extension Study (STICHES) presented at the annual meeting of the American College of Cardiology ought to change the clinical management of patients with coronary artery disease and heart failure with severe left ventricular dysfunction, according to Dr. Robert O. Bonow.

STICHES is the 10-year follow-up of 1,212 such patients who were randomized to coronary artery bypass graft surgery plus optimal guideline-directed medical therapy or to the medical therapy alone. At 10 years, the CABG group showed a significant survival advantage: an all-cause mortality rate of 58.9%, a significant 16% relative risk reduction compared with the 66.1% rate in the medically managed group. Secondary endpoints were also strongly in favor of the CABG group.

These findings indicate CABG is beneficial in patients with ischemic cardiomyopathy, and patients deserve to be so informed, according to Dr. Bonow, a member of the STICHES publication committee and professor of cardiology and director of the Center for Cardiovascular Innovation at Northwestern University in Chicago, who discussed the findings in this video interview.

He reported having no financial conflicts regarding this National Institutes of Health–funded study.

[email protected]

CHICAGO – The results of the Surgical Treatment for Ischemic Heart Failure Extension Study (STICHES) presented at the annual meeting of the American College of Cardiology ought to change the clinical management of patients with coronary artery disease and heart failure with severe left ventricular dysfunction, according to Dr. Robert O. Bonow.

STICHES is the 10-year follow-up of 1,212 such patients who were randomized to coronary artery bypass graft surgery plus optimal guideline-directed medical therapy or to the medical therapy alone. At 10 years, the CABG group showed a significant survival advantage: an all-cause mortality rate of 58.9%, a significant 16% relative risk reduction compared with the 66.1% rate in the medically managed group. Secondary endpoints were also strongly in favor of the CABG group.

These findings indicate CABG is beneficial in patients with ischemic cardiomyopathy, and patients deserve to be so informed, according to Dr. Bonow, a member of the STICHES publication committee and professor of cardiology and director of the Center for Cardiovascular Innovation at Northwestern University in Chicago, who discussed the findings in this video interview.

He reported having no financial conflicts regarding this National Institutes of Health–funded study.

[email protected]

CHICAGO – The results of the Surgical Treatment for Ischemic Heart Failure Extension Study (STICHES) presented at the annual meeting of the American College of Cardiology ought to change the clinical management of patients with coronary artery disease and heart failure with severe left ventricular dysfunction, according to Dr. Robert O. Bonow.

STICHES is the 10-year follow-up of 1,212 such patients who were randomized to coronary artery bypass graft surgery plus optimal guideline-directed medical therapy or to the medical therapy alone. At 10 years, the CABG group showed a significant survival advantage: an all-cause mortality rate of 58.9%, a significant 16% relative risk reduction compared with the 66.1% rate in the medically managed group. Secondary endpoints were also strongly in favor of the CABG group.

These findings indicate CABG is beneficial in patients with ischemic cardiomyopathy, and patients deserve to be so informed, according to Dr. Bonow, a member of the STICHES publication committee and professor of cardiology and director of the Center for Cardiovascular Innovation at Northwestern University in Chicago, who discussed the findings in this video interview.

He reported having no financial conflicts regarding this National Institutes of Health–funded study.

[email protected]

CHICAGO – A new American College of Cardiology expert consensus decision pathway for the use of nonstatin therapies to lower cholesterol in high-risk patients addresses situations not covered by an evidence-based 2013 guideline on managing atherosclerotic cardiovascular disease risk.

Like the 2013 guideline (the 2013 American College of Cardiology/American Heart Association Guideline on the Treatment of Blood Cholesterol to Reduce Atherosclerotic Cardiovascular Disease Risk in Adults), the new guidance emphasizes the importance of a healthy lifestyle, but also addresses the use of two monoclonal antibodies–proprotein convertase subtilisin/kexon 9 (PCSK9) inhibitors–approved for certain patient groups since the 2013 guideline was released, as well as other nonstatin therapies, including ezetimibe and bile acid sequestrants.

“At the time [the 2013 guideline was published] the only really good outcomes data ... were for statin medication and there were no data from clinical trials that showed additional benefit of medications over and above being on the maximally tolerated dose of a statin,” according to Dr. Donald M. Lloyd-Jones, a professor at Northwestern University, Chicago and chair of the writing committee for the new guidance. “However, since 2013, a number of trials have been published that actually move the field forward in our understanding of which patients might benefit from adding non statin therapy on top of effective statin therapy.”

The guidance was developed to address gaps in care until the guidelines can be updated, which will likely take a few years.

Based on findings from recent studies, including the IMPROVE IT trial, which examined ezetimibe as statin add-on therapy after acute coronary syndromes, the HPS2-THRIVE study, which examined use of niacin in high-risk patients, and short-term outcomes studies of PCSK9 inhibitors, which have been shown to dramatically reduce low-density lipoprotein cholesterol levels beyond the lowering provided by statin therapy, the committee developed algorithms for the four main high-risk statin benefit patient groups:

•Adults aged 21 years and older with clinical atherosclerotic cardiovascular disease (ASCVD), on statin for secondary prevention.

•Adults aged 21 years and older with LDL-C greater than or equal to 190 mg/dL not due to secondary modifiable causes, on statin for primary prevention.

•Adults aged 40-75 years without ASCVD but with diabetes and LDL-C of 70-189 mg/dL, on statin for primary prevention.

•Adults aged 40-75 years without clinical ASCVD or diabetes, with LDL-C of 70-189 mg/dL and an estimated 10-year risk for ASCVD of at least 7.5%, on statin for primary prevention.

The guidance suggests a number of steps to take with patients who fail to achieve treatment goals (such as addressing treatment adherence, intensifying lifestyle modifications, using a high-intensity stain, and evaluating for statin intolerance), and lists “clinician-patient discussion factors” to consider for each of a number of patient scenarios (including the potential benefits and risks associated with nonstatin therapies, as well as patient preferences).

Included for each of the patient scenarios is an algorithm for which nonstatin therapies to use in which order, building on the “rock-solid confidence” that for the four statin benefit groups, statins remain the starting point, Dr. Lloyd-Jones said. He discussed the guidance in a video interview.

In general, ezetimibe for those patients who are not achieving the types of reduction in LDL or the amount of risk reduction desired, “should probably be the first choice,” he said.

Bile acid sequestrants can be considered in those who are ezetimibe intolerant and who have triglycerides less than 300 mg/dL.

PCSK9 inhibitors are suggested for consideration only in very high-risk patients with ASCVD or with the familial hypercholesterolemia phenotype who are still not achieving the goal (ideally, a 50% reduction in LDL cholesterol), he said.

The committee did not recommend use of niacin, stating that there is no clear indication for the routine use of niacin preparations as additional nonstatin therapies due to an unfavorable risk-benefit profile.

