We agree with Drs. Arora and Mahmud that emerging mobile health (mHealth) approaches to improving patient engagement will need to demonstrate their value to advance health and healthcare. The potential for mHealth to do this has been often described[1, 2] but, so far, rarely measured or demonstrated.

The technology costs of our tablet‐based intervention[3] were low: 2 iPads at $400 each. The real expense was for personnel: research assistants needed to teach patients how to use the technology effectively. In the future, we hope to shift device and software orientation to patient‐care assistants, nurses, or even digital assistants, nonmedical personnel who have technical expertise with the health‐related devices and software needed to engage with the electronic health record and educational materials. Thus, at least part of the challenge of cost‐effectiveness aside from improved outcomeswill be demonstrating eventual time savings for providers who no longer need to hand deliver or explain paper pamphlets or printouts, or shepherd patients through their digitally assisted education.

One day we may muse, what did we do before mHealth? as we might do now when using mobile technologies for nonhealth‐related tasks like getting directions or making a call. Indeed, who can remember the last time they routinely used a paper map or phonebook for these daily tasks? Our prescription for tablets is a step in that direction, but we will need to also reimagine patient education and related daily tasks at the hospital and system level to realize the potential of lower costs and higher quality care we can achieve using mHealth.[4]

We agree with Drs. Arora and Mahmud that emerging mobile health (mHealth) approaches to improving patient engagement will need to demonstrate their value to advance health and healthcare. The potential for mHealth to do this has been often described[1, 2] but, so far, rarely measured or demonstrated.

The technology costs of our tablet‐based intervention[3] were low: 2 iPads at $400 each. The real expense was for personnel: research assistants needed to teach patients how to use the technology effectively. In the future, we hope to shift device and software orientation to patient‐care assistants, nurses, or even digital assistants, nonmedical personnel who have technical expertise with the health‐related devices and software needed to engage with the electronic health record and educational materials. Thus, at least part of the challenge of cost‐effectiveness aside from improved outcomeswill be demonstrating eventual time savings for providers who no longer need to hand deliver or explain paper pamphlets or printouts, or shepherd patients through their digitally assisted education.

One day we may muse, what did we do before mHealth? as we might do now when using mobile technologies for nonhealth‐related tasks like getting directions or making a call. Indeed, who can remember the last time they routinely used a paper map or phonebook for these daily tasks? Our prescription for tablets is a step in that direction, but we will need to also reimagine patient education and related daily tasks at the hospital and system level to realize the potential of lower costs and higher quality care we can achieve using mHealth.[4]

We agree with Drs. Arora and Mahmud that emerging mobile health (mHealth) approaches to improving patient engagement will need to demonstrate their value to advance health and healthcare. The potential for mHealth to do this has been often described[1, 2] but, so far, rarely measured or demonstrated.

The technology costs of our tablet‐based intervention[3] were low: 2 iPads at $400 each. The real expense was for personnel: research assistants needed to teach patients how to use the technology effectively. In the future, we hope to shift device and software orientation to patient‐care assistants, nurses, or even digital assistants, nonmedical personnel who have technical expertise with the health‐related devices and software needed to engage with the electronic health record and educational materials. Thus, at least part of the challenge of cost‐effectiveness aside from improved outcomeswill be demonstrating eventual time savings for providers who no longer need to hand deliver or explain paper pamphlets or printouts, or shepherd patients through their digitally assisted education.

One day we may muse, what did we do before mHealth? as we might do now when using mobile technologies for nonhealth‐related tasks like getting directions or making a call. Indeed, who can remember the last time they routinely used a paper map or phonebook for these daily tasks? Our prescription for tablets is a step in that direction, but we will need to also reimagine patient education and related daily tasks at the hospital and system level to realize the potential of lower costs and higher quality care we can achieve using mHealth.[4]

Hospital‐based care has become more complex over time. Patients are sicker, with more chronic comorbid conditions requiring greater collaboration to provide coordinated patient care.[1, 2] Care coordination requires an interdisciplinary approach during hospitalization and especially during transitions of care.[3, 4] In addition, hospitals are tasked with managing and improving clinical workflow efficiencies, and implementing electronic health records (EHR)[5] that require healthcare professionals to learn new systems of care and technology. Payment models have also started to shift toward an incentive and penalty‐based structure in the form of value‐based purchasing, readmission penalties, hospital‐acquired conditions, and meaningful use.[4, 6]

In response to these pressures, hospitals are searching for ways to reliably deliver quality care that is safe, effective, patient centered, timely, efficient, and equitable.[7] Previous efforts to improve quality in the general medical inpatient setting have included redesign of the clinical work environment and new workflows through the use of checklists and whiteboards to enhance communication, patient‐centered bedside rounds, standardized protocols and handovers, and integrated clinical decision support using health information technology.[8, 9, 10, 11, 12, 13] Although each of these care coordination activities has potential value, integrating them at the unit level often remains a challenge. Some hospitals have addressed this challenge by establishing and supporting a unit‐based leadership model, where a medical director and nurse manager work together to assess and improve the quality, safety, efficiency, and patient experience‐based mission of the organization.[14, 15] However, there are few descriptions of this leadership model in the current literature. Herein, we present the unit‐based leadership model that has been developed and implemented at 6 hospitals.

MODELS OF UNIT‐BASED LEADERSHIP

The unit‐based leadership model is grounded on the idea that culture and clinical care are products of frontline structure, process, and relationships, and that leaders at the site of care can have the greatest influence on the local work environment.[16, 17] The objective is to influence care and culture at the bedside and the unit, where care is delivered and where alignment with organizational vision and mission must occur. The concept of the inpatient unit medical director is not new, and hospitals in the past have recruited physician leaders to become clinical champions for quality improvement and help establish a collaborative work environment for physicians and unit‐based staff.[18, 19, 20, 21, 22] These studies report on the challenges and benefits of incorporating a medical director to inpatient psychiatry or general care units, but do not provide specific details about the recruitment and responsibilities for unit‐based dyad partnerships, which are critical factors for success on multidisciplinary inpatient care units.

There are several logistical matters to consider when instituting a unit‐based leadership model. These include the composition of the leadership team, selection process of the leaders, the presence of trainees and permanent faculty, and whether the units are able to geographically cohort patients. Other considerations include a clear role description with established shared goals and expectations, and a compensation model that includes effort and incentives. In addition, there should be a clearly established reporting structure to senior leadership, and the unit leaders should be given opportunities for professional growth and development. Table 1 provides a summary overview of 6 hospitals' experiences to date.

DISCUSSION

In reviewing our 6 organization's collective experiences, we identified several common themes and some notable differences across sites. The core of the leadership team was primarily composed of the medical director and nurse manager on the unit. Across all 6 organizations, medical directors had a portion of their effort supported for their leadership work on the unit. Leadership development training was provided at all of our sites, with particular emphasis on quality improvement (QI) methods such as Six‐Sigma, Lean, or Plan, Do, Study, Act (PDSA). Additional leadership development sessions were provided through the organization's human resources or affiliated university. Common outcome measures of interest include patient satisfaction, interdisciplinary practice, and collaboration on the unit, and some hospital‐acquired condition measures. Last, there is a direct reporting relationship to a chief or senior nurse or physician leader within each organization. These commonalities and variances are further detailed below.

OTHER CONSIDERATIONS

Other infrastructure variables that may increase the effectiveness of the unit leadership dyad include unit‐based clinical services (geographic localization), engaging the frontline team members in the design and implementation of change innovations, a commitment to patient and family centered practices on the unit, and enhancing clinical workflow through the support of EHR functions such as concurrent documentation and provider order entry. Geographic localization, placing the fewest possible clinical service providers on the unit to work alongside unit‐based staff, allows for a cohesive interdisciplinary unit‐based team to develop under the dyad leadership, and has been shown to improve communication practices.[9, 31] Beyond geographic localization of patients, it is critical to ensure team members are committed to the changes in workflow by directly involving them through the design and implementation of new models of care taking place on the unit. This commitment starts from the top senior nurse and physician leaders in the organization, and extends to the unit‐based dyad partners, and down to each individual interdisciplinary team member on the unit.[1] Thus, it is critical to clarify roles and responsibilities and how team members on the unit will interact with each other. For some situations, conflict management training will be helpful to the unit‐based leaders to resolve issues. To appreciate potential barriers to successful rollout of this unit leadership model, a phased implementation of pilot units, followed by successive waves, should be considered. Many of the units that instituted unit‐based interdisciplinary team rounds solicited and implemented direct feedback from frontline team members in efforts to improve communication and be more patient centered. Conversely, there are also likely to be situations where the unit‐based leaders will be confronted with hindrances to their unit‐based collaborative improvement efforts. To help prepare the dyad leaders, many of our unit‐based leaders have received specific training on how to coach and conduct difficult conversations with individuals who have performance gaps or are perceived to be hindering the progress of the unit's work. These crucial negotiation skills are not innate among most managers and should be explicitly provided to new leaders across organizations.

The goals and merits of patient‐ and family‐centered care (PFCC) have been well described.[32, 33, 34] Organizational support to teach and disseminate PFCC practices throughout all settings of care may help the leadership dyads implement rounding strategies that engage all staff, patients, and family members throughout the hospital course and during the transitions out of the hospital.

Clinical workflow has become heavily dependent on the EHR systems. For those organizations that have yet to adopt a particular EHR system, the leadership dyads should be involved throughout the EHR design process to help ensure that the technological solutions will be built to assist the clinical workflow, and once the system has been built, the leadership dyad should monitor and enhance the interface between workflow and EHR system so that it can support the creation and advancement of interdisciplinary plans of care on the unit.

CONCLUSION

The care of the hospitalized patient has become more complex over time. Interdisciplinary teamwork needs to be improved at the unit level to achieve the strategic goals of the hospital. Although quality improvement is an organizational goal, change takes place locally. Physician leaders, in partnership with nurse managers, are needed now more than ever to take on this task to improve the hospital‐care experience for patients by functioning as the primary effector arms for changing the landscape of hospital‐based care. We have described characteristics of unit‐based leadership programs adopted across 6 organizations. Hospitalists with clinical experience as the principal providers of inpatient‐based care and quality improvement experience and training, have been key participants in the development and implementation of the local leadership models in each of these hospital systems. We hope the comparison of the various models featured in this article serves as a valuable reference to hospitals and healthcare organizations who are contemplating the incorporation of this model into their strategic plan.

Hospital‐based care has become more complex over time. Patients are sicker, with more chronic comorbid conditions requiring greater collaboration to provide coordinated patient care.[1, 2] Care coordination requires an interdisciplinary approach during hospitalization and especially during transitions of care.[3, 4] In addition, hospitals are tasked with managing and improving clinical workflow efficiencies, and implementing electronic health records (EHR)[5] that require healthcare professionals to learn new systems of care and technology. Payment models have also started to shift toward an incentive and penalty‐based structure in the form of value‐based purchasing, readmission penalties, hospital‐acquired conditions, and meaningful use.[4, 6]

In response to these pressures, hospitals are searching for ways to reliably deliver quality care that is safe, effective, patient centered, timely, efficient, and equitable.[7] Previous efforts to improve quality in the general medical inpatient setting have included redesign of the clinical work environment and new workflows through the use of checklists and whiteboards to enhance communication, patient‐centered bedside rounds, standardized protocols and handovers, and integrated clinical decision support using health information technology.[8, 9, 10, 11, 12, 13] Although each of these care coordination activities has potential value, integrating them at the unit level often remains a challenge. Some hospitals have addressed this challenge by establishing and supporting a unit‐based leadership model, where a medical director and nurse manager work together to assess and improve the quality, safety, efficiency, and patient experience‐based mission of the organization.[14, 15] However, there are few descriptions of this leadership model in the current literature. Herein, we present the unit‐based leadership model that has been developed and implemented at 6 hospitals.

MODELS OF UNIT‐BASED LEADERSHIP

The unit‐based leadership model is grounded on the idea that culture and clinical care are products of frontline structure, process, and relationships, and that leaders at the site of care can have the greatest influence on the local work environment.[16, 17] The objective is to influence care and culture at the bedside and the unit, where care is delivered and where alignment with organizational vision and mission must occur. The concept of the inpatient unit medical director is not new, and hospitals in the past have recruited physician leaders to become clinical champions for quality improvement and help establish a collaborative work environment for physicians and unit‐based staff.[18, 19, 20, 21, 22] These studies report on the challenges and benefits of incorporating a medical director to inpatient psychiatry or general care units, but do not provide specific details about the recruitment and responsibilities for unit‐based dyad partnerships, which are critical factors for success on multidisciplinary inpatient care units.

There are several logistical matters to consider when instituting a unit‐based leadership model. These include the composition of the leadership team, selection process of the leaders, the presence of trainees and permanent faculty, and whether the units are able to geographically cohort patients. Other considerations include a clear role description with established shared goals and expectations, and a compensation model that includes effort and incentives. In addition, there should be a clearly established reporting structure to senior leadership, and the unit leaders should be given opportunities for professional growth and development. Table 1 provides a summary overview of 6 hospitals' experiences to date.

DISCUSSION

In reviewing our 6 organization's collective experiences, we identified several common themes and some notable differences across sites. The core of the leadership team was primarily composed of the medical director and nurse manager on the unit. Across all 6 organizations, medical directors had a portion of their effort supported for their leadership work on the unit. Leadership development training was provided at all of our sites, with particular emphasis on quality improvement (QI) methods such as Six‐Sigma, Lean, or Plan, Do, Study, Act (PDSA). Additional leadership development sessions were provided through the organization's human resources or affiliated university. Common outcome measures of interest include patient satisfaction, interdisciplinary practice, and collaboration on the unit, and some hospital‐acquired condition measures. Last, there is a direct reporting relationship to a chief or senior nurse or physician leader within each organization. These commonalities and variances are further detailed below.

