Immediate complete revascularization during the index procedure might become the new treatment paradigm in patients with an acute coronary syndrome (ACS) and multivessel disease, based on results of the BIOVASC trial.

In the trial, in patients presenting with ACS and multivessel disease, immediate complete revascularization was noninferior to staged complete revascularization for the primary composite outcome and was associated with a reduction in myocardial infarction and unplanned ischemia-driven revascularization.

The BIOVASC trial was presented on March 5 by Roberto Diletti, MD, Erasmus University Medical Center, Rotterdam, the Netherlands, at the joint scientific sessions of the American College of Cardiology and the World Heart Federation. The study was simultaneously published online in The Lancet.

“We did not detect an early safety signal against an immediate complete revascularization strategy,” the authors state in the Lancet paper, adding: “Treating physicians should not be concerned about potential risks associated with immediate treatment of nonculprit lesions.”

They note, “This strategy might be particularly effective in patients with only two-vessel disease and reasonably simple lesions, with a high likelihood of procedural success without excessive use of radiation, contrast dye, or other resources.”

The trial also showed a shorter hospital stay with an immediate complete revascularization strategy.

“Immediate complete revascularization might have potential health economic benefits because of the lower rate of myocardial infarction, including spontaneous myocardial infarction, and unplanned revascularizations, and the shorter overall hospital stay,” the researchers conclude.

Introducing his presentation, Dr. Diletti explained that multiple studies have established the clinical benefit of complete coronary revascularization as compared with exclusive reperfusion of the culprit lesion, but the optimal timing for nonculprit lesion revascularization remains unclear.

The BIOVASC trial, conducted in Belgium, Italy, the Netherlands, and Spain, involved 1,525 patients with ST-segment elevation MI (STEMI) or non-STEMI ACS and multivessel coronary artery disease with a clearly identifiable culprit lesion.

They were randomly assigned to undergo immediate complete revascularization (percutaneous coronary intervention [PCI] of the culprit lesion first, followed by other nonculprit lesions deemed to be clinically significant by the operator during the index procedure) or staged complete revascularization (PCI of only the culprit lesion during the index procedure and PCI of all nonculprit lesions deemed to be clinically significant within 6 weeks after the index procedure).

The primary outcome was the composite of all-cause mortality, MI, any unplanned ischemia-driven revascularization, or cerebrovascular events at 1 year after the index procedure.

The trial had a noninferiority design, with noninferiority of immediate to staged complete revascularization considered to be met if the upper boundary of the 95% confidence interval of the hazard ratio for the primary outcome did not exceed 1.39.

Among the trial population, 40% of patients had STEMI, 52% had non-STEMI, and 8% had unstable angina.

In the immediate complete revascularization group, 16 patients did not receive complete revascularization during the index procedure primarily because of prolonged procedure time, procedural complexity, or excessive contrast dye use. 

In the staged group, 30% of patients underwent all subsequent procedures during the index hospitalization.

Results showed that the primary composite outcome at 1 year occurred in 7.6% of the immediate revascularization group and in 9.4% of the staged group, meeting the noninferiority criteria (HR, 0.78; 95% CI, 0.55-1.11; P for noninferiority = .0011).

Superiority of the immediate over the staged complete revascularization strategy was not met at 1-year follow-up (P for superiority = .17).

However, in the prespecified analysis of clinical events at 30 days after the index procedure, immediate complete revascularization was superior to staged revascularization in terms of the composite primary outcome (2.2% vs. 5.8%; HR, 0.38; P for superiority = .0007).

One-year results showed no difference in all-cause death between the two groups, but the immediate complete revascularization group appeared to have a reduction in MI (1.9% vs. 4.5%)  and fewer unplanned ischemia-driven revascularizations (4.2% vs. 6.7%).

The difference in MI was mainly driven by spontaneous MIs (not procedure related) that predominantly occurred in the time window between the index procedure and the planned date for the staged intervention, and an originally nonculprit lesion was identified as the cause for these events in almost all cases.

Subgroup analysis showed similar results across the patient population, including age, sex, and STEMI vs. non-STEMI presentation.

High rate of MI in staged group

Discussant of the study at the ACC session, Dipti Itchhaporia, MD, University of California, Irvine, said this was a “very important trial.”  

She expressed surprise over the “remarkably high rate” of MI in the staged procedure group and asked Dr. Diletti why that might have occurred.

He responded that the operator may have misjudged the culprit lesion or that patients with ACS may have multiple unstable plaques and “treating the culprit lesion alone does not do the job.”

He added: “We need to look at the data more thoroughly to better understand this, but in both scenarios, immediate complete revascularization would prevent these events.” 

Dr. Itchhaporia also pointed out a low rate of functional imaging used in the study.  

Dr. Diletti replied that this reflected current European practice, but he acknowledged that, “in my opinion this reduces our ability to detect the culprit lesion.”

Commenting at an ACC press conference, David Moliterno, MD, Gill Heart and Vascular Institute, Lexington, Ky., said the trial poses the question  “Can we fix it all at once?” and the results suggest “Yes, we can.”

He said this approach had the advantage of removing any uncertainly as to which was the culprit lesion. “We just fix everything – leave no blockage behind.”

But he pointed out that for  some patients this may not be appropriate, such as those with compromised renal function, in whom excessive amounts of contrast material should be avoided.

CABG still needs to be considered

In a comment accompanying the Lancet publication, Tobias Pustjens, MD, Pieter Vriesendorp, MD, and Arnoud W.J. van’t Hof, MD, Cardiovascular Research Institute Maastricht (the Netherlands), note that more than half of the patients presenting with an ACS have multivessel coronary disease. 

They say the trial results suggest that “pursuing an immediate complete revascularisation strategy, especially in times of reduced hospital capacity and staff scarcity, not only benefits the individual patient in clinical outcomes but can also safely reduce the pressure on health care systems.”

But they also point out that the possibility of coronary artery bypass grafting (CABG) should not be omitted, and that CABG is still the treatment of choice in patients with diabetes or complex coronary artery disease.

They conclude: “The results of the BIOVASC study move clinical practice forward from culprit-only to an immediate, complete revascularisation strategy. … However, further fine tuning of this treatment strategy to substantiate a role for intracoronary physiology assessment, intracoronary imaging, and guidance of the heart team decision is needed.”

The BIOVASC trial was supported by an unrestricted research grant from Biotronik AG. Dr. Diletti has received institutional research grants from Biotronik, Medtronic, ACIST Medical Systems, and Boston Scientific. Dr. van’t Hof has received institutional research grants from Biotronik.

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

Immediate complete revascularization during the index procedure might become the new treatment paradigm in patients with an acute coronary syndrome (ACS) and multivessel disease, based on results of the BIOVASC trial.

In the trial, in patients presenting with ACS and multivessel disease, immediate complete revascularization was noninferior to staged complete revascularization for the primary composite outcome and was associated with a reduction in myocardial infarction and unplanned ischemia-driven revascularization.

The BIOVASC trial was presented on March 5 by Roberto Diletti, MD, Erasmus University Medical Center, Rotterdam, the Netherlands, at the joint scientific sessions of the American College of Cardiology and the World Heart Federation. The study was simultaneously published online in The Lancet.

“We did not detect an early safety signal against an immediate complete revascularization strategy,” the authors state in the Lancet paper, adding: “Treating physicians should not be concerned about potential risks associated with immediate treatment of nonculprit lesions.”

They note, “This strategy might be particularly effective in patients with only two-vessel disease and reasonably simple lesions, with a high likelihood of procedural success without excessive use of radiation, contrast dye, or other resources.”

The trial also showed a shorter hospital stay with an immediate complete revascularization strategy.

“Immediate complete revascularization might have potential health economic benefits because of the lower rate of myocardial infarction, including spontaneous myocardial infarction, and unplanned revascularizations, and the shorter overall hospital stay,” the researchers conclude.

Introducing his presentation, Dr. Diletti explained that multiple studies have established the clinical benefit of complete coronary revascularization as compared with exclusive reperfusion of the culprit lesion, but the optimal timing for nonculprit lesion revascularization remains unclear.

The BIOVASC trial, conducted in Belgium, Italy, the Netherlands, and Spain, involved 1,525 patients with ST-segment elevation MI (STEMI) or non-STEMI ACS and multivessel coronary artery disease with a clearly identifiable culprit lesion.

They were randomly assigned to undergo immediate complete revascularization (percutaneous coronary intervention [PCI] of the culprit lesion first, followed by other nonculprit lesions deemed to be clinically significant by the operator during the index procedure) or staged complete revascularization (PCI of only the culprit lesion during the index procedure and PCI of all nonculprit lesions deemed to be clinically significant within 6 weeks after the index procedure).

The primary outcome was the composite of all-cause mortality, MI, any unplanned ischemia-driven revascularization, or cerebrovascular events at 1 year after the index procedure.

The trial had a noninferiority design, with noninferiority of immediate to staged complete revascularization considered to be met if the upper boundary of the 95% confidence interval of the hazard ratio for the primary outcome did not exceed 1.39.

Among the trial population, 40% of patients had STEMI, 52% had non-STEMI, and 8% had unstable angina.

In the immediate complete revascularization group, 16 patients did not receive complete revascularization during the index procedure primarily because of prolonged procedure time, procedural complexity, or excessive contrast dye use. 

In the staged group, 30% of patients underwent all subsequent procedures during the index hospitalization.

Results showed that the primary composite outcome at 1 year occurred in 7.6% of the immediate revascularization group and in 9.4% of the staged group, meeting the noninferiority criteria (HR, 0.78; 95% CI, 0.55-1.11; P for noninferiority = .0011).

Superiority of the immediate over the staged complete revascularization strategy was not met at 1-year follow-up (P for superiority = .17).

However, in the prespecified analysis of clinical events at 30 days after the index procedure, immediate complete revascularization was superior to staged revascularization in terms of the composite primary outcome (2.2% vs. 5.8%; HR, 0.38; P for superiority = .0007).

One-year results showed no difference in all-cause death between the two groups, but the immediate complete revascularization group appeared to have a reduction in MI (1.9% vs. 4.5%)  and fewer unplanned ischemia-driven revascularizations (4.2% vs. 6.7%).

The difference in MI was mainly driven by spontaneous MIs (not procedure related) that predominantly occurred in the time window between the index procedure and the planned date for the staged intervention, and an originally nonculprit lesion was identified as the cause for these events in almost all cases.

Subgroup analysis showed similar results across the patient population, including age, sex, and STEMI vs. non-STEMI presentation.

High rate of MI in staged group

Discussant of the study at the ACC session, Dipti Itchhaporia, MD, University of California, Irvine, said this was a “very important trial.”  

She expressed surprise over the “remarkably high rate” of MI in the staged procedure group and asked Dr. Diletti why that might have occurred.

He responded that the operator may have misjudged the culprit lesion or that patients with ACS may have multiple unstable plaques and “treating the culprit lesion alone does not do the job.”

He added: “We need to look at the data more thoroughly to better understand this, but in both scenarios, immediate complete revascularization would prevent these events.” 

Dr. Itchhaporia also pointed out a low rate of functional imaging used in the study.  

Dr. Diletti replied that this reflected current European practice, but he acknowledged that, “in my opinion this reduces our ability to detect the culprit lesion.”

Commenting at an ACC press conference, David Moliterno, MD, Gill Heart and Vascular Institute, Lexington, Ky., said the trial poses the question  “Can we fix it all at once?” and the results suggest “Yes, we can.”

He said this approach had the advantage of removing any uncertainly as to which was the culprit lesion. “We just fix everything – leave no blockage behind.”

But he pointed out that for  some patients this may not be appropriate, such as those with compromised renal function, in whom excessive amounts of contrast material should be avoided.

CABG still needs to be considered

In a comment accompanying the Lancet publication, Tobias Pustjens, MD, Pieter Vriesendorp, MD, and Arnoud W.J. van’t Hof, MD, Cardiovascular Research Institute Maastricht (the Netherlands), note that more than half of the patients presenting with an ACS have multivessel coronary disease. 

They say the trial results suggest that “pursuing an immediate complete revascularisation strategy, especially in times of reduced hospital capacity and staff scarcity, not only benefits the individual patient in clinical outcomes but can also safely reduce the pressure on health care systems.”

But they also point out that the possibility of coronary artery bypass grafting (CABG) should not be omitted, and that CABG is still the treatment of choice in patients with diabetes or complex coronary artery disease.

They conclude: “The results of the BIOVASC study move clinical practice forward from culprit-only to an immediate, complete revascularisation strategy. … However, further fine tuning of this treatment strategy to substantiate a role for intracoronary physiology assessment, intracoronary imaging, and guidance of the heart team decision is needed.”

The BIOVASC trial was supported by an unrestricted research grant from Biotronik AG. Dr. Diletti has received institutional research grants from Biotronik, Medtronic, ACIST Medical Systems, and Boston Scientific. Dr. van’t Hof has received institutional research grants from Biotronik.

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

Immediate complete revascularization during the index procedure might become the new treatment paradigm in patients with an acute coronary syndrome (ACS) and multivessel disease, based on results of the BIOVASC trial.

In the trial, in patients presenting with ACS and multivessel disease, immediate complete revascularization was noninferior to staged complete revascularization for the primary composite outcome and was associated with a reduction in myocardial infarction and unplanned ischemia-driven revascularization.

The BIOVASC trial was presented on March 5 by Roberto Diletti, MD, Erasmus University Medical Center, Rotterdam, the Netherlands, at the joint scientific sessions of the American College of Cardiology and the World Heart Federation. The study was simultaneously published online in The Lancet.

“We did not detect an early safety signal against an immediate complete revascularization strategy,” the authors state in the Lancet paper, adding: “Treating physicians should not be concerned about potential risks associated with immediate treatment of nonculprit lesions.”

They note, “This strategy might be particularly effective in patients with only two-vessel disease and reasonably simple lesions, with a high likelihood of procedural success without excessive use of radiation, contrast dye, or other resources.”

The trial also showed a shorter hospital stay with an immediate complete revascularization strategy.

“Immediate complete revascularization might have potential health economic benefits because of the lower rate of myocardial infarction, including spontaneous myocardial infarction, and unplanned revascularizations, and the shorter overall hospital stay,” the researchers conclude.

Introducing his presentation, Dr. Diletti explained that multiple studies have established the clinical benefit of complete coronary revascularization as compared with exclusive reperfusion of the culprit lesion, but the optimal timing for nonculprit lesion revascularization remains unclear.

The BIOVASC trial, conducted in Belgium, Italy, the Netherlands, and Spain, involved 1,525 patients with ST-segment elevation MI (STEMI) or non-STEMI ACS and multivessel coronary artery disease with a clearly identifiable culprit lesion.

They were randomly assigned to undergo immediate complete revascularization (percutaneous coronary intervention [PCI] of the culprit lesion first, followed by other nonculprit lesions deemed to be clinically significant by the operator during the index procedure) or staged complete revascularization (PCI of only the culprit lesion during the index procedure and PCI of all nonculprit lesions deemed to be clinically significant within 6 weeks after the index procedure).

The primary outcome was the composite of all-cause mortality, MI, any unplanned ischemia-driven revascularization, or cerebrovascular events at 1 year after the index procedure.

The trial had a noninferiority design, with noninferiority of immediate to staged complete revascularization considered to be met if the upper boundary of the 95% confidence interval of the hazard ratio for the primary outcome did not exceed 1.39.

Among the trial population, 40% of patients had STEMI, 52% had non-STEMI, and 8% had unstable angina.

In the immediate complete revascularization group, 16 patients did not receive complete revascularization during the index procedure primarily because of prolonged procedure time, procedural complexity, or excessive contrast dye use. 

In the staged group, 30% of patients underwent all subsequent procedures during the index hospitalization.

Results showed that the primary composite outcome at 1 year occurred in 7.6% of the immediate revascularization group and in 9.4% of the staged group, meeting the noninferiority criteria (HR, 0.78; 95% CI, 0.55-1.11; P for noninferiority = .0011).

Superiority of the immediate over the staged complete revascularization strategy was not met at 1-year follow-up (P for superiority = .17).

However, in the prespecified analysis of clinical events at 30 days after the index procedure, immediate complete revascularization was superior to staged revascularization in terms of the composite primary outcome (2.2% vs. 5.8%; HR, 0.38; P for superiority = .0007).

One-year results showed no difference in all-cause death between the two groups, but the immediate complete revascularization group appeared to have a reduction in MI (1.9% vs. 4.5%)  and fewer unplanned ischemia-driven revascularizations (4.2% vs. 6.7%).

The difference in MI was mainly driven by spontaneous MIs (not procedure related) that predominantly occurred in the time window between the index procedure and the planned date for the staged intervention, and an originally nonculprit lesion was identified as the cause for these events in almost all cases.

Subgroup analysis showed similar results across the patient population, including age, sex, and STEMI vs. non-STEMI presentation.

High rate of MI in staged group

Discussant of the study at the ACC session, Dipti Itchhaporia, MD, University of California, Irvine, said this was a “very important trial.”  

She expressed surprise over the “remarkably high rate” of MI in the staged procedure group and asked Dr. Diletti why that might have occurred.

He responded that the operator may have misjudged the culprit lesion or that patients with ACS may have multiple unstable plaques and “treating the culprit lesion alone does not do the job.”

He added: “We need to look at the data more thoroughly to better understand this, but in both scenarios, immediate complete revascularization would prevent these events.” 

Dr. Itchhaporia also pointed out a low rate of functional imaging used in the study.  

Dr. Diletti replied that this reflected current European practice, but he acknowledged that, “in my opinion this reduces our ability to detect the culprit lesion.”

Commenting at an ACC press conference, David Moliterno, MD, Gill Heart and Vascular Institute, Lexington, Ky., said the trial poses the question  “Can we fix it all at once?” and the results suggest “Yes, we can.”

He said this approach had the advantage of removing any uncertainly as to which was the culprit lesion. “We just fix everything – leave no blockage behind.”

But he pointed out that for  some patients this may not be appropriate, such as those with compromised renal function, in whom excessive amounts of contrast material should be avoided.

CABG still needs to be considered

In a comment accompanying the Lancet publication, Tobias Pustjens, MD, Pieter Vriesendorp, MD, and Arnoud W.J. van’t Hof, MD, Cardiovascular Research Institute Maastricht (the Netherlands), note that more than half of the patients presenting with an ACS have multivessel coronary disease. 

They say the trial results suggest that “pursuing an immediate complete revascularisation strategy, especially in times of reduced hospital capacity and staff scarcity, not only benefits the individual patient in clinical outcomes but can also safely reduce the pressure on health care systems.”

But they also point out that the possibility of coronary artery bypass grafting (CABG) should not be omitted, and that CABG is still the treatment of choice in patients with diabetes or complex coronary artery disease.

