TBD Meeting (3134-19)

A novel marker of repolarization may identify patients with cardiomyopathy who would benefit from an implanted cardioverter defibrillator, according to a European research study presented at the annual congress of the European Society of Cardiology and published simultaneously in The Lancet.

High periodic repolarization dynamics were linked to substantial reductions in mortality in a prespecified substudy of the EU-CERT-ICD (European Comparative Effectiveness Research to Assess the Use of Primary Prophylactic Implantable Cardioverter Defibrillators).

The degree of periodic repolarization dynamics correlated with reductions in mortality in the 1,371 patients, 968 of whom had ICD implantation and 403 of whom were treated conservatively, in the prospective, nonrandomized controlled cohort study conducted at 44 centers in 15 countries within the European Union. At a median follow-up of 2-7 years, the ICD group had a mortality rate of 14%; at a follow-up of 1-2 years, the control group had a mortality rate of 16%, resulting in a 43% overall reduction in mortality for the ICD group.

Low periodic repolarization dynamics were associated with a low reduction in ICD-related death, whereas high periodic repolarization dynamics were linked to substantial reductions in mortality. In 199 patients with periodic repolarization dynamics of 7.5% or higher, ICD implantation resulted in a 75% reduction in death, compared with controls. Periodic repolarization dynamics also served as reliable predictors of appropriate shocks in patients with ICDs as well as death in controls.

Because of the link between high periodic repolarization dynamics and greater benefits, cardiologists may be able to use the measure as a marker to individualize treatment decisions about the use of ICDs, said Axel Bauer, MD, director of University Hospital for Internal Medicine III, Cardiology and Angiology at Medical University Innsbruck, Austria, and coauthors. “Better patient selection could lead to a reduced number of devices needing to be implanted to save a life.

“Our results should help patients to make decisions about their treatment that take into account individual circumstances and preferences,” the researchers noted.

SOURCE: Bauer A et al. Lancet. 2019 Sep 2. doi: 10.1016/S0140-6736(19)31996-8.

A novel marker of repolarization may identify patients with cardiomyopathy who would benefit from an implanted cardioverter defibrillator, according to a European research study presented at the annual congress of the European Society of Cardiology and published simultaneously in The Lancet.

High periodic repolarization dynamics were linked to substantial reductions in mortality in a prespecified substudy of the EU-CERT-ICD (European Comparative Effectiveness Research to Assess the Use of Primary Prophylactic Implantable Cardioverter Defibrillators).

The degree of periodic repolarization dynamics correlated with reductions in mortality in the 1,371 patients, 968 of whom had ICD implantation and 403 of whom were treated conservatively, in the prospective, nonrandomized controlled cohort study conducted at 44 centers in 15 countries within the European Union. At a median follow-up of 2-7 years, the ICD group had a mortality rate of 14%; at a follow-up of 1-2 years, the control group had a mortality rate of 16%, resulting in a 43% overall reduction in mortality for the ICD group.

Low periodic repolarization dynamics were associated with a low reduction in ICD-related death, whereas high periodic repolarization dynamics were linked to substantial reductions in mortality. In 199 patients with periodic repolarization dynamics of 7.5% or higher, ICD implantation resulted in a 75% reduction in death, compared with controls. Periodic repolarization dynamics also served as reliable predictors of appropriate shocks in patients with ICDs as well as death in controls.

Because of the link between high periodic repolarization dynamics and greater benefits, cardiologists may be able to use the measure as a marker to individualize treatment decisions about the use of ICDs, said Axel Bauer, MD, director of University Hospital for Internal Medicine III, Cardiology and Angiology at Medical University Innsbruck, Austria, and coauthors. “Better patient selection could lead to a reduced number of devices needing to be implanted to save a life.

“Our results should help patients to make decisions about their treatment that take into account individual circumstances and preferences,” the researchers noted.

SOURCE: Bauer A et al. Lancet. 2019 Sep 2. doi: 10.1016/S0140-6736(19)31996-8.

A novel marker of repolarization may identify patients with cardiomyopathy who would benefit from an implanted cardioverter defibrillator, according to a European research study presented at the annual congress of the European Society of Cardiology and published simultaneously in The Lancet.

High periodic repolarization dynamics were linked to substantial reductions in mortality in a prespecified substudy of the EU-CERT-ICD (European Comparative Effectiveness Research to Assess the Use of Primary Prophylactic Implantable Cardioverter Defibrillators).

The degree of periodic repolarization dynamics correlated with reductions in mortality in the 1,371 patients, 968 of whom had ICD implantation and 403 of whom were treated conservatively, in the prospective, nonrandomized controlled cohort study conducted at 44 centers in 15 countries within the European Union. At a median follow-up of 2-7 years, the ICD group had a mortality rate of 14%; at a follow-up of 1-2 years, the control group had a mortality rate of 16%, resulting in a 43% overall reduction in mortality for the ICD group.

Low periodic repolarization dynamics were associated with a low reduction in ICD-related death, whereas high periodic repolarization dynamics were linked to substantial reductions in mortality. In 199 patients with periodic repolarization dynamics of 7.5% or higher, ICD implantation resulted in a 75% reduction in death, compared with controls. Periodic repolarization dynamics also served as reliable predictors of appropriate shocks in patients with ICDs as well as death in controls.

Because of the link between high periodic repolarization dynamics and greater benefits, cardiologists may be able to use the measure as a marker to individualize treatment decisions about the use of ICDs, said Axel Bauer, MD, director of University Hospital for Internal Medicine III, Cardiology and Angiology at Medical University Innsbruck, Austria, and coauthors. “Better patient selection could lead to a reduced number of devices needing to be implanted to save a life.

“Our results should help patients to make decisions about their treatment that take into account individual circumstances and preferences,” the researchers noted.

SOURCE: Bauer A et al. Lancet. 2019 Sep 2. doi: 10.1016/S0140-6736(19)31996-8.

PARIS – Patients with stable coronary artery disease and type 2 diabetes saw fewer ischemic cardiovascular events when they received dual antiplatelet therapy with ticagrelor plus aspirin, though they also had more major bleeding events than patients receiving placebo plus aspirin.

The subset of patients who had received prior percutaneous coronary intervention (PCI) stood to benefit more from extended dual antiplatelet therapy (DAPT), according to clinical trial results presented to an overflow crowd at the annual congress of the European Society of Cardiology.

Findings from the full study, named The Effect of Ticagrelor on Health Outcomes in Diabetes Mellitus Patients Intervention Study (THEMIS), and from the PCI subgroup analysis were published concurrently with the presentation (N Engl J Med. 2019 Sep 1: DOI: 10.1056/NEJMoa1908077; Lancet. 2019 Sep 1: DOI:https://doi.org/10.1016/S0140-6736(19)31887-2).

“This strategy of long-term dual antiplatelet therapy may be beneficial in selected patients at low risk of bleeding, but at high risk of ischemic events,” said the study’s co-principal investigator Deepak Bhatt, MD, professor of medicine at Harvard Medical School, Boston, and executive director of interventional cardiology programs at Boston’s Brigham and Women’s Hospital. In a video interview, he hypothesized that “prior PCI may serve as a sort of ‘stress test’ for bleeding,” thus identifying a subset of patients who might benefit from long-term DAPT.

Ischemic events, the primary efficacy outcome of THEMIS, occurred in 7.7% of patients taking the P2Y12 receptor antagonist ticagrelor and 8.5% of those receiving placebo, for a hazard ratio of 0.90 favoring ticagrelor (P = .04). Ischemic events included cardiovascular deaths, myocardial infarctions (MIs), and stroke.