OTHER CONSIDERATIONS

Other infrastructure variables that may increase the effectiveness of the unit leadership dyad include unit‐based clinical services (geographic localization), engaging the frontline team members in the design and implementation of change innovations, a commitment to patient and family centered practices on the unit, and enhancing clinical workflow through the support of EHR functions such as concurrent documentation and provider order entry. Geographic localization, placing the fewest possible clinical service providers on the unit to work alongside unit‐based staff, allows for a cohesive interdisciplinary unit‐based team to develop under the dyad leadership, and has been shown to improve communication practices.[9, 31] Beyond geographic localization of patients, it is critical to ensure team members are committed to the changes in workflow by directly involving them through the design and implementation of new models of care taking place on the unit. This commitment starts from the top senior nurse and physician leaders in the organization, and extends to the unit‐based dyad partners, and down to each individual interdisciplinary team member on the unit.[1] Thus, it is critical to clarify roles and responsibilities and how team members on the unit will interact with each other. For some situations, conflict management training will be helpful to the unit‐based leaders to resolve issues. To appreciate potential barriers to successful rollout of this unit leadership model, a phased implementation of pilot units, followed by successive waves, should be considered. Many of the units that instituted unit‐based interdisciplinary team rounds solicited and implemented direct feedback from frontline team members in efforts to improve communication and be more patient centered. Conversely, there are also likely to be situations where the unit‐based leaders will be confronted with hindrances to their unit‐based collaborative improvement efforts. To help prepare the dyad leaders, many of our unit‐based leaders have received specific training on how to coach and conduct difficult conversations with individuals who have performance gaps or are perceived to be hindering the progress of the unit's work. These crucial negotiation skills are not innate among most managers and should be explicitly provided to new leaders across organizations.

The goals and merits of patient‐ and family‐centered care (PFCC) have been well described.[32, 33, 34] Organizational support to teach and disseminate PFCC practices throughout all settings of care may help the leadership dyads implement rounding strategies that engage all staff, patients, and family members throughout the hospital course and during the transitions out of the hospital.

Clinical workflow has become heavily dependent on the EHR systems. For those organizations that have yet to adopt a particular EHR system, the leadership dyads should be involved throughout the EHR design process to help ensure that the technological solutions will be built to assist the clinical workflow, and once the system has been built, the leadership dyad should monitor and enhance the interface between workflow and EHR system so that it can support the creation and advancement of interdisciplinary plans of care on the unit.

CONCLUSION

The care of the hospitalized patient has become more complex over time. Interdisciplinary teamwork needs to be improved at the unit level to achieve the strategic goals of the hospital. Although quality improvement is an organizational goal, change takes place locally. Physician leaders, in partnership with nurse managers, are needed now more than ever to take on this task to improve the hospital‐care experience for patients by functioning as the primary effector arms for changing the landscape of hospital‐based care. We have described characteristics of unit‐based leadership programs adopted across 6 organizations. Hospitalists with clinical experience as the principal providers of inpatient‐based care and quality improvement experience and training, have been key participants in the development and implementation of the local leadership models in each of these hospital systems. We hope the comparison of the various models featured in this article serves as a valuable reference to hospitals and healthcare organizations who are contemplating the incorporation of this model into their strategic plan.

Hospital‐based care has become more complex over time. Patients are sicker, with more chronic comorbid conditions requiring greater collaboration to provide coordinated patient care.[1, 2] Care coordination requires an interdisciplinary approach during hospitalization and especially during transitions of care.[3, 4] In addition, hospitals are tasked with managing and improving clinical workflow efficiencies, and implementing electronic health records (EHR)[5] that require healthcare professionals to learn new systems of care and technology. Payment models have also started to shift toward an incentive and penalty‐based structure in the form of value‐based purchasing, readmission penalties, hospital‐acquired conditions, and meaningful use.[4, 6]

In response to these pressures, hospitals are searching for ways to reliably deliver quality care that is safe, effective, patient centered, timely, efficient, and equitable.[7] Previous efforts to improve quality in the general medical inpatient setting have included redesign of the clinical work environment and new workflows through the use of checklists and whiteboards to enhance communication, patient‐centered bedside rounds, standardized protocols and handovers, and integrated clinical decision support using health information technology.[8, 9, 10, 11, 12, 13] Although each of these care coordination activities has potential value, integrating them at the unit level often remains a challenge. Some hospitals have addressed this challenge by establishing and supporting a unit‐based leadership model, where a medical director and nurse manager work together to assess and improve the quality, safety, efficiency, and patient experience‐based mission of the organization.[14, 15] However, there are few descriptions of this leadership model in the current literature. Herein, we present the unit‐based leadership model that has been developed and implemented at 6 hospitals.

MODELS OF UNIT‐BASED LEADERSHIP

The unit‐based leadership model is grounded on the idea that culture and clinical care are products of frontline structure, process, and relationships, and that leaders at the site of care can have the greatest influence on the local work environment.[16, 17] The objective is to influence care and culture at the bedside and the unit, where care is delivered and where alignment with organizational vision and mission must occur. The concept of the inpatient unit medical director is not new, and hospitals in the past have recruited physician leaders to become clinical champions for quality improvement and help establish a collaborative work environment for physicians and unit‐based staff.[18, 19, 20, 21, 22] These studies report on the challenges and benefits of incorporating a medical director to inpatient psychiatry or general care units, but do not provide specific details about the recruitment and responsibilities for unit‐based dyad partnerships, which are critical factors for success on multidisciplinary inpatient care units.

There are several logistical matters to consider when instituting a unit‐based leadership model. These include the composition of the leadership team, selection process of the leaders, the presence of trainees and permanent faculty, and whether the units are able to geographically cohort patients. Other considerations include a clear role description with established shared goals and expectations, and a compensation model that includes effort and incentives. In addition, there should be a clearly established reporting structure to senior leadership, and the unit leaders should be given opportunities for professional growth and development. Table 1 provides a summary overview of 6 hospitals' experiences to date.

DISCUSSION

In reviewing our 6 organization's collective experiences, we identified several common themes and some notable differences across sites. The core of the leadership team was primarily composed of the medical director and nurse manager on the unit. Across all 6 organizations, medical directors had a portion of their effort supported for their leadership work on the unit. Leadership development training was provided at all of our sites, with particular emphasis on quality improvement (QI) methods such as Six‐Sigma, Lean, or Plan, Do, Study, Act (PDSA). Additional leadership development sessions were provided through the organization's human resources or affiliated university. Common outcome measures of interest include patient satisfaction, interdisciplinary practice, and collaboration on the unit, and some hospital‐acquired condition measures. Last, there is a direct reporting relationship to a chief or senior nurse or physician leader within each organization. These commonalities and variances are further detailed below.

OTHER CONSIDERATIONS

Other infrastructure variables that may increase the effectiveness of the unit leadership dyad include unit‐based clinical services (geographic localization), engaging the frontline team members in the design and implementation of change innovations, a commitment to patient and family centered practices on the unit, and enhancing clinical workflow through the support of EHR functions such as concurrent documentation and provider order entry. Geographic localization, placing the fewest possible clinical service providers on the unit to work alongside unit‐based staff, allows for a cohesive interdisciplinary unit‐based team to develop under the dyad leadership, and has been shown to improve communication practices.[9, 31] Beyond geographic localization of patients, it is critical to ensure team members are committed to the changes in workflow by directly involving them through the design and implementation of new models of care taking place on the unit. This commitment starts from the top senior nurse and physician leaders in the organization, and extends to the unit‐based dyad partners, and down to each individual interdisciplinary team member on the unit.[1] Thus, it is critical to clarify roles and responsibilities and how team members on the unit will interact with each other. For some situations, conflict management training will be helpful to the unit‐based leaders to resolve issues. To appreciate potential barriers to successful rollout of this unit leadership model, a phased implementation of pilot units, followed by successive waves, should be considered. Many of the units that instituted unit‐based interdisciplinary team rounds solicited and implemented direct feedback from frontline team members in efforts to improve communication and be more patient centered. Conversely, there are also likely to be situations where the unit‐based leaders will be confronted with hindrances to their unit‐based collaborative improvement efforts. To help prepare the dyad leaders, many of our unit‐based leaders have received specific training on how to coach and conduct difficult conversations with individuals who have performance gaps or are perceived to be hindering the progress of the unit's work. These crucial negotiation skills are not innate among most managers and should be explicitly provided to new leaders across organizations.

The goals and merits of patient‐ and family‐centered care (PFCC) have been well described.[32, 33, 34] Organizational support to teach and disseminate PFCC practices throughout all settings of care may help the leadership dyads implement rounding strategies that engage all staff, patients, and family members throughout the hospital course and during the transitions out of the hospital.

Clinical workflow has become heavily dependent on the EHR systems. For those organizations that have yet to adopt a particular EHR system, the leadership dyads should be involved throughout the EHR design process to help ensure that the technological solutions will be built to assist the clinical workflow, and once the system has been built, the leadership dyad should monitor and enhance the interface between workflow and EHR system so that it can support the creation and advancement of interdisciplinary plans of care on the unit.

CONCLUSION

The care of the hospitalized patient has become more complex over time. Interdisciplinary teamwork needs to be improved at the unit level to achieve the strategic goals of the hospital. Although quality improvement is an organizational goal, change takes place locally. Physician leaders, in partnership with nurse managers, are needed now more than ever to take on this task to improve the hospital‐care experience for patients by functioning as the primary effector arms for changing the landscape of hospital‐based care. We have described characteristics of unit‐based leadership programs adopted across 6 organizations. Hospitalists with clinical experience as the principal providers of inpatient‐based care and quality improvement experience and training, have been key participants in the development and implementation of the local leadership models in each of these hospital systems. We hope the comparison of the various models featured in this article serves as a valuable reference to hospitals and healthcare organizations who are contemplating the incorporation of this model into their strategic plan.

We are pleased to see positive results from the use of tablet computers (tablets) in engaging patients, as presented by Greyson and colleagues.[1] Patient engagement is correlated with better patient‐reported health outcomes.[2] But how do we justify any additional costs in the current climate?

The answer lies in the value delivered.[3] Achieving high‐value care means delivering the best outcomes at the lowest cost. Indeed, a growing number of studies are demonstrating improved outcomes with mobile technology. In Cleveland, tablet‐based self‐reporting in cancer patients improved communication of symptoms to physicians.[4] In Australia, chronic obstructive pulmonary disease patients engaged in tablet‐facilitated physical rehabilitation reported improved symptoms and exercise tolerance.[5] In Haiti, tablet‐delivered education sustainably improved knowledge of human immunodeficiency virus prevention and behavior among internally displaced women.[6]

What the extant literature is lacking, however, are studies demonstrating the cost‐effectiveness of mobile interventions. Digital platforms are unlikely to gain traction without these data. Some exceptions exist, but they are in the minority.[7] It is clear that engaged patients demonstrate better outcomes. However, future studies exploring the use of digital platforms would be well advised to include measures of cost‐effectiveness to build a true value‐based rationale for their integration into daily practice.

We are pleased to see positive results from the use of tablet computers (tablets) in engaging patients, as presented by Greyson and colleagues.[1] Patient engagement is correlated with better patient‐reported health outcomes.[2] But how do we justify any additional costs in the current climate?

The answer lies in the value delivered.[3] Achieving high‐value care means delivering the best outcomes at the lowest cost. Indeed, a growing number of studies are demonstrating improved outcomes with mobile technology. In Cleveland, tablet‐based self‐reporting in cancer patients improved communication of symptoms to physicians.[4] In Australia, chronic obstructive pulmonary disease patients engaged in tablet‐facilitated physical rehabilitation reported improved symptoms and exercise tolerance.[5] In Haiti, tablet‐delivered education sustainably improved knowledge of human immunodeficiency virus prevention and behavior among internally displaced women.[6]

What the extant literature is lacking, however, are studies demonstrating the cost‐effectiveness of mobile interventions. Digital platforms are unlikely to gain traction without these data. Some exceptions exist, but they are in the minority.[7] It is clear that engaged patients demonstrate better outcomes. However, future studies exploring the use of digital platforms would be well advised to include measures of cost‐effectiveness to build a true value‐based rationale for their integration into daily practice.

We are pleased to see positive results from the use of tablet computers (tablets) in engaging patients, as presented by Greyson and colleagues.[1] Patient engagement is correlated with better patient‐reported health outcomes.[2] But how do we justify any additional costs in the current climate?

The answer lies in the value delivered.[3] Achieving high‐value care means delivering the best outcomes at the lowest cost. Indeed, a growing number of studies are demonstrating improved outcomes with mobile technology. In Cleveland, tablet‐based self‐reporting in cancer patients improved communication of symptoms to physicians.[4] In Australia, chronic obstructive pulmonary disease patients engaged in tablet‐facilitated physical rehabilitation reported improved symptoms and exercise tolerance.[5] In Haiti, tablet‐delivered education sustainably improved knowledge of human immunodeficiency virus prevention and behavior among internally displaced women.[6]

What the extant literature is lacking, however, are studies demonstrating the cost‐effectiveness of mobile interventions. Digital platforms are unlikely to gain traction without these data. Some exceptions exist, but they are in the minority.[7] It is clear that engaged patients demonstrate better outcomes. However, future studies exploring the use of digital platforms would be well advised to include measures of cost‐effectiveness to build a true value‐based rationale for their integration into daily practice.

The management of perioperative medications is a tale of progressive scientific enquiry. Although long‐term use of agents such as aspirin or statins improves clinical outcomes, use during surgery ranges from problematic to protective. The delicate balance between proven long‐term benefits in the nonoperative setting versus short‐term uncertainty in the perioperative setting must be assessed using a lens that incorporates patient risk, surgical process, and pharmacodynamic principles. Advances in our understanding of perioperative physiology, coupled with robust clinical and outcome data, have led to new knowledge and insights regarding how best to manage these medications. As well illustrated by the near 180 change in the use of perioperative ‐blockers to prevent adverse cardiovascular outcomes, these new data have led to substantial progress in surgical safety and patient outcomes.

