Sex-Based Differences in Outcomes Following Peripheral Artery Revascularization: Insights From VOYAGER PAD.

Background Despite high female prevalence of peripheral artery disease (PAD), little is known about sex-based outcomes after lower extremity revascularization (LER) for symptomatic PAD. The effects of rivaroxaban according to sex following LER have not been fully reported. Methods and Results In VOYAGER PAD (Vascular Outcomes Study of ASA [acetylsalicylic acid] Along with Rivaroxaban in Endovascular or Surgical Limb Revascularization for Peripheral Artery Disease), low-dose rivaroxaban versus placebo on a background of aspirin reduced the composite primary efficacy outcome of cardiovascular and limb events in patients with PAD undergoing LER. Unplanned index limb revascularization was prespecified and prospectively ascertained. The primary safety outcome was Thrombolysis in Myocardial Infarction major bleeding. Analyses of outcomes and treatment effects by sex were performed using Cox proportional hazards models. Among 6564 randomly assigned patients followed for a median of 28 months, 1704 (26.0%) were women. Among patients administered placebo, women were at similar risk for the primary efficacy outcome (hazard ratio [HR], 0.90; [95% CI, 0.74-1.09]; P=0.29) as men, while female sex was associated with a trend toward higher risk of unplanned index limb revascularization (HR, 1.18; [95% CI, 1.00-1.40]; P=0.0499). Irrespective of sex, effects of rivaroxaban were consistent for the primary efficacy outcome (P-interaction=0.22), unplanned index limb revascularization (P-interaction=0.64), and bleeding (P-interaction=0.61). Women were more likely than men to discontinue study treatment (HR, 1.13; [95% CI, 1.03-1.25]; P=0.0099). Conclusions Among >1700 women with PAD undergoing LER, women and men were at similar risk for the primary outcome, but a trend for greater risk of unplanned index limb revascularization among women was observed. Effects of rivaroxaban were consistent by sex, though women more often discontinued treatment. Better understanding of sex-based outcomes and treatment adherence following LER is needed. Registration URL: http://clinicaltrials.gov; Unique identifier: NCT02504216

Women, lipids, and atherosclerotic cardiovascular disease:a call to action from the European Atherosclerosis Society

Cardiovascular disease is the leading cause of death in women and men globally, with most due to atherosclerotic cardiovascular disease (ASCVD). Despite progress during the last 30 years, ASCVD mortality is now increasing, with the fastest relative increase in middle-aged women. Missed or delayed diagnosis and undertreatment do not fully explain this burden of disease. Sex-specific factors, such as hypertensive disorders of pregnancy, premature menopause (especially primary ovarian insufficiency), and polycystic ovary syndrome are also relevant, with good evidence that these are associated with greater cardiovascular risk. This position statement from the European Atherosclerosis Society focuses on these factors, as well as sex-specific effects on lipids, including lipoprotein(a), over the life course in women which impact ASCVD risk. Women are also disproportionately impacted (in relative terms) by diabetes, chronic kidney disease, and auto-immune inflammatory disease. All these effects are compounded by sociocultural components related to gender. This panel stresses the need to identify and treat modifiable cardiovascular risk factors earlier in women, especially for those at risk due to sex-specific conditions, to reduce the unacceptably high burden of ASCVD in women.</p

31st Annual Meeting and Associated Programs of the Society for Immunotherapy of Cancer (SITC 2016) : part two