Looking at secondary endpoints, Dr. Bhatt said that there was no difference in cardiovascular deaths between study arms, but that ischemic strokes, all MIs, and ST segment elevation MIs were all less common for patients taking ticagrelor. All-cause mortality was similar between study groups.

Though ischemic events dropped, “This benefit was achieved at the expense of more bleeding,” said Dr. Bhatt. Major bleeding, the primary safety outcome, was seen in 2.2% of those taking ticagrelor and 1.0% of the placebo group, for a hazard ratio of 2.32 (P less than .001). Dr. Bhatt and his collaborators used the Thrombolysis in Myocardial Infarction (TIMI) criteria for major bleeding for ascertainment of this outcome.

Intracranial hemorrhage was also more common for patients on ticagrelor, though incidence was low and the absolute difference was small between groups. This complication occurred in 0.7% of ticagrelor patients and 0.5% of placebo patients, yielding a hazard ratio of 1.71 (P = .0005). “This excess wasn’t in spontaneous or procedural intracranial bleeding, but rather in traumatic intracranial hemorrhage,” said Dr. Bhatt.

Fatal bleeds affected just 0.2% of those on ticagrelor and 0.1% of those receiving placebo; this difference wasn’t statistically significant.

koakes@mdedgecom

Source: Steg PG et al. N Engl J Med. 2019 Sep 1: DOI: 10.1056/NEJMoa1908077; Bhatt DL et al.Lancet. 2019 Sep 1: DOI:https://doi.org/10.1016/S0140-6736(19)31887-2)

PARIS – Patients with stable coronary artery disease and type 2 diabetes saw fewer ischemic cardiovascular events when they received dual antiplatelet therapy with ticagrelor plus aspirin, though they also had more major bleeding events than patients receiving placebo plus aspirin.

The subset of patients who had received prior percutaneous coronary intervention (PCI) stood to benefit more from extended dual antiplatelet therapy (DAPT), according to clinical trial results presented to an overflow crowd at the annual congress of the European Society of Cardiology.

Findings from the full study, named The Effect of Ticagrelor on Health Outcomes in Diabetes Mellitus Patients Intervention Study (THEMIS), and from the PCI subgroup analysis were published concurrently with the presentation (N Engl J Med. 2019 Sep 1: DOI: 10.1056/NEJMoa1908077; Lancet. 2019 Sep 1: DOI:https://doi.org/10.1016/S0140-6736(19)31887-2).

“This strategy of long-term dual antiplatelet therapy may be beneficial in selected patients at low risk of bleeding, but at high risk of ischemic events,” said the study’s co-principal investigator Deepak Bhatt, MD, professor of medicine at Harvard Medical School, Boston, and executive director of interventional cardiology programs at Boston’s Brigham and Women’s Hospital. In a video interview, he hypothesized that “prior PCI may serve as a sort of ‘stress test’ for bleeding,” thus identifying a subset of patients who might benefit from long-term DAPT.

Ischemic events, the primary efficacy outcome of THEMIS, occurred in 7.7% of patients taking the P2Y12 receptor antagonist ticagrelor and 8.5% of those receiving placebo, for a hazard ratio of 0.90 favoring ticagrelor (P = .04). Ischemic events included cardiovascular deaths, myocardial infarctions (MIs), and stroke.

Looking at secondary endpoints, Dr. Bhatt said that there was no difference in cardiovascular deaths between study arms, but that ischemic strokes, all MIs, and ST segment elevation MIs were all less common for patients taking ticagrelor. All-cause mortality was similar between study groups.

Though ischemic events dropped, “This benefit was achieved at the expense of more bleeding,” said Dr. Bhatt. Major bleeding, the primary safety outcome, was seen in 2.2% of those taking ticagrelor and 1.0% of the placebo group, for a hazard ratio of 2.32 (P less than .001). Dr. Bhatt and his collaborators used the Thrombolysis in Myocardial Infarction (TIMI) criteria for major bleeding for ascertainment of this outcome.

Intracranial hemorrhage was also more common for patients on ticagrelor, though incidence was low and the absolute difference was small between groups. This complication occurred in 0.7% of ticagrelor patients and 0.5% of placebo patients, yielding a hazard ratio of 1.71 (P = .0005). “This excess wasn’t in spontaneous or procedural intracranial bleeding, but rather in traumatic intracranial hemorrhage,” said Dr. Bhatt.

Fatal bleeds affected just 0.2% of those on ticagrelor and 0.1% of those receiving placebo; this difference wasn’t statistically significant.

koakes@mdedgecom

Source: Steg PG et al. N Engl J Med. 2019 Sep 1: DOI: 10.1056/NEJMoa1908077; Bhatt DL et al.Lancet. 2019 Sep 1: DOI:https://doi.org/10.1016/S0140-6736(19)31887-2)

PARIS – Patients with stable coronary artery disease and type 2 diabetes saw fewer ischemic cardiovascular events when they received dual antiplatelet therapy with ticagrelor plus aspirin, though they also had more major bleeding events than patients receiving placebo plus aspirin.

The subset of patients who had received prior percutaneous coronary intervention (PCI) stood to benefit more from extended dual antiplatelet therapy (DAPT), according to clinical trial results presented to an overflow crowd at the annual congress of the European Society of Cardiology.

Findings from the full study, named The Effect of Ticagrelor on Health Outcomes in Diabetes Mellitus Patients Intervention Study (THEMIS), and from the PCI subgroup analysis were published concurrently with the presentation (N Engl J Med. 2019 Sep 1: DOI: 10.1056/NEJMoa1908077; Lancet. 2019 Sep 1: DOI:https://doi.org/10.1016/S0140-6736(19)31887-2).

“This strategy of long-term dual antiplatelet therapy may be beneficial in selected patients at low risk of bleeding, but at high risk of ischemic events,” said the study’s co-principal investigator Deepak Bhatt, MD, professor of medicine at Harvard Medical School, Boston, and executive director of interventional cardiology programs at Boston’s Brigham and Women’s Hospital. In a video interview, he hypothesized that “prior PCI may serve as a sort of ‘stress test’ for bleeding,” thus identifying a subset of patients who might benefit from long-term DAPT.

Ischemic events, the primary efficacy outcome of THEMIS, occurred in 7.7% of patients taking the P2Y12 receptor antagonist ticagrelor and 8.5% of those receiving placebo, for a hazard ratio of 0.90 favoring ticagrelor (P = .04). Ischemic events included cardiovascular deaths, myocardial infarctions (MIs), and stroke.

Looking at secondary endpoints, Dr. Bhatt said that there was no difference in cardiovascular deaths between study arms, but that ischemic strokes, all MIs, and ST segment elevation MIs were all less common for patients taking ticagrelor. All-cause mortality was similar between study groups.

Though ischemic events dropped, “This benefit was achieved at the expense of more bleeding,” said Dr. Bhatt. Major bleeding, the primary safety outcome, was seen in 2.2% of those taking ticagrelor and 1.0% of the placebo group, for a hazard ratio of 2.32 (P less than .001). Dr. Bhatt and his collaborators used the Thrombolysis in Myocardial Infarction (TIMI) criteria for major bleeding for ascertainment of this outcome.

Intracranial hemorrhage was also more common for patients on ticagrelor, though incidence was low and the absolute difference was small between groups. This complication occurred in 0.7% of ticagrelor patients and 0.5% of placebo patients, yielding a hazard ratio of 1.71 (P = .0005). “This excess wasn’t in spontaneous or procedural intracranial bleeding, but rather in traumatic intracranial hemorrhage,” said Dr. Bhatt.