In this issue of the Journal of Hospital Medicine, 2 retrospective cohort studies add to this growing body of evidence by examining risks associated with use of angiotensin‐converting enzyme (ACE) inhibitors in the perioperative setting. In the first study, conducted at a single academic medical center, Nielson and colleagues evaluate the association of preoperative ACE‐inhibitor use with hypotension and acute kidney injury in patients undergoing major elective orthopedic surgery.[1] The authors report that patients receiving ACE‐inhibitors were not only more likely to experience hypotension after induction of anesthesia (12.2% vs 6.7%, P = 0.005), but also were more likely to develop postoperative acute kidney injury (odds ratio [OR]: 2.68, 95% confidence interval [CI]: 1.25‐1.99). In the second study which focused solely on patients who were receiving preoperative ACE‐inhibitor therapy, Mudumbai and colleagues used a national Veterans Affairs database to examine the association between failure to resume ACE‐inhibitor treatment after surgery and outcomes at 30 days.[2] The authors found that failure to resume treatment 14 days after surgery was not only common (affecting 1 in 4 patients), but was also associated with increased 30‐day mortality (hazard ratio: 3.44, 95% CI: 3.30‐3.60).[2] Taken together, these 2 studies shed new light on clinical practice and policy implications for the use of these agents in the surgical period. Both sets of authors should be congratulated on moving the needle forward in this enquiry.

ACE‐inhibitors physiologically mediate their effects by preventing the formation of the potent vasoconstrictor angiotensin‐II from its precursor angiotensin‐I. In doing so, they decrease arterial resistance, increase venous capacitance, decrease glomerular filtration pressure, and promote natriuresis. These vascular effects have key benefits for the management of a number of chronic diseases including hypertension, congestive heart failure, and diabetic nephropathy. However, these clinical alterations are often problematic in the perioperative setting. For example, ACE‐inhibitors may cause vasoplegia during anesthetic administration, commonly manifested as hypotension during induction.[3] This hemodynamic alteration has been viewed as being so precarious, that some authors recommend withholding ACE‐inhibitors prior to major cardiovascular procedures such as coronary artery bypass grafting.[4] Although hypotension leads to management challenges (often increasing vasoconstrictor requirements), several studies report that ACE‐inhibitor use during surgery may also be associated with increased risks of acute kidney injury and mortality.[5, 6] However, despite these data, existing literature has not shown a consistent association between ACE‐inhibitor use and adverse postoperative outcomes. For example, a propensity‐matched cohort study of 79,228 patients at the Cleveland Clinic found no difference in hemodynamic characteristics, vasopressor requirements, or cardiorespiratory complications among patients who were or were not using ACE‐inhibitors during noncardiac surgery.[7] Furthermore, some research has also found that withdrawal of ACE‐inhibitors may itself lead to harm. For instance, a contemporary study reported that withdrawal of ACE‐inhibitor therapy in patients undergoing coronary artery bypass was associated with increased in‐hospital cardiovascular events.[8] Given this uncertainty, it is not surprising that management of ACE‐inhibitors in the perioperative period remains a subject of ongoing controversy with clinical reviews often recommending consideration of the risks and benefits associated with use of these agents.[9]

It is important to note that driver of this ambiguity is the very design of relevant studies. For instance, studies that focus on patients undergoing coronary artery bypass grafting surgery have limited external validity, as these patients are very different from those who undergo elective hip or knee replacement (such as those included by Nielsen and colleagues). Additionally, many studies suffer from methodological constraints or biases. For instance, retrospective observational studies often suffer from selection bias and residual confounding; that is, the individuals chosen for inclusion in the study and the variables available for analysis are often limited by available data, curtailing the conclusions that can be generated. Although the use of multivariable regression or propensity score techniques helps address these limitations, residual confounding by unmeasured variables always remains a threat to statistical inference. The potential influence for this bias is particularly relevant when examining the results of the study by Nielsen and colleagues. Another important limitation is survivor bias, a problem inherent in the study by Mudumbai and colleagues. Put simply, for a patient to resume ACE‐inhibitors after surgery, this same patient, must also survive for at least 15 to 30 days after surgery. Thus, for some patients, failure to resume this treatment may simply be a marker of early mortality rather than failure to resume the ACE itself. The potential influence of this bias is supported by an included sensitivity analysis, where a large change in the adjusted OR was observed when patients suffering early mortality were excluded. This swing in effect size suggests that biases related to comparing patients who survived to those who did not with respect to ACE use may, in part, account for the results of the study.

These limitations aside, the studies brought forth by both authors help inform practice with respect to the use of these agents during surgery. In this context, 3 paradigms are relevant for practicing hospitalists.

First, if a patient is maintained on an ACE‐inhibitor before surgery, should the medication be temporarily held before surgery to minimize hypotension during anesthesia? The study by Nielsen and colleagues (comparing those on ACE‐inhibitor treatment to those without), in addition to the evidence generated from other studies in this area[10, 11, 12] suggest that this is a rational decision. Although the existence of a withdrawal state from abrupt cessation of ACE‐inhibitor use is theoretically plausible, this has yet to be reliably reported in the literature. Given the short half‐life of most ACE‐inhibitors, cessation 24 hours before surgery appears to be the most pragmatic clinical approach.

Second, if a patient is on an ACE‐inhibitor before surgery, when should the medication be resumed after surgery? The findings from the study by Mudumbai and colleagues, in addition to contemporary evidence,[7, 8, 13] support the resumption of these agents as soon as possible following operative intervention. Once hemodynamic stability and volume status have been assured, risks associated with postoperative ACE‐inhibitor use appear to be outweighed by benefits, though specific care is likely necessary in those with preexisting renal dysfunction.[14] A program that ensures reconciliation of medications in the postoperative setting may be valuable in ensuring that such treatment is restarted.

Third, if a patient is not on ACE‐inhibitor therapy, should this be started before surgery for perioperative or long‐term benefit? Although neither study examines this issue, the potential for significant risk make this an unattractive option. Future interventional studies with thoughtfully weighed safety parameters may be necessary to assess whether such a paradigm may be valuable.

The studies included in this issue of the Journal of Hospital Medicine suggest that the use of ACE‐inhibitors during the perioperative period may be considered a function of time and place. Resuming ACE‐inhibitors and cessation of treatment at specific intervals in relation to surgery can help ensure positive outcomes. Hospitalists have an important role in this regard, as they are ideally situated to manage these agents in the many patients undergoing surgery across the United States.

Disclosures: Dr. Wijeysundera is supported by a Clinician‐Scientist Award from the Canadian Institutes of Health Research, and a Merit Award from the Department of Anesthesia at the University of Toronto. Dr. Chopra is supported by a Career‐Development Award (1K08HS022835‐01) from the Agency of Healthcare Research and Quality.

The management of perioperative medications is a tale of progressive scientific enquiry. Although long‐term use of agents such as aspirin or statins improves clinical outcomes, use during surgery ranges from problematic to protective. The delicate balance between proven long‐term benefits in the nonoperative setting versus short‐term uncertainty in the perioperative setting must be assessed using a lens that incorporates patient risk, surgical process, and pharmacodynamic principles. Advances in our understanding of perioperative physiology, coupled with robust clinical and outcome data, have led to new knowledge and insights regarding how best to manage these medications. As well illustrated by the near 180 change in the use of perioperative ‐blockers to prevent adverse cardiovascular outcomes, these new data have led to substantial progress in surgical safety and patient outcomes.

In this issue of the Journal of Hospital Medicine, 2 retrospective cohort studies add to this growing body of evidence by examining risks associated with use of angiotensin‐converting enzyme (ACE) inhibitors in the perioperative setting. In the first study, conducted at a single academic medical center, Nielson and colleagues evaluate the association of preoperative ACE‐inhibitor use with hypotension and acute kidney injury in patients undergoing major elective orthopedic surgery.[1] The authors report that patients receiving ACE‐inhibitors were not only more likely to experience hypotension after induction of anesthesia (12.2% vs 6.7%, P = 0.005), but also were more likely to develop postoperative acute kidney injury (odds ratio [OR]: 2.68, 95% confidence interval [CI]: 1.25‐1.99). In the second study which focused solely on patients who were receiving preoperative ACE‐inhibitor therapy, Mudumbai and colleagues used a national Veterans Affairs database to examine the association between failure to resume ACE‐inhibitor treatment after surgery and outcomes at 30 days.[2] The authors found that failure to resume treatment 14 days after surgery was not only common (affecting 1 in 4 patients), but was also associated with increased 30‐day mortality (hazard ratio: 3.44, 95% CI: 3.30‐3.60).[2] Taken together, these 2 studies shed new light on clinical practice and policy implications for the use of these agents in the surgical period. Both sets of authors should be congratulated on moving the needle forward in this enquiry.

ACE‐inhibitors physiologically mediate their effects by preventing the formation of the potent vasoconstrictor angiotensin‐II from its precursor angiotensin‐I. In doing so, they decrease arterial resistance, increase venous capacitance, decrease glomerular filtration pressure, and promote natriuresis. These vascular effects have key benefits for the management of a number of chronic diseases including hypertension, congestive heart failure, and diabetic nephropathy. However, these clinical alterations are often problematic in the perioperative setting. For example, ACE‐inhibitors may cause vasoplegia during anesthetic administration, commonly manifested as hypotension during induction.[3] This hemodynamic alteration has been viewed as being so precarious, that some authors recommend withholding ACE‐inhibitors prior to major cardiovascular procedures such as coronary artery bypass grafting.[4] Although hypotension leads to management challenges (often increasing vasoconstrictor requirements), several studies report that ACE‐inhibitor use during surgery may also be associated with increased risks of acute kidney injury and mortality.[5, 6] However, despite these data, existing literature has not shown a consistent association between ACE‐inhibitor use and adverse postoperative outcomes. For example, a propensity‐matched cohort study of 79,228 patients at the Cleveland Clinic found no difference in hemodynamic characteristics, vasopressor requirements, or cardiorespiratory complications among patients who were or were not using ACE‐inhibitors during noncardiac surgery.[7] Furthermore, some research has also found that withdrawal of ACE‐inhibitors may itself lead to harm. For instance, a contemporary study reported that withdrawal of ACE‐inhibitor therapy in patients undergoing coronary artery bypass was associated with increased in‐hospital cardiovascular events.[8] Given this uncertainty, it is not surprising that management of ACE‐inhibitors in the perioperative period remains a subject of ongoing controversy with clinical reviews often recommending consideration of the risks and benefits associated with use of these agents.[9]

It is important to note that driver of this ambiguity is the very design of relevant studies. For instance, studies that focus on patients undergoing coronary artery bypass grafting surgery have limited external validity, as these patients are very different from those who undergo elective hip or knee replacement (such as those included by Nielsen and colleagues). Additionally, many studies suffer from methodological constraints or biases. For instance, retrospective observational studies often suffer from selection bias and residual confounding; that is, the individuals chosen for inclusion in the study and the variables available for analysis are often limited by available data, curtailing the conclusions that can be generated. Although the use of multivariable regression or propensity score techniques helps address these limitations, residual confounding by unmeasured variables always remains a threat to statistical inference. The potential influence for this bias is particularly relevant when examining the results of the study by Nielsen and colleagues. Another important limitation is survivor bias, a problem inherent in the study by Mudumbai and colleagues. Put simply, for a patient to resume ACE‐inhibitors after surgery, this same patient, must also survive for at least 15 to 30 days after surgery. Thus, for some patients, failure to resume this treatment may simply be a marker of early mortality rather than failure to resume the ACE itself. The potential influence of this bias is supported by an included sensitivity analysis, where a large change in the adjusted OR was observed when patients suffering early mortality were excluded. This swing in effect size suggests that biases related to comparing patients who survived to those who did not with respect to ACE use may, in part, account for the results of the study.

These limitations aside, the studies brought forth by both authors help inform practice with respect to the use of these agents during surgery. In this context, 3 paradigms are relevant for practicing hospitalists.

First, if a patient is maintained on an ACE‐inhibitor before surgery, should the medication be temporarily held before surgery to minimize hypotension during anesthesia? The study by Nielsen and colleagues (comparing those on ACE‐inhibitor treatment to those without), in addition to the evidence generated from other studies in this area[10, 11, 12] suggest that this is a rational decision. Although the existence of a withdrawal state from abrupt cessation of ACE‐inhibitor use is theoretically plausible, this has yet to be reliably reported in the literature. Given the short half‐life of most ACE‐inhibitors, cessation 24 hours before surgery appears to be the most pragmatic clinical approach.

Second, if a patient is on an ACE‐inhibitor before surgery, when should the medication be resumed after surgery? The findings from the study by Mudumbai and colleagues, in addition to contemporary evidence,[7, 8, 13] support the resumption of these agents as soon as possible following operative intervention. Once hemodynamic stability and volume status have been assured, risks associated with postoperative ACE‐inhibitor use appear to be outweighed by benefits, though specific care is likely necessary in those with preexisting renal dysfunction.[14] A program that ensures reconciliation of medications in the postoperative setting may be valuable in ensuring that such treatment is restarted.

Third, if a patient is not on ACE‐inhibitor therapy, should this be started before surgery for perioperative or long‐term benefit? Although neither study examines this issue, the potential for significant risk make this an unattractive option. Future interventional studies with thoughtfully weighed safety parameters may be necessary to assess whether such a paradigm may be valuable.

The studies included in this issue of the Journal of Hospital Medicine suggest that the use of ACE‐inhibitors during the perioperative period may be considered a function of time and place. Resuming ACE‐inhibitors and cessation of treatment at specific intervals in relation to surgery can help ensure positive outcomes. Hospitalists have an important role in this regard, as they are ideally situated to manage these agents in the many patients undergoing surgery across the United States.

Disclosures: Dr. Wijeysundera is supported by a Clinician‐Scientist Award from the Canadian Institutes of Health Research, and a Merit Award from the Department of Anesthesia at the University of Toronto. Dr. Chopra is supported by a Career‐Development Award (1K08HS022835‐01) from the Agency of Healthcare Research and Quality.