Additionally, PCSK9 inhibitors are not recommended in any primary prevention scenarios, he noted.

Dr. Neil J. Stone, chair of the 2013 guideline writing committee, said the new guidance provides a useful tool for clinicians, extending, in a practical way, the current guideline as the field awaits the long-term outcomes data for PCSK9 inhibitors.

Despite some backlash in the wake of the 2013 guideline, which marked a move away from specific cholesterol treatment targets to a cardiovascular disease risk-based approach, the cardiovascular risk calculation formula introduced in that guideline has been shown to be useful and accurate, said Dr. Stone, also of Northwestern University.

“[The new guidance] is simply an amplification and extension of the guideline,” he said, adding that “it’s about a risk discussion, not automatic treatment.”

Dr. Lloyd-Jones and Dr. Stone each reported having no disclosures.

[email protected]

CHICAGO – A new American College of Cardiology expert consensus decision pathway for the use of nonstatin therapies to lower cholesterol in high-risk patients addresses situations not covered by an evidence-based 2013 guideline on managing atherosclerotic cardiovascular disease risk.

Like the 2013 guideline (the 2013 American College of Cardiology/American Heart Association Guideline on the Treatment of Blood Cholesterol to Reduce Atherosclerotic Cardiovascular Disease Risk in Adults), the new guidance emphasizes the importance of a healthy lifestyle, but also addresses the use of two monoclonal antibodies–proprotein convertase subtilisin/kexon 9 (PCSK9) inhibitors–approved for certain patient groups since the 2013 guideline was released, as well as other nonstatin therapies, including ezetimibe and bile acid sequestrants.

“At the time [the 2013 guideline was published] the only really good outcomes data ... were for statin medication and there were no data from clinical trials that showed additional benefit of medications over and above being on the maximally tolerated dose of a statin,” according to Dr. Donald M. Lloyd-Jones, a professor at Northwestern University, Chicago and chair of the writing committee for the new guidance. “However, since 2013, a number of trials have been published that actually move the field forward in our understanding of which patients might benefit from adding non statin therapy on top of effective statin therapy.”

The guidance was developed to address gaps in care until the guidelines can be updated, which will likely take a few years.

Based on findings from recent studies, including the IMPROVE IT trial, which examined ezetimibe as statin add-on therapy after acute coronary syndromes, the HPS2-THRIVE study, which examined use of niacin in high-risk patients, and short-term outcomes studies of PCSK9 inhibitors, which have been shown to dramatically reduce low-density lipoprotein cholesterol levels beyond the lowering provided by statin therapy, the committee developed algorithms for the four main high-risk statin benefit patient groups:

•Adults aged 21 years and older with clinical atherosclerotic cardiovascular disease (ASCVD), on statin for secondary prevention.

•Adults aged 21 years and older with LDL-C greater than or equal to 190 mg/dL not due to secondary modifiable causes, on statin for primary prevention.

•Adults aged 40-75 years without ASCVD but with diabetes and LDL-C of 70-189 mg/dL, on statin for primary prevention.

•Adults aged 40-75 years without clinical ASCVD or diabetes, with LDL-C of 70-189 mg/dL and an estimated 10-year risk for ASCVD of at least 7.5%, on statin for primary prevention.

The guidance suggests a number of steps to take with patients who fail to achieve treatment goals (such as addressing treatment adherence, intensifying lifestyle modifications, using a high-intensity stain, and evaluating for statin intolerance), and lists “clinician-patient discussion factors” to consider for each of a number of patient scenarios (including the potential benefits and risks associated with nonstatin therapies, as well as patient preferences).

Included for each of the patient scenarios is an algorithm for which nonstatin therapies to use in which order, building on the “rock-solid confidence” that for the four statin benefit groups, statins remain the starting point, Dr. Lloyd-Jones said. He discussed the guidance in a video interview.

In general, ezetimibe for those patients who are not achieving the types of reduction in LDL or the amount of risk reduction desired, “should probably be the first choice,” he said.

Bile acid sequestrants can be considered in those who are ezetimibe intolerant and who have triglycerides less than 300 mg/dL.

PCSK9 inhibitors are suggested for consideration only in very high-risk patients with ASCVD or with the familial hypercholesterolemia phenotype who are still not achieving the goal (ideally, a 50% reduction in LDL cholesterol), he said.

The committee did not recommend use of niacin, stating that there is no clear indication for the routine use of niacin preparations as additional nonstatin therapies due to an unfavorable risk-benefit profile.

Additionally, PCSK9 inhibitors are not recommended in any primary prevention scenarios, he noted.

Dr. Neil J. Stone, chair of the 2013 guideline writing committee, said the new guidance provides a useful tool for clinicians, extending, in a practical way, the current guideline as the field awaits the long-term outcomes data for PCSK9 inhibitors.

Despite some backlash in the wake of the 2013 guideline, which marked a move away from specific cholesterol treatment targets to a cardiovascular disease risk-based approach, the cardiovascular risk calculation formula introduced in that guideline has been shown to be useful and accurate, said Dr. Stone, also of Northwestern University.

“[The new guidance] is simply an amplification and extension of the guideline,” he said, adding that “it’s about a risk discussion, not automatic treatment.”

Dr. Lloyd-Jones and Dr. Stone each reported having no disclosures.

[email protected]

CHICAGO – A new American College of Cardiology expert consensus decision pathway for the use of nonstatin therapies to lower cholesterol in high-risk patients addresses situations not covered by an evidence-based 2013 guideline on managing atherosclerotic cardiovascular disease risk.

Like the 2013 guideline (the 2013 American College of Cardiology/American Heart Association Guideline on the Treatment of Blood Cholesterol to Reduce Atherosclerotic Cardiovascular Disease Risk in Adults), the new guidance emphasizes the importance of a healthy lifestyle, but also addresses the use of two monoclonal antibodies–proprotein convertase subtilisin/kexon 9 (PCSK9) inhibitors–approved for certain patient groups since the 2013 guideline was released, as well as other nonstatin therapies, including ezetimibe and bile acid sequestrants.

“At the time [the 2013 guideline was published] the only really good outcomes data ... were for statin medication and there were no data from clinical trials that showed additional benefit of medications over and above being on the maximally tolerated dose of a statin,” according to Dr. Donald M. Lloyd-Jones, a professor at Northwestern University, Chicago and chair of the writing committee for the new guidance. “However, since 2013, a number of trials have been published that actually move the field forward in our understanding of which patients might benefit from adding non statin therapy on top of effective statin therapy.”

The guidance was developed to address gaps in care until the guidelines can be updated, which will likely take a few years.