Fatal bleeds affected just 0.2% of those on ticagrelor and 0.1% of those receiving placebo; this difference wasn’t statistically significant.

koakes@mdedgecom

Source: Steg PG et al. N Engl J Med. 2019 Sep 1: DOI: 10.1056/NEJMoa1908077; Bhatt DL et al.Lancet. 2019 Sep 1: DOI:https://doi.org/10.1016/S0140-6736(19)31887-2)

PARIS – Bleeding after acute coronary syndrome is associated with an increased risk for a new diagnosis of cancer, according to work presented at the annual congress of the European Society of Cardiology.

Of 3,644 patients discharged with dual-antiplatelet therapy after acute coronary syndrome (ACS), 1,215 (33%) had postdischarge bleeding. Taken together, patients who bled had a hazard ratio (HR) of 3.43 for a new cancer diagnosis (P less than .001).

Of the patients in the post-ACS cohort, 227 were newly diagnosed with cancer after discharge, making up 1% of the patients who did not bleed after discharge, and 3.9% of the patients who experienced postdischarge bleeding. Put another way, “[t]he positive predictive value for cancer diagnosis of post-discharge bleeding was 7.7%,” wrote Isabel Muñoz Pousa, MD, and her colleagues in the poster accompanying the presentation.

This elevated risk for cancer diagnosis was driven primarily by the 827 incidents of spontaneous bleeding; here, the HR was 4.38 (P less than .001). The 389 bleeds occuring after trauma, such as bladder catheterization or a fall, did not carry an increased risk for a new cancer diagnosis.

“Spontaneous post-discharge bleeding in ACS patients is strongly associated with subsequent cancer diagnosis within the first 6 months,” wrote Dr. Muñoz Pousa and her colleagues of the Hospital Universitario Alvaro Cunqueiro, Vigo, Spain. The investigators found a median time of 4.6 months from the bleeding episode to cancer diagnosis.

Of all anatomic locations, genitourinary bleeds were the most strongly associated with new cancer: 228 patients saw a HR of 8.63 for a new cancer diagnosis (P less than .001). Bronchopulmonary bleeds, sustained by 56 patients, carried a HR of 4.26 for new cancer diagnosis, and gastrointestinal bleeds a HR of 3.78 (P = .001 and P less than .001, respectively). Dr. Muñoz Pousa and her coinvestigators aggregated data from patients who had bleeding at other sites and saw no significant association with new cancers in this group of patients.

Though patients were initially discharged on dual-antiplatelet therapy, many patients stopped taking the medication over the mean 56.2 months of follow-up. The risk of bleeding did not differ significantly between those who were taking DAPT and those off DAPT, wrote Dr. Muñoz Pousa and her colleagues, adding: “We found a higher incidence of cancer in the first six months after discharge regardless of whether patients were taking dual-antiplatelet therapy or not.”

In their statistical analysis, Dr. Muñoz Pousa and colleagues adjusted for potential confounders, and looked at the effect of bleeding as a time-varying covariate on subsequent cancer diagnosis, using Cox regression models.

“Most of the bleeding episodes in the study were mild,” noted Dr. Munoz Pousa in a press statement. However, she said, “The bleeding events more strongly related with a new cancer diagnosis were severe hemorrhages of unknown cause requiring surgery – for example digestive bleeding needing endoscopic treatment.”

Breaking bleeding severity down by Bleeding Academic Research Consortium (BARC) criteria, the investigators found that most patients had relatively mild bleeding episodes categorized as BARC 1 or 2, with about half of all bleeding falling into the BARC 1 category.

Still, the 436 patients who had BARC 2 bleeding had a hazard ratio of 4.88 for cancer diagnosis, and the 71 BARC 3A patients saw the HR climb to 7.30. The risk for cancer subsequent to bleeding peaked at BARC 3B, with a HR of 12.29 for these 46 individuals (P less than .001 for all). Just 37 patients experienced BARC 3C bleeds, which were associated with a nonsignificant HR of 3.17 for new cancer diagnosis.

Although it’s not known why the post ACS–cancer bleeding association exists, Dr. Munoz Pousa put forward a plausible reason for the link. “A possible explanation is that there is a preexisting subclinical lesion in an organ that is triggered to become cancer by antiplatelet drugs or a stressful situation such as heart attack,” she said in the press release.

Antiplatelet therapy should be taken as prescribed post-ACS, and the physician threshold for further evaluation should be low when a significant spontaneous bleed is seen soon after ACS. “A prompt evaluation of bleeding could be useful for enabling an early detection of cancer in these patients,” said Dr. Munoz Pousa and her colleagues. “Our results suggest that patients should seek medical advice if they experience bleeding after discharge for a heart attack.”

The authors reported no conflicts of interest.
 

[email protected]

SOURCE: Munoz Pousa, I. et al. ESC Congress 2019, Abstract P677.

PARIS – Bleeding after acute coronary syndrome is associated with an increased risk for a new diagnosis of cancer, according to work presented at the annual congress of the European Society of Cardiology.

Of 3,644 patients discharged with dual-antiplatelet therapy after acute coronary syndrome (ACS), 1,215 (33%) had postdischarge bleeding. Taken together, patients who bled had a hazard ratio (HR) of 3.43 for a new cancer diagnosis (P less than .001).

Of the patients in the post-ACS cohort, 227 were newly diagnosed with cancer after discharge, making up 1% of the patients who did not bleed after discharge, and 3.9% of the patients who experienced postdischarge bleeding. Put another way, “[t]he positive predictive value for cancer diagnosis of post-discharge bleeding was 7.7%,” wrote Isabel Muñoz Pousa, MD, and her colleagues in the poster accompanying the presentation.

This elevated risk for cancer diagnosis was driven primarily by the 827 incidents of spontaneous bleeding; here, the HR was 4.38 (P less than .001). The 389 bleeds occuring after trauma, such as bladder catheterization or a fall, did not carry an increased risk for a new cancer diagnosis.

“Spontaneous post-discharge bleeding in ACS patients is strongly associated with subsequent cancer diagnosis within the first 6 months,” wrote Dr. Muñoz Pousa and her colleagues of the Hospital Universitario Alvaro Cunqueiro, Vigo, Spain. The investigators found a median time of 4.6 months from the bleeding episode to cancer diagnosis.

Of all anatomic locations, genitourinary bleeds were the most strongly associated with new cancer: 228 patients saw a HR of 8.63 for a new cancer diagnosis (P less than .001). Bronchopulmonary bleeds, sustained by 56 patients, carried a HR of 4.26 for new cancer diagnosis, and gastrointestinal bleeds a HR of 3.78 (P = .001 and P less than .001, respectively). Dr. Muñoz Pousa and her coinvestigators aggregated data from patients who had bleeding at other sites and saw no significant association with new cancers in this group of patients.

Though patients were initially discharged on dual-antiplatelet therapy, many patients stopped taking the medication over the mean 56.2 months of follow-up. The risk of bleeding did not differ significantly between those who were taking DAPT and those off DAPT, wrote Dr. Muñoz Pousa and her colleagues, adding: “We found a higher incidence of cancer in the first six months after discharge regardless of whether patients were taking dual-antiplatelet therapy or not.”

In their statistical analysis, Dr. Muñoz Pousa and colleagues adjusted for potential confounders, and looked at the effect of bleeding as a time-varying covariate on subsequent cancer diagnosis, using Cox regression models.

“Most of the bleeding episodes in the study were mild,” noted Dr. Munoz Pousa in a press statement. However, she said, “The bleeding events more strongly related with a new cancer diagnosis were severe hemorrhages of unknown cause requiring surgery – for example digestive bleeding needing endoscopic treatment.”