The management of perioperative medications is a tale of progressive scientific enquiry. Although long‐term use of agents such as aspirin or statins improves clinical outcomes, use during surgery ranges from problematic to protective. The delicate balance between proven long‐term benefits in the nonoperative setting versus short‐term uncertainty in the perioperative setting must be assessed using a lens that incorporates patient risk, surgical process, and pharmacodynamic principles. Advances in our understanding of perioperative physiology, coupled with robust clinical and outcome data, have led to new knowledge and insights regarding how best to manage these medications. As well illustrated by the near 180 change in the use of perioperative ‐blockers to prevent adverse cardiovascular outcomes, these new data have led to substantial progress in surgical safety and patient outcomes.

In this issue of the Journal of Hospital Medicine, 2 retrospective cohort studies add to this growing body of evidence by examining risks associated with use of angiotensin‐converting enzyme (ACE) inhibitors in the perioperative setting. In the first study, conducted at a single academic medical center, Nielson and colleagues evaluate the association of preoperative ACE‐inhibitor use with hypotension and acute kidney injury in patients undergoing major elective orthopedic surgery.[1] The authors report that patients receiving ACE‐inhibitors were not only more likely to experience hypotension after induction of anesthesia (12.2% vs 6.7%, P = 0.005), but also were more likely to develop postoperative acute kidney injury (odds ratio [OR]: 2.68, 95% confidence interval [CI]: 1.25‐1.99). In the second study which focused solely on patients who were receiving preoperative ACE‐inhibitor therapy, Mudumbai and colleagues used a national Veterans Affairs database to examine the association between failure to resume ACE‐inhibitor treatment after surgery and outcomes at 30 days.[2] The authors found that failure to resume treatment 14 days after surgery was not only common (affecting 1 in 4 patients), but was also associated with increased 30‐day mortality (hazard ratio: 3.44, 95% CI: 3.30‐3.60).[2] Taken together, these 2 studies shed new light on clinical practice and policy implications for the use of these agents in the surgical period. Both sets of authors should be congratulated on moving the needle forward in this enquiry.

ACE‐inhibitors physiologically mediate their effects by preventing the formation of the potent vasoconstrictor angiotensin‐II from its precursor angiotensin‐I. In doing so, they decrease arterial resistance, increase venous capacitance, decrease glomerular filtration pressure, and promote natriuresis. These vascular effects have key benefits for the management of a number of chronic diseases including hypertension, congestive heart failure, and diabetic nephropathy. However, these clinical alterations are often problematic in the perioperative setting. For example, ACE‐inhibitors may cause vasoplegia during anesthetic administration, commonly manifested as hypotension during induction.[3] This hemodynamic alteration has been viewed as being so precarious, that some authors recommend withholding ACE‐inhibitors prior to major cardiovascular procedures such as coronary artery bypass grafting.[4] Although hypotension leads to management challenges (often increasing vasoconstrictor requirements), several studies report that ACE‐inhibitor use during surgery may also be associated with increased risks of acute kidney injury and mortality.[5, 6] However, despite these data, existing literature has not shown a consistent association between ACE‐inhibitor use and adverse postoperative outcomes. For example, a propensity‐matched cohort study of 79,228 patients at the Cleveland Clinic found no difference in hemodynamic characteristics, vasopressor requirements, or cardiorespiratory complications among patients who were or were not using ACE‐inhibitors during noncardiac surgery.[7] Furthermore, some research has also found that withdrawal of ACE‐inhibitors may itself lead to harm. For instance, a contemporary study reported that withdrawal of ACE‐inhibitor therapy in patients undergoing coronary artery bypass was associated with increased in‐hospital cardiovascular events.[8] Given this uncertainty, it is not surprising that management of ACE‐inhibitors in the perioperative period remains a subject of ongoing controversy with clinical reviews often recommending consideration of the risks and benefits associated with use of these agents.[9]

It is important to note that driver of this ambiguity is the very design of relevant studies. For instance, studies that focus on patients undergoing coronary artery bypass grafting surgery have limited external validity, as these patients are very different from those who undergo elective hip or knee replacement (such as those included by Nielsen and colleagues). Additionally, many studies suffer from methodological constraints or biases. For instance, retrospective observational studies often suffer from selection bias and residual confounding; that is, the individuals chosen for inclusion in the study and the variables available for analysis are often limited by available data, curtailing the conclusions that can be generated. Although the use of multivariable regression or propensity score techniques helps address these limitations, residual confounding by unmeasured variables always remains a threat to statistical inference. The potential influence for this bias is particularly relevant when examining the results of the study by Nielsen and colleagues. Another important limitation is survivor bias, a problem inherent in the study by Mudumbai and colleagues. Put simply, for a patient to resume ACE‐inhibitors after surgery, this same patient, must also survive for at least 15 to 30 days after surgery. Thus, for some patients, failure to resume this treatment may simply be a marker of early mortality rather than failure to resume the ACE itself. The potential influence of this bias is supported by an included sensitivity analysis, where a large change in the adjusted OR was observed when patients suffering early mortality were excluded. This swing in effect size suggests that biases related to comparing patients who survived to those who did not with respect to ACE use may, in part, account for the results of the study.

These limitations aside, the studies brought forth by both authors help inform practice with respect to the use of these agents during surgery. In this context, 3 paradigms are relevant for practicing hospitalists.

First, if a patient is maintained on an ACE‐inhibitor before surgery, should the medication be temporarily held before surgery to minimize hypotension during anesthesia? The study by Nielsen and colleagues (comparing those on ACE‐inhibitor treatment to those without), in addition to the evidence generated from other studies in this area[10, 11, 12] suggest that this is a rational decision. Although the existence of a withdrawal state from abrupt cessation of ACE‐inhibitor use is theoretically plausible, this has yet to be reliably reported in the literature. Given the short half‐life of most ACE‐inhibitors, cessation 24 hours before surgery appears to be the most pragmatic clinical approach.

Second, if a patient is on an ACE‐inhibitor before surgery, when should the medication be resumed after surgery? The findings from the study by Mudumbai and colleagues, in addition to contemporary evidence,[7, 8, 13] support the resumption of these agents as soon as possible following operative intervention. Once hemodynamic stability and volume status have been assured, risks associated with postoperative ACE‐inhibitor use appear to be outweighed by benefits, though specific care is likely necessary in those with preexisting renal dysfunction.[14] A program that ensures reconciliation of medications in the postoperative setting may be valuable in ensuring that such treatment is restarted.

Third, if a patient is not on ACE‐inhibitor therapy, should this be started before surgery for perioperative or long‐term benefit? Although neither study examines this issue, the potential for significant risk make this an unattractive option. Future interventional studies with thoughtfully weighed safety parameters may be necessary to assess whether such a paradigm may be valuable.

The studies included in this issue of the Journal of Hospital Medicine suggest that the use of ACE‐inhibitors during the perioperative period may be considered a function of time and place. Resuming ACE‐inhibitors and cessation of treatment at specific intervals in relation to surgery can help ensure positive outcomes. Hospitalists have an important role in this regard, as they are ideally situated to manage these agents in the many patients undergoing surgery across the United States.

Disclosures: Dr. Wijeysundera is supported by a Clinician‐Scientist Award from the Canadian Institutes of Health Research, and a Merit Award from the Department of Anesthesia at the University of Toronto. Dr. Chopra is supported by a Career‐Development Award (1K08HS022835‐01) from the Agency of Healthcare Research and Quality.

Perioperative medication management requires careful consideration, because surgical patients, especially older ones, may be receiving multiple medications for the treatment of acute or chronic comorbidities.[1] Because patients often present to surgery stabilized on their drug regimens, nonresumption of medications for chronic conditions may be problematic in controlling underlying diseases.[2] For example, nonresumption of cardiovascular medications such as ‐blockers postoperatively has been shown to lead to increased longer‐term mortality.[3] Little data, however, exist to guide practitioners on the postoperative management risks for another widely used class of cardiovascular medication: angiotensin‐converting enzyme inhibitors (ACE‐Is).[4]

About 170 million prescriptions for an ACE‐I are dispensed in the United States annually, which reflects a multiple criteria for their use including hypertension, heart failure, ischemic heart disease, coronary disease risk, diabetes mellitus, chronic kidney disease, recurrent stroke prevention, and vascular disease.[5, 6, 7] ACE‐Is have been shown to improve outcomes in patients with ischemic heart disease and heart failure.[8, 9] An observational study found that perioperative use of an ACE‐I in coronary artery bypass grafting (CABG) patients was associated with increased mortality, use of vasopressors, and postoperative acute renal failure.[10] Data also indicate that patients who continue the use of an ACE‐I perioperatively can experience severe hypotension.[11] As a result, some have recommended that consideration be given to not restarting the ACE‐I perioperatively, especially with hypertensive patients undergoing noncardiac surgery.[12] However, little evidence exists to document benefits and risks of not restarting an ACE‐I in surgical patients for various intervals. To evaluate these risks, we tested the hypothesis that postoperative nonresumption of an ACE‐I occurs frequently for broad cohorts of Veterans Affairs (VA) surgery patients within the first 14 days and is associated with increased 30‐day mortality.

MATERIALS AND METHODS

After institutional review board approval (University of California, San Francisco), we examined surgeries conducted at hospitals at 120 stations within the VA Health Care System (VAHCS). The VAHCS is the largest integrated healthcare system in the United States, with long‐standing electronic medical records capturing detailed demographic, pharmacy, and mortality information.[13] Data were extracted from Medical Statistical Analysis System (SAS) and Corporate Data Warehouse (CDW) files in the VA Informatics and Computing Infrastructure.[14]

Development of the Study Population

To identify surgery patients who were consistently prescribed an ACE‐I preoperatively (Figure 1), we first located 1,213,086 surgical admissions in 846,454 patients from 1999 to 2012 using Medical SAS files and classified them by specialty of the surgeon (eg, neurosurgery, orthopedic, urology, cardiothoracic, general, vascular, plastic, and other [such as gynecology]). We identified comorbidities and cardiovascular risk factors from inpatient/outpatient diagnosis files in the CDW using International Classification of Diseases (ICD‐9) diagnosis codes (see Supporting Information, Tables 1 and 2, in the online version of this article). To ensure chronic preoperative ACE‐I use, we included surgeries with 3 outpatient prescription fills of an ACE‐I and <180‐day gap. ACE‐Is included benazepril, captopril, enalapril, fosinopril, lisinopril, perindopril, quinapril, and ramipril. We excluded cases with a surgery in the prior 90 days and missing diagnosis codes. Our final population was comprised of 294,505 surgical admissions in 240,978 patients.

Figure 1

Table 1.Demographics and Risk Factors of the Study Sample Stratified by Mortality at 30 Days

Parameter	Surgeries, No. (%), Total=294,505	Died by 30‐Days, Total=9,227	P Value
NOTE: Abbreviations: ACE‐I, angiotensin‐converting enzyme inhibitor a No restart (014 days)=no ACE‐I from postoperative day 0 to 14. b Restart (014 days)=angiotensin converting enzyme inhibitors (ACE‐I) restarted from postoperative day 0 to 14. c Restart (1530 days)=ACE‐I restarted from postoperative day 15 to 30. Patients may have more than 1 potential indication for use of an ACE‐I. d Coronary disease risk is defined as the presence of 2 or more of the following heart disease risk factors: acute myocardial infarction, cardiovascular disease, chronic heart failure, hypertension, hyperlipidemia, diabetes with or without complications, smoking, age >60 years. e Comorbidities were aggregated using an approach reported by Gagne et al. that combines the Charlson and Elixhauser measures. f Preoperative ACE‐I gap was defined as the number of days without a fill of an ACE‐I prescription. g Center surgical volume quartiles were defined using the total number of surgeries done at a hospital for the study period (19992012). h Center restart quartiles were defined using the total number of surgery patients who were restarted on their ACE‐I by 14 days at a hospital for the study period. i Minor complications were based on the presence of 1 or more of the following complications: arrhythmia, postoperative bleeding, deep venous thrombosis, pneumonia, pulmonary embolism, sepsis, and urinary tract infection. j Major complications were based on the presence of 1 or more of the following complications: myocardial infarction, renal failure, and stroke.
No restart, 014 daysa	59,949 (20%)	7.3%	<0.001
Restart, 014 daysb	220,317 (75%)	2.1%
Restart, 1530 daysc	14,239 (5%)	1.7%
Age, y
<60	74,326 (14%)	1.7%	<0.001
6170	97,731 (24%)	2.3%
7190	119,775 (60%)	4.6%
>90	2,673 (1%)	6.9%
Gender
Female	7,186 (2%)	1.6%	<0.001
Male	287,319 (98%)	3.2%
Indications for use of ACE‐I
Hypertension	270,486 (92%)	2.8%	<0.001
Ischemic heart disease	129,212 (44%)	3.8%	<0.001
Vascular disease	75,410 (26%)	3.7%	<0.001
Heart failure	59,809 (20%)	5.7%	<0.001
Chronic kidney disease	8,804 (3%)	4.9%	<0.001
Diabetes mellitus	170,320 (58%)	3.0%	<0.001
Coronary disease riskd	280,958 (95%)	3.1%	<0.001
Stroke	22,285 (8%)	5.2%	<0.001
Comorbidity scoree
0	72,126 (24%)	1.4%	<0.001
1	59,609 (20%)	1.5%
2 4	116,914 (40%)	3.5%
>4	45,856 (16%)	7.0%
Preoperative ACE‐I gap, daysf
045	21,383 (7%)	3.7%	<0.001
4690	30,237 (10%)	3.8%
91180	242,885 (83%)	3.0%
Surgical specialty
General	98,210 (33%)	4.6%	<0.001
Neurosurgery	15,423 (5%)	2.3%
Orthopedic	51,600 (18%)	1.9%
Plastic	12,547 (4%)	3.8%
Thoracic	44,728 (15%)	3.2%
Urology	34,595 (12%)	1.5%
Vascular	34,228 (12%)	2.8%
Other (gynecology)	3,174 (1%)	1.4%
Year of surgery
19992002	66,689 (23%)	4.2%	<0.001
20032005	75,420 (26%)	3.4%
20062008	76,563 (26%)	2.8%
20092012	75,833 (26%)	2.2%
No. of prior surgeries
0	215,443 (74%)	3.2%	0.413
1	56,419 (19%)	3.1%
2	22,643 (7%)	3.1%
Length of stay, d
1	40,538 (14%)	1.4%	<0.001
23	59,817 (20%)	1.4%
47	83,366 (28%)	2.0%
821	83,379 (28%)	4.7%
>21	27,405 (9%)	8.0%
Center surgical volume quartileg
0%25%	74,846 (25%)	3.7%	<0.001
25%50%	74,569 (25%)	3.1%
50%75%	69,947 (24%)	2.8%
75%100%	75,143 (26%)	2.8%
Center restart quartileh
0%25%	73,750 (25%)	3.1%	0.014
25%50%	81,071 (28%)	3.0%
50%75%	83,952 (29%)	3.3%
75%100%	55,732 (19%)	3.2%
No complication	80,700 (27%)	1.3%	<0.001
Minor complicationi	181,924 (62%)	4.2%	<0.001
Major complicationj	46,977 (16%)	8.3%	<0.001
Complications
Arrhythmia	3,037 (1%)	2.0%	<0.001
Bleeding	12,887 (4%)	4.8%	<0.001
Deep venous thrombosis	6,075 (2%)	3.6%	<0.001
Myocardial infarction	9,114 (3%)	7.7%	<0.001
Pneumonia	109,660 (37%)	5.1%	<0.001
Pulmonary embolism	5,064 (2%)	6.2%	<0.001
Renal failure	25,513 (9%)	11.0%	<0.001
Sepsis	5,846 (2%)	16.5%	<0.001
Stroke	19,546 (7%)	5.0%	<0.001
Urinary tract infection	32,548 (11%)	4.9%	<0.001