Based on findings from recent studies, including the IMPROVE IT trial, which examined ezetimibe as statin add-on therapy after acute coronary syndromes, the HPS2-THRIVE study, which examined use of niacin in high-risk patients, and short-term outcomes studies of PCSK9 inhibitors, which have been shown to dramatically reduce low-density lipoprotein cholesterol levels beyond the lowering provided by statin therapy, the committee developed algorithms for the four main high-risk statin benefit patient groups:

•Adults aged 21 years and older with clinical atherosclerotic cardiovascular disease (ASCVD), on statin for secondary prevention.

•Adults aged 21 years and older with LDL-C greater than or equal to 190 mg/dL not due to secondary modifiable causes, on statin for primary prevention.

•Adults aged 40-75 years without ASCVD but with diabetes and LDL-C of 70-189 mg/dL, on statin for primary prevention.

•Adults aged 40-75 years without clinical ASCVD or diabetes, with LDL-C of 70-189 mg/dL and an estimated 10-year risk for ASCVD of at least 7.5%, on statin for primary prevention.

The guidance suggests a number of steps to take with patients who fail to achieve treatment goals (such as addressing treatment adherence, intensifying lifestyle modifications, using a high-intensity stain, and evaluating for statin intolerance), and lists “clinician-patient discussion factors” to consider for each of a number of patient scenarios (including the potential benefits and risks associated with nonstatin therapies, as well as patient preferences).

Included for each of the patient scenarios is an algorithm for which nonstatin therapies to use in which order, building on the “rock-solid confidence” that for the four statin benefit groups, statins remain the starting point, Dr. Lloyd-Jones said. He discussed the guidance in a video interview.

In general, ezetimibe for those patients who are not achieving the types of reduction in LDL or the amount of risk reduction desired, “should probably be the first choice,” he said.

Bile acid sequestrants can be considered in those who are ezetimibe intolerant and who have triglycerides less than 300 mg/dL.

PCSK9 inhibitors are suggested for consideration only in very high-risk patients with ASCVD or with the familial hypercholesterolemia phenotype who are still not achieving the goal (ideally, a 50% reduction in LDL cholesterol), he said.

The committee did not recommend use of niacin, stating that there is no clear indication for the routine use of niacin preparations as additional nonstatin therapies due to an unfavorable risk-benefit profile.

Additionally, PCSK9 inhibitors are not recommended in any primary prevention scenarios, he noted.

Dr. Neil J. Stone, chair of the 2013 guideline writing committee, said the new guidance provides a useful tool for clinicians, extending, in a practical way, the current guideline as the field awaits the long-term outcomes data for PCSK9 inhibitors.

Despite some backlash in the wake of the 2013 guideline, which marked a move away from specific cholesterol treatment targets to a cardiovascular disease risk-based approach, the cardiovascular risk calculation formula introduced in that guideline has been shown to be useful and accurate, said Dr. Stone, also of Northwestern University.

“[The new guidance] is simply an amplification and extension of the guideline,” he said, adding that “it’s about a risk discussion, not automatic treatment.”

Dr. Lloyd-Jones and Dr. Stone each reported having no disclosures.

[email protected]

Mona Hanna-Attisha, MD, MPH, the director of the pediatric residency program at Hurley Children’s Hospital and an assistant professor of pediatrics at Michigan State University, has been instrumental in the fight for clean and safe water for residents in Flint, Mich.

Dr. Hanna-Attisha has been a fundamental co-site leader with the SHM I-PASS mentored implementation program and minimized her role in the program as she became the unofficial spokesperson for the Flint water crisis. In January 2016, Dr. Hanna-Attisha took on the lead role for the Pediatric Public Health Initiative with Michigan State University and Hurley Children’s Hospital.

Dr. Hanna-Attisha is a Michigan native and completed her undergraduate degree at the University of Michigan in Ann Arbor. She completed medical school at Michigan State University College of Human Medicine, completed her residency and chief residency at the Children’s Hospital of Michigan, and earned her master’s degree at the University of Michigan School of Public Health.

Dr. Hanna-Attisha’s training and experience has focused heavily on environmental toxins and health disparities, so it’s no surprise that she is deeply involved with addressing the public health emergency in Flint as well as taking measures to ensure continued research and action regarding the impact the contaminated water had on the residents of Flint. Dr. Hanna-Attisha is working with a team of experts to develop evidence-based interventions that will aid in improving the health and development of children and families affected by Flint’s contaminated water. She is educating families on nutrition and diets high in iron, calcium, and vitamin C in order to help manage the effects of contamination.

A report from a Virginia Tech Research Team ignited the investigation into Flint’s water issues and also fueled Dr. Hanna-Attisha’s investigation into the blood-lead levels in the children of Flint. It has been close to two years that the residents of Flint have been exposed to severely toxic levels of lead from the city’s tap water, and Dr. Hanna-Attisha’s analysis of children’s blood-lead levels has been highlighted and published in numerous publications, including the American Journal of Public Health.

The water crisis in Flint hits close to home for Dr. Hanna-Attisha, and the dedication she has to her local community is astounding. It shows in the work she has been doing in her new role with the Pediatric Public Health Initiative.

SHM is proud of all the outstanding work she is doing and appreciates her contributions to the SHM I-PASS program. To keep up to date with Dr. Hanna-Attisha, follow her on Twitter @MonaHannaA.

Mobola Owolabi is senior project manager in SHM’s Center for Hospital Innovation and Improvement.

Mona Hanna-Attisha, MD, MPH, the director of the pediatric residency program at Hurley Children’s Hospital and an assistant professor of pediatrics at Michigan State University, has been instrumental in the fight for clean and safe water for residents in Flint, Mich.

Dr. Hanna-Attisha has been a fundamental co-site leader with the SHM I-PASS mentored implementation program and minimized her role in the program as she became the unofficial spokesperson for the Flint water crisis. In January 2016, Dr. Hanna-Attisha took on the lead role for the Pediatric Public Health Initiative with Michigan State University and Hurley Children’s Hospital.

Dr. Hanna-Attisha is a Michigan native and completed her undergraduate degree at the University of Michigan in Ann Arbor. She completed medical school at Michigan State University College of Human Medicine, completed her residency and chief residency at the Children’s Hospital of Michigan, and earned her master’s degree at the University of Michigan School of Public Health.

Dr. Hanna-Attisha’s training and experience has focused heavily on environmental toxins and health disparities, so it’s no surprise that she is deeply involved with addressing the public health emergency in Flint as well as taking measures to ensure continued research and action regarding the impact the contaminated water had on the residents of Flint. Dr. Hanna-Attisha is working with a team of experts to develop evidence-based interventions that will aid in improving the health and development of children and families affected by Flint’s contaminated water. She is educating families on nutrition and diets high in iron, calcium, and vitamin C in order to help manage the effects of contamination.

A report from a Virginia Tech Research Team ignited the investigation into Flint’s water issues and also fueled Dr. Hanna-Attisha’s investigation into the blood-lead levels in the children of Flint. It has been close to two years that the residents of Flint have been exposed to severely toxic levels of lead from the city’s tap water, and Dr. Hanna-Attisha’s analysis of children’s blood-lead levels has been highlighted and published in numerous publications, including the American Journal of Public Health.