They conclude: “The results of the BIOVASC study move clinical practice forward from culprit-only to an immediate, complete revascularisation strategy. … However, further fine tuning of this treatment strategy to substantiate a role for intracoronary physiology assessment, intracoronary imaging, and guidance of the heart team decision is needed.”

The BIOVASC trial was supported by an unrestricted research grant from Biotronik AG. Dr. Diletti has received institutional research grants from Biotronik, Medtronic, ACIST Medical Systems, and Boston Scientific. Dr. van’t Hof has received institutional research grants from Biotronik.

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

NEW ORLEANS – In patients undergoing percutaneous intervention (PCI) for complex coronary lesions, intravascular imaging is superior to angiography for reducing the risk of target lesion failure (TLF), according to results of a randomized trial.

Previous studies have produced the same conclusion, but the advantage was demonstrated this time in a multicenter well-powered randomized trial, principal investigator Joo Yong Hahn, MD, PhD, said at the joint scientific sessions of the American College of Cardiology and the World Heart Federation.

Ted Bosworth/MDedge News

The earlier studies “were not definitive,” said Dr. Hahn, pointing out that even those that were randomized lacked sufficient duration of follow-up or were not inclusive of a broad array of types of complex PCI.

In this clinical outcomes–driven study, called RENOVATE-COMPLEX-PCI, 1,639 patients undergoing complex PCI in 20 South Korean treatment centers were randomized in a 2:1 ratio to PCI guided by intravascular imaging or angiography alone. There were nine types of complex PCI eligible for trial entry, including bifurcated lesions, long lesions (expected stent length ≥ 38 mm), total coronary occlusions, lesions requiring multiple stents, severely calcified lesions, and lesions in multiple vessels.

Intravascular imaging in the experimental arm could be performed with either intravascular ultrasound (IVUS) or optical coherence tomography (OCT), according to Dr. Hahn. Because one might be better than the other for specific patient and lesions characteristics, the type of intravascular imaging in the experimental group was selected at the discretion of the treating investigator, reported Dr. Hahn, of the Heart Vascular Stroke Institute, Samsung Medical Center, Sungkyunkwan University, Seoul.

The primary TLF endpoint was defined as death from cardiovascular causes, target-vessel-related MI, and target-vessel revascularization.

Risk reduction of > 35% observed

After a median of 2.1 years of follow-up, the lower TLF incidence in the group with PCI guided by intravascular imaging (7.7% vs. 12.3%) translated into a 36% reduction in risk (hazard ratio, 0.64; P = .008).

Intravascular imaging was associated with a numerical reduction of each component of TLF. In the case of death from cardiovascular causes, the confidence interval remained below the line of unity (HR 0.47; 95% CI, 0.24-0.93).

Although this was not true for target vessel–related MI (HR, 0.74, 95% CI, 0.45-1.22) or target vessel revascularization (HR, 0.66; 95% CI, 0.36-1.22), it was also true of TLF without procedural-related MI (HR, 0.59; 95% CI, 0.39-0.90) and cardiac death or target vessel–related MI (HR, 0.63; 95% CI, 0.42-0.93).

With few exceptions, all of the secondary outcomes “moved in the right direction” to favor intravascular imaging, including death from any cause (HR 0.71, 95% CI, 0.44-1.15), reported Dr. Hahn, who noted that the results were simultaneously published in the New England Journal of Medicine.

When compared, there were no major baseline differences in the 1,092 patients with PCI guided by intravascular imaging relative to the 547 guided by angiography. The median age was 65.5 years. Most (79%) were male. About half (51%) had an acute coronary syndrome and the remainder had stable ischemic heart disease. The proportions of patients with hypertension (61%), dyslipidemia (51%), and diabetes (38%) were substantial. About 18% of patients were current smokers, 24% had a previous PCI, and 7% had a previous MI.

Stent types were similar in the two groups, and they were delivered by radial access. Procedural success was achieved in about 98% of both groups. Almost all patients were discharged on a statin, aspirin, and a P2Y₁₂ inhibitor, and the other specific postprocedural medications were comparable in the two groups.

Advantage of intravascular imaging consistent

Of the complex lesions, most (55%) had diffuse long coronary artery lesions, but other types of complex PCI, including bifurcated lesions (22%), chronic total occlusions (20%), severely calcified lesions (14%), and ostial lesions of a major coronary artery (15%) were represented. Across these lesion types, intravascular imaging was favored over angiography for TLF at least numerically. The potential exceptions were lesions requiring at least three stents (HR, 1.24; 95% CI, 0.49-3.18), but confidence intervals were wide.

The trial was unblinded, but Dr. Hahn reported that imaging analyses were performed at a core laboratory and events were adjudicated by a committee with members unaware of trial group assignments.

One unanswered question is cost. Because intravascular imaging adds cost to PCI relative to angiography, cost-effectiveness analyses are needed to provide context for the decision to use this approach in all complex PCI patients. These analyses are planned.

Based on the consistency of these trial results with previous studies, almost all of which showed the same thing, “the intravascular imaging world has spoken,” said Wayne B. Batchelor, MD, director of interventional cardiology, Inova Heart and Vascular Institute, Fairfax, Va. “The only question now is when will the interventional community is going to listen.”

Ted Bosworth/MDedge News

Dr. Batchelor predicted that these data will change the mindset of many practitioners “to shift the debate to why not do it [intravascular imaging] from why do it.”

“Only about 15% of PCI is performed with intravascular imaging in the United States, and these [results] argue that this number needs to go up,” Dr. Batchelor said. Although he said there are technical reasons, such as diffuse lesions or small vessels, that prevent intravascular imaging from being used in every complex patient, he suggested the data are compelling.

“If you apply this to the one million patients undergoing PCI in the United States, this will translate potentially into tens of thousands of patients protected from the TVF endpoint,” Dr. Batchelor said.

Dr. Hahn reports no potential conflicts of interest, but this investigator-initiated trial received funding from Boston Scientific and Abbott Vascular. Dr. Batchelor reports financial relationships with Abbott Vascular, Boston Scientific, Idorsia, Medtronic, and V-Wave Medical.

NEW ORLEANS – In patients undergoing percutaneous intervention (PCI) for complex coronary lesions, intravascular imaging is superior to angiography for reducing the risk of target lesion failure (TLF), according to results of a randomized trial.

Previous studies have produced the same conclusion, but the advantage was demonstrated this time in a multicenter well-powered randomized trial, principal investigator Joo Yong Hahn, MD, PhD, said at the joint scientific sessions of the American College of Cardiology and the World Heart Federation.

Ted Bosworth/MDedge News

The earlier studies “were not definitive,” said Dr. Hahn, pointing out that even those that were randomized lacked sufficient duration of follow-up or were not inclusive of a broad array of types of complex PCI.

In this clinical outcomes–driven study, called RENOVATE-COMPLEX-PCI, 1,639 patients undergoing complex PCI in 20 South Korean treatment centers were randomized in a 2:1 ratio to PCI guided by intravascular imaging or angiography alone. There were nine types of complex PCI eligible for trial entry, including bifurcated lesions, long lesions (expected stent length ≥ 38 mm), total coronary occlusions, lesions requiring multiple stents, severely calcified lesions, and lesions in multiple vessels.

Intravascular imaging in the experimental arm could be performed with either intravascular ultrasound (IVUS) or optical coherence tomography (OCT), according to Dr. Hahn. Because one might be better than the other for specific patient and lesions characteristics, the type of intravascular imaging in the experimental group was selected at the discretion of the treating investigator, reported Dr. Hahn, of the Heart Vascular Stroke Institute, Samsung Medical Center, Sungkyunkwan University, Seoul.

The primary TLF endpoint was defined as death from cardiovascular causes, target-vessel-related MI, and target-vessel revascularization.

Risk reduction of > 35% observed

After a median of 2.1 years of follow-up, the lower TLF incidence in the group with PCI guided by intravascular imaging (7.7% vs. 12.3%) translated into a 36% reduction in risk (hazard ratio, 0.64; P = .008).

Intravascular imaging was associated with a numerical reduction of each component of TLF. In the case of death from cardiovascular causes, the confidence interval remained below the line of unity (HR 0.47; 95% CI, 0.24-0.93).

Although this was not true for target vessel–related MI (HR, 0.74, 95% CI, 0.45-1.22) or target vessel revascularization (HR, 0.66; 95% CI, 0.36-1.22), it was also true of TLF without procedural-related MI (HR, 0.59; 95% CI, 0.39-0.90) and cardiac death or target vessel–related MI (HR, 0.63; 95% CI, 0.42-0.93).

With few exceptions, all of the secondary outcomes “moved in the right direction” to favor intravascular imaging, including death from any cause (HR 0.71, 95% CI, 0.44-1.15), reported Dr. Hahn, who noted that the results were simultaneously published in the New England Journal of Medicine.

When compared, there were no major baseline differences in the 1,092 patients with PCI guided by intravascular imaging relative to the 547 guided by angiography. The median age was 65.5 years. Most (79%) were male. About half (51%) had an acute coronary syndrome and the remainder had stable ischemic heart disease. The proportions of patients with hypertension (61%), dyslipidemia (51%), and diabetes (38%) were substantial. About 18% of patients were current smokers, 24% had a previous PCI, and 7% had a previous MI.

Stent types were similar in the two groups, and they were delivered by radial access. Procedural success was achieved in about 98% of both groups. Almost all patients were discharged on a statin, aspirin, and a P2Y₁₂ inhibitor, and the other specific postprocedural medications were comparable in the two groups.

Advantage of intravascular imaging consistent

Of the complex lesions, most (55%) had diffuse long coronary artery lesions, but other types of complex PCI, including bifurcated lesions (22%), chronic total occlusions (20%), severely calcified lesions (14%), and ostial lesions of a major coronary artery (15%) were represented. Across these lesion types, intravascular imaging was favored over angiography for TLF at least numerically. The potential exceptions were lesions requiring at least three stents (HR, 1.24; 95% CI, 0.49-3.18), but confidence intervals were wide.

The trial was unblinded, but Dr. Hahn reported that imaging analyses were performed at a core laboratory and events were adjudicated by a committee with members unaware of trial group assignments.

One unanswered question is cost. Because intravascular imaging adds cost to PCI relative to angiography, cost-effectiveness analyses are needed to provide context for the decision to use this approach in all complex PCI patients. These analyses are planned.

Based on the consistency of these trial results with previous studies, almost all of which showed the same thing, “the intravascular imaging world has spoken,” said Wayne B. Batchelor, MD, director of interventional cardiology, Inova Heart and Vascular Institute, Fairfax, Va. “The only question now is when will the interventional community is going to listen.”

Ted Bosworth/MDedge News

Dr. Batchelor predicted that these data will change the mindset of many practitioners “to shift the debate to why not do it [intravascular imaging] from why do it.”

“Only about 15% of PCI is performed with intravascular imaging in the United States, and these [results] argue that this number needs to go up,” Dr. Batchelor said. Although he said there are technical reasons, such as diffuse lesions or small vessels, that prevent intravascular imaging from being used in every complex patient, he suggested the data are compelling.

“If you apply this to the one million patients undergoing PCI in the United States, this will translate potentially into tens of thousands of patients protected from the TVF endpoint,” Dr. Batchelor said.

Dr. Hahn reports no potential conflicts of interest, but this investigator-initiated trial received funding from Boston Scientific and Abbott Vascular. Dr. Batchelor reports financial relationships with Abbott Vascular, Boston Scientific, Idorsia, Medtronic, and V-Wave Medical.

NEW ORLEANS – In patients undergoing percutaneous intervention (PCI) for complex coronary lesions, intravascular imaging is superior to angiography for reducing the risk of target lesion failure (TLF), according to results of a randomized trial.

Previous studies have produced the same conclusion, but the advantage was demonstrated this time in a multicenter well-powered randomized trial, principal investigator Joo Yong Hahn, MD, PhD, said at the joint scientific sessions of the American College of Cardiology and the World Heart Federation.

Ted Bosworth/MDedge News

The earlier studies “were not definitive,” said Dr. Hahn, pointing out that even those that were randomized lacked sufficient duration of follow-up or were not inclusive of a broad array of types of complex PCI.

In this clinical outcomes–driven study, called RENOVATE-COMPLEX-PCI, 1,639 patients undergoing complex PCI in 20 South Korean treatment centers were randomized in a 2:1 ratio to PCI guided by intravascular imaging or angiography alone. There were nine types of complex PCI eligible for trial entry, including bifurcated lesions, long lesions (expected stent length ≥ 38 mm), total coronary occlusions, lesions requiring multiple stents, severely calcified lesions, and lesions in multiple vessels.

Intravascular imaging in the experimental arm could be performed with either intravascular ultrasound (IVUS) or optical coherence tomography (OCT), according to Dr. Hahn. Because one might be better than the other for specific patient and lesions characteristics, the type of intravascular imaging in the experimental group was selected at the discretion of the treating investigator, reported Dr. Hahn, of the Heart Vascular Stroke Institute, Samsung Medical Center, Sungkyunkwan University, Seoul.

The primary TLF endpoint was defined as death from cardiovascular causes, target-vessel-related MI, and target-vessel revascularization.

Risk reduction of > 35% observed

After a median of 2.1 years of follow-up, the lower TLF incidence in the group with PCI guided by intravascular imaging (7.7% vs. 12.3%) translated into a 36% reduction in risk (hazard ratio, 0.64; P = .008).

Intravascular imaging was associated with a numerical reduction of each component of TLF. In the case of death from cardiovascular causes, the confidence interval remained below the line of unity (HR 0.47; 95% CI, 0.24-0.93).

Although this was not true for target vessel–related MI (HR, 0.74, 95% CI, 0.45-1.22) or target vessel revascularization (HR, 0.66; 95% CI, 0.36-1.22), it was also true of TLF without procedural-related MI (HR, 0.59; 95% CI, 0.39-0.90) and cardiac death or target vessel–related MI (HR, 0.63; 95% CI, 0.42-0.93).

With few exceptions, all of the secondary outcomes “moved in the right direction” to favor intravascular imaging, including death from any cause (HR 0.71, 95% CI, 0.44-1.15), reported Dr. Hahn, who noted that the results were simultaneously published in the New England Journal of Medicine.

When compared, there were no major baseline differences in the 1,092 patients with PCI guided by intravascular imaging relative to the 547 guided by angiography. The median age was 65.5 years. Most (79%) were male. About half (51%) had an acute coronary syndrome and the remainder had stable ischemic heart disease. The proportions of patients with hypertension (61%), dyslipidemia (51%), and diabetes (38%) were substantial. About 18% of patients were current smokers, 24% had a previous PCI, and 7% had a previous MI.

Stent types were similar in the two groups, and they were delivered by radial access. Procedural success was achieved in about 98% of both groups. Almost all patients were discharged on a statin, aspirin, and a P2Y₁₂ inhibitor, and the other specific postprocedural medications were comparable in the two groups.

Advantage of intravascular imaging consistent

Of the complex lesions, most (55%) had diffuse long coronary artery lesions, but other types of complex PCI, including bifurcated lesions (22%), chronic total occlusions (20%), severely calcified lesions (14%), and ostial lesions of a major coronary artery (15%) were represented. Across these lesion types, intravascular imaging was favored over angiography for TLF at least numerically. The potential exceptions were lesions requiring at least three stents (HR, 1.24; 95% CI, 0.49-3.18), but confidence intervals were wide.

The trial was unblinded, but Dr. Hahn reported that imaging analyses were performed at a core laboratory and events were adjudicated by a committee with members unaware of trial group assignments.

One unanswered question is cost. Because intravascular imaging adds cost to PCI relative to angiography, cost-effectiveness analyses are needed to provide context for the decision to use this approach in all complex PCI patients. These analyses are planned.

Based on the consistency of these trial results with previous studies, almost all of which showed the same thing, “the intravascular imaging world has spoken,” said Wayne B. Batchelor, MD, director of interventional cardiology, Inova Heart and Vascular Institute, Fairfax, Va. “The only question now is when will the interventional community is going to listen.”

Ted Bosworth/MDedge News

Dr. Batchelor predicted that these data will change the mindset of many practitioners “to shift the debate to why not do it [intravascular imaging] from why do it.”

“Only about 15% of PCI is performed with intravascular imaging in the United States, and these [results] argue that this number needs to go up,” Dr. Batchelor said. Although he said there are technical reasons, such as diffuse lesions or small vessels, that prevent intravascular imaging from being used in every complex patient, he suggested the data are compelling.

“If you apply this to the one million patients undergoing PCI in the United States, this will translate potentially into tens of thousands of patients protected from the TVF endpoint,” Dr. Batchelor said.

Dr. Hahn reports no potential conflicts of interest, but this investigator-initiated trial received funding from Boston Scientific and Abbott Vascular. Dr. Batchelor reports financial relationships with Abbott Vascular, Boston Scientific, Idorsia, Medtronic, and V-Wave Medical.

There is no magical amount of viable ventricular myocardium that makes percutaneous coronary intervention (PCI) an effective addition to optimal medical therapy (OMT) in stable patients with coronary disease and poor ventricular function, suggests an analysis from a major trial.

The REVIVED-BCIS2 trial recently made waves when it showed no clinical advantage from adding PCI to OMT in stable patients with severe ischemic left ventricular (LV) dysfunction. All the patients had shown viable but dysfunctional myocardium that could potentially be revascularized.

But in a secondary analysis, extent of such hibernating heart muscle was not a good predictor of clinical outcomes, which in the trial meant death from any cause or hospitalization for heart failure (HHF).

Burden of myocardial scar tissue, however, turned out to be a potent predictor of clinical risk regardless of coronary disease severity or even LV ejection fraction (LVEF).

Because myocardial viability tracks poorly with outcomes in patients like those enrolled in the trial, as the new analysis suggests, conventional viability testing isn’t an effective guide for deciding who among them should get PCI, Divaka Perera, MD, said in an interview.

Dr. Perera, of King’s College London and the trial’s principal investigator, presented the REVIVED-BCIS2 secondary results at the joint scientific sessions of the American College of Cardiology and the World Heart Federation..

Viability testing for ischemia, he noted, is often used in practice to aid revascularization decisions. As the extent of myocardial viability can vary, it’s been asked – ever since the trial’s primary publication – whether there could be “a sweet spot or Goldilocks zone of viability that would allow prediction of which patients will do better with PCI compared to medical therapy,” Dr. Perera said. “The trial conclusively shows that is not the case.”

That the extent of hibernating myocardium, which is viable but dysfunctional, didn’t predict clinical outcomes or LV functional recovery “is disruptive of current practice and challenges a view that’s been held for decades.”

The trial’s 700 patients receiving OMT had been randomly assigned to undergo PCI or not, 347 and 353 patients, respectively. About 12% of the total were women.

About 70% of patients underwent baseline and follow-up myocardial viability testing using cardiac magnetic resonance (CMR) imaging with late gadolinium enhancement for estimation of scar burden; the remainder underwent dobutamine-stress echocardiography. All imaging assessments were conducted at independent core laboratories, Dr. Perera reported.