Table 2.Risk of 30‐day Mortality Associated With No Restart vs Restart of an ACE‐I

Unadjusted Hazard for 30‐Day Mortality (OR [95% CI])			Adjusted hazard for 30 day mortality (OR [95% CI])
Restart (014 Days) (Referent)a	No Restart, 014 Daysb	Restart, 1530 Daysc	Restart, 014 Days (Referent)	No Restart, 014 Days	Restart, 1530 Days
NOTE: Abbreviations: ACE‐I, angiotensin‐converting enzyme inhibitors; CI, confidence interval, NA, nonapplicable; OR, odds ratio. a Restart (014 days)=ACE‐I restarted from postoperative day 0 to 14. b No restart (014 days)=no ACE‐I from postoperative day 0 to 14. c Restart (1530 days)=ACE‐I restarted from postoperative day 15 to 30. d All P values were statistically significant (P<0.001). Restart day 1530 was not included in this model.
1	3.44 (3.303.60)d	0.23 (0.200.26)d	1	2.79 (2.672.92)d	0.24 (0.210.28)d
Restart, 014 Days (Referent)	No Restart, 014 Days	NA	Restart, 014 Days (Referent)	No Restart, 014 Days	NA
1	2.92 (2.803.05)d	NA27	1	2.39 (2.292.50)d	NA27

Postoperative Medication Use

We defined patients as postoperative restart (014 days) if an ACE‐I was administered in‐hospital (oral or intravenous) or a postdischarge outpatient ACE‐I prescription was filled in the 14 days following surgery. In absence of ACE‐I administration or prescription during postoperative days 0 to 14, patients were classified as no restart (014 days). Intraclass changes from one ACE‐I to another were considered a restart if they occurred within 0 to 14 days of surgery. We also tracked ACE‐I prescription fills through postoperative day 15 to 30 (ie, restart [1530 days]) and noted administration or filling of oral medications. Oral medications were classified as tablets or caplets in formularies.

Patient Characteristics

We categorized patients by age strata: <60, 61 to 70, 71 to 90, and >90 years old; gender; and epochs (every 34 years starting from calendar year 1999). We tracked prior surgery admissions and length of stay.

Hospital Factors

To account for clustering of surgeries and hospital‐related factors affecting ACE‐I use practices, we divided hospitals into quartiles of (1) total surgical volume based on total number of surgeries done at a hospital from 1999 to 2012 (0%25%, n<2378; 50%, n=3498; 75%, n=4531; highest surgical volume, 8162); and (2) percent of cases restarted on ACE‐I at 14 days (71%, 76%, 79%, and 100%).

Indications, Patient Illness Severity, and Complications

We determined probable indications for ACE‐I usage (ie, heart failure) and comorbidities using ICD‐9 codes in medical records prior to surgical admissions (see Supporting Information, Tables 1 and 2, in the online version of this article). Comorbidities were aggregated using algorithms developed by Gagne aggregating comorbidity conditions (defined by Elixhauser) into scores similar to Charlson scores.[15] The Gagne score has higher correlation with 30‐day, 90‐day, 180‐day, and 1‐year mortality than Charlson scores.[15]

After evaluating secondary diagnosis codes in the clinic or hospital visits prior to surgery date, complications were defined using codes newly incident after surgery and up to 90 days following discharge. We organized complications into major and minor. Major complications were myocardial infarction, renal failure, and stroke; minor complications included arrhythmia, postoperative bleeding, deep venous thrombosis, pneumonia, pulmonary embolism, sepsis, and urinary tract infection.

Mortality

Deaths were ascertained from VA Vital Status files.

RESULTS

Table 1 describes the characteristics and 30‐day mortality rates for our cohort. By postoperative day 14, 75% of the study sample (n=220,317) had restarted an ACE‐I (Figure 1). Our sample consisted primarily of older men with a substantial comorbidity burden and multiple indications for an ACE‐I. Most patients had 1 surgical episode, with the largest fraction undergoing general surgery overall. A third of the cases had lengths of stay >1 week, and surgeries occurred throughout the study period. The largest number of surgeries was noted for centers in 75% to 100% surgical volume and 50% to 75% restart quartiles. Most surgeries had no or minor complications.

The no restart (014 days) group had a higher 30‐day mortality rate (7.3%) compared to those who restarted by postoperative day 14 (2.1%) or 30 (1.7%). The highest mortality rates were found in patients aged >90 years, with a >4 comorbidity index or hospital stays >3 weeks, and those experiencing major postoperative complications.

DISCUSSION

The results from this national retrospective study confirm our hypothesis that nonresumption of an ACE‐I for 14 or more postoperative days occurs frequently for VA surgery patients. However, we found that nonresumption of an ACE‐I during the first 2 weeks after surgery is independently associated with increased 30‐day mortality. Our study is one of the first to examine the patterns and risks of postoperative ACE‐I management across a large and varied surgical population.[11, 17]

The lack of inpatient and outpatient ACE‐I prescription use by postoperative day 14 across multiple surgery classes suggests that surgical patients may be prone to short‐term nonresumption of an ACE‐I. Our intention in using a 14‐day window to evaluate restarting strategies was to account for immediate postoperative management. After surgery, careful appraisal of whether medications should be restarted is often necessary in the face of substantially deranged physiology, hypercoagulability, and blood loss.[18] After physiologic stabilization over several days, cardiovascular drugs are usually restarted thereafter to help manage chronic comorbidities.[19] One immediate conclusion from our findings is that ACE‐I are commonly discontinued perioperatively (potentially due to concerns for hypotension), and are often not restarted.[20, 21, 22, 23, 24, 25]

Our rates of ACE‐I nonresumption are comparable to rates of nonresumption reported postoperatively for other medications and raise concerns for inadequate medication reconciliation in surgical cohorts. Bell et al. conducted a population‐based cohort study of patients undergoing elective surgery and found that 11.4% of 45,220 patients chronically prescribed warfarin were not restarted by postoperative day 180.[22] A subsequent study showed intensive care unit (ICU) admission was associated with increased rates of not restarting 4 of 5 medication groups (range, 4.5%19.4%; statins, antiplatelet/anticoagulant agents, levothyroxine, respiratory inhalers, and gastric acid‐suppressing drugs).[21] One‐year follow‐up showed elevated odds for the secondary composite outcome of death in the statins group (odds ratio [OR]: 1.07; 95% CI: 1.03‐1.11) and antiplatelet/anticoagulant agents group (OR: 1.10; 95% CI: 1.03‐1.16). Drenger et al. noted a 50% rate for no restart of ACE‐I after CABG surgery; restarting was associated with a decreased composite outcome of cardiac, cerebral, and renal events and in‐hospital mortality (OR: 0.50; 95% CI: 0.38‐0.66).[26] Because medication management has been noted to be problematic at care transitions, the inpatient medication reconciliation recommendations articulated in recent Joint Commission National Patient Safety Goals may be particularly relevant for high‐risk surgical patients who experience multiple transitions of care (ie, operating room to ICU to surgical ward to rehabilitation unit to discharge).[19, 24, 27]

In examining the crucial interval for the surgical patientthe postoperative period when medication changes are commonwe found a nearly 2.5‐fold increase in risk for 30‐day mortality associated with nonresumption of an ACE‐I.[4, 19, 28] We also noted that those who were restarted later on day 15 to 30 fared better than those not restarted (Table 2). Similar effect sizes have been found with postoperative nonresumption of other cardiovascular medications. Not restarting chronic ‐blocker treatment after surgery is associated with a significant 1‐year mortality risk (HR: 2.7; 95% CI: 1.25.9).[29] Postoperative statin withdrawal (>4 days) is an independent predictor of postoperative myonecrosis (OR: 2.9; 95% CI: 1.6‐5.5).[30, 31] Biologic mechanisms contributing to mortality after a temporary failure to restart an ACE‐I are speculative and were not addressed in this study. Potential mechanisms may lie with hypertensive rebound and associated cardiac decompensation. Withdrawing an ACE‐I can cause rapid increases in blood pressure within 48 hours on home self‐measured blood pressure in hypertensive patients and in diabetic patients with chronic renal failure.[32, 33] Patients with heart failure or coronary artery disease may then experience myocardial ischemia in the context of elevated blood pressure. Not restarting an ACE‐I may also lead to compromised microcirculatory flow with renal complications and mortality.[34, 35]

Alternative explanations for the magnitude of our findings may lie with unmeasured confounders. Our analysis did not evaluate potential interactions arising from the failure to restart of all other medications (eg, ‐blockers) or evaluate changes to angiotensin receptor blockers (ARBs). In addition, our study lacked data on health system variations or emergent versus elective surgeries. However, a key starting point of our analysis was distinguishing between purposeful versus potentially unintentional nonresumption of an ACE‐I. To accomplish this, we included patients who had at least 3 prescription ACE‐I fills prior to surgery, evaluated the preoperative indications for an ACE‐I and the ability to take postoperative oral medications (eg, immortal time bias), and accounted for minor and major postoperative complications.

To address bias from unmeasured confounders, we conducted sensitivity analyses in more homogeneous subpopulations. With each sensitivity analysis, we found consistently strong associations between increased 30‐day mortality and nonresumption of an ACE‐I (Table 3). Strong effects were observed in patients without major complications and with low comorbidity burdens, patients in whom we would not expect an effect. Because deaths in postoperative day 0 to 2 could be attributed to surgical factors (ie, hemorrhage) or that patients who did not restart an ACE‐I in postoperative day 0 to 14 were too sick to tolerate oral medications, we excluded these patients along with patients who died before postoperative day 14. Both sensitivity analyses maintained our primary finding. Somewhat attenuated risks were found when we examined ACE‐I nonresumption by individual surgery types, perhaps reflective of differences in comorbidity burden.

Finally, although this study did not examine predictors of nonresumption, our models showed that in the context of postoperative ACE‐I management, factors including increasing age, being male, those with heart failure, and surgeries conducted in centers with low surgical volume were associated with increased 30‐day mortality (Table 4). Future research might consider how reinstitution of an ACE‐I occurs in these subpopulations to identify potential mechanisms for nonresumption.

Our study has several strengths. We examined patients over a decade, considered all major types of surgery, and studied patients across a healthcare system. Moreover, we used computerized prescription data and medical records (eg, discharge diagnosis, ICD‐9 codes) to derive risk factors. VA prescription data are standardized and accurate because of intensive efforts to contain costs.[36] Within VA data, the estimated sensitivity of computerized diagnoses exceeds 80% in the administrative files, with specificity of 91% to 100% for common diagnoses such as coronary artery disease.[37] These records also carefully and accurately identify death.[38]

We also identified potential limitations to our study. First, a retrospective, observational, cohort study may be prone to selection bias, and therefore we report associations that are not necessarily causal relationships. However, our methods are supported by the fact that we developed a large study sample consisting of consecutive surgical patients over a decade and noted large effect sizes across multiple subpopulations. Second, for group assignment, we used prescription records rather than medication administration data. Nevertheless, a cohort analysis focusing on exposure is standard for epidemiologic studies and shows outcomes of care resulting from daily clinical practice.[39] Third, we did not study the cause of death, data that may help to identify potential causal pathways between not restarting an ACE‐I and mortality. Fourth, our results come from VA medical centers and so may not be generalizable to non‐VA institutions. However, the length of observation under conditions of routine clinical practice at multiple medical centers and a diverse set of surgical procedures support the external validity of our study results. Fifth, we did not have clinical data accounting for surgeon‐level effects potentially affecting rates of nonresumption of an ACE‐I, American Society of Anesthesiology physical status, information on perioperative hypotension or vasopressors, or the presence of a postoperative primary care visit.

In conclusion, in the VA Healthcare System, temporary nonresumption of an ACE‐I is common. Postoperative nonresumption of an ACE‐I, although sometimes indicated and appropriate, is associated with increased risk of mortality. Careful attention to the issue of eventual reinstitution of medications for chronic conditions, such as an ACE‐I, is indicated to avoid unnecessary mortality. Because early experience showed that dose titration was a key for successful application of an ACE‐I, practitioners may also need to consider dose modification rather than simply continuation or not restarting.[40] Future research is needed to confirm our results in other healthcare systems and to define mechanisms that link postoperative nonresumption of an ACE‐I to mortality.