The water crisis in Flint hits close to home for Dr. Hanna-Attisha, and the dedication she has to her local community is astounding. It shows in the work she has been doing in her new role with the Pediatric Public Health Initiative.

SHM is proud of all the outstanding work she is doing and appreciates her contributions to the SHM I-PASS program. To keep up to date with Dr. Hanna-Attisha, follow her on Twitter @MonaHannaA.

Mobola Owolabi is senior project manager in SHM’s Center for Hospital Innovation and Improvement.

Mona Hanna-Attisha, MD, MPH, the director of the pediatric residency program at Hurley Children’s Hospital and an assistant professor of pediatrics at Michigan State University, has been instrumental in the fight for clean and safe water for residents in Flint, Mich.

Dr. Hanna-Attisha has been a fundamental co-site leader with the SHM I-PASS mentored implementation program and minimized her role in the program as she became the unofficial spokesperson for the Flint water crisis. In January 2016, Dr. Hanna-Attisha took on the lead role for the Pediatric Public Health Initiative with Michigan State University and Hurley Children’s Hospital.

Dr. Hanna-Attisha is a Michigan native and completed her undergraduate degree at the University of Michigan in Ann Arbor. She completed medical school at Michigan State University College of Human Medicine, completed her residency and chief residency at the Children’s Hospital of Michigan, and earned her master’s degree at the University of Michigan School of Public Health.

Dr. Hanna-Attisha’s training and experience has focused heavily on environmental toxins and health disparities, so it’s no surprise that she is deeply involved with addressing the public health emergency in Flint as well as taking measures to ensure continued research and action regarding the impact the contaminated water had on the residents of Flint. Dr. Hanna-Attisha is working with a team of experts to develop evidence-based interventions that will aid in improving the health and development of children and families affected by Flint’s contaminated water. She is educating families on nutrition and diets high in iron, calcium, and vitamin C in order to help manage the effects of contamination.

A report from a Virginia Tech Research Team ignited the investigation into Flint’s water issues and also fueled Dr. Hanna-Attisha’s investigation into the blood-lead levels in the children of Flint. It has been close to two years that the residents of Flint have been exposed to severely toxic levels of lead from the city’s tap water, and Dr. Hanna-Attisha’s analysis of children’s blood-lead levels has been highlighted and published in numerous publications, including the American Journal of Public Health.

The water crisis in Flint hits close to home for Dr. Hanna-Attisha, and the dedication she has to her local community is astounding. It shows in the work she has been doing in her new role with the Pediatric Public Health Initiative.

SHM is proud of all the outstanding work she is doing and appreciates her contributions to the SHM I-PASS program. To keep up to date with Dr. Hanna-Attisha, follow her on Twitter @MonaHannaA.

Mobola Owolabi is senior project manager in SHM’s Center for Hospital Innovation and Improvement.

CHICAGO – The success in the HOPE-3 trial of a two-pronged strategy of a statin plus moderate-dose antihypertensive therapy has expanded the boundaries of primary preventive pharmacotherapy to incorporate many intermediate-cardiovascular-risk patients without cardiovascular disease.

In the Heart Outcomes Evaluation (HOPE)-3 trial, the combination of rosuvastatin (Crestor) at 10 mg/day plus antihypertensive therapy with 16 mg/day of candesartan and 12.5 mg/day of hydrochlorothiazide reduced cardiovascular events in intermediate-risk patients with hypertension, regardless of their baseline LDL-cholesterol and inflammatory biomarker levels. In nonhypertensive study participants, however, blood pressure-lowering therapy provided no added benefit beyond that achieved with the statin alone, which yielded a 25% relative risk reduction in cardiovascular events compared with placebo, Dr. Salim Yusuf reported at the annual meeting of the American College of Cardiology.

The HOPE-3 trial was the first formal study of the polypill concept of fixed-dose, low-dose combination therapy as a public health tool for primary prevention in an intermediate-risk population without cardiovascular disease. It’s a simple, low-cost, safe, pragmatic preventive strategy that doesn’t require baseline laboratory measurements, dose titration visits, or frequent safety monitoring, he noted.

“The original concept of the polypill was to give it to everyone over age 55. We found in HOPE-3 that the polypill concept is not valid for everybody. It demonstrated benefit in hypertensives but not in nonhypertensives, where a statin alone was beneficial,” said Dr. Yusuf, professor of medicine and executive director of the Population Health Research Institute at McMaster University in Hamilton, Ont.

“The clinical implication is that statins should be used much more widely than they currently are. Most guidelines for hypertension don’t say to give a statin. But HOPE-3 is saying hypertensives will benefit. About half of the 40% reduction in the risk of cardiovascular events we saw with combination therapy in patients in the highest third for baseline systolic blood pressure – that is, above 143.5 mm Hg, with a mean of 154 mm Hg – was due to the rosuvastatin and half to the antihypertensive therapy. Our study suggests you can essentially double the benefit of lowering blood pressure in hypertensives if you also lower cholesterol simultaneously,” he noted. Dr. Yusuf discussed the findings in a video interview.

The double-blind trial included a diverse population of 12,705 men age 55 or older and women age 65 or older in 21 countries. All were at intermediate cardiovascular risk by conventional stratification methods; none had a history of cardiovascular disease. They were randomized to rosuvastatin or placebo, dual antihypertensive therapy or placebo, or to all three medications or double placebo. The combined-therapy group experienced a 33.7 mg/dL greater drop in LDL-cholesterol and a 6.2 mm Hg bigger reduction in systolic blood pressure than in patients on dual placebo.

During a median followup of 5.6 years, the composite rate of cardiovascular death, nonfatal MI, or nonfatal stroke was 3.6% in the combined-therapy group and 5.0% with dual placebo, for a relative risk reduction of 29%. The number needed to treat for 5.6 years in order to prevent one event of the composite outcome was 72. However, the separation in the event rate curves for the two groups grew larger over time. With an additional planned followup of 3-5 years in HOPE-3, it’s likely the benefits will become even greater, according to Dr. Yusuf.

Combination therapy proved safe. Muscle aches and weakness as well as lightheadedness were more common in the combined treatment group than with dual placebo. However, permanent discontinuation rates were similar in the two groups.

HOPE-3 coinvestigator Dr. Eva Lonn presented the comparison between patients randomized to antihypertensive therapy without rosuvastatin or to placebo. In a prespecified subgroup analysis, active treatment resulted in a significant 27% reduction in the risk of the composite outcome compared with placebo in patients in the top one-third of baseline systolic blood pressure, no benefit in those with a systolic blood pressure of 131.6-143.5 mm Hg, and a suggestion of possible harm in patients whose systolic pressure at enrollment was 131.5 mm Hg or less.