Breaking bleeding severity down by Bleeding Academic Research Consortium (BARC) criteria, the investigators found that most patients had relatively mild bleeding episodes categorized as BARC 1 or 2, with about half of all bleeding falling into the BARC 1 category.

Still, the 436 patients who had BARC 2 bleeding had a hazard ratio of 4.88 for cancer diagnosis, and the 71 BARC 3A patients saw the HR climb to 7.30. The risk for cancer subsequent to bleeding peaked at BARC 3B, with a HR of 12.29 for these 46 individuals (P less than .001 for all). Just 37 patients experienced BARC 3C bleeds, which were associated with a nonsignificant HR of 3.17 for new cancer diagnosis.

Although it’s not known why the post ACS–cancer bleeding association exists, Dr. Munoz Pousa put forward a plausible reason for the link. “A possible explanation is that there is a preexisting subclinical lesion in an organ that is triggered to become cancer by antiplatelet drugs or a stressful situation such as heart attack,” she said in the press release.

Antiplatelet therapy should be taken as prescribed post-ACS, and the physician threshold for further evaluation should be low when a significant spontaneous bleed is seen soon after ACS. “A prompt evaluation of bleeding could be useful for enabling an early detection of cancer in these patients,” said Dr. Munoz Pousa and her colleagues. “Our results suggest that patients should seek medical advice if they experience bleeding after discharge for a heart attack.”

The authors reported no conflicts of interest.
 

[email protected]

SOURCE: Munoz Pousa, I. et al. ESC Congress 2019, Abstract P677.

PARIS – Bleeding after acute coronary syndrome is associated with an increased risk for a new diagnosis of cancer, according to work presented at the annual congress of the European Society of Cardiology.

Of 3,644 patients discharged with dual-antiplatelet therapy after acute coronary syndrome (ACS), 1,215 (33%) had postdischarge bleeding. Taken together, patients who bled had a hazard ratio (HR) of 3.43 for a new cancer diagnosis (P less than .001).

Of the patients in the post-ACS cohort, 227 were newly diagnosed with cancer after discharge, making up 1% of the patients who did not bleed after discharge, and 3.9% of the patients who experienced postdischarge bleeding. Put another way, “[t]he positive predictive value for cancer diagnosis of post-discharge bleeding was 7.7%,” wrote Isabel Muñoz Pousa, MD, and her colleagues in the poster accompanying the presentation.

This elevated risk for cancer diagnosis was driven primarily by the 827 incidents of spontaneous bleeding; here, the HR was 4.38 (P less than .001). The 389 bleeds occuring after trauma, such as bladder catheterization or a fall, did not carry an increased risk for a new cancer diagnosis.

“Spontaneous post-discharge bleeding in ACS patients is strongly associated with subsequent cancer diagnosis within the first 6 months,” wrote Dr. Muñoz Pousa and her colleagues of the Hospital Universitario Alvaro Cunqueiro, Vigo, Spain. The investigators found a median time of 4.6 months from the bleeding episode to cancer diagnosis.

Of all anatomic locations, genitourinary bleeds were the most strongly associated with new cancer: 228 patients saw a HR of 8.63 for a new cancer diagnosis (P less than .001). Bronchopulmonary bleeds, sustained by 56 patients, carried a HR of 4.26 for new cancer diagnosis, and gastrointestinal bleeds a HR of 3.78 (P = .001 and P less than .001, respectively). Dr. Muñoz Pousa and her coinvestigators aggregated data from patients who had bleeding at other sites and saw no significant association with new cancers in this group of patients.

Though patients were initially discharged on dual-antiplatelet therapy, many patients stopped taking the medication over the mean 56.2 months of follow-up. The risk of bleeding did not differ significantly between those who were taking DAPT and those off DAPT, wrote Dr. Muñoz Pousa and her colleagues, adding: “We found a higher incidence of cancer in the first six months after discharge regardless of whether patients were taking dual-antiplatelet therapy or not.”

In their statistical analysis, Dr. Muñoz Pousa and colleagues adjusted for potential confounders, and looked at the effect of bleeding as a time-varying covariate on subsequent cancer diagnosis, using Cox regression models.

“Most of the bleeding episodes in the study were mild,” noted Dr. Munoz Pousa in a press statement. However, she said, “The bleeding events more strongly related with a new cancer diagnosis were severe hemorrhages of unknown cause requiring surgery – for example digestive bleeding needing endoscopic treatment.”

Breaking bleeding severity down by Bleeding Academic Research Consortium (BARC) criteria, the investigators found that most patients had relatively mild bleeding episodes categorized as BARC 1 or 2, with about half of all bleeding falling into the BARC 1 category.

Still, the 436 patients who had BARC 2 bleeding had a hazard ratio of 4.88 for cancer diagnosis, and the 71 BARC 3A patients saw the HR climb to 7.30. The risk for cancer subsequent to bleeding peaked at BARC 3B, with a HR of 12.29 for these 46 individuals (P less than .001 for all). Just 37 patients experienced BARC 3C bleeds, which were associated with a nonsignificant HR of 3.17 for new cancer diagnosis.

Although it’s not known why the post ACS–cancer bleeding association exists, Dr. Munoz Pousa put forward a plausible reason for the link. “A possible explanation is that there is a preexisting subclinical lesion in an organ that is triggered to become cancer by antiplatelet drugs or a stressful situation such as heart attack,” she said in the press release.

Antiplatelet therapy should be taken as prescribed post-ACS, and the physician threshold for further evaluation should be low when a significant spontaneous bleed is seen soon after ACS. “A prompt evaluation of bleeding could be useful for enabling an early detection of cancer in these patients,” said Dr. Munoz Pousa and her colleagues. “Our results suggest that patients should seek medical advice if they experience bleeding after discharge for a heart attack.”

The authors reported no conflicts of interest.
 

[email protected]

SOURCE: Munoz Pousa, I. et al. ESC Congress 2019, Abstract P677.

PARIS – Older patients with non-ST-elevation acute coronary syndrome who were assigned to 12 months of dual antiplatelet therapy with clopidogrel experienced significantly less major and minor bleeding than with ticagrelor or prasugrel and were similarly protected from thrombotic events in the prospective randomized POPular AGE trial, Marieke E. Gimbel, MD, reported at the annual congress of the European Society of Cardiology.

“Therefore, we consider clopidogrel the preferred treatment in patients age 70 or older with non-ST-elevation ACS,” said Dr. Gimbel, a cardiologist at St. Antonius Hospital in Nieuwegein, The Netherlands.

This stance is contrary to both the current ESC and U.S. guidelines on management of non-ST-elevation ACS, which preferentially recommend ticagrelor and prasugrel over clopidogrel, chiefly on the basis of the large PLATO (N Engl J Med 2009;361:1045-57) and TRITON TIMI 38 (N Engl J Med 2007;357:2001-15) randomized trials. Those studies from the previous decade reported significantly lower rates of the composite endpoint of cardiovascular death, acute MI, or stroke in patients on ticagrelor or prasugrel, respectively, than with clopidogrel. But this benefit came at a cost of significantly higher rates of TIMI major bleeding than with clopidogrel, and multiple studies have shown that major bleeding in ACS patients is associated with a sharply increased risk of death.

Bleeding is an issue of particular concern in the elderly. But older patients were greatly underrepresented in PLATO and TRITON, where they comprised just 13%-15% of participants, even though registry studies would suggest older individuals make up about 35% of all patients with non-ST-elevation ACS. Selective inclusion of elderly patients in the major trials means those study results can’t legitimately be extrapolated to the entire elderly patient population.

“The best course of action in the elderly has been unclear,” Dr. Gimbel argued.