Extent of myocardial viability was defined three ways: volume of hibernating heart muscle, total volume of viable myocardium, and scar burden – all expressed as a percentage of total LV volume.

Every 10% increment in LV volume found to be hibernating related to a hazard ratio of 0.98 (95% confidence interval, 0.93-1.04; P = .56) for all-cause mortality or HHF at a median of 3.3 years. The analysis was adjusted for age, sex, diabetes, previous HHF, chronic renal failure, extent of CAD, type of viability testing, and baseline LVEF.

The adjusted HR for the same percentage increment in total viable myocardium was marginally significantly reduced at 0.93 (95% CI, 0.87-1.00; P = .048).

The correlation with scar burden was stronger. The adjusted composite-endpoint HR per 10% increment in scar burden was significantly increased at 1.18 (95% CI, 1.04-1.33; P = .009).

Extent of myocardial viability by tertiles, regardless of viability definition, did not highlight any group with a reduced risk for death or HHF, or group with better LV functional recovery, from OMT plus PCI, compared with OMT alone.

The findings appear to suggest that scar burden, but not extent of viability as it’s usually measured, may effectively guide PCI decisions in such patients, Dr. Perera said.

“I would say that viability testing as we understand it now, based on the paradigm of hibernating myocardium, is very useful,” he said, “but that is not the only information we can get from a viability test.”

Scar burden can also be determined from the same tests but isn’t typically looked at. “We’re actually collecting this information  but not using it,” Dr. Perera said. “When we do, it is really powerfully predictive” of both clinical outcomes and LV functional recovery. “Yet scar burden is not in any of the guidelines for stratifying risk.”

REVIVED-BCIS2 was funded by the National Institute for Health and Care Research Health Technology Assessment Program. Dr. Perera had no disclosures.

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

There is no magical amount of viable ventricular myocardium that makes percutaneous coronary intervention (PCI) an effective addition to optimal medical therapy (OMT) in stable patients with coronary disease and poor ventricular function, suggests an analysis from a major trial.

The REVIVED-BCIS2 trial recently made waves when it showed no clinical advantage from adding PCI to OMT in stable patients with severe ischemic left ventricular (LV) dysfunction. All the patients had shown viable but dysfunctional myocardium that could potentially be revascularized.

But in a secondary analysis, extent of such hibernating heart muscle was not a good predictor of clinical outcomes, which in the trial meant death from any cause or hospitalization for heart failure (HHF).

Burden of myocardial scar tissue, however, turned out to be a potent predictor of clinical risk regardless of coronary disease severity or even LV ejection fraction (LVEF).

Because myocardial viability tracks poorly with outcomes in patients like those enrolled in the trial, as the new analysis suggests, conventional viability testing isn’t an effective guide for deciding who among them should get PCI, Divaka Perera, MD, said in an interview.

Dr. Perera, of King’s College London and the trial’s principal investigator, presented the REVIVED-BCIS2 secondary results at the joint scientific sessions of the American College of Cardiology and the World Heart Federation..

Viability testing for ischemia, he noted, is often used in practice to aid revascularization decisions. As the extent of myocardial viability can vary, it’s been asked – ever since the trial’s primary publication – whether there could be “a sweet spot or Goldilocks zone of viability that would allow prediction of which patients will do better with PCI compared to medical therapy,” Dr. Perera said. “The trial conclusively shows that is not the case.”

That the extent of hibernating myocardium, which is viable but dysfunctional, didn’t predict clinical outcomes or LV functional recovery “is disruptive of current practice and challenges a view that’s been held for decades.”

The trial’s 700 patients receiving OMT had been randomly assigned to undergo PCI or not, 347 and 353 patients, respectively. About 12% of the total were women.

About 70% of patients underwent baseline and follow-up myocardial viability testing using cardiac magnetic resonance (CMR) imaging with late gadolinium enhancement for estimation of scar burden; the remainder underwent dobutamine-stress echocardiography. All imaging assessments were conducted at independent core laboratories, Dr. Perera reported.

Extent of myocardial viability was defined three ways: volume of hibernating heart muscle, total volume of viable myocardium, and scar burden – all expressed as a percentage of total LV volume.

Every 10% increment in LV volume found to be hibernating related to a hazard ratio of 0.98 (95% confidence interval, 0.93-1.04; P = .56) for all-cause mortality or HHF at a median of 3.3 years. The analysis was adjusted for age, sex, diabetes, previous HHF, chronic renal failure, extent of CAD, type of viability testing, and baseline LVEF.

The adjusted HR for the same percentage increment in total viable myocardium was marginally significantly reduced at 0.93 (95% CI, 0.87-1.00; P = .048).

The correlation with scar burden was stronger. The adjusted composite-endpoint HR per 10% increment in scar burden was significantly increased at 1.18 (95% CI, 1.04-1.33; P = .009).

Extent of myocardial viability by tertiles, regardless of viability definition, did not highlight any group with a reduced risk for death or HHF, or group with better LV functional recovery, from OMT plus PCI, compared with OMT alone.

The findings appear to suggest that scar burden, but not extent of viability as it’s usually measured, may effectively guide PCI decisions in such patients, Dr. Perera said.

“I would say that viability testing as we understand it now, based on the paradigm of hibernating myocardium, is very useful,” he said, “but that is not the only information we can get from a viability test.”

Scar burden can also be determined from the same tests but isn’t typically looked at. “We’re actually collecting this information  but not using it,” Dr. Perera said. “When we do, it is really powerfully predictive” of both clinical outcomes and LV functional recovery. “Yet scar burden is not in any of the guidelines for stratifying risk.”

REVIVED-BCIS2 was funded by the National Institute for Health and Care Research Health Technology Assessment Program. Dr. Perera had no disclosures.

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

There is no magical amount of viable ventricular myocardium that makes percutaneous coronary intervention (PCI) an effective addition to optimal medical therapy (OMT) in stable patients with coronary disease and poor ventricular function, suggests an analysis from a major trial.

The REVIVED-BCIS2 trial recently made waves when it showed no clinical advantage from adding PCI to OMT in stable patients with severe ischemic left ventricular (LV) dysfunction. All the patients had shown viable but dysfunctional myocardium that could potentially be revascularized.

But in a secondary analysis, extent of such hibernating heart muscle was not a good predictor of clinical outcomes, which in the trial meant death from any cause or hospitalization for heart failure (HHF).

Burden of myocardial scar tissue, however, turned out to be a potent predictor of clinical risk regardless of coronary disease severity or even LV ejection fraction (LVEF).

Because myocardial viability tracks poorly with outcomes in patients like those enrolled in the trial, as the new analysis suggests, conventional viability testing isn’t an effective guide for deciding who among them should get PCI, Divaka Perera, MD, said in an interview.

Dr. Perera, of King’s College London and the trial’s principal investigator, presented the REVIVED-BCIS2 secondary results at the joint scientific sessions of the American College of Cardiology and the World Heart Federation..

Viability testing for ischemia, he noted, is often used in practice to aid revascularization decisions. As the extent of myocardial viability can vary, it’s been asked – ever since the trial’s primary publication – whether there could be “a sweet spot or Goldilocks zone of viability that would allow prediction of which patients will do better with PCI compared to medical therapy,” Dr. Perera said. “The trial conclusively shows that is not the case.”

That the extent of hibernating myocardium, which is viable but dysfunctional, didn’t predict clinical outcomes or LV functional recovery “is disruptive of current practice and challenges a view that’s been held for decades.”

The trial’s 700 patients receiving OMT had been randomly assigned to undergo PCI or not, 347 and 353 patients, respectively. About 12% of the total were women.

About 70% of patients underwent baseline and follow-up myocardial viability testing using cardiac magnetic resonance (CMR) imaging with late gadolinium enhancement for estimation of scar burden; the remainder underwent dobutamine-stress echocardiography. All imaging assessments were conducted at independent core laboratories, Dr. Perera reported.

Extent of myocardial viability was defined three ways: volume of hibernating heart muscle, total volume of viable myocardium, and scar burden – all expressed as a percentage of total LV volume.

Every 10% increment in LV volume found to be hibernating related to a hazard ratio of 0.98 (95% confidence interval, 0.93-1.04; P = .56) for all-cause mortality or HHF at a median of 3.3 years. The analysis was adjusted for age, sex, diabetes, previous HHF, chronic renal failure, extent of CAD, type of viability testing, and baseline LVEF.

The adjusted HR for the same percentage increment in total viable myocardium was marginally significantly reduced at 0.93 (95% CI, 0.87-1.00; P = .048).

The correlation with scar burden was stronger. The adjusted composite-endpoint HR per 10% increment in scar burden was significantly increased at 1.18 (95% CI, 1.04-1.33; P = .009).

Extent of myocardial viability by tertiles, regardless of viability definition, did not highlight any group with a reduced risk for death or HHF, or group with better LV functional recovery, from OMT plus PCI, compared with OMT alone.

The findings appear to suggest that scar burden, but not extent of viability as it’s usually measured, may effectively guide PCI decisions in such patients, Dr. Perera said.

“I would say that viability testing as we understand it now, based on the paradigm of hibernating myocardium, is very useful,” he said, “but that is not the only information we can get from a viability test.”

Scar burden can also be determined from the same tests but isn’t typically looked at. “We’re actually collecting this information  but not using it,” Dr. Perera said. “When we do, it is really powerfully predictive” of both clinical outcomes and LV functional recovery. “Yet scar burden is not in any of the guidelines for stratifying risk.”

REVIVED-BCIS2 was funded by the National Institute for Health and Care Research Health Technology Assessment Program. Dr. Perera had no disclosures.

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

NEW ORLEANS – Atorvastatin treatment of patients with lymphoma undergoing treatment with an anthracycline significantly cut the incidence of incident cardiac dysfunction by about two-thirds during 12 months of treatment, in a multicenter, randomized trial with 300 enrolled patients.

“These data support the use of atorvastatin among patients with lymphoma being treated with anthracyclines where prevention of cardiac systolic dysfunction is important,” concluded Tomas G. Neilan, MD, at the joint scientific sessions of the American College of Cardiology and the World Heart Federation.

Mitchel L. Zoler/MDedge News

He highlighted that an important difference between the new study, STOP-CA, and a major prior study with a neutral effect published in 2022, was that STOP-CA “was powered for a major change” in cardiac function as the study’s primary outcome, a decline from baseline in left ventricular ejection fraction (LVEF) of at least 10% that also reduced ejection fraction to less than 55%.

“We can consider these medications [atorvastatin] for patients at higher risk for cardiac toxicity from anthracyclines, such as patients who receive a higher dose of an anthracycline, older patients, people with obesity, and women, commented Anita Deswal, MD, professor and chair of the department of cardiology at the University of Texas MD Anderson Cancer Center, Houston, who was not involved with the study.
 

A basis for an ‘important discussion’ with patients

“For patients receiving higher doses of anthracyclines, the STOP-CA trial says that whether to start a statin for cardiac protection is now an important discussion” for these patients to have with their treating clinicians. ”That was not the case before today,” commented Ronald M. Witteles, MD, a cardiologist and professor who specializes in cardio-oncology at Stanford (Calif.) University.

“For a patient being treated for lymphoma or for another cancer and treated with equal or higher anthracycline doses, such as patients with a sarcoma, this trial’s results at the very least warrant a discussion between physicians and patients to make the decision,” Dr. Witteles, who was not involved in the study, said in an interview. But he also cautioned that “whether an individual patient should take a statin in this scenario is still not a no-brainer. While the trial was positive, it was for an imaging rather than for a clinical endpoint.”

Experts noted that a similar study with the clinical endpoint of heart failure would require both many more randomized patients as well as much longer follow-up. STOP-CA was not powered for this endpoint. During its 12-month duration, a total of 11 patients developed heart failure, with no between group difference.

STOP-CA enrolled adults with lymphoma (Hodgkin or non-Hodgkin) and scheduled to undergo anthracycline treatment at eight U.S. centers and one in Canada, and excluded patients already on statin treatment or those for whom a statin was already indicated. Of the 300 enrolled patients, 286 had 12-month follow-up. Randomization assigned patients to receive either 40 mg daily of atorvastatin or placebo.

Their cumulative, median anthracycline dose was 300 mg/m², which is typical for treating lymphoma, but higher than the typical dose use for patients with breast cancer. At baseline, average LVEF was 63%, and after 12 months this had declined to 59%. Forty-six of the 286 patients assessed after 12 months fulfilled the primary outcome of at least a 10–percentage point reduction from baseline in their LVEF and a decline in LVEF to less than 55%. Researchers used cardiac MR to assess LVEF at baseline, and in most patients at follow-up, but a minority of patients had their follow-up assessments by echocardiography because of logistical issues. Greater than 90% of patients were adherent to their assigned regimen.

Tripled incidence of cardiac dysfunction in placebo patients

The incidence of this outcome was 9% among the patients who received atorvastatin, and 22% among those on placebo, a significant difference. The calculated odds of the primary outcome was 2.9-fold more likely among the patients treated with placebo, compared with those who received atorvastatin, also a significant difference.

The study’s secondary outcome was patients who had at least a 5% drop from baseline in their LVEF and with a LVEF of less than 55% after 12 months. This outcome occurred in 13% of patients treated with atorvastatin and in 29% of those who received placebo, a significant difference.

The atorvastatin and placebo arms showed no significant differences in adverse events during the study, with roughly similar incidence rates for muscle pain, elevated liver enzymes, and renal failure. None of the enrolled patients developed myositis.

Atorvastatin treatment also produced an expected average 37% decline from baseline in levels of LDL cholesterol.

“This was a well-designed and important trial,” said Dr. Witteles. “Anthracyclines remain a mainstay of cancer therapies for a number of malignancies, such as lymphoma and sarcoma, and the cardiac side effects of development of cardiac dysfunction are unequivocally real.”
 

The importance of a clinically meaningful effect

The results especially contrast with the findings from the PREVENT study, published in 2022, which compared a daily, 40-mg atorvastatin treatment with placebo in 279 randomized patients with breast cancer and treated for 24 months. However, patients in PREVENT had a cumulative, median anthracycline dose of 240 mg/m², and the study’s primary outcome was the average change from baseline in LVEF after 24 months of treatment, which was a reduction of 0.08 percentage points in the placebo arm, a nonsignificant difference.

In STOP-CA, the average change in LVEF from baseline was a 1–percentage point reduction in the placebo arm, compared with the atorvastatin-treated patients, a difference that was statistically significant, but “not clinically significant,” said Dr. Neilan, director of the cardio-oncology program at Massachusetts General Hospital, Boston. He cited the good fortune of the STOP-CA investigators when they received a recommendation from reviewers early on to design their study to track a clinically meaningful change in LVEF rather than just looking at the average overall change.

Mitchel L. Zoler/MDedge News

Dr. Deswal also noted that it is unlikely that future studies will examine the efficacy of a statin for preventing LVEF in patients across the range of cancers that are eligible for anthracycline treatment. As a result, she predicted that “we may have to extrapolate” the results from STOP-CA to patients with other cancer types.

STOP-CA received no commercial funding. Dr. Neilan has been a consultant for and received fees from Abbvie, Amgen, Bristol-Myers Squibb, CRC Oncology, Genentech, Roche, and Sanofi, and has received grant funding from AstraZeneca and Bristol Myers Squib. Dr. Deswal and Dr. Witteles had no relevant disclosures.

NEW ORLEANS – Atorvastatin treatment of patients with lymphoma undergoing treatment with an anthracycline significantly cut the incidence of incident cardiac dysfunction by about two-thirds during 12 months of treatment, in a multicenter, randomized trial with 300 enrolled patients.

“These data support the use of atorvastatin among patients with lymphoma being treated with anthracyclines where prevention of cardiac systolic dysfunction is important,” concluded Tomas G. Neilan, MD, at the joint scientific sessions of the American College of Cardiology and the World Heart Federation.

Mitchel L. Zoler/MDedge News

He highlighted that an important difference between the new study, STOP-CA, and a major prior study with a neutral effect published in 2022, was that STOP-CA “was powered for a major change” in cardiac function as the study’s primary outcome, a decline from baseline in left ventricular ejection fraction (LVEF) of at least 10% that also reduced ejection fraction to less than 55%.

“We can consider these medications [atorvastatin] for patients at higher risk for cardiac toxicity from anthracyclines, such as patients who receive a higher dose of an anthracycline, older patients, people with obesity, and women, commented Anita Deswal, MD, professor and chair of the department of cardiology at the University of Texas MD Anderson Cancer Center, Houston, who was not involved with the study.
 

A basis for an ‘important discussion’ with patients

“For patients receiving higher doses of anthracyclines, the STOP-CA trial says that whether to start a statin for cardiac protection is now an important discussion” for these patients to have with their treating clinicians. ”That was not the case before today,” commented Ronald M. Witteles, MD, a cardiologist and professor who specializes in cardio-oncology at Stanford (Calif.) University.

“For a patient being treated for lymphoma or for another cancer and treated with equal or higher anthracycline doses, such as patients with a sarcoma, this trial’s results at the very least warrant a discussion between physicians and patients to make the decision,” Dr. Witteles, who was not involved in the study, said in an interview. But he also cautioned that “whether an individual patient should take a statin in this scenario is still not a no-brainer. While the trial was positive, it was for an imaging rather than for a clinical endpoint.”

Experts noted that a similar study with the clinical endpoint of heart failure would require both many more randomized patients as well as much longer follow-up. STOP-CA was not powered for this endpoint. During its 12-month duration, a total of 11 patients developed heart failure, with no between group difference.

STOP-CA enrolled adults with lymphoma (Hodgkin or non-Hodgkin) and scheduled to undergo anthracycline treatment at eight U.S. centers and one in Canada, and excluded patients already on statin treatment or those for whom a statin was already indicated. Of the 300 enrolled patients, 286 had 12-month follow-up. Randomization assigned patients to receive either 40 mg daily of atorvastatin or placebo.

Their cumulative, median anthracycline dose was 300 mg/m², which is typical for treating lymphoma, but higher than the typical dose use for patients with breast cancer. At baseline, average LVEF was 63%, and after 12 months this had declined to 59%. Forty-six of the 286 patients assessed after 12 months fulfilled the primary outcome of at least a 10–percentage point reduction from baseline in their LVEF and a decline in LVEF to less than 55%. Researchers used cardiac MR to assess LVEF at baseline, and in most patients at follow-up, but a minority of patients had their follow-up assessments by echocardiography because of logistical issues. Greater than 90% of patients were adherent to their assigned regimen.

Tripled incidence of cardiac dysfunction in placebo patients

The incidence of this outcome was 9% among the patients who received atorvastatin, and 22% among those on placebo, a significant difference. The calculated odds of the primary outcome was 2.9-fold more likely among the patients treated with placebo, compared with those who received atorvastatin, also a significant difference.