Thus, the study helps define the minimum blood pressure at which antihypertensive therapy becomes beneficial, noted Dr. Lonn, professor of cardiology at McMaster University.

Dr. Yusuf said enthusiasm for the polypill concept as a means of reducing the growing global burden of cardiovascular disease remains strong among many experts. There is broad interest in a polypill for secondary prevention that will include aspirin, a beta blocker, and an ACE inhibitor of angiotensin receptor blocker as a low-cost means of improving medication adherence. And several large clinical trials of the polypill concept for primary prevention are underway, including a randomized trial conducted by Dr. Yusuf and coworkers in which several thousand high-risk subjects without baseline cardiovascular disease will receive a combination of a statin plus not two but three antihypertensive drugs.

Discussant Dr. Donald M. Lloyd-Jones commented, “What strikes me about HOPE-3 is that this is a population at risk, but not at particularly high risk.” And yet these patients benefited from statin therapy regardless of their baseline LDL, noted Dr. Lloyd-Jones, chair of the department of preventive medicine at Northwestern University, Chicago, and an architect of the risk-based approach to statin use that’s a centerpiece of the current ACC/AHA guidelines on atherosclerotic cardiovascular risk reduction.

In an interview, Dr. Sidney C. Smith, Jr., said the HOPE-3 data are “worthy of consideration” as experts meet at ACC 16 to begin updating guidelines for the treatment of hypertension. In particular, the key findings that moderate-risk hypertensive patients benefited from a statin regardless of their baseline LDL and initiation of blood pressure-lowering therapy was beneficial for patients with a systolic blood pressure in the 140s but not in those with a systolic pressure in the 120s and 130s could be practice changing, according to Dr. Smith, professor of medicine at the University of North Carolina, Chapel Hill.

Drs. Yusuf and Lonn reported receiving institutional research grants from the Canadian Institutes of Health Research and AstraZeneca, which funded the trial.

Simultaneous with the presentation of the HOPE-3 results at ACC 16 in Chicago, the study on cholesterol lowering and the study on blood pressure and cholesterol lowering led by Dr. Yusef as well as the study on blood pressure lowering led by Dr. Lonn were published online at NEJM.org.

[email protected]

CHICAGO – The success in the HOPE-3 trial of a two-pronged strategy of a statin plus moderate-dose antihypertensive therapy has expanded the boundaries of primary preventive pharmacotherapy to incorporate many intermediate-cardiovascular-risk patients without cardiovascular disease.

In the Heart Outcomes Evaluation (HOPE)-3 trial, the combination of rosuvastatin (Crestor) at 10 mg/day plus antihypertensive therapy with 16 mg/day of candesartan and 12.5 mg/day of hydrochlorothiazide reduced cardiovascular events in intermediate-risk patients with hypertension, regardless of their baseline LDL-cholesterol and inflammatory biomarker levels. In nonhypertensive study participants, however, blood pressure-lowering therapy provided no added benefit beyond that achieved with the statin alone, which yielded a 25% relative risk reduction in cardiovascular events compared with placebo, Dr. Salim Yusuf reported at the annual meeting of the American College of Cardiology.

The HOPE-3 trial was the first formal study of the polypill concept of fixed-dose, low-dose combination therapy as a public health tool for primary prevention in an intermediate-risk population without cardiovascular disease. It’s a simple, low-cost, safe, pragmatic preventive strategy that doesn’t require baseline laboratory measurements, dose titration visits, or frequent safety monitoring, he noted.

“The original concept of the polypill was to give it to everyone over age 55. We found in HOPE-3 that the polypill concept is not valid for everybody. It demonstrated benefit in hypertensives but not in nonhypertensives, where a statin alone was beneficial,” said Dr. Yusuf, professor of medicine and executive director of the Population Health Research Institute at McMaster University in Hamilton, Ont.

“The clinical implication is that statins should be used much more widely than they currently are. Most guidelines for hypertension don’t say to give a statin. But HOPE-3 is saying hypertensives will benefit. About half of the 40% reduction in the risk of cardiovascular events we saw with combination therapy in patients in the highest third for baseline systolic blood pressure – that is, above 143.5 mm Hg, with a mean of 154 mm Hg – was due to the rosuvastatin and half to the antihypertensive therapy. Our study suggests you can essentially double the benefit of lowering blood pressure in hypertensives if you also lower cholesterol simultaneously,” he noted. Dr. Yusuf discussed the findings in a video interview.

The double-blind trial included a diverse population of 12,705 men age 55 or older and women age 65 or older in 21 countries. All were at intermediate cardiovascular risk by conventional stratification methods; none had a history of cardiovascular disease. They were randomized to rosuvastatin or placebo, dual antihypertensive therapy or placebo, or to all three medications or double placebo. The combined-therapy group experienced a 33.7 mg/dL greater drop in LDL-cholesterol and a 6.2 mm Hg bigger reduction in systolic blood pressure than in patients on dual placebo.

During a median followup of 5.6 years, the composite rate of cardiovascular death, nonfatal MI, or nonfatal stroke was 3.6% in the combined-therapy group and 5.0% with dual placebo, for a relative risk reduction of 29%. The number needed to treat for 5.6 years in order to prevent one event of the composite outcome was 72. However, the separation in the event rate curves for the two groups grew larger over time. With an additional planned followup of 3-5 years in HOPE-3, it’s likely the benefits will become even greater, according to Dr. Yusuf.

Combination therapy proved safe. Muscle aches and weakness as well as lightheadedness were more common in the combined treatment group than with dual placebo. However, permanent discontinuation rates were similar in the two groups.

HOPE-3 coinvestigator Dr. Eva Lonn presented the comparison between patients randomized to antihypertensive therapy without rosuvastatin or to placebo. In a prespecified subgroup analysis, active treatment resulted in a significant 27% reduction in the risk of the composite outcome compared with placebo in patients in the top one-third of baseline systolic blood pressure, no benefit in those with a systolic blood pressure of 131.6-143.5 mm Hg, and a suggestion of possible harm in patients whose systolic pressure at enrollment was 131.5 mm Hg or less.

Thus, the study helps define the minimum blood pressure at which antihypertensive therapy becomes beneficial, noted Dr. Lonn, professor of cardiology at McMaster University.

Dr. Yusuf said enthusiasm for the polypill concept as a means of reducing the growing global burden of cardiovascular disease remains strong among many experts. There is broad interest in a polypill for secondary prevention that will include aspirin, a beta blocker, and an ACE inhibitor of angiotensin receptor blocker as a low-cost means of improving medication adherence. And several large clinical trials of the polypill concept for primary prevention are underway, including a randomized trial conducted by Dr. Yusuf and coworkers in which several thousand high-risk subjects without baseline cardiovascular disease will receive a combination of a statin plus not two but three antihypertensive drugs.