The POPular AGE (POP AGE) trial was an open-label study featuring independent blinded adjudication of clinical events. The median age of participants was 77 years, and about one-quarter had a prior MI. It was basically an all-comers study in which 1,003 non-ST-elevation ACS patients age 70 or older at 11 Dutch medical centers were randomized within 3 days of hospital admission to 12 months of dual antiplatelet therapy with either ticagrelor or one of the two more potent antiplatelet agents. Although the choice of ticagrelor or prasugrel was left to the physician, it’s noteworthy that 94% of patients in the high-potency P2Y12 inhibitor study arm were discharged on ticagrelor. At 12 months, the adherence rate to the assigned regimen was 76% in the clopidogrel group and just 51% in what was essentially the ticagrelor arm. Bleeding was the number-one reason for the much higher discontinuation rate in the ticagrelor group, followed by initiation of oral anticoagulation and dyspnea.

The primary safety endpoint in POP AGE was the rate of major and minor bleeding as defined in the PLATO study. The rate was 17.6% with clopidogrel, compared with 23.1% in the ticagrelor group, for a highly significant 26% reduction in relative risk. Of note, the PLATO major bleeding rate was 4.4% with clopidogrel, versus 8% with ticagrelor/prasugrel.

The coprimary endpoint was net clinical benefit, defined as a composite of all-cause mortality, MI, stroke, and PLATO major and minor bleeding. The rate was 30.7% with ticagrelor and 27.3% in the clopidogrel group, for an absolute 3.4% risk difference favoring clopidogrel, which barely missed the prespecified cutoff for noninferiority. Indeed, even though the 12-month follow-up was 99.6% complete, Dr. Gimbel raised the possibility that when the results come in for the final 0.4% of the study population, the difference in net clinical benefit may reach significance.

In any case, she noted there was no between-group difference in the key secondary endpoint of death, MI, or stroke, with rates of 12.8% and 12.5% in the clopidogrel and ticagrelor groups, respectively.

“One might expect a higher ischemic event rate with clopidogrel compared to ticagrelor. However, in these elderly patients there was no difference between the two treatment strategies,” the cardiologist observed.

POP AGE is hailed as ‘a wake up call’

In an interview, Freek Verheugt, MD, PhD, professor emeritus of cardiology at Radboud University in Nijmegen, The Netherlands, called POP AGE “a very important study.”

“The problem with most studies in the elderly is that they are post hoc analyses from huge trials like PLATO and TRITON, and also the thrombolysis and primary PCI studies. The elderly do very well in those studies, because only the very fit elderly are included in the megatrials. It’s much more important to do a prospective randomized trial in the elderly only, and this is one of the very few done so far,” he observed.

Bleeding is a major problem in the elderly with ACS. It leads to more MIs, strokes, and increased mortality.

“Even minor bleeding is an issue,” Dr. Verheugt added. “Minor bleeding is a major problem, because patients who encounter minor bleeding – nose bleeds, gum bleeds, or even in their underwear – they do away with all drugs. They stop their antithrombotic, but they also stop their statin, their ACE inhibitor – their lifesavers – and that’s why they die.”

So is POP AGE a practice-changing study?

“No, of course not,” the cardiologist scoffed. “To be practice-changing you need several trials going in the same direction. But I think if there are more data prospectively accrued in the elderly alone, showing the same, then POP AGE would be practice-changing.”

“In my personal view, this study is a wake-up call. If you have an elderly, frail patient presenting with ACS, strongly consider good, old clopidogrel. Although people say that 30% of patients on clopidogrel don’t have appropriate platelet inhibition, that’s a laboratory finding. It’s not a clinical finding. POP AGE gave us a clinical finding showing that they do quite well,” he said.

Dr. Verheugt was on the independent data safety monitoring board for POP AGE, funded by ZonMw, a Dutch governmental research organization. Neither Dr. Verheugt nor Dr. Gimbel reported having any financial conflicts of interest.
 

[email protected]

SOURCE: Gimbel ME. ESC 2019, Abstract 84.


 

PARIS – Older patients with non-ST-elevation acute coronary syndrome who were assigned to 12 months of dual antiplatelet therapy with clopidogrel experienced significantly less major and minor bleeding than with ticagrelor or prasugrel and were similarly protected from thrombotic events in the prospective randomized POPular AGE trial, Marieke E. Gimbel, MD, reported at the annual congress of the European Society of Cardiology.

“Therefore, we consider clopidogrel the preferred treatment in patients age 70 or older with non-ST-elevation ACS,” said Dr. Gimbel, a cardiologist at St. Antonius Hospital in Nieuwegein, The Netherlands.

This stance is contrary to both the current ESC and U.S. guidelines on management of non-ST-elevation ACS, which preferentially recommend ticagrelor and prasugrel over clopidogrel, chiefly on the basis of the large PLATO (N Engl J Med 2009;361:1045-57) and TRITON TIMI 38 (N Engl J Med 2007;357:2001-15) randomized trials. Those studies from the previous decade reported significantly lower rates of the composite endpoint of cardiovascular death, acute MI, or stroke in patients on ticagrelor or prasugrel, respectively, than with clopidogrel. But this benefit came at a cost of significantly higher rates of TIMI major bleeding than with clopidogrel, and multiple studies have shown that major bleeding in ACS patients is associated with a sharply increased risk of death.

Bleeding is an issue of particular concern in the elderly. But older patients were greatly underrepresented in PLATO and TRITON, where they comprised just 13%-15% of participants, even though registry studies would suggest older individuals make up about 35% of all patients with non-ST-elevation ACS. Selective inclusion of elderly patients in the major trials means those study results can’t legitimately be extrapolated to the entire elderly patient population.

“The best course of action in the elderly has been unclear,” Dr. Gimbel argued.

The POPular AGE (POP AGE) trial was an open-label study featuring independent blinded adjudication of clinical events. The median age of participants was 77 years, and about one-quarter had a prior MI. It was basically an all-comers study in which 1,003 non-ST-elevation ACS patients age 70 or older at 11 Dutch medical centers were randomized within 3 days of hospital admission to 12 months of dual antiplatelet therapy with either ticagrelor or one of the two more potent antiplatelet agents. Although the choice of ticagrelor or prasugrel was left to the physician, it’s noteworthy that 94% of patients in the high-potency P2Y12 inhibitor study arm were discharged on ticagrelor. At 12 months, the adherence rate to the assigned regimen was 76% in the clopidogrel group and just 51% in what was essentially the ticagrelor arm. Bleeding was the number-one reason for the much higher discontinuation rate in the ticagrelor group, followed by initiation of oral anticoagulation and dyspnea.

The primary safety endpoint in POP AGE was the rate of major and minor bleeding as defined in the PLATO study. The rate was 17.6% with clopidogrel, compared with 23.1% in the ticagrelor group, for a highly significant 26% reduction in relative risk. Of note, the PLATO major bleeding rate was 4.4% with clopidogrel, versus 8% with ticagrelor/prasugrel.

The coprimary endpoint was net clinical benefit, defined as a composite of all-cause mortality, MI, stroke, and PLATO major and minor bleeding. The rate was 30.7% with ticagrelor and 27.3% in the clopidogrel group, for an absolute 3.4% risk difference favoring clopidogrel, which barely missed the prespecified cutoff for noninferiority. Indeed, even though the 12-month follow-up was 99.6% complete, Dr. Gimbel raised the possibility that when the results come in for the final 0.4% of the study population, the difference in net clinical benefit may reach significance.

In any case, she noted there was no between-group difference in the key secondary endpoint of death, MI, or stroke, with rates of 12.8% and 12.5% in the clopidogrel and ticagrelor groups, respectively.