The study’s secondary outcome was patients who had at least a 5% drop from baseline in their LVEF and with a LVEF of less than 55% after 12 months. This outcome occurred in 13% of patients treated with atorvastatin and in 29% of those who received placebo, a significant difference.

The atorvastatin and placebo arms showed no significant differences in adverse events during the study, with roughly similar incidence rates for muscle pain, elevated liver enzymes, and renal failure. None of the enrolled patients developed myositis.

Atorvastatin treatment also produced an expected average 37% decline from baseline in levels of LDL cholesterol.

“This was a well-designed and important trial,” said Dr. Witteles. “Anthracyclines remain a mainstay of cancer therapies for a number of malignancies, such as lymphoma and sarcoma, and the cardiac side effects of development of cardiac dysfunction are unequivocally real.”
 

The importance of a clinically meaningful effect

The results especially contrast with the findings from the PREVENT study, published in 2022, which compared a daily, 40-mg atorvastatin treatment with placebo in 279 randomized patients with breast cancer and treated for 24 months. However, patients in PREVENT had a cumulative, median anthracycline dose of 240 mg/m², and the study’s primary outcome was the average change from baseline in LVEF after 24 months of treatment, which was a reduction of 0.08 percentage points in the placebo arm, a nonsignificant difference.

In STOP-CA, the average change in LVEF from baseline was a 1–percentage point reduction in the placebo arm, compared with the atorvastatin-treated patients, a difference that was statistically significant, but “not clinically significant,” said Dr. Neilan, director of the cardio-oncology program at Massachusetts General Hospital, Boston. He cited the good fortune of the STOP-CA investigators when they received a recommendation from reviewers early on to design their study to track a clinically meaningful change in LVEF rather than just looking at the average overall change.

Mitchel L. Zoler/MDedge News

Dr. Deswal also noted that it is unlikely that future studies will examine the efficacy of a statin for preventing LVEF in patients across the range of cancers that are eligible for anthracycline treatment. As a result, she predicted that “we may have to extrapolate” the results from STOP-CA to patients with other cancer types.

STOP-CA received no commercial funding. Dr. Neilan has been a consultant for and received fees from Abbvie, Amgen, Bristol-Myers Squibb, CRC Oncology, Genentech, Roche, and Sanofi, and has received grant funding from AstraZeneca and Bristol Myers Squib. Dr. Deswal and Dr. Witteles had no relevant disclosures.

NEW ORLEANS – Atorvastatin treatment of patients with lymphoma undergoing treatment with an anthracycline significantly cut the incidence of incident cardiac dysfunction by about two-thirds during 12 months of treatment, in a multicenter, randomized trial with 300 enrolled patients.

“These data support the use of atorvastatin among patients with lymphoma being treated with anthracyclines where prevention of cardiac systolic dysfunction is important,” concluded Tomas G. Neilan, MD, at the joint scientific sessions of the American College of Cardiology and the World Heart Federation.

Mitchel L. Zoler/MDedge News

He highlighted that an important difference between the new study, STOP-CA, and a major prior study with a neutral effect published in 2022, was that STOP-CA “was powered for a major change” in cardiac function as the study’s primary outcome, a decline from baseline in left ventricular ejection fraction (LVEF) of at least 10% that also reduced ejection fraction to less than 55%.

“We can consider these medications [atorvastatin] for patients at higher risk for cardiac toxicity from anthracyclines, such as patients who receive a higher dose of an anthracycline, older patients, people with obesity, and women, commented Anita Deswal, MD, professor and chair of the department of cardiology at the University of Texas MD Anderson Cancer Center, Houston, who was not involved with the study.
 

A basis for an ‘important discussion’ with patients

“For patients receiving higher doses of anthracyclines, the STOP-CA trial says that whether to start a statin for cardiac protection is now an important discussion” for these patients to have with their treating clinicians. ”That was not the case before today,” commented Ronald M. Witteles, MD, a cardiologist and professor who specializes in cardio-oncology at Stanford (Calif.) University.

“For a patient being treated for lymphoma or for another cancer and treated with equal or higher anthracycline doses, such as patients with a sarcoma, this trial’s results at the very least warrant a discussion between physicians and patients to make the decision,” Dr. Witteles, who was not involved in the study, said in an interview. But he also cautioned that “whether an individual patient should take a statin in this scenario is still not a no-brainer. While the trial was positive, it was for an imaging rather than for a clinical endpoint.”

Experts noted that a similar study with the clinical endpoint of heart failure would require both many more randomized patients as well as much longer follow-up. STOP-CA was not powered for this endpoint. During its 12-month duration, a total of 11 patients developed heart failure, with no between group difference.

STOP-CA enrolled adults with lymphoma (Hodgkin or non-Hodgkin) and scheduled to undergo anthracycline treatment at eight U.S. centers and one in Canada, and excluded patients already on statin treatment or those for whom a statin was already indicated. Of the 300 enrolled patients, 286 had 12-month follow-up. Randomization assigned patients to receive either 40 mg daily of atorvastatin or placebo.

Their cumulative, median anthracycline dose was 300 mg/m², which is typical for treating lymphoma, but higher than the typical dose use for patients with breast cancer. At baseline, average LVEF was 63%, and after 12 months this had declined to 59%. Forty-six of the 286 patients assessed after 12 months fulfilled the primary outcome of at least a 10–percentage point reduction from baseline in their LVEF and a decline in LVEF to less than 55%. Researchers used cardiac MR to assess LVEF at baseline, and in most patients at follow-up, but a minority of patients had their follow-up assessments by echocardiography because of logistical issues. Greater than 90% of patients were adherent to their assigned regimen.

Tripled incidence of cardiac dysfunction in placebo patients

The incidence of this outcome was 9% among the patients who received atorvastatin, and 22% among those on placebo, a significant difference. The calculated odds of the primary outcome was 2.9-fold more likely among the patients treated with placebo, compared with those who received atorvastatin, also a significant difference.

The study’s secondary outcome was patients who had at least a 5% drop from baseline in their LVEF and with a LVEF of less than 55% after 12 months. This outcome occurred in 13% of patients treated with atorvastatin and in 29% of those who received placebo, a significant difference.

The atorvastatin and placebo arms showed no significant differences in adverse events during the study, with roughly similar incidence rates for muscle pain, elevated liver enzymes, and renal failure. None of the enrolled patients developed myositis.

Atorvastatin treatment also produced an expected average 37% decline from baseline in levels of LDL cholesterol.

“This was a well-designed and important trial,” said Dr. Witteles. “Anthracyclines remain a mainstay of cancer therapies for a number of malignancies, such as lymphoma and sarcoma, and the cardiac side effects of development of cardiac dysfunction are unequivocally real.”
 

The importance of a clinically meaningful effect

The results especially contrast with the findings from the PREVENT study, published in 2022, which compared a daily, 40-mg atorvastatin treatment with placebo in 279 randomized patients with breast cancer and treated for 24 months. However, patients in PREVENT had a cumulative, median anthracycline dose of 240 mg/m², and the study’s primary outcome was the average change from baseline in LVEF after 24 months of treatment, which was a reduction of 0.08 percentage points in the placebo arm, a nonsignificant difference.

In STOP-CA, the average change in LVEF from baseline was a 1–percentage point reduction in the placebo arm, compared with the atorvastatin-treated patients, a difference that was statistically significant, but “not clinically significant,” said Dr. Neilan, director of the cardio-oncology program at Massachusetts General Hospital, Boston. He cited the good fortune of the STOP-CA investigators when they received a recommendation from reviewers early on to design their study to track a clinically meaningful change in LVEF rather than just looking at the average overall change.

Mitchel L. Zoler/MDedge News

Dr. Deswal also noted that it is unlikely that future studies will examine the efficacy of a statin for preventing LVEF in patients across the range of cancers that are eligible for anthracycline treatment. As a result, she predicted that “we may have to extrapolate” the results from STOP-CA to patients with other cancer types.

STOP-CA received no commercial funding. Dr. Neilan has been a consultant for and received fees from Abbvie, Amgen, Bristol-Myers Squibb, CRC Oncology, Genentech, Roche, and Sanofi, and has received grant funding from AstraZeneca and Bristol Myers Squib. Dr. Deswal and Dr. Witteles had no relevant disclosures.

A new approach to lowering cholesterol with the use of bempedoic acid (Nexletol, Esperion) brought about a significant reduction in cardiovascular events in patients intolerant to statins in the large phase 3, placebo-controlled CLEAR Outcomes trial.

The drug lowered LDL cholesterol by 21% in the study and reduced the composite primary endpoint, including cardiovascular death, MI, stroke, or coronary revascularization, by 13%; MI was reduced by 23% and coronary revascularization, by 19%.

The drug was also well tolerated in the mixed population of primary and secondary prevention patients unable or unwilling to take statins.

Mitchel L. Zoler/MDedge News

“These findings establish bempedoic acid as an effective approach to reduce major cardiovascular events in statin-intolerant patients,” study chair, Steven E. Nissen, MD, of the Cleveland Clinic concluded.

Dr. Nissen presented the CLEAR Outcomes trial at the joint scientific sessions of the American College of Cardiology and the World Heart Federation.

The study was simultaneously published online in the New England Journal of Medicine. Top-line results were previously reported in December 2022.

Dr. Nissen pointed out that, while in the current study bempedoic acid was studied as monotherapy, he believes the drug will mainly be used in clinical practice in combination with ezetimibe, a combination shown to reduce LDL by 38%. “I think this is how it will be used in clinical practice. So, we can get an almost 40% LDL reduction – that’s about the same as 40 mg simvastatin or 20 mg atorvastatin – without giving a statin. And I think that’s where I see the potential of this therapy,” he said.

Dr. Nissen described statin intolerance as “a vexing problem” that prevents many patients from achieving LDL cholesterol levels associated with cardiovascular benefits.

He explained that bempedoic acid, an adenosine triphosphate citrate lyase inhibitor, inhibits hepatic cholesterol synthesis upstream of hydroxymethylglutaryl coenzyme A reductase, the enzyme inhibited by statins. Bempedoic acid is a prodrug activated in the liver, but not in peripheral tissues, resulting in a low incidence of muscle-related adverse events. Although bempedoic acid is approved for lowering LDL cholesterol, this is the first trial to assess its effects on cardiovascular outcomes.
 

CLEAR Outcomes

The CLEAR Outcomes trial included 13,970 patients (48% women) from 32 countries who were unable or unwilling to take statins owing to unacceptable adverse effects and who had, or were at high risk for, cardiovascular disease. They were randomly assigned to oral bempedoic acid, 180 mg daily, or placebo.

The mean LDL cholesterol level at baseline was 139 mg/dL in both groups, and after 6 months, the reduction in the level was greater with bempedoic acid than with placebo by 29.2 mg/dL (a 21.1% reduction).

The drug was also associated with a 22% reduction in high-sensitivity C-reactive protein.

After a median duration of follow-up of 40.6 months, the incidence of a primary endpoint (cardiovascular death, MI, stroke, or coronary revascularization) was significantly lower (by 13%) with bempedoic acid than with placebo (11.7% vs. 13.3%; hazard ratio, 0.87; P = .004).

The absolute risk reduction was 1.6 percentage points, and the number needed to treat for 40 months to prevent one event was 63.

The secondary composite endpoint of cardiovascular death/stroke/MI was reduced by 15% (8.2% vs. 9.5%; HR, 0.85; P = .006). Fatal or nonfatal MI was reduced by 23% (3.7% vs. 4.8%; HR, 0.77; P = .002), and coronary revascularization was reduced by 19% (6.2% vs. 7.6%; HR, 0.81; P = .001).

Bempedoic acid had no significant effects on fatal or nonfatal stroke, death from cardiovascular causes, and death from any cause.

Subgroup analysis showed similar results across all groups and no difference in treatment effect between men and women.

Adverse events were reported by 25% of patients in both groups, with adverse events leading to discontinuation reported by 10.8% of the bempedoic acid group and 10.4% of the placebo group.

Muscle disorders were reported in 15.0% of the bempedoic acid group versus 15.4% of the placebo group. And there was also no difference in new cases of diabetes (16.1% vs. 17.1%).

Bempedoic acid was associated with small increases in the incidence of gout (3.1% vs. 2.1%) and cholelithiasis (2.2% vs. 1.2%), and also small increases in serum creatinine, uric acid, and hepatic enzyme levels.

In the NEJM article, the authors pointed out that the concept of statin intolerance remains controversial. Some recent studies suggested that reported adverse effects represent an anticipation of harm, often described as the “nocebo” effect.

“Whether real or perceived, statin intolerance remains a vexing clinical problem that can prevent patients who are guideline eligible for statin treatment from reaching LDL cholesterol levels associated with clinical benefits. Accordingly, alternative nonstatin therapies are needed to manage the LDL cholesterol level in these patients,” they wrote.

“Management of patients unable or unwilling to take statins represents a challenging and frustrating clinical issue. Regardless whether this problem represents the ‘nocebo’ effect or actual intolerance, these high-risk patients need effective alternative therapies,” Dr. Nissen concluded. “The CLEAR Outcomes trial provides a sound rationale for use of bempedoic acid to reduce major adverse cardiovascular outcomes in patients intolerant to statins.”
 

‘Compelling findings’

Discussing the trial at the ACC late-breaking clinical trial session, Michelle O’Donoghue, MD, Brigham and Women’s Hospital, Boston, noted that this is the largest trial to date in statin-intolerant patients.

She pointed out that although the issue of statin intolerance remains controversial, adherence to statins is often not good, so this is an important patient population to study.

She said it was “quite remarkable” that 48% of the study were women, adding: “There is still much that we need to understand about why women appear to be less willing or able to tolerate statin therapy.” 

Dr. O’Donoghue concluded that the study showed “compelling findings,” and the event reduction was in line with what would be expected from the LDL cholesterol reduction, further supporting the LDL cholesterol hypothesis. 

She added: “Bempedoic acid is an important addition to our arsenal of nonstatin LDL-lowering therapies. And while it was overall well tolerated, it did not get a complete free pass, as there were some modest safety concerns.”

In an editorial accompanying the NEJM publication, John Alexander, MD, Duke Clinical Research Institute, Durham, N.C., wrote: “The compelling results of the CLEAR Outcomes trial will and should increase the use of bempedoic acid in patients with established atherosclerotic vascular disease and in those at high risk for vascular disease who are unable or unwilling to take statins.”

He warned, however, that it is premature to consider bempedoic acid as an alternative to statins. “Given the overwhelming evidence of the vascular benefits of statins, clinicians should continue their efforts to prescribe them at the maximum tolerated doses for appropriate patients, including those who may have discontinued statins because of presumed side effects.”.

Dr. Alexander also pointed out that although bempedoic acid also reduces the LDL cholesterol level in patients taking statins, the clinical benefits of bempedoic acid added to standard statin therapy are unknown. 

On the observation that bempedoic acid had no observed effect on mortality, he noted that “Many individual trials of statins have also not shown an effect of the agent on mortality; it was only through the meta-analysis of multiple clinical trials that the effects of statins on mortality became clear.”

“Bempedoic acid has now entered the list of evidence-based alternatives to statins for primary and secondary prevention in patients at high cardiovascular risk,” Dr. Alexander concluded. “The benefits of bempedoic acid are now clearer, and it is now our responsibility to translate this information into better primary and secondary prevention for more at-risk patients, who will, as a result, benefit from fewer cardiovascular events.”

In a second editorial, John F. Keaney Jr., MD, Brigham and Women’s Hospital, said the lack of a clear association between bempedoic acid and muscle disorders, new-onset diabetes, or worsening hyperglycemia is “welcome news” for statin-intolerant patients.

But he cautioned that “these data must be interpreted cautiously, because bempedoic acid, when combined with a statin, appears to enhance the occurrence of muscle symptoms. Moreover, bempedoic acid has its own reported side effects, including tendon rupture, increased uric acid levels, gout, and reduced glomerular filtration rate, which are not seen with statin use.”

In terms of drug interactions, Dr. Keaney noted that bempedoic acid can increase the circulating levels of simvastatin and pravastatin, so it should not be used in patients who are receiving these agents at doses above 20 mg and 40 mg, respectively. Similarly, bempedoic acid should not be used with fibrates other than fenofibrate because of concerns regarding cholelithiasis.

“Available data clearly indicate that bempedoic acid can be used as an adjunct to statin and nonstatin therapies (except as noted above) to produce an additional 16%-26% reduction in the LDL cholesterol level,” he added. “However, it is not yet clear to what extent adjunctive bempedoic acid will further reduce the risk of cardiovascular events.”

The CLEAR Outcomes trial was supported by Esperion Therapeutics. Dr. Nissen reported receiving grants from AbbVie, AstraZeneca, Bristol-Myers Squibb, Eli Lilly, Esperion, Novartis, and Silence Pharmaceuticals and consultancies with Amgen and Glenmark Pharmaceuticals.

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

A new approach to lowering cholesterol with the use of bempedoic acid (Nexletol, Esperion) brought about a significant reduction in cardiovascular events in patients intolerant to statins in the large phase 3, placebo-controlled CLEAR Outcomes trial.

The drug lowered LDL cholesterol by 21% in the study and reduced the composite primary endpoint, including cardiovascular death, MI, stroke, or coronary revascularization, by 13%; MI was reduced by 23% and coronary revascularization, by 19%.

The drug was also well tolerated in the mixed population of primary and secondary prevention patients unable or unwilling to take statins.

Mitchel L. Zoler/MDedge News

“These findings establish bempedoic acid as an effective approach to reduce major cardiovascular events in statin-intolerant patients,” study chair, Steven E. Nissen, MD, of the Cleveland Clinic concluded.

Dr. Nissen presented the CLEAR Outcomes trial at the joint scientific sessions of the American College of Cardiology and the World Heart Federation.

The study was simultaneously published online in the New England Journal of Medicine. Top-line results were previously reported in December 2022.

Dr. Nissen pointed out that, while in the current study bempedoic acid was studied as monotherapy, he believes the drug will mainly be used in clinical practice in combination with ezetimibe, a combination shown to reduce LDL by 38%. “I think this is how it will be used in clinical practice. So, we can get an almost 40% LDL reduction – that’s about the same as 40 mg simvastatin or 20 mg atorvastatin – without giving a statin. And I think that’s where I see the potential of this therapy,” he said.

Dr. Nissen described statin intolerance as “a vexing problem” that prevents many patients from achieving LDL cholesterol levels associated with cardiovascular benefits.

He explained that bempedoic acid, an adenosine triphosphate citrate lyase inhibitor, inhibits hepatic cholesterol synthesis upstream of hydroxymethylglutaryl coenzyme A reductase, the enzyme inhibited by statins. Bempedoic acid is a prodrug activated in the liver, but not in peripheral tissues, resulting in a low incidence of muscle-related adverse events. Although bempedoic acid is approved for lowering LDL cholesterol, this is the first trial to assess its effects on cardiovascular outcomes.
 