Discussant Dr. Donald M. Lloyd-Jones commented, “What strikes me about HOPE-3 is that this is a population at risk, but not at particularly high risk.” And yet these patients benefited from statin therapy regardless of their baseline LDL, noted Dr. Lloyd-Jones, chair of the department of preventive medicine at Northwestern University, Chicago, and an architect of the risk-based approach to statin use that’s a centerpiece of the current ACC/AHA guidelines on atherosclerotic cardiovascular risk reduction.

In an interview, Dr. Sidney C. Smith, Jr., said the HOPE-3 data are “worthy of consideration” as experts meet at ACC 16 to begin updating guidelines for the treatment of hypertension. In particular, the key findings that moderate-risk hypertensive patients benefited from a statin regardless of their baseline LDL and initiation of blood pressure-lowering therapy was beneficial for patients with a systolic blood pressure in the 140s but not in those with a systolic pressure in the 120s and 130s could be practice changing, according to Dr. Smith, professor of medicine at the University of North Carolina, Chapel Hill.

Drs. Yusuf and Lonn reported receiving institutional research grants from the Canadian Institutes of Health Research and AstraZeneca, which funded the trial.

Simultaneous with the presentation of the HOPE-3 results at ACC 16 in Chicago, the study on cholesterol lowering and the study on blood pressure and cholesterol lowering led by Dr. Yusef as well as the study on blood pressure lowering led by Dr. Lonn were published online at NEJM.org.

[email protected]

CHICAGO – The success in the HOPE-3 trial of a two-pronged strategy of a statin plus moderate-dose antihypertensive therapy has expanded the boundaries of primary preventive pharmacotherapy to incorporate many intermediate-cardiovascular-risk patients without cardiovascular disease.

In the Heart Outcomes Evaluation (HOPE)-3 trial, the combination of rosuvastatin (Crestor) at 10 mg/day plus antihypertensive therapy with 16 mg/day of candesartan and 12.5 mg/day of hydrochlorothiazide reduced cardiovascular events in intermediate-risk patients with hypertension, regardless of their baseline LDL-cholesterol and inflammatory biomarker levels. In nonhypertensive study participants, however, blood pressure-lowering therapy provided no added benefit beyond that achieved with the statin alone, which yielded a 25% relative risk reduction in cardiovascular events compared with placebo, Dr. Salim Yusuf reported at the annual meeting of the American College of Cardiology.

The HOPE-3 trial was the first formal study of the polypill concept of fixed-dose, low-dose combination therapy as a public health tool for primary prevention in an intermediate-risk population without cardiovascular disease. It’s a simple, low-cost, safe, pragmatic preventive strategy that doesn’t require baseline laboratory measurements, dose titration visits, or frequent safety monitoring, he noted.

“The original concept of the polypill was to give it to everyone over age 55. We found in HOPE-3 that the polypill concept is not valid for everybody. It demonstrated benefit in hypertensives but not in nonhypertensives, where a statin alone was beneficial,” said Dr. Yusuf, professor of medicine and executive director of the Population Health Research Institute at McMaster University in Hamilton, Ont.

“The clinical implication is that statins should be used much more widely than they currently are. Most guidelines for hypertension don’t say to give a statin. But HOPE-3 is saying hypertensives will benefit. About half of the 40% reduction in the risk of cardiovascular events we saw with combination therapy in patients in the highest third for baseline systolic blood pressure – that is, above 143.5 mm Hg, with a mean of 154 mm Hg – was due to the rosuvastatin and half to the antihypertensive therapy. Our study suggests you can essentially double the benefit of lowering blood pressure in hypertensives if you also lower cholesterol simultaneously,” he noted. Dr. Yusuf discussed the findings in a video interview.

The double-blind trial included a diverse population of 12,705 men age 55 or older and women age 65 or older in 21 countries. All were at intermediate cardiovascular risk by conventional stratification methods; none had a history of cardiovascular disease. They were randomized to rosuvastatin or placebo, dual antihypertensive therapy or placebo, or to all three medications or double placebo. The combined-therapy group experienced a 33.7 mg/dL greater drop in LDL-cholesterol and a 6.2 mm Hg bigger reduction in systolic blood pressure than in patients on dual placebo.

During a median followup of 5.6 years, the composite rate of cardiovascular death, nonfatal MI, or nonfatal stroke was 3.6% in the combined-therapy group and 5.0% with dual placebo, for a relative risk reduction of 29%. The number needed to treat for 5.6 years in order to prevent one event of the composite outcome was 72. However, the separation in the event rate curves for the two groups grew larger over time. With an additional planned followup of 3-5 years in HOPE-3, it’s likely the benefits will become even greater, according to Dr. Yusuf.

Combination therapy proved safe. Muscle aches and weakness as well as lightheadedness were more common in the combined treatment group than with dual placebo. However, permanent discontinuation rates were similar in the two groups.

HOPE-3 coinvestigator Dr. Eva Lonn presented the comparison between patients randomized to antihypertensive therapy without rosuvastatin or to placebo. In a prespecified subgroup analysis, active treatment resulted in a significant 27% reduction in the risk of the composite outcome compared with placebo in patients in the top one-third of baseline systolic blood pressure, no benefit in those with a systolic blood pressure of 131.6-143.5 mm Hg, and a suggestion of possible harm in patients whose systolic pressure at enrollment was 131.5 mm Hg or less.

Thus, the study helps define the minimum blood pressure at which antihypertensive therapy becomes beneficial, noted Dr. Lonn, professor of cardiology at McMaster University.

Dr. Yusuf said enthusiasm for the polypill concept as a means of reducing the growing global burden of cardiovascular disease remains strong among many experts. There is broad interest in a polypill for secondary prevention that will include aspirin, a beta blocker, and an ACE inhibitor of angiotensin receptor blocker as a low-cost means of improving medication adherence. And several large clinical trials of the polypill concept for primary prevention are underway, including a randomized trial conducted by Dr. Yusuf and coworkers in which several thousand high-risk subjects without baseline cardiovascular disease will receive a combination of a statin plus not two but three antihypertensive drugs.

Discussant Dr. Donald M. Lloyd-Jones commented, “What strikes me about HOPE-3 is that this is a population at risk, but not at particularly high risk.” And yet these patients benefited from statin therapy regardless of their baseline LDL, noted Dr. Lloyd-Jones, chair of the department of preventive medicine at Northwestern University, Chicago, and an architect of the risk-based approach to statin use that’s a centerpiece of the current ACC/AHA guidelines on atherosclerotic cardiovascular risk reduction.

In an interview, Dr. Sidney C. Smith, Jr., said the HOPE-3 data are “worthy of consideration” as experts meet at ACC 16 to begin updating guidelines for the treatment of hypertension. In particular, the key findings that moderate-risk hypertensive patients benefited from a statin regardless of their baseline LDL and initiation of blood pressure-lowering therapy was beneficial for patients with a systolic blood pressure in the 140s but not in those with a systolic pressure in the 120s and 130s could be practice changing, according to Dr. Smith, professor of medicine at the University of North Carolina, Chapel Hill.