“One might expect a higher ischemic event rate with clopidogrel compared to ticagrelor. However, in these elderly patients there was no difference between the two treatment strategies,” the cardiologist observed.

POP AGE is hailed as ‘a wake up call’

In an interview, Freek Verheugt, MD, PhD, professor emeritus of cardiology at Radboud University in Nijmegen, The Netherlands, called POP AGE “a very important study.”

“The problem with most studies in the elderly is that they are post hoc analyses from huge trials like PLATO and TRITON, and also the thrombolysis and primary PCI studies. The elderly do very well in those studies, because only the very fit elderly are included in the megatrials. It’s much more important to do a prospective randomized trial in the elderly only, and this is one of the very few done so far,” he observed.

Bleeding is a major problem in the elderly with ACS. It leads to more MIs, strokes, and increased mortality.

“Even minor bleeding is an issue,” Dr. Verheugt added. “Minor bleeding is a major problem, because patients who encounter minor bleeding – nose bleeds, gum bleeds, or even in their underwear – they do away with all drugs. They stop their antithrombotic, but they also stop their statin, their ACE inhibitor – their lifesavers – and that’s why they die.”

So is POP AGE a practice-changing study?

“No, of course not,” the cardiologist scoffed. “To be practice-changing you need several trials going in the same direction. But I think if there are more data prospectively accrued in the elderly alone, showing the same, then POP AGE would be practice-changing.”

“In my personal view, this study is a wake-up call. If you have an elderly, frail patient presenting with ACS, strongly consider good, old clopidogrel. Although people say that 30% of patients on clopidogrel don’t have appropriate platelet inhibition, that’s a laboratory finding. It’s not a clinical finding. POP AGE gave us a clinical finding showing that they do quite well,” he said.

Dr. Verheugt was on the independent data safety monitoring board for POP AGE, funded by ZonMw, a Dutch governmental research organization. Neither Dr. Verheugt nor Dr. Gimbel reported having any financial conflicts of interest.
 

[email protected]

SOURCE: Gimbel ME. ESC 2019, Abstract 84.


 

PARIS – Older patients with non-ST-elevation acute coronary syndrome who were assigned to 12 months of dual antiplatelet therapy with clopidogrel experienced significantly less major and minor bleeding than with ticagrelor or prasugrel and were similarly protected from thrombotic events in the prospective randomized POPular AGE trial, Marieke E. Gimbel, MD, reported at the annual congress of the European Society of Cardiology.

“Therefore, we consider clopidogrel the preferred treatment in patients age 70 or older with non-ST-elevation ACS,” said Dr. Gimbel, a cardiologist at St. Antonius Hospital in Nieuwegein, The Netherlands.

This stance is contrary to both the current ESC and U.S. guidelines on management of non-ST-elevation ACS, which preferentially recommend ticagrelor and prasugrel over clopidogrel, chiefly on the basis of the large PLATO (N Engl J Med 2009;361:1045-57) and TRITON TIMI 38 (N Engl J Med 2007;357:2001-15) randomized trials. Those studies from the previous decade reported significantly lower rates of the composite endpoint of cardiovascular death, acute MI, or stroke in patients on ticagrelor or prasugrel, respectively, than with clopidogrel. But this benefit came at a cost of significantly higher rates of TIMI major bleeding than with clopidogrel, and multiple studies have shown that major bleeding in ACS patients is associated with a sharply increased risk of death.

Bleeding is an issue of particular concern in the elderly. But older patients were greatly underrepresented in PLATO and TRITON, where they comprised just 13%-15% of participants, even though registry studies would suggest older individuals make up about 35% of all patients with non-ST-elevation ACS. Selective inclusion of elderly patients in the major trials means those study results can’t legitimately be extrapolated to the entire elderly patient population.

“The best course of action in the elderly has been unclear,” Dr. Gimbel argued.

The POPular AGE (POP AGE) trial was an open-label study featuring independent blinded adjudication of clinical events. The median age of participants was 77 years, and about one-quarter had a prior MI. It was basically an all-comers study in which 1,003 non-ST-elevation ACS patients age 70 or older at 11 Dutch medical centers were randomized within 3 days of hospital admission to 12 months of dual antiplatelet therapy with either ticagrelor or one of the two more potent antiplatelet agents. Although the choice of ticagrelor or prasugrel was left to the physician, it’s noteworthy that 94% of patients in the high-potency P2Y12 inhibitor study arm were discharged on ticagrelor. At 12 months, the adherence rate to the assigned regimen was 76% in the clopidogrel group and just 51% in what was essentially the ticagrelor arm. Bleeding was the number-one reason for the much higher discontinuation rate in the ticagrelor group, followed by initiation of oral anticoagulation and dyspnea.

The primary safety endpoint in POP AGE was the rate of major and minor bleeding as defined in the PLATO study. The rate was 17.6% with clopidogrel, compared with 23.1% in the ticagrelor group, for a highly significant 26% reduction in relative risk. Of note, the PLATO major bleeding rate was 4.4% with clopidogrel, versus 8% with ticagrelor/prasugrel.

The coprimary endpoint was net clinical benefit, defined as a composite of all-cause mortality, MI, stroke, and PLATO major and minor bleeding. The rate was 30.7% with ticagrelor and 27.3% in the clopidogrel group, for an absolute 3.4% risk difference favoring clopidogrel, which barely missed the prespecified cutoff for noninferiority. Indeed, even though the 12-month follow-up was 99.6% complete, Dr. Gimbel raised the possibility that when the results come in for the final 0.4% of the study population, the difference in net clinical benefit may reach significance.

In any case, she noted there was no between-group difference in the key secondary endpoint of death, MI, or stroke, with rates of 12.8% and 12.5% in the clopidogrel and ticagrelor groups, respectively.

“One might expect a higher ischemic event rate with clopidogrel compared to ticagrelor. However, in these elderly patients there was no difference between the two treatment strategies,” the cardiologist observed.

POP AGE is hailed as ‘a wake up call’

In an interview, Freek Verheugt, MD, PhD, professor emeritus of cardiology at Radboud University in Nijmegen, The Netherlands, called POP AGE “a very important study.”

“The problem with most studies in the elderly is that they are post hoc analyses from huge trials like PLATO and TRITON, and also the thrombolysis and primary PCI studies. The elderly do very well in those studies, because only the very fit elderly are included in the megatrials. It’s much more important to do a prospective randomized trial in the elderly only, and this is one of the very few done so far,” he observed.

Bleeding is a major problem in the elderly with ACS. It leads to more MIs, strokes, and increased mortality.

“Even minor bleeding is an issue,” Dr. Verheugt added. “Minor bleeding is a major problem, because patients who encounter minor bleeding – nose bleeds, gum bleeds, or even in their underwear – they do away with all drugs. They stop their antithrombotic, but they also stop their statin, their ACE inhibitor – their lifesavers – and that’s why they die.”

So is POP AGE a practice-changing study?

“No, of course not,” the cardiologist scoffed. “To be practice-changing you need several trials going in the same direction. But I think if there are more data prospectively accrued in the elderly alone, showing the same, then POP AGE would be practice-changing.”

“In my personal view, this study is a wake-up call. If you have an elderly, frail patient presenting with ACS, strongly consider good, old clopidogrel. Although people say that 30% of patients on clopidogrel don’t have appropriate platelet inhibition, that’s a laboratory finding. It’s not a clinical finding. POP AGE gave us a clinical finding showing that they do quite well,” he said.