CLEAR Outcomes

The CLEAR Outcomes trial included 13,970 patients (48% women) from 32 countries who were unable or unwilling to take statins owing to unacceptable adverse effects and who had, or were at high risk for, cardiovascular disease. They were randomly assigned to oral bempedoic acid, 180 mg daily, or placebo.

The mean LDL cholesterol level at baseline was 139 mg/dL in both groups, and after 6 months, the reduction in the level was greater with bempedoic acid than with placebo by 29.2 mg/dL (a 21.1% reduction).

The drug was also associated with a 22% reduction in high-sensitivity C-reactive protein.

After a median duration of follow-up of 40.6 months, the incidence of a primary endpoint (cardiovascular death, MI, stroke, or coronary revascularization) was significantly lower (by 13%) with bempedoic acid than with placebo (11.7% vs. 13.3%; hazard ratio, 0.87; P = .004).

The absolute risk reduction was 1.6 percentage points, and the number needed to treat for 40 months to prevent one event was 63.

The secondary composite endpoint of cardiovascular death/stroke/MI was reduced by 15% (8.2% vs. 9.5%; HR, 0.85; P = .006). Fatal or nonfatal MI was reduced by 23% (3.7% vs. 4.8%; HR, 0.77; P = .002), and coronary revascularization was reduced by 19% (6.2% vs. 7.6%; HR, 0.81; P = .001).

Bempedoic acid had no significant effects on fatal or nonfatal stroke, death from cardiovascular causes, and death from any cause.

Subgroup analysis showed similar results across all groups and no difference in treatment effect between men and women.

Adverse events were reported by 25% of patients in both groups, with adverse events leading to discontinuation reported by 10.8% of the bempedoic acid group and 10.4% of the placebo group.

Muscle disorders were reported in 15.0% of the bempedoic acid group versus 15.4% of the placebo group. And there was also no difference in new cases of diabetes (16.1% vs. 17.1%).

Bempedoic acid was associated with small increases in the incidence of gout (3.1% vs. 2.1%) and cholelithiasis (2.2% vs. 1.2%), and also small increases in serum creatinine, uric acid, and hepatic enzyme levels.

In the NEJM article, the authors pointed out that the concept of statin intolerance remains controversial. Some recent studies suggested that reported adverse effects represent an anticipation of harm, often described as the “nocebo” effect.

“Whether real or perceived, statin intolerance remains a vexing clinical problem that can prevent patients who are guideline eligible for statin treatment from reaching LDL cholesterol levels associated with clinical benefits. Accordingly, alternative nonstatin therapies are needed to manage the LDL cholesterol level in these patients,” they wrote.

“Management of patients unable or unwilling to take statins represents a challenging and frustrating clinical issue. Regardless whether this problem represents the ‘nocebo’ effect or actual intolerance, these high-risk patients need effective alternative therapies,” Dr. Nissen concluded. “The CLEAR Outcomes trial provides a sound rationale for use of bempedoic acid to reduce major adverse cardiovascular outcomes in patients intolerant to statins.”
 

‘Compelling findings’

Discussing the trial at the ACC late-breaking clinical trial session, Michelle O’Donoghue, MD, Brigham and Women’s Hospital, Boston, noted that this is the largest trial to date in statin-intolerant patients.

She pointed out that although the issue of statin intolerance remains controversial, adherence to statins is often not good, so this is an important patient population to study.

She said it was “quite remarkable” that 48% of the study were women, adding: “There is still much that we need to understand about why women appear to be less willing or able to tolerate statin therapy.” 

Dr. O’Donoghue concluded that the study showed “compelling findings,” and the event reduction was in line with what would be expected from the LDL cholesterol reduction, further supporting the LDL cholesterol hypothesis. 

She added: “Bempedoic acid is an important addition to our arsenal of nonstatin LDL-lowering therapies. And while it was overall well tolerated, it did not get a complete free pass, as there were some modest safety concerns.”

In an editorial accompanying the NEJM publication, John Alexander, MD, Duke Clinical Research Institute, Durham, N.C., wrote: “The compelling results of the CLEAR Outcomes trial will and should increase the use of bempedoic acid in patients with established atherosclerotic vascular disease and in those at high risk for vascular disease who are unable or unwilling to take statins.”

He warned, however, that it is premature to consider bempedoic acid as an alternative to statins. “Given the overwhelming evidence of the vascular benefits of statins, clinicians should continue their efforts to prescribe them at the maximum tolerated doses for appropriate patients, including those who may have discontinued statins because of presumed side effects.”.

Dr. Alexander also pointed out that although bempedoic acid also reduces the LDL cholesterol level in patients taking statins, the clinical benefits of bempedoic acid added to standard statin therapy are unknown. 

On the observation that bempedoic acid had no observed effect on mortality, he noted that “Many individual trials of statins have also not shown an effect of the agent on mortality; it was only through the meta-analysis of multiple clinical trials that the effects of statins on mortality became clear.”

“Bempedoic acid has now entered the list of evidence-based alternatives to statins for primary and secondary prevention in patients at high cardiovascular risk,” Dr. Alexander concluded. “The benefits of bempedoic acid are now clearer, and it is now our responsibility to translate this information into better primary and secondary prevention for more at-risk patients, who will, as a result, benefit from fewer cardiovascular events.”

In a second editorial, John F. Keaney Jr., MD, Brigham and Women’s Hospital, said the lack of a clear association between bempedoic acid and muscle disorders, new-onset diabetes, or worsening hyperglycemia is “welcome news” for statin-intolerant patients.

But he cautioned that “these data must be interpreted cautiously, because bempedoic acid, when combined with a statin, appears to enhance the occurrence of muscle symptoms. Moreover, bempedoic acid has its own reported side effects, including tendon rupture, increased uric acid levels, gout, and reduced glomerular filtration rate, which are not seen with statin use.”

In terms of drug interactions, Dr. Keaney noted that bempedoic acid can increase the circulating levels of simvastatin and pravastatin, so it should not be used in patients who are receiving these agents at doses above 20 mg and 40 mg, respectively. Similarly, bempedoic acid should not be used with fibrates other than fenofibrate because of concerns regarding cholelithiasis.

“Available data clearly indicate that bempedoic acid can be used as an adjunct to statin and nonstatin therapies (except as noted above) to produce an additional 16%-26% reduction in the LDL cholesterol level,” he added. “However, it is not yet clear to what extent adjunctive bempedoic acid will further reduce the risk of cardiovascular events.”

The CLEAR Outcomes trial was supported by Esperion Therapeutics. Dr. Nissen reported receiving grants from AbbVie, AstraZeneca, Bristol-Myers Squibb, Eli Lilly, Esperion, Novartis, and Silence Pharmaceuticals and consultancies with Amgen and Glenmark Pharmaceuticals.

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

A new approach to lowering cholesterol with the use of bempedoic acid (Nexletol, Esperion) brought about a significant reduction in cardiovascular events in patients intolerant to statins in the large phase 3, placebo-controlled CLEAR Outcomes trial.

The drug lowered LDL cholesterol by 21% in the study and reduced the composite primary endpoint, including cardiovascular death, MI, stroke, or coronary revascularization, by 13%; MI was reduced by 23% and coronary revascularization, by 19%.

The drug was also well tolerated in the mixed population of primary and secondary prevention patients unable or unwilling to take statins.

Mitchel L. Zoler/MDedge News

“These findings establish bempedoic acid as an effective approach to reduce major cardiovascular events in statin-intolerant patients,” study chair, Steven E. Nissen, MD, of the Cleveland Clinic concluded.

Dr. Nissen presented the CLEAR Outcomes trial at the joint scientific sessions of the American College of Cardiology and the World Heart Federation.

The study was simultaneously published online in the New England Journal of Medicine. Top-line results were previously reported in December 2022.

Dr. Nissen pointed out that, while in the current study bempedoic acid was studied as monotherapy, he believes the drug will mainly be used in clinical practice in combination with ezetimibe, a combination shown to reduce LDL by 38%. “I think this is how it will be used in clinical practice. So, we can get an almost 40% LDL reduction – that’s about the same as 40 mg simvastatin or 20 mg atorvastatin – without giving a statin. And I think that’s where I see the potential of this therapy,” he said.

Dr. Nissen described statin intolerance as “a vexing problem” that prevents many patients from achieving LDL cholesterol levels associated with cardiovascular benefits.

He explained that bempedoic acid, an adenosine triphosphate citrate lyase inhibitor, inhibits hepatic cholesterol synthesis upstream of hydroxymethylglutaryl coenzyme A reductase, the enzyme inhibited by statins. Bempedoic acid is a prodrug activated in the liver, but not in peripheral tissues, resulting in a low incidence of muscle-related adverse events. Although bempedoic acid is approved for lowering LDL cholesterol, this is the first trial to assess its effects on cardiovascular outcomes.
 

CLEAR Outcomes

The CLEAR Outcomes trial included 13,970 patients (48% women) from 32 countries who were unable or unwilling to take statins owing to unacceptable adverse effects and who had, or were at high risk for, cardiovascular disease. They were randomly assigned to oral bempedoic acid, 180 mg daily, or placebo.

The mean LDL cholesterol level at baseline was 139 mg/dL in both groups, and after 6 months, the reduction in the level was greater with bempedoic acid than with placebo by 29.2 mg/dL (a 21.1% reduction).

The drug was also associated with a 22% reduction in high-sensitivity C-reactive protein.

After a median duration of follow-up of 40.6 months, the incidence of a primary endpoint (cardiovascular death, MI, stroke, or coronary revascularization) was significantly lower (by 13%) with bempedoic acid than with placebo (11.7% vs. 13.3%; hazard ratio, 0.87; P = .004).

The absolute risk reduction was 1.6 percentage points, and the number needed to treat for 40 months to prevent one event was 63.

The secondary composite endpoint of cardiovascular death/stroke/MI was reduced by 15% (8.2% vs. 9.5%; HR, 0.85; P = .006). Fatal or nonfatal MI was reduced by 23% (3.7% vs. 4.8%; HR, 0.77; P = .002), and coronary revascularization was reduced by 19% (6.2% vs. 7.6%; HR, 0.81; P = .001).

Bempedoic acid had no significant effects on fatal or nonfatal stroke, death from cardiovascular causes, and death from any cause.

Subgroup analysis showed similar results across all groups and no difference in treatment effect between men and women.

Adverse events were reported by 25% of patients in both groups, with adverse events leading to discontinuation reported by 10.8% of the bempedoic acid group and 10.4% of the placebo group.

Muscle disorders were reported in 15.0% of the bempedoic acid group versus 15.4% of the placebo group. And there was also no difference in new cases of diabetes (16.1% vs. 17.1%).

Bempedoic acid was associated with small increases in the incidence of gout (3.1% vs. 2.1%) and cholelithiasis (2.2% vs. 1.2%), and also small increases in serum creatinine, uric acid, and hepatic enzyme levels.

In the NEJM article, the authors pointed out that the concept of statin intolerance remains controversial. Some recent studies suggested that reported adverse effects represent an anticipation of harm, often described as the “nocebo” effect.

“Whether real or perceived, statin intolerance remains a vexing clinical problem that can prevent patients who are guideline eligible for statin treatment from reaching LDL cholesterol levels associated with clinical benefits. Accordingly, alternative nonstatin therapies are needed to manage the LDL cholesterol level in these patients,” they wrote.

“Management of patients unable or unwilling to take statins represents a challenging and frustrating clinical issue. Regardless whether this problem represents the ‘nocebo’ effect or actual intolerance, these high-risk patients need effective alternative therapies,” Dr. Nissen concluded. “The CLEAR Outcomes trial provides a sound rationale for use of bempedoic acid to reduce major adverse cardiovascular outcomes in patients intolerant to statins.”
 

‘Compelling findings’

Discussing the trial at the ACC late-breaking clinical trial session, Michelle O’Donoghue, MD, Brigham and Women’s Hospital, Boston, noted that this is the largest trial to date in statin-intolerant patients.

She pointed out that although the issue of statin intolerance remains controversial, adherence to statins is often not good, so this is an important patient population to study.

She said it was “quite remarkable” that 48% of the study were women, adding: “There is still much that we need to understand about why women appear to be less willing or able to tolerate statin therapy.” 

Dr. O’Donoghue concluded that the study showed “compelling findings,” and the event reduction was in line with what would be expected from the LDL cholesterol reduction, further supporting the LDL cholesterol hypothesis. 

She added: “Bempedoic acid is an important addition to our arsenal of nonstatin LDL-lowering therapies. And while it was overall well tolerated, it did not get a complete free pass, as there were some modest safety concerns.”

In an editorial accompanying the NEJM publication, John Alexander, MD, Duke Clinical Research Institute, Durham, N.C., wrote: “The compelling results of the CLEAR Outcomes trial will and should increase the use of bempedoic acid in patients with established atherosclerotic vascular disease and in those at high risk for vascular disease who are unable or unwilling to take statins.”

He warned, however, that it is premature to consider bempedoic acid as an alternative to statins. “Given the overwhelming evidence of the vascular benefits of statins, clinicians should continue their efforts to prescribe them at the maximum tolerated doses for appropriate patients, including those who may have discontinued statins because of presumed side effects.”.

Dr. Alexander also pointed out that although bempedoic acid also reduces the LDL cholesterol level in patients taking statins, the clinical benefits of bempedoic acid added to standard statin therapy are unknown. 

On the observation that bempedoic acid had no observed effect on mortality, he noted that “Many individual trials of statins have also not shown an effect of the agent on mortality; it was only through the meta-analysis of multiple clinical trials that the effects of statins on mortality became clear.”

“Bempedoic acid has now entered the list of evidence-based alternatives to statins for primary and secondary prevention in patients at high cardiovascular risk,” Dr. Alexander concluded. “The benefits of bempedoic acid are now clearer, and it is now our responsibility to translate this information into better primary and secondary prevention for more at-risk patients, who will, as a result, benefit from fewer cardiovascular events.”

In a second editorial, John F. Keaney Jr., MD, Brigham and Women’s Hospital, said the lack of a clear association between bempedoic acid and muscle disorders, new-onset diabetes, or worsening hyperglycemia is “welcome news” for statin-intolerant patients.

But he cautioned that “these data must be interpreted cautiously, because bempedoic acid, when combined with a statin, appears to enhance the occurrence of muscle symptoms. Moreover, bempedoic acid has its own reported side effects, including tendon rupture, increased uric acid levels, gout, and reduced glomerular filtration rate, which are not seen with statin use.”

In terms of drug interactions, Dr. Keaney noted that bempedoic acid can increase the circulating levels of simvastatin and pravastatin, so it should not be used in patients who are receiving these agents at doses above 20 mg and 40 mg, respectively. Similarly, bempedoic acid should not be used with fibrates other than fenofibrate because of concerns regarding cholelithiasis.

“Available data clearly indicate that bempedoic acid can be used as an adjunct to statin and nonstatin therapies (except as noted above) to produce an additional 16%-26% reduction in the LDL cholesterol level,” he added. “However, it is not yet clear to what extent adjunctive bempedoic acid will further reduce the risk of cardiovascular events.”

The CLEAR Outcomes trial was supported by Esperion Therapeutics. Dr. Nissen reported receiving grants from AbbVie, AstraZeneca, Bristol-Myers Squibb, Eli Lilly, Esperion, Novartis, and Silence Pharmaceuticals and consultancies with Amgen and Glenmark Pharmaceuticals.

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

NEW ORLEANS – In the first pivotal randomized, controlled trial of a transcatheter device for the repair of severe tricuspid regurgitation, a large reduction in valve dysfunction was associated with substantial improvement in quality of life (QOL) persisting out of 1 year of follow-up, according to results of the TRILUMINATE trial.

Based on the low procedural risks of the repair, the principal investigator, Paul Sorajja, MD, called the results “very clinically meaningful” as he presented the results at the joint scientific sessions of the American College of Cardiology and the World Heart Federation.

Ted Bosworth/MDedge News

Conducted at 65 centers in the United States, Canada, and North America, TRILUMINATE evaluated a transcatheter end-to-end (TEER) repair performed with the TriClip G4 Delivery System (Abbott). The study included two cohorts, both of which will be followed for 5 years. One included patients with very severe tricuspid regurgitation enrolled in a single arm. Data on this cohort is expected later in 2023.

In the randomized portion of the study, 350 patients enrolled with severe tricuspid regurgitation underwent TEER with a clipping device and then were followed on the guideline-directed therapy (GDMT) for heart failure they were receiving at baseline. The control group was managed on GDMT alone.

The primary composite endpoint at 1 year was a composite of death from any cause and/or tricuspid valve surgery, hospitalization for heart failure, and quality of life as measured with the Kansas City Cardiomyopathy questionnaire (KCCQ).
 

Benefit driven by quality of life

For the primary endpoint, the win ratio, a statistical calculation of those who did relative to those who did not benefit, was 1.48, signifying a 48% advantage (P = .02). This was driven almost entirely by the KCCQ endpoint. There was no significant difference death and/or tricuspid valve surgery, which occurred in about 10% of both groups (P = .75) or heart failure hospitalization, which was occurred in slightly more patients randomized to repair (14.9% vs. 12.1%; P = .41).

For KCCQ, the mean increase at 1 year was 12.3 points in the repair group versus 0.6 points (P < .001) in the control group. With an increase of 5-10 points typically considered to be clinically meaningful, the advantage of repair over GDMT at the threshold of 15 points or greater was highly statistically significant (49.7% vs. 26.4%; P < .0001).

This advantage was attributed to control of regurgitation. The proportion achieving moderate or less regurgitation sustained at 1 year was 87% in the repair group versus 4.8% in the GDMT group (P < .0001).

When assessed independent of treatment, KCCQ benefits at 1 year increased in a stepwise fashion as severity of regurgitation was reduced, climbing from 2 points if there was no improvement to 6 points with one grade in improvement and then to 18 points with at least a two-grade improvement.

For regurgitation, “the repair was extremely effective,” said Dr. Sorajja of Allina Health Minneapolis Heart Institute at Abbott Northwestern Hospital, Minneapolis. He added that the degree of regurgitation control in the TRILUMINATE trial “is the highest ever reported.” With previous trials with other transcatheter devices in development, the improvement so far has been on the order of 70%-80%.

For enrollment in TRILUMINATE, patients were required to have at least an intermediate risk of morbidity or mortality from tricuspid valve surgery. Exclusion criteria included a left ventricular ejection fraction (LVEF) less than 20% and severe pulmonary hypertension.

More than 70% of patients had the highest (torrential) or second highest (massive) category of regurgitation on a five-level scale by echocardiography. Almost all the remaining were at the third level (severe).

Of those enrolled, the average age was roughly 78 years. About 55% were women. Nearly 60% were in New York Heart Association class III or IV heart failure and most had significant comorbidities, including hypertension (> 80%), atrial fibrillation (about 90%), and renal disease (35%). Patients with diabetes (16%), chronic obstructive pulmonary disease (10%), and liver disease (7.5%) were represented in lower numbers.
 