Drs. Yusuf and Lonn reported receiving institutional research grants from the Canadian Institutes of Health Research and AstraZeneca, which funded the trial.

Simultaneous with the presentation of the HOPE-3 results at ACC 16 in Chicago, the study on cholesterol lowering and the study on blood pressure and cholesterol lowering led by Dr. Yusef as well as the study on blood pressure lowering led by Dr. Lonn were published online at NEJM.org.

[email protected]

Anopheles gambiae mosquito

Photo by James Gathany

Researchers believe they may have discovered a male-determining gene in the malaria-carrying mosquito species Anopheles gambiae.

The discovery of this gene provides scientists with a foundation for studying male mosquito biology.

And this is significant because male mosquitoes offer the potential to develop novel vector control strategies to combat malaria because males do not feed on blood or transmit disease.

One vector control method under development involves genetic modification of the mosquito to bias the population sex ratio toward males.

Modeling has shown the most efficient means for genetic modification of mosquitoes is engineering a driving Y chromosome.

A molecular-level understanding of the Y chromosome of the malaria-carrying mosquito is important to inform and optimize this type of a strategy.

So Omar Akbari, PhD, of the University of California, Riverside, and his colleagues set out to gain such an understanding.

The team used multiple genome sequencing techniques to identify an extensive dataset of Y chromosome sequences and explore their organization and evolution in the Anopheles gambiae complex, a group of at least 7 morphologically indistinguishable species of mosquitoes in the genus Anopheles.

This revealed that only 1 gene, YG2, is exclusive to the Y chromosome across the species complex and may therefore be a male-determining gene.

Dr Akbari and his colleagues described this discovery in PNAS.

Anopheles gambiae mosquito

Photo by James Gathany

Researchers believe they may have discovered a male-determining gene in the malaria-carrying mosquito species Anopheles gambiae.

The discovery of this gene provides scientists with a foundation for studying male mosquito biology.

And this is significant because male mosquitoes offer the potential to develop novel vector control strategies to combat malaria because males do not feed on blood or transmit disease.

One vector control method under development involves genetic modification of the mosquito to bias the population sex ratio toward males.

Modeling has shown the most efficient means for genetic modification of mosquitoes is engineering a driving Y chromosome.

A molecular-level understanding of the Y chromosome of the malaria-carrying mosquito is important to inform and optimize this type of a strategy.

So Omar Akbari, PhD, of the University of California, Riverside, and his colleagues set out to gain such an understanding.

The team used multiple genome sequencing techniques to identify an extensive dataset of Y chromosome sequences and explore their organization and evolution in the Anopheles gambiae complex, a group of at least 7 morphologically indistinguishable species of mosquitoes in the genus Anopheles.

This revealed that only 1 gene, YG2, is exclusive to the Y chromosome across the species complex and may therefore be a male-determining gene.

Dr Akbari and his colleagues described this discovery in PNAS.

Anopheles gambiae mosquito

Photo by James Gathany

Researchers believe they may have discovered a male-determining gene in the malaria-carrying mosquito species Anopheles gambiae.

The discovery of this gene provides scientists with a foundation for studying male mosquito biology.

And this is significant because male mosquitoes offer the potential to develop novel vector control strategies to combat malaria because males do not feed on blood or transmit disease.

One vector control method under development involves genetic modification of the mosquito to bias the population sex ratio toward males.

Modeling has shown the most efficient means for genetic modification of mosquitoes is engineering a driving Y chromosome.

A molecular-level understanding of the Y chromosome of the malaria-carrying mosquito is important to inform and optimize this type of a strategy.

So Omar Akbari, PhD, of the University of California, Riverside, and his colleagues set out to gain such an understanding.

The team used multiple genome sequencing techniques to identify an extensive dataset of Y chromosome sequences and explore their organization and evolution in the Anopheles gambiae complex, a group of at least 7 morphologically indistinguishable species of mosquitoes in the genus Anopheles.

This revealed that only 1 gene, YG2, is exclusive to the Y chromosome across the species complex and may therefore be a male-determining gene.

Dr Akbari and his colleagues described this discovery in PNAS.

High-dose cyclophosphamide is safe and effective when given as prophylaxis for chronic graft-versus-host disease (GVHD) to patients who have undergone transplantation of mobilized blood cells, finds a phase 2 trial reported in Blood.

Investigators led by Dr. Marco Mielcarek, medical director of the Adult Blood and Marrow Transplant Program and an oncologist at the Fred Hutchinson Cancer Research Center in Seattle, Washington, enrolled in the trial 43 patients with high-risk hematologic malignancies.

The patients underwent myeloablative conditioning followed by transplantation with growth factor–mobilized blood cells from related or unrelated donors, and were given high-dose cyclophosphamide on two early posttransplantation days.

Main results showed that the cumulative 1-year incidence of chronic GVHD was 16%, less than half of the roughly 35% seen historically with conventional immunosuppression.

Moreover, cyclophosphamide did not appear to compromise engraftment or control of the underlying malignancy. Only a single patient, one with an HLA-mismatched donor, had failure of primary engraftment; after amendment of the protocol to require HLA matching, there were no additional cases. Just 17% of patients experienced a recurrence of their malignancy by 2 years.

Taken together, the findings suggest that high-dose cyclophosphamide—as combined with two myeloablative conditioning options (to accommodate different malignancies) and with posttransplantation cyclosporine (to reduce the risk of acute GVHD)—may eliminate most of the drawbacks to using mobilized blood cells for transplantation, according to the investigators.

“If these findings are confirmed in future studies, HLA-matched mobilized blood cell transplantation may gain even greater acceptance and further replace marrow as a source of stem cells for most indications,” they maintain.

The patients studied had a median age of 43 years, and slightly more than half were in remission without minimal residual disease.

Blood cells were mobilized with granulocyte colony-stimulating factor (G-CSF). Overall, 28% of patients received grafts from related donors, while 72% received grafts from unrelated donors.

For pretransplant conditioning, patients received fludarabine and targeted busulfan, or total body irradiation with use of a minimum dose of 12 Gy.

The patients were given cyclophosphamide at 50 mg/kg per day on days 3 and 4 after transplantation. This was followed by cyclosporine starting on day 5.

The cumulative 1-year incidence of chronic GVHD as defined by National Institutes of Health criteria (i.e., that requiring systemic immunosuppressive therapy)—the trial’s primary endpoint—was 16%, which fell just short of the goal of 15% the investigators were aiming for (Blood. 2016;127:1502-8). Analyses failed to identify any predictors of this outcome.