Perioperative medication management requires careful consideration, because surgical patients, especially older ones, may be receiving multiple medications for the treatment of acute or chronic comorbidities.[1] Because patients often present to surgery stabilized on their drug regimens, nonresumption of medications for chronic conditions may be problematic in controlling underlying diseases.[2] For example, nonresumption of cardiovascular medications such as ‐blockers postoperatively has been shown to lead to increased longer‐term mortality.[3] Little data, however, exist to guide practitioners on the postoperative management risks for another widely used class of cardiovascular medication: angiotensin‐converting enzyme inhibitors (ACE‐Is).[4]

About 170 million prescriptions for an ACE‐I are dispensed in the United States annually, which reflects a multiple criteria for their use including hypertension, heart failure, ischemic heart disease, coronary disease risk, diabetes mellitus, chronic kidney disease, recurrent stroke prevention, and vascular disease.[5, 6, 7] ACE‐Is have been shown to improve outcomes in patients with ischemic heart disease and heart failure.[8, 9] An observational study found that perioperative use of an ACE‐I in coronary artery bypass grafting (CABG) patients was associated with increased mortality, use of vasopressors, and postoperative acute renal failure.[10] Data also indicate that patients who continue the use of an ACE‐I perioperatively can experience severe hypotension.[11] As a result, some have recommended that consideration be given to not restarting the ACE‐I perioperatively, especially with hypertensive patients undergoing noncardiac surgery.[12] However, little evidence exists to document benefits and risks of not restarting an ACE‐I in surgical patients for various intervals. To evaluate these risks, we tested the hypothesis that postoperative nonresumption of an ACE‐I occurs frequently for broad cohorts of Veterans Affairs (VA) surgery patients within the first 14 days and is associated with increased 30‐day mortality.

MATERIALS AND METHODS

After institutional review board approval (University of California, San Francisco), we examined surgeries conducted at hospitals at 120 stations within the VA Health Care System (VAHCS). The VAHCS is the largest integrated healthcare system in the United States, with long‐standing electronic medical records capturing detailed demographic, pharmacy, and mortality information.[13] Data were extracted from Medical Statistical Analysis System (SAS) and Corporate Data Warehouse (CDW) files in the VA Informatics and Computing Infrastructure.[14]

Development of the Study Population

To identify surgery patients who were consistently prescribed an ACE‐I preoperatively (Figure 1), we first located 1,213,086 surgical admissions in 846,454 patients from 1999 to 2012 using Medical SAS files and classified them by specialty of the surgeon (eg, neurosurgery, orthopedic, urology, cardiothoracic, general, vascular, plastic, and other [such as gynecology]). We identified comorbidities and cardiovascular risk factors from inpatient/outpatient diagnosis files in the CDW using International Classification of Diseases (ICD‐9) diagnosis codes (see Supporting Information, Tables 1 and 2, in the online version of this article). To ensure chronic preoperative ACE‐I use, we included surgeries with 3 outpatient prescription fills of an ACE‐I and <180‐day gap. ACE‐Is included benazepril, captopril, enalapril, fosinopril, lisinopril, perindopril, quinapril, and ramipril. We excluded cases with a surgery in the prior 90 days and missing diagnosis codes. Our final population was comprised of 294,505 surgical admissions in 240,978 patients.

Figure 1

Table 1.Demographics and Risk Factors of the Study Sample Stratified by Mortality at 30 Days

Parameter	Surgeries, No. (%), Total=294,505	Died by 30‐Days, Total=9,227	P Value
NOTE: Abbreviations: ACE‐I, angiotensin‐converting enzyme inhibitor a No restart (014 days)=no ACE‐I from postoperative day 0 to 14. b Restart (014 days)=angiotensin converting enzyme inhibitors (ACE‐I) restarted from postoperative day 0 to 14. c Restart (1530 days)=ACE‐I restarted from postoperative day 15 to 30. Patients may have more than 1 potential indication for use of an ACE‐I. d Coronary disease risk is defined as the presence of 2 or more of the following heart disease risk factors: acute myocardial infarction, cardiovascular disease, chronic heart failure, hypertension, hyperlipidemia, diabetes with or without complications, smoking, age >60 years. e Comorbidities were aggregated using an approach reported by Gagne et al. that combines the Charlson and Elixhauser measures. f Preoperative ACE‐I gap was defined as the number of days without a fill of an ACE‐I prescription. g Center surgical volume quartiles were defined using the total number of surgeries done at a hospital for the study period (19992012). h Center restart quartiles were defined using the total number of surgery patients who were restarted on their ACE‐I by 14 days at a hospital for the study period. i Minor complications were based on the presence of 1 or more of the following complications: arrhythmia, postoperative bleeding, deep venous thrombosis, pneumonia, pulmonary embolism, sepsis, and urinary tract infection. j Major complications were based on the presence of 1 or more of the following complications: myocardial infarction, renal failure, and stroke.
No restart, 014 daysa	59,949 (20%)	7.3%	<0.001
Restart, 014 daysb	220,317 (75%)	2.1%
Restart, 1530 daysc	14,239 (5%)	1.7%
Age, y
<60	74,326 (14%)	1.7%	<0.001
6170	97,731 (24%)	2.3%
7190	119,775 (60%)	4.6%
>90	2,673 (1%)	6.9%
Gender
Female	7,186 (2%)	1.6%	<0.001
Male	287,319 (98%)	3.2%
Indications for use of ACE‐I
Hypertension	270,486 (92%)	2.8%	<0.001
Ischemic heart disease	129,212 (44%)	3.8%	<0.001
Vascular disease	75,410 (26%)	3.7%	<0.001
Heart failure	59,809 (20%)	5.7%	<0.001
Chronic kidney disease	8,804 (3%)	4.9%	<0.001
Diabetes mellitus	170,320 (58%)	3.0%	<0.001
Coronary disease riskd	280,958 (95%)	3.1%	<0.001
Stroke	22,285 (8%)	5.2%	<0.001
Comorbidity scoree
0	72,126 (24%)	1.4%	<0.001
1	59,609 (20%)	1.5%
2 4	116,914 (40%)	3.5%
>4	45,856 (16%)	7.0%
Preoperative ACE‐I gap, daysf
045	21,383 (7%)	3.7%	<0.001
4690	30,237 (10%)	3.8%
91180	242,885 (83%)	3.0%
Surgical specialty
General	98,210 (33%)	4.6%	<0.001
Neurosurgery	15,423 (5%)	2.3%
Orthopedic	51,600 (18%)	1.9%
Plastic	12,547 (4%)	3.8%
Thoracic	44,728 (15%)	3.2%
Urology	34,595 (12%)	1.5%
Vascular	34,228 (12%)	2.8%
Other (gynecology)	3,174 (1%)	1.4%
Year of surgery
19992002	66,689 (23%)	4.2%	<0.001
20032005	75,420 (26%)	3.4%
20062008	76,563 (26%)	2.8%
20092012	75,833 (26%)	2.2%
No. of prior surgeries
0	215,443 (74%)	3.2%	0.413
1	56,419 (19%)	3.1%
2	22,643 (7%)	3.1%
Length of stay, d
1	40,538 (14%)	1.4%	<0.001
23	59,817 (20%)	1.4%
47	83,366 (28%)	2.0%
821	83,379 (28%)	4.7%
>21	27,405 (9%)	8.0%
Center surgical volume quartileg
0%25%	74,846 (25%)	3.7%	<0.001
25%50%	74,569 (25%)	3.1%
50%75%	69,947 (24%)	2.8%
75%100%	75,143 (26%)	2.8%
Center restart quartileh
0%25%	73,750 (25%)	3.1%	0.014
25%50%	81,071 (28%)	3.0%
50%75%	83,952 (29%)	3.3%
75%100%	55,732 (19%)	3.2%
No complication	80,700 (27%)	1.3%	<0.001
Minor complicationi	181,924 (62%)	4.2%	<0.001
Major complicationj	46,977 (16%)	8.3%	<0.001
Complications
Arrhythmia	3,037 (1%)	2.0%	<0.001
Bleeding	12,887 (4%)	4.8%	<0.001
Deep venous thrombosis	6,075 (2%)	3.6%	<0.001
Myocardial infarction	9,114 (3%)	7.7%	<0.001
Pneumonia	109,660 (37%)	5.1%	<0.001
Pulmonary embolism	5,064 (2%)	6.2%	<0.001
Renal failure	25,513 (9%)	11.0%	<0.001
Sepsis	5,846 (2%)	16.5%	<0.001
Stroke	19,546 (7%)	5.0%	<0.001
Urinary tract infection	32,548 (11%)	4.9%	<0.001

Table 2.Risk of 30‐day Mortality Associated With No Restart vs Restart of an ACE‐I

Unadjusted Hazard for 30‐Day Mortality (OR [95% CI])			Adjusted hazard for 30 day mortality (OR [95% CI])
Restart (014 Days) (Referent)a	No Restart, 014 Daysb	Restart, 1530 Daysc	Restart, 014 Days (Referent)	No Restart, 014 Days	Restart, 1530 Days
NOTE: Abbreviations: ACE‐I, angiotensin‐converting enzyme inhibitors; CI, confidence interval, NA, nonapplicable; OR, odds ratio. a Restart (014 days)=ACE‐I restarted from postoperative day 0 to 14. b No restart (014 days)=no ACE‐I from postoperative day 0 to 14. c Restart (1530 days)=ACE‐I restarted from postoperative day 15 to 30. d All P values were statistically significant (P<0.001). Restart day 1530 was not included in this model.
1	3.44 (3.303.60)d	0.23 (0.200.26)d	1	2.79 (2.672.92)d	0.24 (0.210.28)d
Restart, 014 Days (Referent)	No Restart, 014 Days	NA	Restart, 014 Days (Referent)	No Restart, 014 Days	NA
1	2.92 (2.803.05)d	NA27	1	2.39 (2.292.50)d	NA27

Postoperative Medication Use

We defined patients as postoperative restart (014 days) if an ACE‐I was administered in‐hospital (oral or intravenous) or a postdischarge outpatient ACE‐I prescription was filled in the 14 days following surgery. In absence of ACE‐I administration or prescription during postoperative days 0 to 14, patients were classified as no restart (014 days). Intraclass changes from one ACE‐I to another were considered a restart if they occurred within 0 to 14 days of surgery. We also tracked ACE‐I prescription fills through postoperative day 15 to 30 (ie, restart [1530 days]) and noted administration or filling of oral medications. Oral medications were classified as tablets or caplets in formularies.

Patient Characteristics

We categorized patients by age strata: <60, 61 to 70, 71 to 90, and >90 years old; gender; and epochs (every 34 years starting from calendar year 1999). We tracked prior surgery admissions and length of stay.

Hospital Factors

To account for clustering of surgeries and hospital‐related factors affecting ACE‐I use practices, we divided hospitals into quartiles of (1) total surgical volume based on total number of surgeries done at a hospital from 1999 to 2012 (0%25%, n<2378; 50%, n=3498; 75%, n=4531; highest surgical volume, 8162); and (2) percent of cases restarted on ACE‐I at 14 days (71%, 76%, 79%, and 100%).

Indications, Patient Illness Severity, and Complications

We determined probable indications for ACE‐I usage (ie, heart failure) and comorbidities using ICD‐9 codes in medical records prior to surgical admissions (see Supporting Information, Tables 1 and 2, in the online version of this article). Comorbidities were aggregated using algorithms developed by Gagne aggregating comorbidity conditions (defined by Elixhauser) into scores similar to Charlson scores.[15] The Gagne score has higher correlation with 30‐day, 90‐day, 180‐day, and 1‐year mortality than Charlson scores.[15]

After evaluating secondary diagnosis codes in the clinic or hospital visits prior to surgery date, complications were defined using codes newly incident after surgery and up to 90 days following discharge. We organized complications into major and minor. Major complications were myocardial infarction, renal failure, and stroke; minor complications included arrhythmia, postoperative bleeding, deep venous thrombosis, pneumonia, pulmonary embolism, sepsis, and urinary tract infection.

Mortality

Deaths were ascertained from VA Vital Status files.

RESULTS

Table 1 describes the characteristics and 30‐day mortality rates for our cohort. By postoperative day 14, 75% of the study sample (n=220,317) had restarted an ACE‐I (Figure 1). Our sample consisted primarily of older men with a substantial comorbidity burden and multiple indications for an ACE‐I. Most patients had 1 surgical episode, with the largest fraction undergoing general surgery overall. A third of the cases had lengths of stay >1 week, and surgeries occurred throughout the study period. The largest number of surgeries was noted for centers in 75% to 100% surgical volume and 50% to 75% restart quartiles. Most surgeries had no or minor complications.

The no restart (014 days) group had a higher 30‐day mortality rate (7.3%) compared to those who restarted by postoperative day 14 (2.1%) or 30 (1.7%). The highest mortality rates were found in patients aged >90 years, with a >4 comorbidity index or hospital stays >3 weeks, and those experiencing major postoperative complications.