Surgery is not necessarily an option

All enrolled patients were considered to be at intermediate or greater risk for mortality with surgical replacement of the tricuspid valve, but Dr. Sorajja pointed out that surgery, which involves valve replacement, is not necessarily an alternative to valve repair. Even in fit patients, the high morbidity, mortality, and extended hospital stay associated with surgical valve replacement makes this procedure unattractive.

In this trial, most patients who underwent the transcatheter procedure were discharged within a day. The safety was excellent, Dr. Sorajja said. Only three patients (1.7%) had a major adverse event. This included two cases of new-onset renal failure and one cardiovascular death. There were no cases of endocarditis requiring surgery or any other type of nonelective cardiovascular surgery, including for any device-related issue.

In the sick population enrolled, Dr. Sorajja characterized the number of adverse events over 1 year as “very low.”

Ted Bosworth/MDedge News

These results are important, according to Kendra Grubb, MD, surgical director of the Structural Heart and Valve Center, Emory University, Atlanta. While she expressed surprise that there was no signal of benefit on hard endpoints at 1 year, she emphasized that “these patients feel terrible,” and they are frustrating to manage because surgery is often contraindicated or impractical.

“Finally, we have something for this group,” she said, noting that the mortality from valve replacement surgery even among patients who are fit enough for surgery to be considered is about 10%.

Ajay Kirtane, MD, director of the Cardiac Catheterization Laboratories at Columbia University, New York, was more circumspect. He agreed that the improvement in QOL was encouraging, but cautioned that QOL is a particularly soft outcome in a nonrandomized trial in which patients may feel better just knowing that there regurgitation has been controlled. He found the lack of benefit on hard outcomes not just surprising but “disappointing.”

Still, he agreed the improvement in QOL is potentially meaningful for a procedure that appears to be relatively safe.

Dr. Sorajja reported financial relationships with Boston Scientific, Edwards Lifesciences, Foldax. 4C Medical, Gore Medtronic, Phillips, Siemens, Shifamed, Vdyne, xDot, and Abbott Structural, which provided funding for this trial. Dr. Grubb reported financial relationships with Abbott Vascular, Ancora Heart, Bioventrix, Boston Scientific, Edwards Lifesciences, 4C Medical, JenaValve, and Medtronic. Dr. Kirtane reported financial relationships with Abbott Vascular, Amgen, Boston Scientific, Chiesi, Medtronic, Opsens, Phillips, ReCor, Regeneron, and Zoll.

NEW ORLEANS – In the first pivotal randomized, controlled trial of a transcatheter device for the repair of severe tricuspid regurgitation, a large reduction in valve dysfunction was associated with substantial improvement in quality of life (QOL) persisting out of 1 year of follow-up, according to results of the TRILUMINATE trial.

Based on the low procedural risks of the repair, the principal investigator, Paul Sorajja, MD, called the results “very clinically meaningful” as he presented the results at the joint scientific sessions of the American College of Cardiology and the World Heart Federation.

Ted Bosworth/MDedge News

Conducted at 65 centers in the United States, Canada, and North America, TRILUMINATE evaluated a transcatheter end-to-end (TEER) repair performed with the TriClip G4 Delivery System (Abbott). The study included two cohorts, both of which will be followed for 5 years. One included patients with very severe tricuspid regurgitation enrolled in a single arm. Data on this cohort is expected later in 2023.

In the randomized portion of the study, 350 patients enrolled with severe tricuspid regurgitation underwent TEER with a clipping device and then were followed on the guideline-directed therapy (GDMT) for heart failure they were receiving at baseline. The control group was managed on GDMT alone.

The primary composite endpoint at 1 year was a composite of death from any cause and/or tricuspid valve surgery, hospitalization for heart failure, and quality of life as measured with the Kansas City Cardiomyopathy questionnaire (KCCQ).
 

Benefit driven by quality of life

For the primary endpoint, the win ratio, a statistical calculation of those who did relative to those who did not benefit, was 1.48, signifying a 48% advantage (P = .02). This was driven almost entirely by the KCCQ endpoint. There was no significant difference death and/or tricuspid valve surgery, which occurred in about 10% of both groups (P = .75) or heart failure hospitalization, which was occurred in slightly more patients randomized to repair (14.9% vs. 12.1%; P = .41).

For KCCQ, the mean increase at 1 year was 12.3 points in the repair group versus 0.6 points (P < .001) in the control group. With an increase of 5-10 points typically considered to be clinically meaningful, the advantage of repair over GDMT at the threshold of 15 points or greater was highly statistically significant (49.7% vs. 26.4%; P < .0001).

This advantage was attributed to control of regurgitation. The proportion achieving moderate or less regurgitation sustained at 1 year was 87% in the repair group versus 4.8% in the GDMT group (P < .0001).

When assessed independent of treatment, KCCQ benefits at 1 year increased in a stepwise fashion as severity of regurgitation was reduced, climbing from 2 points if there was no improvement to 6 points with one grade in improvement and then to 18 points with at least a two-grade improvement.

For regurgitation, “the repair was extremely effective,” said Dr. Sorajja of Allina Health Minneapolis Heart Institute at Abbott Northwestern Hospital, Minneapolis. He added that the degree of regurgitation control in the TRILUMINATE trial “is the highest ever reported.” With previous trials with other transcatheter devices in development, the improvement so far has been on the order of 70%-80%.

For enrollment in TRILUMINATE, patients were required to have at least an intermediate risk of morbidity or mortality from tricuspid valve surgery. Exclusion criteria included a left ventricular ejection fraction (LVEF) less than 20% and severe pulmonary hypertension.

More than 70% of patients had the highest (torrential) or second highest (massive) category of regurgitation on a five-level scale by echocardiography. Almost all the remaining were at the third level (severe).

Of those enrolled, the average age was roughly 78 years. About 55% were women. Nearly 60% were in New York Heart Association class III or IV heart failure and most had significant comorbidities, including hypertension (> 80%), atrial fibrillation (about 90%), and renal disease (35%). Patients with diabetes (16%), chronic obstructive pulmonary disease (10%), and liver disease (7.5%) were represented in lower numbers.
 

Surgery is not necessarily an option

All enrolled patients were considered to be at intermediate or greater risk for mortality with surgical replacement of the tricuspid valve, but Dr. Sorajja pointed out that surgery, which involves valve replacement, is not necessarily an alternative to valve repair. Even in fit patients, the high morbidity, mortality, and extended hospital stay associated with surgical valve replacement makes this procedure unattractive.

In this trial, most patients who underwent the transcatheter procedure were discharged within a day. The safety was excellent, Dr. Sorajja said. Only three patients (1.7%) had a major adverse event. This included two cases of new-onset renal failure and one cardiovascular death. There were no cases of endocarditis requiring surgery or any other type of nonelective cardiovascular surgery, including for any device-related issue.

In the sick population enrolled, Dr. Sorajja characterized the number of adverse events over 1 year as “very low.”

Ted Bosworth/MDedge News

These results are important, according to Kendra Grubb, MD, surgical director of the Structural Heart and Valve Center, Emory University, Atlanta. While she expressed surprise that there was no signal of benefit on hard endpoints at 1 year, she emphasized that “these patients feel terrible,” and they are frustrating to manage because surgery is often contraindicated or impractical.

“Finally, we have something for this group,” she said, noting that the mortality from valve replacement surgery even among patients who are fit enough for surgery to be considered is about 10%.

Ajay Kirtane, MD, director of the Cardiac Catheterization Laboratories at Columbia University, New York, was more circumspect. He agreed that the improvement in QOL was encouraging, but cautioned that QOL is a particularly soft outcome in a nonrandomized trial in which patients may feel better just knowing that there regurgitation has been controlled. He found the lack of benefit on hard outcomes not just surprising but “disappointing.”

Still, he agreed the improvement in QOL is potentially meaningful for a procedure that appears to be relatively safe.

Dr. Sorajja reported financial relationships with Boston Scientific, Edwards Lifesciences, Foldax. 4C Medical, Gore Medtronic, Phillips, Siemens, Shifamed, Vdyne, xDot, and Abbott Structural, which provided funding for this trial. Dr. Grubb reported financial relationships with Abbott Vascular, Ancora Heart, Bioventrix, Boston Scientific, Edwards Lifesciences, 4C Medical, JenaValve, and Medtronic. Dr. Kirtane reported financial relationships with Abbott Vascular, Amgen, Boston Scientific, Chiesi, Medtronic, Opsens, Phillips, ReCor, Regeneron, and Zoll.

NEW ORLEANS – In the first pivotal randomized, controlled trial of a transcatheter device for the repair of severe tricuspid regurgitation, a large reduction in valve dysfunction was associated with substantial improvement in quality of life (QOL) persisting out of 1 year of follow-up, according to results of the TRILUMINATE trial.

Based on the low procedural risks of the repair, the principal investigator, Paul Sorajja, MD, called the results “very clinically meaningful” as he presented the results at the joint scientific sessions of the American College of Cardiology and the World Heart Federation.

Ted Bosworth/MDedge News

Conducted at 65 centers in the United States, Canada, and North America, TRILUMINATE evaluated a transcatheter end-to-end (TEER) repair performed with the TriClip G4 Delivery System (Abbott). The study included two cohorts, both of which will be followed for 5 years. One included patients with very severe tricuspid regurgitation enrolled in a single arm. Data on this cohort is expected later in 2023.

In the randomized portion of the study, 350 patients enrolled with severe tricuspid regurgitation underwent TEER with a clipping device and then were followed on the guideline-directed therapy (GDMT) for heart failure they were receiving at baseline. The control group was managed on GDMT alone.

The primary composite endpoint at 1 year was a composite of death from any cause and/or tricuspid valve surgery, hospitalization for heart failure, and quality of life as measured with the Kansas City Cardiomyopathy questionnaire (KCCQ).
 

Benefit driven by quality of life

For the primary endpoint, the win ratio, a statistical calculation of those who did relative to those who did not benefit, was 1.48, signifying a 48% advantage (P = .02). This was driven almost entirely by the KCCQ endpoint. There was no significant difference death and/or tricuspid valve surgery, which occurred in about 10% of both groups (P = .75) or heart failure hospitalization, which was occurred in slightly more patients randomized to repair (14.9% vs. 12.1%; P = .41).

For KCCQ, the mean increase at 1 year was 12.3 points in the repair group versus 0.6 points (P < .001) in the control group. With an increase of 5-10 points typically considered to be clinically meaningful, the advantage of repair over GDMT at the threshold of 15 points or greater was highly statistically significant (49.7% vs. 26.4%; P < .0001).

This advantage was attributed to control of regurgitation. The proportion achieving moderate or less regurgitation sustained at 1 year was 87% in the repair group versus 4.8% in the GDMT group (P < .0001).

When assessed independent of treatment, KCCQ benefits at 1 year increased in a stepwise fashion as severity of regurgitation was reduced, climbing from 2 points if there was no improvement to 6 points with one grade in improvement and then to 18 points with at least a two-grade improvement.

For regurgitation, “the repair was extremely effective,” said Dr. Sorajja of Allina Health Minneapolis Heart Institute at Abbott Northwestern Hospital, Minneapolis. He added that the degree of regurgitation control in the TRILUMINATE trial “is the highest ever reported.” With previous trials with other transcatheter devices in development, the improvement so far has been on the order of 70%-80%.

For enrollment in TRILUMINATE, patients were required to have at least an intermediate risk of morbidity or mortality from tricuspid valve surgery. Exclusion criteria included a left ventricular ejection fraction (LVEF) less than 20% and severe pulmonary hypertension.

More than 70% of patients had the highest (torrential) or second highest (massive) category of regurgitation on a five-level scale by echocardiography. Almost all the remaining were at the third level (severe).

Of those enrolled, the average age was roughly 78 years. About 55% were women. Nearly 60% were in New York Heart Association class III or IV heart failure and most had significant comorbidities, including hypertension (> 80%), atrial fibrillation (about 90%), and renal disease (35%). Patients with diabetes (16%), chronic obstructive pulmonary disease (10%), and liver disease (7.5%) were represented in lower numbers.
 

Surgery is not necessarily an option

All enrolled patients were considered to be at intermediate or greater risk for mortality with surgical replacement of the tricuspid valve, but Dr. Sorajja pointed out that surgery, which involves valve replacement, is not necessarily an alternative to valve repair. Even in fit patients, the high morbidity, mortality, and extended hospital stay associated with surgical valve replacement makes this procedure unattractive.

In this trial, most patients who underwent the transcatheter procedure were discharged within a day. The safety was excellent, Dr. Sorajja said. Only three patients (1.7%) had a major adverse event. This included two cases of new-onset renal failure and one cardiovascular death. There were no cases of endocarditis requiring surgery or any other type of nonelective cardiovascular surgery, including for any device-related issue.

In the sick population enrolled, Dr. Sorajja characterized the number of adverse events over 1 year as “very low.”

Ted Bosworth/MDedge News

These results are important, according to Kendra Grubb, MD, surgical director of the Structural Heart and Valve Center, Emory University, Atlanta. While she expressed surprise that there was no signal of benefit on hard endpoints at 1 year, she emphasized that “these patients feel terrible,” and they are frustrating to manage because surgery is often contraindicated or impractical.

“Finally, we have something for this group,” she said, noting that the mortality from valve replacement surgery even among patients who are fit enough for surgery to be considered is about 10%.

Ajay Kirtane, MD, director of the Cardiac Catheterization Laboratories at Columbia University, New York, was more circumspect. He agreed that the improvement in QOL was encouraging, but cautioned that QOL is a particularly soft outcome in a nonrandomized trial in which patients may feel better just knowing that there regurgitation has been controlled. He found the lack of benefit on hard outcomes not just surprising but “disappointing.”

Still, he agreed the improvement in QOL is potentially meaningful for a procedure that appears to be relatively safe.

Dr. Sorajja reported financial relationships with Boston Scientific, Edwards Lifesciences, Foldax. 4C Medical, Gore Medtronic, Phillips, Siemens, Shifamed, Vdyne, xDot, and Abbott Structural, which provided funding for this trial. Dr. Grubb reported financial relationships with Abbott Vascular, Ancora Heart, Bioventrix, Boston Scientific, Edwards Lifesciences, 4C Medical, JenaValve, and Medtronic. Dr. Kirtane reported financial relationships with Abbott Vascular, Amgen, Boston Scientific, Chiesi, Medtronic, Opsens, Phillips, ReCor, Regeneron, and Zoll.

Vidyard Video

Additional videos from SGS are available here, including these recent offerings:

• Perineal leiomyoma after 4th degree laceration

• Tips and tricks for a successful rollerball endometrial ablation

• Resection of infected sacrohysteropexy mesh

Vidyard Video

Additional videos from SGS are available here, including these recent offerings:

• Perineal leiomyoma after 4th degree laceration

• Tips and tricks for a successful rollerball endometrial ablation

• Resection of infected sacrohysteropexy mesh

Vidyard Video

Additional videos from SGS are available here, including these recent offerings:

• Perineal leiomyoma after 4th degree laceration

• Tips and tricks for a successful rollerball endometrial ablation

• Resection of infected sacrohysteropexy mesh

Liver transplant recipients with nonalcoholic steatohepatitis (NASH) who received grafts from older donors are at higher risk for posttransplant death, especially from infection, according to a new study.

All-cause mortality was twice as high and death from an infectious cause was more than three times as high for patients with NASH who received liver grafts from octogenarian donors than for those who received a liver from someone younger than 50.

“The findings from this study implicate a critical need to investigate donor age as an important risk factor for poorer host and graft survival,” wrote the authors, led by David Lee, MD, of the University of Maryland, Baltimore.

“Given the possibility of infectious graft complications, post–liver transplant follow-ups may need to be more comprehensive and frequent in these individuals who receive grafts from older donors,” they add.

The study was published online in Digestive and Liver Disease.
 

Donor age trends

Dr. Lee and colleagues pulled data from the United Network for Organ Sharing (UNOS) Standard Transplant Analysis and Research database, a national database of deidentified donor and recipient transplant data. The analysis excluded recipients younger than 18, those with a living donor, those who had hepatocellular carcinoma prior to transplant, and those who had been diagnosed with additional liver disorders apart from NASH.

The team identified 8,88 recipients with NASH who received a liver transplant from 2005–2019. They stratified recipients by donor age. The 5,187 patients who received livers from donors who were younger than 50 served as the reference group. The remainder were placed into four cohorts – 1,842 whose donors were in their 50s, 1,290 whose donors were in their 60s, 504 whose donors were in their 70s, and 65 whose donors were in their 80s.

The researchers found that in comparison with the reference group, the average age of recipients in each donor-age cohort was progressively older. Two donor-age cohorts had significantly higher proportions of recipients with diabetes than the 46.5% in the reference group – the sexagenarian cohort (51.7%) and the octogenarian group (66.2%).

The median follow-up time ranged from 2.35–3.61 years across all age groups.

The researchers found that for all donor-age groups excluding donors in their 60s, recipients had higher risk of all-cause mortality after transplant than the reference group. Recipients with donors in their 50s had a 16% greater risk for death (P = .01), and recipients with donors in their 70s had a 20% greater risk (P = .05). For recipients with octogenarian donors, the adjusted hazard ratio for all-cause mortality was 2.01 (P < .001).

Only recipients in the octogenarian donor cohort were at increased risk of graft failure, compared with the reference group (aHR, 3.72; P = .002).

As donor age increased, the recipient’s risk of dying from sepsis and infectious causes rose, compared with the reference group. Recipients’ likelihood of sepsis death increased by 71% (P = .001) with donors in their 50s, 73% (P = .003) with donors in their 60s, and 76% (P = .03) with donors in their 70s. For recipients with octogenarian donors, the risk more than tripled (aHR, 3.58; P = .007). Likewise, recipients with donors in their 70s were 73% more likely to die from infectious causes. That risk nearly quadrupled among those with donors in their 80s.
 

Recipient factors at play?

While the study found a relationship between liver donor age and recipient outcomes, it is not clear whether any other recipient factors may have contributed to the higher risk of all-cause mortality, sad Nancy Reau, MD, chief of the hepatology section at Rush University Medical Center, Chicago. The researchers did not parse out whether younger recipients did better with older organs than older recipients or whether older recipients fared worse with younger organs, she said in an interview.

“I wasn’t convinced that they had demonstrated that the recipient may not have played a role in that,” said Dr. Reau, who wasn’t involved with the study.

The analysis only a found an increased risk of graft failure among recipients who received organs from octogenarian donors, so factors other than liver transplant may have contributed to all-cause mortality, she noted.

The UNOS database has some limitations, noted Timothy Pruett, MD, who directs the liver transplant program at the University of Minnesota, Minneapolis. Because the database pulls information from transplantation centers across the country, it can be difficult to standardize specific patient variables in the data.