Background The immunological escape of tumors represents one of the main ob- stacles to the treatment of malignancies. The blockade of PD-1 or CTLA-4 receptors represented a milestone in the history of immunotherapy. However, immune checkpoint inhibitors seem to be effective in specific cohorts of patients. It has been proposed that their efficacy relies on the presence of an immunological response. Thus, we hypothesized that disruption of the PD-L1/PD-1 axis would synergize with our oncolytic vaccine platform PeptiCRAd. Methods We used murine B16OVA in vivo tumor models and flow cytometry analysis to investigate the immunological background. Results First, we found that high-burden B16OVA tumors were refractory to combination immunotherapy. However, with a more aggressive schedule, tumors with a lower burden were more susceptible to the combination of PeptiCRAd and PD-L1 blockade. The therapy signifi- cantly increased the median survival of mice (Fig. 7). Interestingly, the reduced growth of contralaterally injected B16F10 cells sug- gested the presence of a long lasting immunological memory also against non-targeted antigens. Concerning the functional state of tumor infiltrating lymphocytes (TILs), we found that all the immune therapies would enhance the percentage of activated (PD-1pos TIM- 3neg) T lymphocytes and reduce the amount of exhausted (PD-1pos TIM-3pos) cells compared to placebo. As expected, we found that PeptiCRAd monotherapy could increase the number of antigen spe- cific CD8+ T cells compared to other treatments. However, only the combination with PD-L1 blockade could significantly increase the ra- tio between activated and exhausted pentamer positive cells (p= 0.0058), suggesting that by disrupting the PD-1/PD-L1 axis we could decrease the amount of dysfunctional antigen specific T cells. We ob- served that the anatomical location deeply influenced the state of CD4+ and CD8+ T lymphocytes. In fact, TIM-3 expression was in- creased by 2 fold on TILs compared to splenic and lymphoid T cells. In the CD8+ compartment, the expression of PD-1 on the surface seemed to be restricted to the tumor micro-environment, while CD4 + T cells had a high expression of PD-1 also in lymphoid organs. Interestingly, we found that the levels of PD-1 were significantly higher on CD8+ T cells than on CD4+ T cells into the tumor micro- environment (p < 0.0001). Conclusions In conclusion, we demonstrated that the efficacy of immune check- point inhibitors might be strongly enhanced by their combination with cancer vaccines. PeptiCRAd was able to increase the number of antigen-specific T cells and PD-L1 blockade prevented their exhaus- tion, resulting in long-lasting immunological memory and increased median survival

Glycoprotein IIb/IIIa inhibitor use in patients with acute myocardial infarction undergoing PCI: insights from the TRANSLATE ACS study

Introduction: Concomitant use of glycoprotein IIb/IIIa inhibitors (GPI) and P2Y inhibitors increases bleeding risk. How GPIs are being used with faster onset, higher potency P2Y inhibitors are unclear. Methods and results: We studied 11,781 myocardial infarction (MI) patients treated with percutaneous coronary intervention (PCI) at 233 hospitals in the TRANSLATE ACS study (2010–2012). We used propensity matching to compare 6-week major adverse cardiac events (MACE: death, recurrent MI, stroke, or unplanned revascularization) and BARC 2+ bleeding events between patients who did and did not receive planned GPI. Planned and bailout GPI were used in 4,983 (42.2%) and 229 (4.4%) MI patients undergoing PCI, respectively. Patients receiving planned GPI were younger (58 vs. 61 years), more likely to present with STEMI (62.6% vs. 45.4%) or have stent thrombosis (4.2% vs. 2.1%, all P 6 hr prior to PCI versus earlier (27.8% vs. 44.4%, both P < 0.01). After propensity matching, planned GPI use was not associated with any difference in MACE (6.4% vs. 5.5% OR 1.18; 95% CI: 0.99–1.57), however, the risk of BARC 2+ bleeding was higher in patients who received planned GPI (11.3% vs. 8.7%; OR 1.34; 95% CI: 1.13–1.59). Conclusion: Planned GPI use as reported by practicing physicians was prevalent between 2010 and 2012 and was associated with increased risk of bleeding but not lower MACE

Long-Term Patient Outcomes After Femoropopliteal Peripheral Vascular Intervention in Patients With Intermittent Claudication

BACKGROUND: In patients with intermittent claudication (IC), short-term amputation rates from clinical trial data following lower extremity femoropopliteal (FP) peripheral vascular intervention (PVI) are \u3c1% with unknown longer-term rates. OBJECTIVES: The aim of this study was to identify revascularization and amputation rates following PVI in the FP segment and to assess 4-year amputation and revascularization rates after FP PVI for IC. METHODS: From 2016 to 2020, 19,324 patients undergoing FP PVI for IC were included from the PINC AI Healthcare Database and evaluated by treatment level (superficial femoral artery [SFA], popliteal artery [POP], or both). The primary outcome was index limb amputation (ILA) assessed by Kaplan-Meier estimate. The secondary outcomes were index limb major amputation and repeat revascularization. HRs were estimated using Cox proportional hazard regression. RESULTS: The 4-year index limb amputation rate following FP PVI was 4.3% (95% CI: 4.0-4.7), with a major amputation rate of 3.2% (95% CI: 2.9-3.5). After POP PVI, ILA was significantly higher than SFA alone (7.5% vs 3.4%) or both segment PVI (5.5%). In multivariate analysis, POP PVI was associated with higher ILA rates at 4 years compared with isolated SFA PVI (HR: 2.10; 95% CI: 1.52-2.91) and index limb major amputation (HR: 1.98; 95% CI: 1.32-2.95). Repeat FP revascularization rates were 15.2%; they were highest in patients undergoing both SFA and POP PVI (18.7%; P \u3c 0.0001) compared with SFA (13.9%) and POP (17.1%) only. CONCLUSIONS: IC patients undergoing FP PVI had 4-year rates of index limb repeat revascularization of 16.7% and ILA rates of 4.3%. Further risk factors for amputation requires further investigation