DISCUSSION

The results from this national retrospective study confirm our hypothesis that nonresumption of an ACE‐I for 14 or more postoperative days occurs frequently for VA surgery patients. However, we found that nonresumption of an ACE‐I during the first 2 weeks after surgery is independently associated with increased 30‐day mortality. Our study is one of the first to examine the patterns and risks of postoperative ACE‐I management across a large and varied surgical population.[11, 17]

The lack of inpatient and outpatient ACE‐I prescription use by postoperative day 14 across multiple surgery classes suggests that surgical patients may be prone to short‐term nonresumption of an ACE‐I. Our intention in using a 14‐day window to evaluate restarting strategies was to account for immediate postoperative management. After surgery, careful appraisal of whether medications should be restarted is often necessary in the face of substantially deranged physiology, hypercoagulability, and blood loss.[18] After physiologic stabilization over several days, cardiovascular drugs are usually restarted thereafter to help manage chronic comorbidities.[19] One immediate conclusion from our findings is that ACE‐I are commonly discontinued perioperatively (potentially due to concerns for hypotension), and are often not restarted.[20, 21, 22, 23, 24, 25]

Our rates of ACE‐I nonresumption are comparable to rates of nonresumption reported postoperatively for other medications and raise concerns for inadequate medication reconciliation in surgical cohorts. Bell et al. conducted a population‐based cohort study of patients undergoing elective surgery and found that 11.4% of 45,220 patients chronically prescribed warfarin were not restarted by postoperative day 180.[22] A subsequent study showed intensive care unit (ICU) admission was associated with increased rates of not restarting 4 of 5 medication groups (range, 4.5%19.4%; statins, antiplatelet/anticoagulant agents, levothyroxine, respiratory inhalers, and gastric acid‐suppressing drugs).[21] One‐year follow‐up showed elevated odds for the secondary composite outcome of death in the statins group (odds ratio [OR]: 1.07; 95% CI: 1.03‐1.11) and antiplatelet/anticoagulant agents group (OR: 1.10; 95% CI: 1.03‐1.16). Drenger et al. noted a 50% rate for no restart of ACE‐I after CABG surgery; restarting was associated with a decreased composite outcome of cardiac, cerebral, and renal events and in‐hospital mortality (OR: 0.50; 95% CI: 0.38‐0.66).[26] Because medication management has been noted to be problematic at care transitions, the inpatient medication reconciliation recommendations articulated in recent Joint Commission National Patient Safety Goals may be particularly relevant for high‐risk surgical patients who experience multiple transitions of care (ie, operating room to ICU to surgical ward to rehabilitation unit to discharge).[19, 24, 27]

In examining the crucial interval for the surgical patientthe postoperative period when medication changes are commonwe found a nearly 2.5‐fold increase in risk for 30‐day mortality associated with nonresumption of an ACE‐I.[4, 19, 28] We also noted that those who were restarted later on day 15 to 30 fared better than those not restarted (Table 2). Similar effect sizes have been found with postoperative nonresumption of other cardiovascular medications. Not restarting chronic ‐blocker treatment after surgery is associated with a significant 1‐year mortality risk (HR: 2.7; 95% CI: 1.25.9).[29] Postoperative statin withdrawal (>4 days) is an independent predictor of postoperative myonecrosis (OR: 2.9; 95% CI: 1.6‐5.5).[30, 31] Biologic mechanisms contributing to mortality after a temporary failure to restart an ACE‐I are speculative and were not addressed in this study. Potential mechanisms may lie with hypertensive rebound and associated cardiac decompensation. Withdrawing an ACE‐I can cause rapid increases in blood pressure within 48 hours on home self‐measured blood pressure in hypertensive patients and in diabetic patients with chronic renal failure.[32, 33] Patients with heart failure or coronary artery disease may then experience myocardial ischemia in the context of elevated blood pressure. Not restarting an ACE‐I may also lead to compromised microcirculatory flow with renal complications and mortality.[34, 35]

Alternative explanations for the magnitude of our findings may lie with unmeasured confounders. Our analysis did not evaluate potential interactions arising from the failure to restart of all other medications (eg, ‐blockers) or evaluate changes to angiotensin receptor blockers (ARBs). In addition, our study lacked data on health system variations or emergent versus elective surgeries. However, a key starting point of our analysis was distinguishing between purposeful versus potentially unintentional nonresumption of an ACE‐I. To accomplish this, we included patients who had at least 3 prescription ACE‐I fills prior to surgery, evaluated the preoperative indications for an ACE‐I and the ability to take postoperative oral medications (eg, immortal time bias), and accounted for minor and major postoperative complications.

To address bias from unmeasured confounders, we conducted sensitivity analyses in more homogeneous subpopulations. With each sensitivity analysis, we found consistently strong associations between increased 30‐day mortality and nonresumption of an ACE‐I (Table 3). Strong effects were observed in patients without major complications and with low comorbidity burdens, patients in whom we would not expect an effect. Because deaths in postoperative day 0 to 2 could be attributed to surgical factors (ie, hemorrhage) or that patients who did not restart an ACE‐I in postoperative day 0 to 14 were too sick to tolerate oral medications, we excluded these patients along with patients who died before postoperative day 14. Both sensitivity analyses maintained our primary finding. Somewhat attenuated risks were found when we examined ACE‐I nonresumption by individual surgery types, perhaps reflective of differences in comorbidity burden.

Finally, although this study did not examine predictors of nonresumption, our models showed that in the context of postoperative ACE‐I management, factors including increasing age, being male, those with heart failure, and surgeries conducted in centers with low surgical volume were associated with increased 30‐day mortality (Table 4). Future research might consider how reinstitution of an ACE‐I occurs in these subpopulations to identify potential mechanisms for nonresumption.

Our study has several strengths. We examined patients over a decade, considered all major types of surgery, and studied patients across a healthcare system. Moreover, we used computerized prescription data and medical records (eg, discharge diagnosis, ICD‐9 codes) to derive risk factors. VA prescription data are standardized and accurate because of intensive efforts to contain costs.[36] Within VA data, the estimated sensitivity of computerized diagnoses exceeds 80% in the administrative files, with specificity of 91% to 100% for common diagnoses such as coronary artery disease.[37] These records also carefully and accurately identify death.[38]

We also identified potential limitations to our study. First, a retrospective, observational, cohort study may be prone to selection bias, and therefore we report associations that are not necessarily causal relationships. However, our methods are supported by the fact that we developed a large study sample consisting of consecutive surgical patients over a decade and noted large effect sizes across multiple subpopulations. Second, for group assignment, we used prescription records rather than medication administration data. Nevertheless, a cohort analysis focusing on exposure is standard for epidemiologic studies and shows outcomes of care resulting from daily clinical practice.[39] Third, we did not study the cause of death, data that may help to identify potential causal pathways between not restarting an ACE‐I and mortality. Fourth, our results come from VA medical centers and so may not be generalizable to non‐VA institutions. However, the length of observation under conditions of routine clinical practice at multiple medical centers and a diverse set of surgical procedures support the external validity of our study results. Fifth, we did not have clinical data accounting for surgeon‐level effects potentially affecting rates of nonresumption of an ACE‐I, American Society of Anesthesiology physical status, information on perioperative hypotension or vasopressors, or the presence of a postoperative primary care visit.

In conclusion, in the VA Healthcare System, temporary nonresumption of an ACE‐I is common. Postoperative nonresumption of an ACE‐I, although sometimes indicated and appropriate, is associated with increased risk of mortality. Careful attention to the issue of eventual reinstitution of medications for chronic conditions, such as an ACE‐I, is indicated to avoid unnecessary mortality. Because early experience showed that dose titration was a key for successful application of an ACE‐I, practitioners may also need to consider dose modification rather than simply continuation or not restarting.[40] Future research is needed to confirm our results in other healthcare systems and to define mechanisms that link postoperative nonresumption of an ACE‐I to mortality.

Perioperative medication management requires careful consideration, because surgical patients, especially older ones, may be receiving multiple medications for the treatment of acute or chronic comorbidities.[1] Because patients often present to surgery stabilized on their drug regimens, nonresumption of medications for chronic conditions may be problematic in controlling underlying diseases.[2] For example, nonresumption of cardiovascular medications such as ‐blockers postoperatively has been shown to lead to increased longer‐term mortality.[3] Little data, however, exist to guide practitioners on the postoperative management risks for another widely used class of cardiovascular medication: angiotensin‐converting enzyme inhibitors (ACE‐Is).[4]

About 170 million prescriptions for an ACE‐I are dispensed in the United States annually, which reflects a multiple criteria for their use including hypertension, heart failure, ischemic heart disease, coronary disease risk, diabetes mellitus, chronic kidney disease, recurrent stroke prevention, and vascular disease.[5, 6, 7] ACE‐Is have been shown to improve outcomes in patients with ischemic heart disease and heart failure.[8, 9] An observational study found that perioperative use of an ACE‐I in coronary artery bypass grafting (CABG) patients was associated with increased mortality, use of vasopressors, and postoperative acute renal failure.[10] Data also indicate that patients who continue the use of an ACE‐I perioperatively can experience severe hypotension.[11] As a result, some have recommended that consideration be given to not restarting the ACE‐I perioperatively, especially with hypertensive patients undergoing noncardiac surgery.[12] However, little evidence exists to document benefits and risks of not restarting an ACE‐I in surgical patients for various intervals. To evaluate these risks, we tested the hypothesis that postoperative nonresumption of an ACE‐I occurs frequently for broad cohorts of Veterans Affairs (VA) surgery patients within the first 14 days and is associated with increased 30‐day mortality.

MATERIALS AND METHODS

After institutional review board approval (University of California, San Francisco), we examined surgeries conducted at hospitals at 120 stations within the VA Health Care System (VAHCS). The VAHCS is the largest integrated healthcare system in the United States, with long‐standing electronic medical records capturing detailed demographic, pharmacy, and mortality information.[13] Data were extracted from Medical Statistical Analysis System (SAS) and Corporate Data Warehouse (CDW) files in the VA Informatics and Computing Infrastructure.[14]

Development of the Study Population

To identify surgery patients who were consistently prescribed an ACE‐I preoperatively (Figure 1), we first located 1,213,086 surgical admissions in 846,454 patients from 1999 to 2012 using Medical SAS files and classified them by specialty of the surgeon (eg, neurosurgery, orthopedic, urology, cardiothoracic, general, vascular, plastic, and other [such as gynecology]). We identified comorbidities and cardiovascular risk factors from inpatient/outpatient diagnosis files in the CDW using International Classification of Diseases (ICD‐9) diagnosis codes (see Supporting Information, Tables 1 and 2, in the online version of this article). To ensure chronic preoperative ACE‐I use, we included surgeries with 3 outpatient prescription fills of an ACE‐I and <180‐day gap. ACE‐Is included benazepril, captopril, enalapril, fosinopril, lisinopril, perindopril, quinapril, and ramipril. We excluded cases with a surgery in the prior 90 days and missing diagnosis codes. Our final population was comprised of 294,505 surgical admissions in 240,978 patients.

Figure 1

Table 1.Demographics and Risk Factors of the Study Sample Stratified by Mortality at 30 Days

Parameter	Surgeries, No. (%), Total=294,505	Died by 30‐Days, Total=9,227	P Value
NOTE: Abbreviations: ACE‐I, angiotensin‐converting enzyme inhibitor a No restart (014 days)=no ACE‐I from postoperative day 0 to 14. b Restart (014 days)=angiotensin converting enzyme inhibitors (ACE‐I) restarted from postoperative day 0 to 14. c Restart (1530 days)=ACE‐I restarted from postoperative day 15 to 30. Patients may have more than 1 potential indication for use of an ACE‐I. d Coronary disease risk is defined as the presence of 2 or more of the following heart disease risk factors: acute myocardial infarction, cardiovascular disease, chronic heart failure, hypertension, hyperlipidemia, diabetes with or without complications, smoking, age >60 years. e Comorbidities were aggregated using an approach reported by Gagne et al. that combines the Charlson and Elixhauser measures. f Preoperative ACE‐I gap was defined as the number of days without a fill of an ACE‐I prescription. g Center surgical volume quartiles were defined using the total number of surgeries done at a hospital for the study period (19992012). h Center restart quartiles were defined using the total number of surgery patients who were restarted on their ACE‐I by 14 days at a hospital for the study period. i Minor complications were based on the presence of 1 or more of the following complications: arrhythmia, postoperative bleeding, deep venous thrombosis, pneumonia, pulmonary embolism, sepsis, and urinary tract infection. j Major complications were based on the presence of 1 or more of the following complications: myocardial infarction, renal failure, and stroke.
No restart, 014 daysa	59,949 (20%)	7.3%	<0.001
Restart, 014 daysb	220,317 (75%)	2.1%
Restart, 1530 daysc	14,239 (5%)	1.7%
Age, y
<60	74,326 (14%)	1.7%	<0.001
6170	97,731 (24%)	2.3%
7190	119,775 (60%)	4.6%
>90	2,673 (1%)	6.9%
Gender
Female	7,186 (2%)	1.6%	<0.001
Male	287,319 (98%)	3.2%
Indications for use of ACE‐I
Hypertension	270,486 (92%)	2.8%	<0.001
Ischemic heart disease	129,212 (44%)	3.8%	<0.001
Vascular disease	75,410 (26%)	3.7%	<0.001
Heart failure	59,809 (20%)	5.7%	<0.001
Chronic kidney disease	8,804 (3%)	4.9%	<0.001
Diabetes mellitus	170,320 (58%)	3.0%	<0.001
Coronary disease riskd	280,958 (95%)	3.1%	<0.001
Stroke	22,285 (8%)	5.2%	<0.001
Comorbidity scoree
0	72,126 (24%)	1.4%	<0.001
1	59,609 (20%)	1.5%
2 4	116,914 (40%)	3.5%
>4	45,856 (16%)	7.0%
Preoperative ACE‐I gap, daysf
045	21,383 (7%)	3.7%	<0.001
4690	30,237 (10%)	3.8%
91180	242,885 (83%)	3.0%
Surgical specialty
General	98,210 (33%)	4.6%	<0.001
Neurosurgery	15,423 (5%)	2.3%
Orthopedic	51,600 (18%)	1.9%
Plastic	12,547 (4%)	3.8%
Thoracic	44,728 (15%)	3.2%
Urology	34,595 (12%)	1.5%
Vascular	34,228 (12%)	2.8%
Other (gynecology)	3,174 (1%)	1.4%
Year of surgery
19992002	66,689 (23%)	4.2%	<0.001
20032005	75,420 (26%)	3.4%
20062008	76,563 (26%)	2.8%
20092012	75,833 (26%)	2.2%
No. of prior surgeries
0	215,443 (74%)	3.2%	0.413
1	56,419 (19%)	3.1%
2	22,643 (7%)	3.1%
Length of stay, d
1	40,538 (14%)	1.4%	<0.001
23	59,817 (20%)	1.4%
47	83,366 (28%)	2.0%
821	83,379 (28%)	4.7%
>21	27,405 (9%)	8.0%
Center surgical volume quartileg
0%25%	74,846 (25%)	3.7%	<0.001
25%50%	74,569 (25%)	3.1%
50%75%	69,947 (24%)	2.8%
75%100%	75,143 (26%)	2.8%
Center restart quartileh
0%25%	73,750 (25%)	3.1%	0.014
25%50%	81,071 (28%)	3.0%
50%75%	83,952 (29%)	3.3%
75%100%	55,732 (19%)	3.2%
No complication	80,700 (27%)	1.3%	<0.001
Minor complicationi	181,924 (62%)	4.2%	<0.001
Major complicationj	46,977 (16%)	8.3%	<0.001
Complications
Arrhythmia	3,037 (1%)	2.0%	<0.001
Bleeding	12,887 (4%)	4.8%	<0.001
Deep venous thrombosis	6,075 (2%)	3.6%	<0.001
Myocardial infarction	9,114 (3%)	7.7%	<0.001
Pneumonia	109,660 (37%)	5.1%	<0.001
Pulmonary embolism	5,064 (2%)	6.2%	<0.001
Renal failure	25,513 (9%)	11.0%	<0.001
Sepsis	5,846 (2%)	16.5%	<0.001
Stroke	19,546 (7%)	5.0%	<0.001
Urinary tract infection	32,548 (11%)	4.9%	<0.001