Although the estimated cumulative incidence of grade 2 acute GVHD was high, at 77%, none of the patients developed grade 3 or 4 acute GVHD, according to the investigators, who disclosed that they had no competing financial interests.

The single patient who experienced failure of primary engraftment had familial myelodysplastic syndrome and had received a graft from an HLA A-antigen–mismatched unrelated donor.

The 2-year cumulative incidence of nonrelapse mortality was 14%, and the 2-year cumulative incidence of recurrent malignancy was 17%. Projected overall survival was 70%.

Among the 42 patients having at least a year of follow-up, 50% were alive and free of relapse without any systemic immunosuppression at 1 year after transplantation.

High-dose cyclophosphamide is safe and effective when given as prophylaxis for chronic graft-versus-host disease (GVHD) to patients who have undergone transplantation of mobilized blood cells, finds a phase 2 trial reported in Blood.

Investigators led by Dr. Marco Mielcarek, medical director of the Adult Blood and Marrow Transplant Program and an oncologist at the Fred Hutchinson Cancer Research Center in Seattle, Washington, enrolled in the trial 43 patients with high-risk hematologic malignancies.

The patients underwent myeloablative conditioning followed by transplantation with growth factor–mobilized blood cells from related or unrelated donors, and were given high-dose cyclophosphamide on two early posttransplantation days.

Main results showed that the cumulative 1-year incidence of chronic GVHD was 16%, less than half of the roughly 35% seen historically with conventional immunosuppression.

Moreover, cyclophosphamide did not appear to compromise engraftment or control of the underlying malignancy. Only a single patient, one with an HLA-mismatched donor, had failure of primary engraftment; after amendment of the protocol to require HLA matching, there were no additional cases. Just 17% of patients experienced a recurrence of their malignancy by 2 years.

Taken together, the findings suggest that high-dose cyclophosphamide—as combined with two myeloablative conditioning options (to accommodate different malignancies) and with posttransplantation cyclosporine (to reduce the risk of acute GVHD)—may eliminate most of the drawbacks to using mobilized blood cells for transplantation, according to the investigators.

“If these findings are confirmed in future studies, HLA-matched mobilized blood cell transplantation may gain even greater acceptance and further replace marrow as a source of stem cells for most indications,” they maintain.

The patients studied had a median age of 43 years, and slightly more than half were in remission without minimal residual disease.

Blood cells were mobilized with granulocyte colony-stimulating factor (G-CSF). Overall, 28% of patients received grafts from related donors, while 72% received grafts from unrelated donors.

For pretransplant conditioning, patients received fludarabine and targeted busulfan, or total body irradiation with use of a minimum dose of 12 Gy.

The patients were given cyclophosphamide at 50 mg/kg per day on days 3 and 4 after transplantation. This was followed by cyclosporine starting on day 5.

The cumulative 1-year incidence of chronic GVHD as defined by National Institutes of Health criteria (i.e., that requiring systemic immunosuppressive therapy)—the trial’s primary endpoint—was 16%, which fell just short of the goal of 15% the investigators were aiming for (Blood. 2016;127:1502-8). Analyses failed to identify any predictors of this outcome.

Although the estimated cumulative incidence of grade 2 acute GVHD was high, at 77%, none of the patients developed grade 3 or 4 acute GVHD, according to the investigators, who disclosed that they had no competing financial interests.

The single patient who experienced failure of primary engraftment had familial myelodysplastic syndrome and had received a graft from an HLA A-antigen–mismatched unrelated donor.

The 2-year cumulative incidence of nonrelapse mortality was 14%, and the 2-year cumulative incidence of recurrent malignancy was 17%. Projected overall survival was 70%.

Among the 42 patients having at least a year of follow-up, 50% were alive and free of relapse without any systemic immunosuppression at 1 year after transplantation.

High-dose cyclophosphamide is safe and effective when given as prophylaxis for chronic graft-versus-host disease (GVHD) to patients who have undergone transplantation of mobilized blood cells, finds a phase 2 trial reported in Blood.

Investigators led by Dr. Marco Mielcarek, medical director of the Adult Blood and Marrow Transplant Program and an oncologist at the Fred Hutchinson Cancer Research Center in Seattle, Washington, enrolled in the trial 43 patients with high-risk hematologic malignancies.

The patients underwent myeloablative conditioning followed by transplantation with growth factor–mobilized blood cells from related or unrelated donors, and were given high-dose cyclophosphamide on two early posttransplantation days.

Main results showed that the cumulative 1-year incidence of chronic GVHD was 16%, less than half of the roughly 35% seen historically with conventional immunosuppression.

Moreover, cyclophosphamide did not appear to compromise engraftment or control of the underlying malignancy. Only a single patient, one with an HLA-mismatched donor, had failure of primary engraftment; after amendment of the protocol to require HLA matching, there were no additional cases. Just 17% of patients experienced a recurrence of their malignancy by 2 years.

Taken together, the findings suggest that high-dose cyclophosphamide—as combined with two myeloablative conditioning options (to accommodate different malignancies) and with posttransplantation cyclosporine (to reduce the risk of acute GVHD)—may eliminate most of the drawbacks to using mobilized blood cells for transplantation, according to the investigators.

“If these findings are confirmed in future studies, HLA-matched mobilized blood cell transplantation may gain even greater acceptance and further replace marrow as a source of stem cells for most indications,” they maintain.

The patients studied had a median age of 43 years, and slightly more than half were in remission without minimal residual disease.

Blood cells were mobilized with granulocyte colony-stimulating factor (G-CSF). Overall, 28% of patients received grafts from related donors, while 72% received grafts from unrelated donors.

For pretransplant conditioning, patients received fludarabine and targeted busulfan, or total body irradiation with use of a minimum dose of 12 Gy.

The patients were given cyclophosphamide at 50 mg/kg per day on days 3 and 4 after transplantation. This was followed by cyclosporine starting on day 5.

The cumulative 1-year incidence of chronic GVHD as defined by National Institutes of Health criteria (i.e., that requiring systemic immunosuppressive therapy)—the trial’s primary endpoint—was 16%, which fell just short of the goal of 15% the investigators were aiming for (Blood. 2016;127:1502-8). Analyses failed to identify any predictors of this outcome.

Although the estimated cumulative incidence of grade 2 acute GVHD was high, at 77%, none of the patients developed grade 3 or 4 acute GVHD, according to the investigators, who disclosed that they had no competing financial interests.

The single patient who experienced failure of primary engraftment had familial myelodysplastic syndrome and had received a graft from an HLA A-antigen–mismatched unrelated donor.

The 2-year cumulative incidence of nonrelapse mortality was 14%, and the 2-year cumulative incidence of recurrent malignancy was 17%. Projected overall survival was 70%.

Among the 42 patients having at least a year of follow-up, 50% were alive and free of relapse without any systemic immunosuppression at 1 year after transplantation.