Dr. Verheugt was on the independent data safety monitoring board for POP AGE, funded by ZonMw, a Dutch governmental research organization. Neither Dr. Verheugt nor Dr. Gimbel reported having any financial conflicts of interest.
 

[email protected]

SOURCE: Gimbel ME. ESC 2019, Abstract 84.


 

Revascularization of more than just the culprit lesion in patients with ST-elevation myocardial infarctions could significantly reduce their risk of cardiovascular death or myocardial infarction, according to results of the COMPLETE trial, presented at the annual congress of the European Society of Cardiology.

The report, simultaneously published online in the New England Journal of Medicine, detailed the outcomes of COMPLETE (the Complete versus Culprit-Only Revascularization Strategies to Treat Multivessel Disease after Early PCI for STEMI), a study in 4,041 patients who had experienced an ST-elevation myocardial infarction (STEMI), who had multi-vessel coronary artery disease, and who had undergone successful percutaneous coronary intervention of the culprit lesion.

Participants were randomized either to complete revascularization of all angiographically significant nonculprit lesions, or to no further revascularization, and were followed for a median of 3 years.

Of the patients who underwent complete revascularization, 7.8% experienced either cardiovascular death or another myocardial infarction, compared with 10.5% of those who only had revascularization of the culprit lesion, representing a significant 26% reduction (P = .004) in the incidence of this composite coprimary outcome.

The decrease in events was driven by a significant 32% reduction in the incidence of new myocardial infarction – particularly non-STEMI, new STEMI, and myocardial infarction type 1 – in the complete revascularization group, with only a 7% reduction in the incidence of death from cardiovascular causes.

With the second coprimary outcome of a composite of cardiovascular death, myocardial infarction, or ischemia-driven revascularization, this was seen in 8.9% of patients in the complete revascularization group compared with 16.7% of patients with the culprit-lesion-only group; a significant 49% reduction in incidence (P less than .001).

The authors calculated that 37 complete revascularizations would need to be performed to prevent one incidence of cardiovascular death or myocardial infarction. To prevent cardiovascular death, myocardial infarction, or ischemia-driven revascularization, the number needed to treat was 13.

The timing of complete revascularization did not appear to affect the benefits of the procedure, which were consistent among patients who underwent complete revascularization during their index hospitalization and in those who underwent the procedure after hospital discharge. Investigators had to specify before randomization whether the patient would undergo complete revascularization during the index hospitalization or after discharge but within 45 days.

The study also did not find any significant differences between the two groups in the risks of major bleeding, stroke, or stent thrombosis. However, the complete revascularization group did experience a nonsignificant 59% higher odds of contrast-associated acute kidney injury, which was attributed to the nonculprit lesion revascularization in seven patients in the complete revascularization group.

Dr. Shamir R. Mehta, of the Population Health Research Institute at McMaster University, Ontario, and coauthors noted that previous trials of complete-revascularization strategies in patients with STEMI were smaller and had included revascularization as part of a composite primary outcome.

“In the absence of a reduction in irreversible events such as cardiovascular death or new myocardial infarction, the clinical relevance of performing early nonculprit-lesion PCI in all patients with multivessel coronary artery disease to prevent later PCI in a smaller number of those patients is debatable,” they wrote. “We have now found that routine nonculprit-lesion PCI with the goal of complete revascularization confers a reduction in the long-term risk of cardiovascular death or myocardial infarction.”

No patients with cardiogenic shock were enrolled in the study, so the results could not be extrapolated to that patient group.

SOURCE: Mehta S et al. N Engl J Med. 2019 Sep. 1. doi: 10.1056/NEJMoa1907775.

Revascularization of more than just the culprit lesion in patients with ST-elevation myocardial infarctions could significantly reduce their risk of cardiovascular death or myocardial infarction, according to results of the COMPLETE trial, presented at the annual congress of the European Society of Cardiology.

The report, simultaneously published online in the New England Journal of Medicine, detailed the outcomes of COMPLETE (the Complete versus Culprit-Only Revascularization Strategies to Treat Multivessel Disease after Early PCI for STEMI), a study in 4,041 patients who had experienced an ST-elevation myocardial infarction (STEMI), who had multi-vessel coronary artery disease, and who had undergone successful percutaneous coronary intervention of the culprit lesion.

Participants were randomized either to complete revascularization of all angiographically significant nonculprit lesions, or to no further revascularization, and were followed for a median of 3 years.

Of the patients who underwent complete revascularization, 7.8% experienced either cardiovascular death or another myocardial infarction, compared with 10.5% of those who only had revascularization of the culprit lesion, representing a significant 26% reduction (P = .004) in the incidence of this composite coprimary outcome.

The decrease in events was driven by a significant 32% reduction in the incidence of new myocardial infarction – particularly non-STEMI, new STEMI, and myocardial infarction type 1 – in the complete revascularization group, with only a 7% reduction in the incidence of death from cardiovascular causes.

With the second coprimary outcome of a composite of cardiovascular death, myocardial infarction, or ischemia-driven revascularization, this was seen in 8.9% of patients in the complete revascularization group compared with 16.7% of patients with the culprit-lesion-only group; a significant 49% reduction in incidence (P less than .001).

The authors calculated that 37 complete revascularizations would need to be performed to prevent one incidence of cardiovascular death or myocardial infarction. To prevent cardiovascular death, myocardial infarction, or ischemia-driven revascularization, the number needed to treat was 13.

The timing of complete revascularization did not appear to affect the benefits of the procedure, which were consistent among patients who underwent complete revascularization during their index hospitalization and in those who underwent the procedure after hospital discharge. Investigators had to specify before randomization whether the patient would undergo complete revascularization during the index hospitalization or after discharge but within 45 days.

The study also did not find any significant differences between the two groups in the risks of major bleeding, stroke, or stent thrombosis. However, the complete revascularization group did experience a nonsignificant 59% higher odds of contrast-associated acute kidney injury, which was attributed to the nonculprit lesion revascularization in seven patients in the complete revascularization group.

Dr. Shamir R. Mehta, of the Population Health Research Institute at McMaster University, Ontario, and coauthors noted that previous trials of complete-revascularization strategies in patients with STEMI were smaller and had included revascularization as part of a composite primary outcome.

“In the absence of a reduction in irreversible events such as cardiovascular death or new myocardial infarction, the clinical relevance of performing early nonculprit-lesion PCI in all patients with multivessel coronary artery disease to prevent later PCI in a smaller number of those patients is debatable,” they wrote. “We have now found that routine nonculprit-lesion PCI with the goal of complete revascularization confers a reduction in the long-term risk of cardiovascular death or myocardial infarction.”

No patients with cardiogenic shock were enrolled in the study, so the results could not be extrapolated to that patient group.

SOURCE: Mehta S et al. N Engl J Med. 2019 Sep. 1. doi: 10.1056/NEJMoa1907775.

Revascularization of more than just the culprit lesion in patients with ST-elevation myocardial infarctions could significantly reduce their risk of cardiovascular death or myocardial infarction, according to results of the COMPLETE trial, presented at the annual congress of the European Society of Cardiology.

The report, simultaneously published online in the New England Journal of Medicine, detailed the outcomes of COMPLETE (the Complete versus Culprit-Only Revascularization Strategies to Treat Multivessel Disease after Early PCI for STEMI), a study in 4,041 patients who had experienced an ST-elevation myocardial infarction (STEMI), who had multi-vessel coronary artery disease, and who had undergone successful percutaneous coronary intervention of the culprit lesion.

Participants were randomized either to complete revascularization of all angiographically significant nonculprit lesions, or to no further revascularization, and were followed for a median of 3 years.