While it’s clear that a patient died, it’s less certain whether an infection was the cause of death and whether that infection was somehow associated with the liver, noted Dr. Pruett, who wasn’t involved in the research. For example, a patient could have had broken a hip, gone to the hospital, and contracted pneumonia, which led to their death.

“There’s just not much granularity in the database, and we can’t overextrapolate what we see,” Dr. Pruett said in an interview.
 

Knowledge gaps

Dr. Lee agreed that more research is needed to understand what may be driving higher mortality rates among patients who receive older organs. “There are still a lot of gaps in knowledge with respect to why.”

Dr. Reau said she is curious as to whether certain comorbidities, such as previous infection, diabetes, or obesity, could predict worse outcomes for recipients with older organs.

“We would love to give all of our patients younger organs, but if that leads to even more disparity in need [compared] to availability and the alternative is not surviving, I think you have to place [this work] into context,” she said.

The study findings shouldn’t be used to deter patients with NASH from considering older organs, Dr. Reau said. More insight as to which populations might want to be choosier owing to an elevated risk would be beneficial, she added.

Dr. Lee, Dr. Pruett, and Dr. Reau reported no relevant financial relationships.

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

Liver transplant recipients with nonalcoholic steatohepatitis (NASH) who received grafts from older donors are at higher risk for posttransplant death, especially from infection, according to a new study.

All-cause mortality was twice as high and death from an infectious cause was more than three times as high for patients with NASH who received liver grafts from octogenarian donors than for those who received a liver from someone younger than 50.

“The findings from this study implicate a critical need to investigate donor age as an important risk factor for poorer host and graft survival,” wrote the authors, led by David Lee, MD, of the University of Maryland, Baltimore.

“Given the possibility of infectious graft complications, post–liver transplant follow-ups may need to be more comprehensive and frequent in these individuals who receive grafts from older donors,” they add.

The study was published online in Digestive and Liver Disease.
 

Donor age trends

Dr. Lee and colleagues pulled data from the United Network for Organ Sharing (UNOS) Standard Transplant Analysis and Research database, a national database of deidentified donor and recipient transplant data. The analysis excluded recipients younger than 18, those with a living donor, those who had hepatocellular carcinoma prior to transplant, and those who had been diagnosed with additional liver disorders apart from NASH.

The team identified 8,88 recipients with NASH who received a liver transplant from 2005–2019. They stratified recipients by donor age. The 5,187 patients who received livers from donors who were younger than 50 served as the reference group. The remainder were placed into four cohorts – 1,842 whose donors were in their 50s, 1,290 whose donors were in their 60s, 504 whose donors were in their 70s, and 65 whose donors were in their 80s.

The researchers found that in comparison with the reference group, the average age of recipients in each donor-age cohort was progressively older. Two donor-age cohorts had significantly higher proportions of recipients with diabetes than the 46.5% in the reference group – the sexagenarian cohort (51.7%) and the octogenarian group (66.2%).

The median follow-up time ranged from 2.35–3.61 years across all age groups.

The researchers found that for all donor-age groups excluding donors in their 60s, recipients had higher risk of all-cause mortality after transplant than the reference group. Recipients with donors in their 50s had a 16% greater risk for death (P = .01), and recipients with donors in their 70s had a 20% greater risk (P = .05). For recipients with octogenarian donors, the adjusted hazard ratio for all-cause mortality was 2.01 (P < .001).

Only recipients in the octogenarian donor cohort were at increased risk of graft failure, compared with the reference group (aHR, 3.72; P = .002).

As donor age increased, the recipient’s risk of dying from sepsis and infectious causes rose, compared with the reference group. Recipients’ likelihood of sepsis death increased by 71% (P = .001) with donors in their 50s, 73% (P = .003) with donors in their 60s, and 76% (P = .03) with donors in their 70s. For recipients with octogenarian donors, the risk more than tripled (aHR, 3.58; P = .007). Likewise, recipients with donors in their 70s were 73% more likely to die from infectious causes. That risk nearly quadrupled among those with donors in their 80s.
 

Recipient factors at play?

While the study found a relationship between liver donor age and recipient outcomes, it is not clear whether any other recipient factors may have contributed to the higher risk of all-cause mortality, sad Nancy Reau, MD, chief of the hepatology section at Rush University Medical Center, Chicago. The researchers did not parse out whether younger recipients did better with older organs than older recipients or whether older recipients fared worse with younger organs, she said in an interview.

“I wasn’t convinced that they had demonstrated that the recipient may not have played a role in that,” said Dr. Reau, who wasn’t involved with the study.

The analysis only a found an increased risk of graft failure among recipients who received organs from octogenarian donors, so factors other than liver transplant may have contributed to all-cause mortality, she noted.

The UNOS database has some limitations, noted Timothy Pruett, MD, who directs the liver transplant program at the University of Minnesota, Minneapolis. Because the database pulls information from transplantation centers across the country, it can be difficult to standardize specific patient variables in the data.

While it’s clear that a patient died, it’s less certain whether an infection was the cause of death and whether that infection was somehow associated with the liver, noted Dr. Pruett, who wasn’t involved in the research. For example, a patient could have had broken a hip, gone to the hospital, and contracted pneumonia, which led to their death.

“There’s just not much granularity in the database, and we can’t overextrapolate what we see,” Dr. Pruett said in an interview.
 

Knowledge gaps

Dr. Lee agreed that more research is needed to understand what may be driving higher mortality rates among patients who receive older organs. “There are still a lot of gaps in knowledge with respect to why.”

Dr. Reau said she is curious as to whether certain comorbidities, such as previous infection, diabetes, or obesity, could predict worse outcomes for recipients with older organs.

“We would love to give all of our patients younger organs, but if that leads to even more disparity in need [compared] to availability and the alternative is not surviving, I think you have to place [this work] into context,” she said.

The study findings shouldn’t be used to deter patients with NASH from considering older organs, Dr. Reau said. More insight as to which populations might want to be choosier owing to an elevated risk would be beneficial, she added.

Dr. Lee, Dr. Pruett, and Dr. Reau reported no relevant financial relationships.

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

Liver transplant recipients with nonalcoholic steatohepatitis (NASH) who received grafts from older donors are at higher risk for posttransplant death, especially from infection, according to a new study.

All-cause mortality was twice as high and death from an infectious cause was more than three times as high for patients with NASH who received liver grafts from octogenarian donors than for those who received a liver from someone younger than 50.

“The findings from this study implicate a critical need to investigate donor age as an important risk factor for poorer host and graft survival,” wrote the authors, led by David Lee, MD, of the University of Maryland, Baltimore.

“Given the possibility of infectious graft complications, post–liver transplant follow-ups may need to be more comprehensive and frequent in these individuals who receive grafts from older donors,” they add.

The study was published online in Digestive and Liver Disease.
 

Donor age trends

Dr. Lee and colleagues pulled data from the United Network for Organ Sharing (UNOS) Standard Transplant Analysis and Research database, a national database of deidentified donor and recipient transplant data. The analysis excluded recipients younger than 18, those with a living donor, those who had hepatocellular carcinoma prior to transplant, and those who had been diagnosed with additional liver disorders apart from NASH.

The team identified 8,88 recipients with NASH who received a liver transplant from 2005–2019. They stratified recipients by donor age. The 5,187 patients who received livers from donors who were younger than 50 served as the reference group. The remainder were placed into four cohorts – 1,842 whose donors were in their 50s, 1,290 whose donors were in their 60s, 504 whose donors were in their 70s, and 65 whose donors were in their 80s.

The researchers found that in comparison with the reference group, the average age of recipients in each donor-age cohort was progressively older. Two donor-age cohorts had significantly higher proportions of recipients with diabetes than the 46.5% in the reference group – the sexagenarian cohort (51.7%) and the octogenarian group (66.2%).

The median follow-up time ranged from 2.35–3.61 years across all age groups.

The researchers found that for all donor-age groups excluding donors in their 60s, recipients had higher risk of all-cause mortality after transplant than the reference group. Recipients with donors in their 50s had a 16% greater risk for death (P = .01), and recipients with donors in their 70s had a 20% greater risk (P = .05). For recipients with octogenarian donors, the adjusted hazard ratio for all-cause mortality was 2.01 (P < .001).

Only recipients in the octogenarian donor cohort were at increased risk of graft failure, compared with the reference group (aHR, 3.72; P = .002).

As donor age increased, the recipient’s risk of dying from sepsis and infectious causes rose, compared with the reference group. Recipients’ likelihood of sepsis death increased by 71% (P = .001) with donors in their 50s, 73% (P = .003) with donors in their 60s, and 76% (P = .03) with donors in their 70s. For recipients with octogenarian donors, the risk more than tripled (aHR, 3.58; P = .007). Likewise, recipients with donors in their 70s were 73% more likely to die from infectious causes. That risk nearly quadrupled among those with donors in their 80s.
 

Recipient factors at play?

While the study found a relationship between liver donor age and recipient outcomes, it is not clear whether any other recipient factors may have contributed to the higher risk of all-cause mortality, sad Nancy Reau, MD, chief of the hepatology section at Rush University Medical Center, Chicago. The researchers did not parse out whether younger recipients did better with older organs than older recipients or whether older recipients fared worse with younger organs, she said in an interview.

“I wasn’t convinced that they had demonstrated that the recipient may not have played a role in that,” said Dr. Reau, who wasn’t involved with the study.

The analysis only a found an increased risk of graft failure among recipients who received organs from octogenarian donors, so factors other than liver transplant may have contributed to all-cause mortality, she noted.

The UNOS database has some limitations, noted Timothy Pruett, MD, who directs the liver transplant program at the University of Minnesota, Minneapolis. Because the database pulls information from transplantation centers across the country, it can be difficult to standardize specific patient variables in the data.

While it’s clear that a patient died, it’s less certain whether an infection was the cause of death and whether that infection was somehow associated with the liver, noted Dr. Pruett, who wasn’t involved in the research. For example, a patient could have had broken a hip, gone to the hospital, and contracted pneumonia, which led to their death.

“There’s just not much granularity in the database, and we can’t overextrapolate what we see,” Dr. Pruett said in an interview.
 

Knowledge gaps

Dr. Lee agreed that more research is needed to understand what may be driving higher mortality rates among patients who receive older organs. “There are still a lot of gaps in knowledge with respect to why.”

Dr. Reau said she is curious as to whether certain comorbidities, such as previous infection, diabetes, or obesity, could predict worse outcomes for recipients with older organs.

“We would love to give all of our patients younger organs, but if that leads to even more disparity in need [compared] to availability and the alternative is not surviving, I think you have to place [this work] into context,” she said.

The study findings shouldn’t be used to deter patients with NASH from considering older organs, Dr. Reau said. More insight as to which populations might want to be choosier owing to an elevated risk would be beneficial, she added.

Dr. Lee, Dr. Pruett, and Dr. Reau reported no relevant financial relationships.

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

Prescribing a biologic for people with Crohn’s disease is a complicated process that includes consideration of previous therapy, the severity of disease, cost, and other factors. Missing, however, has been the ability to accurately predict endoscopic response to a specific biologic agent to guide choice of therapy.

New peripheral blood biomarkers based on DNA methylation could soon help predict endoscopic response to adalimumab, vedolizumab, and ustekinumab for people with Crohn’s disease.

Although the biomarker panels are not yet clinically available, researchers demonstrated that they are accurate, valid, stable over time, and largely specific to each of the three biologic agents.

“Evidence over the last 10 years has shown a consistent difference in DNA methylation between people with IBD [inflammatory bowel disease] and healthy controls. Many of these studies suggest a role for DNA methylation for treatment response prediction,” Vincent Joustra, PhD, said when presenting results of the EPIC-CD trial at the annual congress of the European Crohn’s and Colitis Organisation.

After comparing endoscopic responders to nonresponders in different datasets. researchers found that “DNA methylation profiles are, in fact, associated with response to adalimumab, vedolizumab, and ustekinumab,” added Dr. Joustra, visiting fellow in the department of gastroenterology and hepatology at Amsterdam University Medical Centers.

DNA methylation – the presence or absence of a methyl group on a specific DNA location called a CpG – does not change a person’s genotype. Rather, the methylation process either activates or deactivates a gene’s expression. It can be used to predict treatment response.

Within the past 2 decades, “biologics have revolutionized care of IBD patients. Yet, despite their clinical efficacy, treatment choice is currently based on trial and error, which is suboptimal,” Dr. Joustra said.

Adding biomarkers to improve biologic medication selection is “urgently needed,” he added. “However, such biomarkers are not available for practice today.”
 

Methylation methodology

Dr. Joustra and colleagues prospectively studied DNA methylation in the peripheral blood samples of 184 adults with Crohn’s disease. They compared the biomarkers at baseline in people set to start biologic therapy and again at a median of 28 weeks following treatment with adalimumab (58 patients), vedolizumab (64 patients), and ustekinumab (62 patients).

Participants were divided into a discovery cohort to identify relevant biomarkers and a validation cohort to confirm the findings. Results were validated against a separate cohort of patients at Oxford (England) University.

Response was strictly defined as a decrease of at least 50% in a simple endoscopic score for Crohn’s disease, corticosteroid-free clinical response or remission using the Harvey Bradshaw Index, and/or biochemical response or remission.

Before patients were treated, the investigators created three epigenetic panels. The CpG loci of interest were identified using the Infinium MethylationEPIC BeadChip array, which measures over 850,000 CpG sites across the whole genome.
 

Key findings

One epigenetic panel featured 100 CpG loci relevant for adalimumab that correlated to an “endoscopic response with high accuracy,” with an area under the curve of 0.73 upon validation. A second panel, created for vedolizumab, included 22 CpG loci and had an AUC accuracy of 0.89. The third panel, specific to ustekinumab, had 68 CpG loci and an AUC accuracy of 0.94.

The markers are largely unique to each agent. Only two CpG loci overlapped between adalimumab and ustekinumab, Dr. Joustra said.

“Importantly, our model was able to predict response prior to treatment in a completely different set of patients from the Oxford validation cohort with an AUC of 0.75,” Dr. Joustra said.

A secondary analysis revealed no differences in the stability and robustness of the methylation markers between baseline and 28 weeks. This finding implies that the biomarkers are stable during the induction and maintenance phases of treatment.

“Of course, we need to clinically validate our findings in a clinical trial, which is ongoing,” Dr. Joustra said. This work will continue in the EPIC-CD study, as well as in the OMICROHN clinical trial.
 

Promising start

“These are really interesting findings that address an area of importance in treating patients with Crohn’s disease,” said ECCO session comoderator Tim Raine, PhD, who was not affiliated with the research.

“The team found a signature that appears to provide helpful prediction of response to specific treatments. Importantly, this signature appeared to be stable over time, to be specific to individual drugs, and could be validated in an external cohort of patients,” added Dr. Raine, consultant gastroenterologist at Cambridge (England) University Hospitals NHS Trust.

Although the technologies used in EPIC-CD are not yet routinely available in clinical practice, “the methodologies are well established, and with appropriate development in a validated laboratory, as well as further validation work, could form a useful test for gastroenterologists treating patients with Crohn’s disease,” Dr. Raine said.

The study was independently supported. Dr. Joustra and Dr. Raine reported no relevant financial relationships.

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

Prescribing a biologic for people with Crohn’s disease is a complicated process that includes consideration of previous therapy, the severity of disease, cost, and other factors. Missing, however, has been the ability to accurately predict endoscopic response to a specific biologic agent to guide choice of therapy.

New peripheral blood biomarkers based on DNA methylation could soon help predict endoscopic response to adalimumab, vedolizumab, and ustekinumab for people with Crohn’s disease.

Although the biomarker panels are not yet clinically available, researchers demonstrated that they are accurate, valid, stable over time, and largely specific to each of the three biologic agents.

“Evidence over the last 10 years has shown a consistent difference in DNA methylation between people with IBD [inflammatory bowel disease] and healthy controls. Many of these studies suggest a role for DNA methylation for treatment response prediction,” Vincent Joustra, PhD, said when presenting results of the EPIC-CD trial at the annual congress of the European Crohn’s and Colitis Organisation.

After comparing endoscopic responders to nonresponders in different datasets. researchers found that “DNA methylation profiles are, in fact, associated with response to adalimumab, vedolizumab, and ustekinumab,” added Dr. Joustra, visiting fellow in the department of gastroenterology and hepatology at Amsterdam University Medical Centers.

DNA methylation – the presence or absence of a methyl group on a specific DNA location called a CpG – does not change a person’s genotype. Rather, the methylation process either activates or deactivates a gene’s expression. It can be used to predict treatment response.

Within the past 2 decades, “biologics have revolutionized care of IBD patients. Yet, despite their clinical efficacy, treatment choice is currently based on trial and error, which is suboptimal,” Dr. Joustra said.

Adding biomarkers to improve biologic medication selection is “urgently needed,” he added. “However, such biomarkers are not available for practice today.”
 

Methylation methodology

Dr. Joustra and colleagues prospectively studied DNA methylation in the peripheral blood samples of 184 adults with Crohn’s disease. They compared the biomarkers at baseline in people set to start biologic therapy and again at a median of 28 weeks following treatment with adalimumab (58 patients), vedolizumab (64 patients), and ustekinumab (62 patients).

Participants were divided into a discovery cohort to identify relevant biomarkers and a validation cohort to confirm the findings. Results were validated against a separate cohort of patients at Oxford (England) University.

Response was strictly defined as a decrease of at least 50% in a simple endoscopic score for Crohn’s disease, corticosteroid-free clinical response or remission using the Harvey Bradshaw Index, and/or biochemical response or remission.

Before patients were treated, the investigators created three epigenetic panels. The CpG loci of interest were identified using the Infinium MethylationEPIC BeadChip array, which measures over 850,000 CpG sites across the whole genome.
 

Key findings

One epigenetic panel featured 100 CpG loci relevant for adalimumab that correlated to an “endoscopic response with high accuracy,” with an area under the curve of 0.73 upon validation. A second panel, created for vedolizumab, included 22 CpG loci and had an AUC accuracy of 0.89. The third panel, specific to ustekinumab, had 68 CpG loci and an AUC accuracy of 0.94.

The markers are largely unique to each agent. Only two CpG loci overlapped between adalimumab and ustekinumab, Dr. Joustra said.

“Importantly, our model was able to predict response prior to treatment in a completely different set of patients from the Oxford validation cohort with an AUC of 0.75,” Dr. Joustra said.

A secondary analysis revealed no differences in the stability and robustness of the methylation markers between baseline and 28 weeks. This finding implies that the biomarkers are stable during the induction and maintenance phases of treatment.

“Of course, we need to clinically validate our findings in a clinical trial, which is ongoing,” Dr. Joustra said. This work will continue in the EPIC-CD study, as well as in the OMICROHN clinical trial.
 