Table 2.Risk of 30‐day Mortality Associated With No Restart vs Restart of an ACE‐I

Unadjusted Hazard for 30‐Day Mortality (OR [95% CI])			Adjusted hazard for 30 day mortality (OR [95% CI])
Restart (014 Days) (Referent)a	No Restart, 014 Daysb	Restart, 1530 Daysc	Restart, 014 Days (Referent)	No Restart, 014 Days	Restart, 1530 Days
NOTE: Abbreviations: ACE‐I, angiotensin‐converting enzyme inhibitors; CI, confidence interval, NA, nonapplicable; OR, odds ratio. a Restart (014 days)=ACE‐I restarted from postoperative day 0 to 14. b No restart (014 days)=no ACE‐I from postoperative day 0 to 14. c Restart (1530 days)=ACE‐I restarted from postoperative day 15 to 30. d All P values were statistically significant (P<0.001). Restart day 1530 was not included in this model.
1	3.44 (3.303.60)d	0.23 (0.200.26)d	1	2.79 (2.672.92)d	0.24 (0.210.28)d
Restart, 014 Days (Referent)	No Restart, 014 Days	NA	Restart, 014 Days (Referent)	No Restart, 014 Days	NA
1	2.92 (2.803.05)d	NA27	1	2.39 (2.292.50)d	NA27

Postoperative Medication Use

We defined patients as postoperative restart (014 days) if an ACE‐I was administered in‐hospital (oral or intravenous) or a postdischarge outpatient ACE‐I prescription was filled in the 14 days following surgery. In absence of ACE‐I administration or prescription during postoperative days 0 to 14, patients were classified as no restart (014 days). Intraclass changes from one ACE‐I to another were considered a restart if they occurred within 0 to 14 days of surgery. We also tracked ACE‐I prescription fills through postoperative day 15 to 30 (ie, restart [1530 days]) and noted administration or filling of oral medications. Oral medications were classified as tablets or caplets in formularies.

Patient Characteristics

We categorized patients by age strata: <60, 61 to 70, 71 to 90, and >90 years old; gender; and epochs (every 34 years starting from calendar year 1999). We tracked prior surgery admissions and length of stay.

Hospital Factors

To account for clustering of surgeries and hospital‐related factors affecting ACE‐I use practices, we divided hospitals into quartiles of (1) total surgical volume based on total number of surgeries done at a hospital from 1999 to 2012 (0%25%, n<2378; 50%, n=3498; 75%, n=4531; highest surgical volume, 8162); and (2) percent of cases restarted on ACE‐I at 14 days (71%, 76%, 79%, and 100%).

Indications, Patient Illness Severity, and Complications

We determined probable indications for ACE‐I usage (ie, heart failure) and comorbidities using ICD‐9 codes in medical records prior to surgical admissions (see Supporting Information, Tables 1 and 2, in the online version of this article). Comorbidities were aggregated using algorithms developed by Gagne aggregating comorbidity conditions (defined by Elixhauser) into scores similar to Charlson scores.[15] The Gagne score has higher correlation with 30‐day, 90‐day, 180‐day, and 1‐year mortality than Charlson scores.[15]

After evaluating secondary diagnosis codes in the clinic or hospital visits prior to surgery date, complications were defined using codes newly incident after surgery and up to 90 days following discharge. We organized complications into major and minor. Major complications were myocardial infarction, renal failure, and stroke; minor complications included arrhythmia, postoperative bleeding, deep venous thrombosis, pneumonia, pulmonary embolism, sepsis, and urinary tract infection.

Mortality

Deaths were ascertained from VA Vital Status files.

RESULTS

Table 1 describes the characteristics and 30‐day mortality rates for our cohort. By postoperative day 14, 75% of the study sample (n=220,317) had restarted an ACE‐I (Figure 1). Our sample consisted primarily of older men with a substantial comorbidity burden and multiple indications for an ACE‐I. Most patients had 1 surgical episode, with the largest fraction undergoing general surgery overall. A third of the cases had lengths of stay >1 week, and surgeries occurred throughout the study period. The largest number of surgeries was noted for centers in 75% to 100% surgical volume and 50% to 75% restart quartiles. Most surgeries had no or minor complications.

The no restart (014 days) group had a higher 30‐day mortality rate (7.3%) compared to those who restarted by postoperative day 14 (2.1%) or 30 (1.7%). The highest mortality rates were found in patients aged >90 years, with a >4 comorbidity index or hospital stays >3 weeks, and those experiencing major postoperative complications.

DISCUSSION

The results from this national retrospective study confirm our hypothesis that nonresumption of an ACE‐I for 14 or more postoperative days occurs frequently for VA surgery patients. However, we found that nonresumption of an ACE‐I during the first 2 weeks after surgery is independently associated with increased 30‐day mortality. Our study is one of the first to examine the patterns and risks of postoperative ACE‐I management across a large and varied surgical population.[11, 17]

The lack of inpatient and outpatient ACE‐I prescription use by postoperative day 14 across multiple surgery classes suggests that surgical patients may be prone to short‐term nonresumption of an ACE‐I. Our intention in using a 14‐day window to evaluate restarting strategies was to account for immediate postoperative management. After surgery, careful appraisal of whether medications should be restarted is often necessary in the face of substantially deranged physiology, hypercoagulability, and blood loss.[18] After physiologic stabilization over several days, cardiovascular drugs are usually restarted thereafter to help manage chronic comorbidities.[19] One immediate conclusion from our findings is that ACE‐I are commonly discontinued perioperatively (potentially due to concerns for hypotension), and are often not restarted.[20, 21, 22, 23, 24, 25]

Our rates of ACE‐I nonresumption are comparable to rates of nonresumption reported postoperatively for other medications and raise concerns for inadequate medication reconciliation in surgical cohorts. Bell et al. conducted a population‐based cohort study of patients undergoing elective surgery and found that 11.4% of 45,220 patients chronically prescribed warfarin were not restarted by postoperative day 180.[22] A subsequent study showed intensive care unit (ICU) admission was associated with increased rates of not restarting 4 of 5 medication groups (range, 4.5%19.4%; statins, antiplatelet/anticoagulant agents, levothyroxine, respiratory inhalers, and gastric acid‐suppressing drugs).[21] One‐year follow‐up showed elevated odds for the secondary composite outcome of death in the statins group (odds ratio [OR]: 1.07; 95% CI: 1.03‐1.11) and antiplatelet/anticoagulant agents group (OR: 1.10; 95% CI: 1.03‐1.16). Drenger et al. noted a 50% rate for no restart of ACE‐I after CABG surgery; restarting was associated with a decreased composite outcome of cardiac, cerebral, and renal events and in‐hospital mortality (OR: 0.50; 95% CI: 0.38‐0.66).[26] Because medication management has been noted to be problematic at care transitions, the inpatient medication reconciliation recommendations articulated in recent Joint Commission National Patient Safety Goals may be particularly relevant for high‐risk surgical patients who experience multiple transitions of care (ie, operating room to ICU to surgical ward to rehabilitation unit to discharge).[19, 24, 27]

In examining the crucial interval for the surgical patientthe postoperative period when medication changes are commonwe found a nearly 2.5‐fold increase in risk for 30‐day mortality associated with nonresumption of an ACE‐I.[4, 19, 28] We also noted that those who were restarted later on day 15 to 30 fared better than those not restarted (Table 2). Similar effect sizes have been found with postoperative nonresumption of other cardiovascular medications. Not restarting chronic ‐blocker treatment after surgery is associated with a significant 1‐year mortality risk (HR: 2.7; 95% CI: 1.25.9).[29] Postoperative statin withdrawal (>4 days) is an independent predictor of postoperative myonecrosis (OR: 2.9; 95% CI: 1.6‐5.5).[30, 31] Biologic mechanisms contributing to mortality after a temporary failure to restart an ACE‐I are speculative and were not addressed in this study. Potential mechanisms may lie with hypertensive rebound and associated cardiac decompensation. Withdrawing an ACE‐I can cause rapid increases in blood pressure within 48 hours on home self‐measured blood pressure in hypertensive patients and in diabetic patients with chronic renal failure.[32, 33] Patients with heart failure or coronary artery disease may then experience myocardial ischemia in the context of elevated blood pressure. Not restarting an ACE‐I may also lead to compromised microcirculatory flow with renal complications and mortality.[34, 35]

Alternative explanations for the magnitude of our findings may lie with unmeasured confounders. Our analysis did not evaluate potential interactions arising from the failure to restart of all other medications (eg, ‐blockers) or evaluate changes to angiotensin receptor blockers (ARBs). In addition, our study lacked data on health system variations or emergent versus elective surgeries. However, a key starting point of our analysis was distinguishing between purposeful versus potentially unintentional nonresumption of an ACE‐I. To accomplish this, we included patients who had at least 3 prescription ACE‐I fills prior to surgery, evaluated the preoperative indications for an ACE‐I and the ability to take postoperative oral medications (eg, immortal time bias), and accounted for minor and major postoperative complications.

To address bias from unmeasured confounders, we conducted sensitivity analyses in more homogeneous subpopulations. With each sensitivity analysis, we found consistently strong associations between increased 30‐day mortality and nonresumption of an ACE‐I (Table 3). Strong effects were observed in patients without major complications and with low comorbidity burdens, patients in whom we would not expect an effect. Because deaths in postoperative day 0 to 2 could be attributed to surgical factors (ie, hemorrhage) or that patients who did not restart an ACE‐I in postoperative day 0 to 14 were too sick to tolerate oral medications, we excluded these patients along with patients who died before postoperative day 14. Both sensitivity analyses maintained our primary finding. Somewhat attenuated risks were found when we examined ACE‐I nonresumption by individual surgery types, perhaps reflective of differences in comorbidity burden.

Finally, although this study did not examine predictors of nonresumption, our models showed that in the context of postoperative ACE‐I management, factors including increasing age, being male, those with heart failure, and surgeries conducted in centers with low surgical volume were associated with increased 30‐day mortality (Table 4). Future research might consider how reinstitution of an ACE‐I occurs in these subpopulations to identify potential mechanisms for nonresumption.

Our study has several strengths. We examined patients over a decade, considered all major types of surgery, and studied patients across a healthcare system. Moreover, we used computerized prescription data and medical records (eg, discharge diagnosis, ICD‐9 codes) to derive risk factors. VA prescription data are standardized and accurate because of intensive efforts to contain costs.[36] Within VA data, the estimated sensitivity of computerized diagnoses exceeds 80% in the administrative files, with specificity of 91% to 100% for common diagnoses such as coronary artery disease.[37] These records also carefully and accurately identify death.[38]

We also identified potential limitations to our study. First, a retrospective, observational, cohort study may be prone to selection bias, and therefore we report associations that are not necessarily causal relationships. However, our methods are supported by the fact that we developed a large study sample consisting of consecutive surgical patients over a decade and noted large effect sizes across multiple subpopulations. Second, for group assignment, we used prescription records rather than medication administration data. Nevertheless, a cohort analysis focusing on exposure is standard for epidemiologic studies and shows outcomes of care resulting from daily clinical practice.[39] Third, we did not study the cause of death, data that may help to identify potential causal pathways between not restarting an ACE‐I and mortality. Fourth, our results come from VA medical centers and so may not be generalizable to non‐VA institutions. However, the length of observation under conditions of routine clinical practice at multiple medical centers and a diverse set of surgical procedures support the external validity of our study results. Fifth, we did not have clinical data accounting for surgeon‐level effects potentially affecting rates of nonresumption of an ACE‐I, American Society of Anesthesiology physical status, information on perioperative hypotension or vasopressors, or the presence of a postoperative primary care visit.

In conclusion, in the VA Healthcare System, temporary nonresumption of an ACE‐I is common. Postoperative nonresumption of an ACE‐I, although sometimes indicated and appropriate, is associated with increased risk of mortality. Careful attention to the issue of eventual reinstitution of medications for chronic conditions, such as an ACE‐I, is indicated to avoid unnecessary mortality. Because early experience showed that dose titration was a key for successful application of an ACE‐I, practitioners may also need to consider dose modification rather than simply continuation or not restarting.[40] Future research is needed to confirm our results in other healthcare systems and to define mechanisms that link postoperative nonresumption of an ACE‐I to mortality.