Of the patients who underwent complete revascularization, 7.8% experienced either cardiovascular death or another myocardial infarction, compared with 10.5% of those who only had revascularization of the culprit lesion, representing a significant 26% reduction (P = .004) in the incidence of this composite coprimary outcome.

The decrease in events was driven by a significant 32% reduction in the incidence of new myocardial infarction – particularly non-STEMI, new STEMI, and myocardial infarction type 1 – in the complete revascularization group, with only a 7% reduction in the incidence of death from cardiovascular causes.

With the second coprimary outcome of a composite of cardiovascular death, myocardial infarction, or ischemia-driven revascularization, this was seen in 8.9% of patients in the complete revascularization group compared with 16.7% of patients with the culprit-lesion-only group; a significant 49% reduction in incidence (P less than .001).

The authors calculated that 37 complete revascularizations would need to be performed to prevent one incidence of cardiovascular death or myocardial infarction. To prevent cardiovascular death, myocardial infarction, or ischemia-driven revascularization, the number needed to treat was 13.

The timing of complete revascularization did not appear to affect the benefits of the procedure, which were consistent among patients who underwent complete revascularization during their index hospitalization and in those who underwent the procedure after hospital discharge. Investigators had to specify before randomization whether the patient would undergo complete revascularization during the index hospitalization or after discharge but within 45 days.

The study also did not find any significant differences between the two groups in the risks of major bleeding, stroke, or stent thrombosis. However, the complete revascularization group did experience a nonsignificant 59% higher odds of contrast-associated acute kidney injury, which was attributed to the nonculprit lesion revascularization in seven patients in the complete revascularization group.

Dr. Shamir R. Mehta, of the Population Health Research Institute at McMaster University, Ontario, and coauthors noted that previous trials of complete-revascularization strategies in patients with STEMI were smaller and had included revascularization as part of a composite primary outcome.

“In the absence of a reduction in irreversible events such as cardiovascular death or new myocardial infarction, the clinical relevance of performing early nonculprit-lesion PCI in all patients with multivessel coronary artery disease to prevent later PCI in a smaller number of those patients is debatable,” they wrote. “We have now found that routine nonculprit-lesion PCI with the goal of complete revascularization confers a reduction in the long-term risk of cardiovascular death or myocardial infarction.”

No patients with cardiogenic shock were enrolled in the study, so the results could not be extrapolated to that patient group.

SOURCE: Mehta S et al. N Engl J Med. 2019 Sep. 1. doi: 10.1056/NEJMoa1907775.

PARIS – Lower levels of physical activity over time were linked to a significantly increased risk of both cardiovascular and all-cause mortality, according to results from a prospective cohort study that followed more than 23,000 adults for over 2 decades.

“Individuals who remained physically inactive, or who decreased their physical activity over 22 years, had substantially increased risk of dying from all causes, and from cardiovascular disease,” Trine Moholdt, PhD, said at a press conference at the annual congress of the European Society of Cardiology.

“The bad news is that sustained inactivity was associated with a 99% increase in all-cause mortality and 168% increase in cardiovascular deaths” compared with sustained physical activity, she said.

The news was similarly bad for individuals who had been highly active and then became inactive; this cohort had an increase in all-cause mortality of 116% and sustained a 173% increase in cardiovascular deaths. “Previous activity levels – they don’t count. You have to keep it up,” said Dr. Moholdt, speaking in a video interview.

However, the risk associated with inactivity was attenuated for those patients who became more active over the course of the study period; their risk was still higher than that of those who had sustained activity, but lower than those who remained inactive. “It’s never too late to start being physically active,” said Dr. Moholdt.

All groups were compared with individuals who remained highly active over the study period; this reference group had the lowest risk of both cardiovascular and all-cause death.

Dr. Moholdt noted a limitation of most previous research into how physical activity relates to cardiovascular and all-cause mortality: Data are obtained just at baseline, and then associated with a downstream outcome. “But people change!” she said, so it’s important to track how activity levels change over time.

To that end, the Nord-Trøndelag Health Study (HUNT study) measured activity levels for 23,156 participants at two points, and then assessed cardiovascular and all-cause mortality, over a period of 22 years.

[email protected]

SOURCE: Moholdt T. et al. ESC Congress 2019, Abstract P627.

PARIS – Lower levels of physical activity over time were linked to a significantly increased risk of both cardiovascular and all-cause mortality, according to results from a prospective cohort study that followed more than 23,000 adults for over 2 decades.

“Individuals who remained physically inactive, or who decreased their physical activity over 22 years, had substantially increased risk of dying from all causes, and from cardiovascular disease,” Trine Moholdt, PhD, said at a press conference at the annual congress of the European Society of Cardiology.

“The bad news is that sustained inactivity was associated with a 99% increase in all-cause mortality and 168% increase in cardiovascular deaths” compared with sustained physical activity, she said.

The news was similarly bad for individuals who had been highly active and then became inactive; this cohort had an increase in all-cause mortality of 116% and sustained a 173% increase in cardiovascular deaths. “Previous activity levels – they don’t count. You have to keep it up,” said Dr. Moholdt, speaking in a video interview.

However, the risk associated with inactivity was attenuated for those patients who became more active over the course of the study period; their risk was still higher than that of those who had sustained activity, but lower than those who remained inactive. “It’s never too late to start being physically active,” said Dr. Moholdt.

All groups were compared with individuals who remained highly active over the study period; this reference group had the lowest risk of both cardiovascular and all-cause death.

Dr. Moholdt noted a limitation of most previous research into how physical activity relates to cardiovascular and all-cause mortality: Data are obtained just at baseline, and then associated with a downstream outcome. “But people change!” she said, so it’s important to track how activity levels change over time.

To that end, the Nord-Trøndelag Health Study (HUNT study) measured activity levels for 23,156 participants at two points, and then assessed cardiovascular and all-cause mortality, over a period of 22 years.

[email protected]

SOURCE: Moholdt T. et al. ESC Congress 2019, Abstract P627.

PARIS – Lower levels of physical activity over time were linked to a significantly increased risk of both cardiovascular and all-cause mortality, according to results from a prospective cohort study that followed more than 23,000 adults for over 2 decades.

“Individuals who remained physically inactive, or who decreased their physical activity over 22 years, had substantially increased risk of dying from all causes, and from cardiovascular disease,” Trine Moholdt, PhD, said at a press conference at the annual congress of the European Society of Cardiology.

“The bad news is that sustained inactivity was associated with a 99% increase in all-cause mortality and 168% increase in cardiovascular deaths” compared with sustained physical activity, she said.

The news was similarly bad for individuals who had been highly active and then became inactive; this cohort had an increase in all-cause mortality of 116% and sustained a 173% increase in cardiovascular deaths. “Previous activity levels – they don’t count. You have to keep it up,” said Dr. Moholdt, speaking in a video interview.

However, the risk associated with inactivity was attenuated for those patients who became more active over the course of the study period; their risk was still higher than that of those who had sustained activity, but lower than those who remained inactive. “It’s never too late to start being physically active,” said Dr. Moholdt.

All groups were compared with individuals who remained highly active over the study period; this reference group had the lowest risk of both cardiovascular and all-cause death.

Dr. Moholdt noted a limitation of most previous research into how physical activity relates to cardiovascular and all-cause mortality: Data are obtained just at baseline, and then associated with a downstream outcome. “But people change!” she said, so it’s important to track how activity levels change over time.

To that end, the Nord-Trøndelag Health Study (HUNT study) measured activity levels for 23,156 participants at two points, and then assessed cardiovascular and all-cause mortality, over a period of 22 years.

[email protected]

SOURCE: Moholdt T. et al. ESC Congress 2019, Abstract P627.