Promising start

“These are really interesting findings that address an area of importance in treating patients with Crohn’s disease,” said ECCO session comoderator Tim Raine, PhD, who was not affiliated with the research.

“The team found a signature that appears to provide helpful prediction of response to specific treatments. Importantly, this signature appeared to be stable over time, to be specific to individual drugs, and could be validated in an external cohort of patients,” added Dr. Raine, consultant gastroenterologist at Cambridge (England) University Hospitals NHS Trust.

Although the technologies used in EPIC-CD are not yet routinely available in clinical practice, “the methodologies are well established, and with appropriate development in a validated laboratory, as well as further validation work, could form a useful test for gastroenterologists treating patients with Crohn’s disease,” Dr. Raine said.

The study was independently supported. Dr. Joustra and Dr. Raine reported no relevant financial relationships.

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

Prescribing a biologic for people with Crohn’s disease is a complicated process that includes consideration of previous therapy, the severity of disease, cost, and other factors. Missing, however, has been the ability to accurately predict endoscopic response to a specific biologic agent to guide choice of therapy.

New peripheral blood biomarkers based on DNA methylation could soon help predict endoscopic response to adalimumab, vedolizumab, and ustekinumab for people with Crohn’s disease.

Although the biomarker panels are not yet clinically available, researchers demonstrated that they are accurate, valid, stable over time, and largely specific to each of the three biologic agents.

“Evidence over the last 10 years has shown a consistent difference in DNA methylation between people with IBD [inflammatory bowel disease] and healthy controls. Many of these studies suggest a role for DNA methylation for treatment response prediction,” Vincent Joustra, PhD, said when presenting results of the EPIC-CD trial at the annual congress of the European Crohn’s and Colitis Organisation.

After comparing endoscopic responders to nonresponders in different datasets. researchers found that “DNA methylation profiles are, in fact, associated with response to adalimumab, vedolizumab, and ustekinumab,” added Dr. Joustra, visiting fellow in the department of gastroenterology and hepatology at Amsterdam University Medical Centers.

DNA methylation – the presence or absence of a methyl group on a specific DNA location called a CpG – does not change a person’s genotype. Rather, the methylation process either activates or deactivates a gene’s expression. It can be used to predict treatment response.

Within the past 2 decades, “biologics have revolutionized care of IBD patients. Yet, despite their clinical efficacy, treatment choice is currently based on trial and error, which is suboptimal,” Dr. Joustra said.

Adding biomarkers to improve biologic medication selection is “urgently needed,” he added. “However, such biomarkers are not available for practice today.”
 

Methylation methodology

Dr. Joustra and colleagues prospectively studied DNA methylation in the peripheral blood samples of 184 adults with Crohn’s disease. They compared the biomarkers at baseline in people set to start biologic therapy and again at a median of 28 weeks following treatment with adalimumab (58 patients), vedolizumab (64 patients), and ustekinumab (62 patients).

Participants were divided into a discovery cohort to identify relevant biomarkers and a validation cohort to confirm the findings. Results were validated against a separate cohort of patients at Oxford (England) University.

Response was strictly defined as a decrease of at least 50% in a simple endoscopic score for Crohn’s disease, corticosteroid-free clinical response or remission using the Harvey Bradshaw Index, and/or biochemical response or remission.

Before patients were treated, the investigators created three epigenetic panels. The CpG loci of interest were identified using the Infinium MethylationEPIC BeadChip array, which measures over 850,000 CpG sites across the whole genome.
 

Key findings

One epigenetic panel featured 100 CpG loci relevant for adalimumab that correlated to an “endoscopic response with high accuracy,” with an area under the curve of 0.73 upon validation. A second panel, created for vedolizumab, included 22 CpG loci and had an AUC accuracy of 0.89. The third panel, specific to ustekinumab, had 68 CpG loci and an AUC accuracy of 0.94.

The markers are largely unique to each agent. Only two CpG loci overlapped between adalimumab and ustekinumab, Dr. Joustra said.

“Importantly, our model was able to predict response prior to treatment in a completely different set of patients from the Oxford validation cohort with an AUC of 0.75,” Dr. Joustra said.

A secondary analysis revealed no differences in the stability and robustness of the methylation markers between baseline and 28 weeks. This finding implies that the biomarkers are stable during the induction and maintenance phases of treatment.

“Of course, we need to clinically validate our findings in a clinical trial, which is ongoing,” Dr. Joustra said. This work will continue in the EPIC-CD study, as well as in the OMICROHN clinical trial.
 

Promising start

“These are really interesting findings that address an area of importance in treating patients with Crohn’s disease,” said ECCO session comoderator Tim Raine, PhD, who was not affiliated with the research.

“The team found a signature that appears to provide helpful prediction of response to specific treatments. Importantly, this signature appeared to be stable over time, to be specific to individual drugs, and could be validated in an external cohort of patients,” added Dr. Raine, consultant gastroenterologist at Cambridge (England) University Hospitals NHS Trust.

Although the technologies used in EPIC-CD are not yet routinely available in clinical practice, “the methodologies are well established, and with appropriate development in a validated laboratory, as well as further validation work, could form a useful test for gastroenterologists treating patients with Crohn’s disease,” Dr. Raine said.

The study was independently supported. Dr. Joustra and Dr. Raine reported no relevant financial relationships.

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

When the Food and Drug Administration first approved the da Vinci Surgical System (Intuitive Surgical, Sunnyvale, Calif.) for adult use in 2000, it altered the face of minimally invasive surgery across a multitude of specialties. Improved three-dimensional visualization and enhanced instrument articulation facilitates complex dissections and intracorporeal suturing. While the standard of care for gender-affirming vaginoplasty remains the single-stage penile inversion vaginoplasty, robotic procedures are quickly emerging as alternative options for both primary and revisional surgeries.

The single-stage penile inversion vaginoplasty requires an adequate amount of penoscrotal tissue not only to line a neovaginal canal that measures 12-15 cm, but also to create external vulvar structures. While this is often sufficient in most candidates, there is an increasing number of patients who are receiving puberty blockers, resulting in penoscrotal hypoplasia.

Alternatively, there are patients who experience loss of vaginal depth and vaginal stenosis who seek revisional surgeries. Additional donor sites for skin grafting are available and include the lower abdomen and thighs, although patients may not want these donor site scars. With these donor sites, there is also concern about graft contracture, which could lead to recurrent vaginal stenosis.¹ Robotic peritoneal vaginoplasty and robotic enteric vaginoplasty can serve as additional options for patients seeking revisional surgery or who have insufficient genital skin. One benefit of using peritoneal flaps is that they are hairless and are well vascularized with minimal donor site morbidity.¹ Currently, there are two predominant techniques that utilize peritoneal flaps: the modified Davydov procedure and the tubularized urachus-peritoneal hinge flap.

The modified Davydov technique, which originated in the treatment of congenital vaginal agenesis in cisgender women, involves the creation of anterior and posterior peritoneal flaps. This type of peritoneal vaginoplasty is more commonly utilized for primary cases.

Ideally, there is a robotic surgeon (typically a urologist) working in tandem with the perineal surgeon. The robotic surgeon makes a horizontal incision along the peritoneal ridge at the rectovesical junction and continues the dissection within Denonvilliers fascia, between the prostate and rectum, to the pelvic floor. This dissection is like that performed in a robot-assisted laparoscopic prostatectomy.

Simultaneously, the perineal surgeon will break through the pelvic floor with assistance of the robotic view. Peritoneal flaps are raised from the anterior rectum and posterior bladder.^2,3 In primary cases, the penoscrotal flap is introduced into the abdomen from the perineum and sutured to the anterior and posterior peritoneum to create a circumferential canal. At the apex of the neovagina, these anterior and posterior flaps are then sutured together.^2,3

The tubularized urachus-peritoneal hinge flap technique is predominantly used for revision cases in patients who experienced neovaginal shortening and desire increased neovaginal depth. As peritoneal reach is limited, candidates for this procedure must have both adequate width and neovaginal canal depth.⁴ Once intra-abdominal access is achieved, an anterior peritoneal flap is mobilized to the level of the bladder and rotated 180 degrees inferiorly.⁴ The superior aspect of the flap is flipped is mobilized and is sutured to the peritoneum at the apex of the neovaginal canal.

The main benefit of these procedures, compared with traditional techniques, is increased neovaginal depth. The average vaginal length in patients undergoing peritoneal vaginoplasties is 14.2 cm, compared with 11.6 cm achieved in those using skin grafts.^1,3 However, many surgeons report achieving 14-15 cm of depth with the traditional vaginoplasty. There are insufficient short- and long-term data for the peritoneal technique to recommend this as a first-line procedure.

Complications for peritoneal vaginoplasty procedures are similar to those of single-stage penile inversion vaginoplasty cases but with additional operative risks associated with laparoscopic/robotic surgery. These risks include injury to viscera and major vessels during initial intra-abdominal access, intra-abdominal adhesions, port site hernias, need to convert to an open procedure, and equipment malfunction.² Additional postoperative risks include pelvic abscess formation, dehiscence of the peritoneal-vaginal incision, and peritoneal perforation during dilation.^2,3 Surgeons and institutions must also weigh the cost of using the robot versus the cost of additional revisional surgical procedures. While initial studies evaluating robotic peritoneal vaginoplasty procedures have yielded promising preliminary results, additional studies are warranted.

Dr. Brandt is an ob.gyn. and fellowship-trained gender-affirming surgeon in West Reading, Pa.

References

1. Salibian AA et al. Plast Reconstr Surg. 2021;147(4):634e-43e.

2. Dy GW et al. In: Nikolavsky D and Blakely SA, eds. Urological care for the transgender patient: A comprehensive guide. Switzerland: Springer, 2021:237-48.

3. Jacoby A et al. J Urol. 2019;201(6):1171-5.

4. Smith SM et al. J Sex Med. 2022;10(6):100572.

When the Food and Drug Administration first approved the da Vinci Surgical System (Intuitive Surgical, Sunnyvale, Calif.) for adult use in 2000, it altered the face of minimally invasive surgery across a multitude of specialties. Improved three-dimensional visualization and enhanced instrument articulation facilitates complex dissections and intracorporeal suturing. While the standard of care for gender-affirming vaginoplasty remains the single-stage penile inversion vaginoplasty, robotic procedures are quickly emerging as alternative options for both primary and revisional surgeries.

The single-stage penile inversion vaginoplasty requires an adequate amount of penoscrotal tissue not only to line a neovaginal canal that measures 12-15 cm, but also to create external vulvar structures. While this is often sufficient in most candidates, there is an increasing number of patients who are receiving puberty blockers, resulting in penoscrotal hypoplasia.

Alternatively, there are patients who experience loss of vaginal depth and vaginal stenosis who seek revisional surgeries. Additional donor sites for skin grafting are available and include the lower abdomen and thighs, although patients may not want these donor site scars. With these donor sites, there is also concern about graft contracture, which could lead to recurrent vaginal stenosis.¹ Robotic peritoneal vaginoplasty and robotic enteric vaginoplasty can serve as additional options for patients seeking revisional surgery or who have insufficient genital skin. One benefit of using peritoneal flaps is that they are hairless and are well vascularized with minimal donor site morbidity.¹ Currently, there are two predominant techniques that utilize peritoneal flaps: the modified Davydov procedure and the tubularized urachus-peritoneal hinge flap.

The modified Davydov technique, which originated in the treatment of congenital vaginal agenesis in cisgender women, involves the creation of anterior and posterior peritoneal flaps. This type of peritoneal vaginoplasty is more commonly utilized for primary cases.

Ideally, there is a robotic surgeon (typically a urologist) working in tandem with the perineal surgeon. The robotic surgeon makes a horizontal incision along the peritoneal ridge at the rectovesical junction and continues the dissection within Denonvilliers fascia, between the prostate and rectum, to the pelvic floor. This dissection is like that performed in a robot-assisted laparoscopic prostatectomy.

Simultaneously, the perineal surgeon will break through the pelvic floor with assistance of the robotic view. Peritoneal flaps are raised from the anterior rectum and posterior bladder.^2,3 In primary cases, the penoscrotal flap is introduced into the abdomen from the perineum and sutured to the anterior and posterior peritoneum to create a circumferential canal. At the apex of the neovagina, these anterior and posterior flaps are then sutured together.^2,3

The tubularized urachus-peritoneal hinge flap technique is predominantly used for revision cases in patients who experienced neovaginal shortening and desire increased neovaginal depth. As peritoneal reach is limited, candidates for this procedure must have both adequate width and neovaginal canal depth.⁴ Once intra-abdominal access is achieved, an anterior peritoneal flap is mobilized to the level of the bladder and rotated 180 degrees inferiorly.⁴ The superior aspect of the flap is flipped is mobilized and is sutured to the peritoneum at the apex of the neovaginal canal.

The main benefit of these procedures, compared with traditional techniques, is increased neovaginal depth. The average vaginal length in patients undergoing peritoneal vaginoplasties is 14.2 cm, compared with 11.6 cm achieved in those using skin grafts.^1,3 However, many surgeons report achieving 14-15 cm of depth with the traditional vaginoplasty. There are insufficient short- and long-term data for the peritoneal technique to recommend this as a first-line procedure.

Complications for peritoneal vaginoplasty procedures are similar to those of single-stage penile inversion vaginoplasty cases but with additional operative risks associated with laparoscopic/robotic surgery. These risks include injury to viscera and major vessels during initial intra-abdominal access, intra-abdominal adhesions, port site hernias, need to convert to an open procedure, and equipment malfunction.² Additional postoperative risks include pelvic abscess formation, dehiscence of the peritoneal-vaginal incision, and peritoneal perforation during dilation.^2,3 Surgeons and institutions must also weigh the cost of using the robot versus the cost of additional revisional surgical procedures. While initial studies evaluating robotic peritoneal vaginoplasty procedures have yielded promising preliminary results, additional studies are warranted.

Dr. Brandt is an ob.gyn. and fellowship-trained gender-affirming surgeon in West Reading, Pa.

References

1. Salibian AA et al. Plast Reconstr Surg. 2021;147(4):634e-43e.

2. Dy GW et al. In: Nikolavsky D and Blakely SA, eds. Urological care for the transgender patient: A comprehensive guide. Switzerland: Springer, 2021:237-48.

3. Jacoby A et al. J Urol. 2019;201(6):1171-5.

4. Smith SM et al. J Sex Med. 2022;10(6):100572.

When the Food and Drug Administration first approved the da Vinci Surgical System (Intuitive Surgical, Sunnyvale, Calif.) for adult use in 2000, it altered the face of minimally invasive surgery across a multitude of specialties. Improved three-dimensional visualization and enhanced instrument articulation facilitates complex dissections and intracorporeal suturing. While the standard of care for gender-affirming vaginoplasty remains the single-stage penile inversion vaginoplasty, robotic procedures are quickly emerging as alternative options for both primary and revisional surgeries.

The single-stage penile inversion vaginoplasty requires an adequate amount of penoscrotal tissue not only to line a neovaginal canal that measures 12-15 cm, but also to create external vulvar structures. While this is often sufficient in most candidates, there is an increasing number of patients who are receiving puberty blockers, resulting in penoscrotal hypoplasia.

Alternatively, there are patients who experience loss of vaginal depth and vaginal stenosis who seek revisional surgeries. Additional donor sites for skin grafting are available and include the lower abdomen and thighs, although patients may not want these donor site scars. With these donor sites, there is also concern about graft contracture, which could lead to recurrent vaginal stenosis.¹ Robotic peritoneal vaginoplasty and robotic enteric vaginoplasty can serve as additional options for patients seeking revisional surgery or who have insufficient genital skin. One benefit of using peritoneal flaps is that they are hairless and are well vascularized with minimal donor site morbidity.¹ Currently, there are two predominant techniques that utilize peritoneal flaps: the modified Davydov procedure and the tubularized urachus-peritoneal hinge flap.

The modified Davydov technique, which originated in the treatment of congenital vaginal agenesis in cisgender women, involves the creation of anterior and posterior peritoneal flaps. This type of peritoneal vaginoplasty is more commonly utilized for primary cases.

Ideally, there is a robotic surgeon (typically a urologist) working in tandem with the perineal surgeon. The robotic surgeon makes a horizontal incision along the peritoneal ridge at the rectovesical junction and continues the dissection within Denonvilliers fascia, between the prostate and rectum, to the pelvic floor. This dissection is like that performed in a robot-assisted laparoscopic prostatectomy.

Simultaneously, the perineal surgeon will break through the pelvic floor with assistance of the robotic view. Peritoneal flaps are raised from the anterior rectum and posterior bladder.^2,3 In primary cases, the penoscrotal flap is introduced into the abdomen from the perineum and sutured to the anterior and posterior peritoneum to create a circumferential canal. At the apex of the neovagina, these anterior and posterior flaps are then sutured together.^2,3

The tubularized urachus-peritoneal hinge flap technique is predominantly used for revision cases in patients who experienced neovaginal shortening and desire increased neovaginal depth. As peritoneal reach is limited, candidates for this procedure must have both adequate width and neovaginal canal depth.⁴ Once intra-abdominal access is achieved, an anterior peritoneal flap is mobilized to the level of the bladder and rotated 180 degrees inferiorly.⁴ The superior aspect of the flap is flipped is mobilized and is sutured to the peritoneum at the apex of the neovaginal canal.

The main benefit of these procedures, compared with traditional techniques, is increased neovaginal depth. The average vaginal length in patients undergoing peritoneal vaginoplasties is 14.2 cm, compared with 11.6 cm achieved in those using skin grafts.^1,3 However, many surgeons report achieving 14-15 cm of depth with the traditional vaginoplasty. There are insufficient short- and long-term data for the peritoneal technique to recommend this as a first-line procedure.

Complications for peritoneal vaginoplasty procedures are similar to those of single-stage penile inversion vaginoplasty cases but with additional operative risks associated with laparoscopic/robotic surgery. These risks include injury to viscera and major vessels during initial intra-abdominal access, intra-abdominal adhesions, port site hernias, need to convert to an open procedure, and equipment malfunction.² Additional postoperative risks include pelvic abscess formation, dehiscence of the peritoneal-vaginal incision, and peritoneal perforation during dilation.^2,3 Surgeons and institutions must also weigh the cost of using the robot versus the cost of additional revisional surgical procedures. While initial studies evaluating robotic peritoneal vaginoplasty procedures have yielded promising preliminary results, additional studies are warranted.

Dr. Brandt is an ob.gyn. and fellowship-trained gender-affirming surgeon in West Reading, Pa.

References

1. Salibian AA et al. Plast Reconstr Surg. 2021;147(4):634e-43e.

2. Dy GW et al. In: Nikolavsky D and Blakely SA, eds. Urological care for the transgender patient: A comprehensive guide. Switzerland: Springer, 2021:237-48.

3. Jacoby A et al. J Urol. 2019;201(6):1171-5.

4. Smith SM et al. J Sex Med. 2022;10(6):100572.