Women, lipids, and atherosclerotic cardiovascular disease: a call to action from the European Atherosclerosis Society

Cardiovascular disease is the leading cause of death in women and men globally, with most due to atherosclerotic cardiovascular disease (ASCVD). Despite progress during the last 30 years, ASCVD mortality is now increasing, with the fastest relative increase in middle-aged women. Missed or delayed diagnosis and undertreatment do not fully explain this burden of disease. Sex-specific factors, such as hypertensive disorders of pregnancy, premature menopause (especially primary ovarian insufficiency), and polycystic ovary syndrome are also relevant, with good evidence that these are associated with greater cardiovascular risk. This position statement from the European Atherosclerosis Society focuses on these factors, as well as sex-specific effects on lipids, including lipoprotein(a), over the life course in women which impact ASCVD risk. Women are also disproportionately impacted (in relative terms) by diabetes, chronic kidney disease, and auto-immune inflammatory disease. All these effects are compounded by sociocultural components related to gender. This panel stresses the need to identify and treat modifiable cardiovascular risk factors earlier in women, especially for those at risk due to sex-specific conditions, to reduce the unacceptably high burden of ASCVD in women. [GRAPHICS]

Management of Persistent Angina After Myocardial Infarction Treated With Percutaneous Coronary Intervention: Insights From the TRANSLATE-ACS Study.

Angina has important implications for patients' quality of life and healthcare utilization. Angina management after acute myocardial infarction (MI) treated with percutaneous coronary intervention (PCI) is unknown.TRANSLATE-ACS (Treatment With Adenosine Diphosphate Receptor Inhibitors: Longitudinal Assessment of Treatment Patterns and Events After Acute Coronary Syndrome) was a longitudinal study of MI patients treated with percutaneous coronary intervention at 233 US hospitals from 2010 to 2012. Among patients with self-reported angina at 6 weeks post-MI, we described patterns of angina and antianginal medication use through 1 year postdischarge. Of 10 870 percutaneous coronary intervention-treated MI patients, 3190 (29.3%) reported angina symptoms at 6 weeks post-MI; of these, 658 (20.6%) had daily/weekly angina while 2532 (79.4%) had monthly angina. Among patients with 6-week angina, 2936 (92.0%) received β-blockers during the 1 year post-MI, yet only 743 (23.3%) were treated with other antianginal medications. At 1 year, 1056 patients (33.1%) with 6-week angina reported persistent angina symptoms. Of these, only 31.2% had been prescribed non-β-blocker antianginal medications at any time in the past year. Among patients undergoing revascularization during follow-up, only 25.9% were on ≥1 non-β-blocker anti-anginal medication at the time of the procedure.Angina is present in one third of percutaneous coronary intervention-treated MI patients as early as 6 weeks after discharge, and many of these patients have persistent angina at 1 year. Non-β-blocker antianginal medications are infrequently used in these patients, even among those with persistent angina and those undergoing revascularization

Women, lipids, and atherosclerotic cardiovascular disease:a call to action from the European Atherosclerosis Society

Cardiovascular disease is the leading cause of death in women and men globally, with most due to atherosclerotic cardiovascular disease (ASCVD). Despite progress during the last 30 years, ASCVD mortality is now increasing, with the fastest relative increase in middle-aged women. Missed or delayed diagnosis and undertreatment do not fully explain this burden of disease. Sex-specific factors, such as hypertensive disorders of pregnancy, premature menopause (especially primary ovarian insufficiency), and polycystic ovary syndrome are also relevant, with good evidence that these are associated with greater cardiovascular risk. This position statement from the European Atherosclerosis Society focuses on these factors, as well as sex-specific effects on lipids, including lipoprotein(a), over the life course in women which impact ASCVD risk. Women are also disproportionately impacted (in relative terms) by diabetes, chronic kidney disease, and auto-immune inflammatory disease. All these effects are compounded by sociocultural components related to gender. This panel stresses the need to identify and treat modifiable cardiovascular risk factors earlier in women, especially for those at risk due to sex-specific conditions, to reduce the unacceptably high burden of ASCVD in women.</p