Gender differences in the development of heart failure after acute coronary syndrome: Insight from the CORALYS registry.

BACKGROUND: Impact of gender on heart remodeling after acute coronary syndrome (ACS) and consequently on development of heart failure (HF) remains to be elucidated. METHODS: CORALYS is a multicenter, retrospective, observational registry enrolling consecutive patients admitted for ACS and treated with percutaneous coronary intervention. HF hospitalization was the primary endpoint while all-cause mortality and the composite endpoint of incidence of first HF hospitalization and cardiovascular mortality were the secondary ones. RESULTS: Among 14,699 patients enrolled in CORALYS registry, 4578 (31%) were women and 10,121 (69%) males. Women were older, had more frequently hypertension and diabetes and less frequently smoking habit. History of myocardial infarction (MI), STEMI at admission and multivessel disease were less common in women. After median follow up of 2.9 ± 1.8 years, women had higher incidence of primary and secondary endpoints and female sex was an independent predictor of HF hospitalization (HR 1.26;1.05-1.50; p = 0.011) and cardiovascular death/HF hospitalization (HR 1.18;1.02-1.37; p = 0.022). At multivariable analysis women and men share as predictors of HF diabetes, history of cancer, chronic kidney disease, atrial fibrillation, complete revascularization and left ventricular ejection fraction. Chronic obstructive pulmonary disease (HR 2.34;1.70-3.22, p < 0.001) and diuretics treatment (HR 1.61;1.27-2.04, p < 0.001) were predictor of HF in men, while history of previous MI (HR 1.46;1.08-1.97, p = 0.015) and treatment with inhibitors of renin-angiotensin system (HR 0.69;0,49-0.96 all 95% CI, p = 0.030) in women. CONCLUSIONS: Women are at increased risk of HF after ACS and gender seems to be an outcome-modifier of the relationship between a variable and primary outcome.

Comparison of Stroke and Bleeding Risk Profile in Patients With Atrial Fibrillation and Chronic Kidney Disease.

Clinical decision making on anticoagulation in patients with chronic kidney disease with atrial fibrillation (AF) is challenging. The current strategies are based on small observational studies with conflicting results. This study explores the impact of glomerular filtration rate (GFR) in the embolic-hemorrhagic balance among a large cohort of patients with AF. The study cohort included 15,457 patients diagnosed with AF between January 2014 and April 2020. The risk of ischemic stroke and major bleeding was determined by competing risk regression. During a mean follow-up of 4.29 ± 1.82 years, 3,678 patients (23.80%) died, 850 (5.50%) had an ischemic stroke, and 961 (6.22%) had a major bleeding. The incidence of stroke and bleeding increased as baseline GFR decreased. Interestingly, in GFR <30 ml/min/1.73 m2, the bleeding risk was clearly higher than the embolic risk. As GFR decreased, anticoagulation was associated with an increased bleeding risk (subdistribution hazard ratio 1.700, 95% confidence interval [CI] 1.13 to 2.54, p = 0.009 for patients with GFR 30 to 59 ml/min/1.73 m2 and 2.00, 95% CI 0.77 to 5.21, p = 0.156 for subjects with <30 ml/min/1.73 m2 compared with those with GFR >60 ml/min/1.73 m2, respectively), but it was not associated with a decrease in embolic risk in patients with GFR <30 ml/min/1.73 m2 (subdistribution hazard ratio 1.91, 95% CI 0.73 to 5.04, p = 0.189) In GFR <30 ml/min/1.73 m2, the increase of major bleeding risk was higher than the increase of ischemic stroke risk, with a negative anticoagulation balance (greater increase in bleeding than reduction in embolism).

Long-term prognostic impact of beta-blockers in patients with Takotsubo syndrome: Results from the RETAKO Registry.

BACKGROUND: No evidence-based therapy has yet been established for Takotsubo syndrome (TTS). Given the putative harmful effects of catecholamines in patients with TTS, beta-blockers may potentially decrease the intensity of the detrimental cardiac effects in those patients. OBJECTIVE: The purpose of this study was to assess the impact of beta-blocker therapy on long-term mortality and TTS recurrence. METHODS: The cohort study used the national Spanish Registry on TakoTsubo Syndrome (RETAKO). A total of 970 TTS post-discharge survivors, without pheochromocytoma, left ventricular outflow tract obstruction, sustained ventricular arrhythmias, and significant bradyarrhythmias, between January 1, 2003, and July 31, 2018, were assessed. Cox regression analysis and inverse probability weighting (IPW) propensity score analysis were used to evaluate the association between beta-blocker therapy and survival free of TTS recurrence. RESULTS: From 970 TTS patients, 582 (60.0%) received beta-blockers. During a mean follow-up of 2.5±3.3 years, there were 87 deaths (3.6 per 100 patients/year) and 29 TTS recurrences (1.2 per 100 patient/year). There was no significant difference in follow-up mortality or TTS recurrence in unadjusted and adjusted Cox analysis (hazard ratio [HR] 0.86, 95% confidence interval [CI] 0.59-1.27, and 0.95, 95% CI 0.57-1.13, respectively). After weighting and adjusting by IPW, differences in one-year survival free of TTS recurrence between patients treated and untreated with beta-blockers were not found (average treatment effect -0.01, 95% CI -0.07 to 0.04; p=0.621). CONCLUSIONS: In this observational nationwide study from Spain, there was no significant association between beta-blocker therapy and follow-up survival free of TTS recurrence.

Bleeding and embolic risk in patients with atrial fibrillation and cancer.

INTRODUCTION AND OBJECTIVES: The impact of cancer on clinical outcomes in patients with atrial fibrillation (AF) is unclear. The aim of this study was to assess how cancer influences the prediction and risk of embolic and hemorrhagic events in patients with AF. METHODS: The study population comprised 16 056 patients from a Spanish health area diagnosed with AF between 2014 and 2018. Of these, 1137 (7.1%) had a history of cancer. During a median follow-up of 4.9 years, we assessed the relationship between cancer and bleeding and embolic events by competing risk analysis, considering death as a competing risk. RESULTS: No association was detected between an increased risk of embolic events and cancer overall (sHR, 0.73; 95%CI, 0.41-1.26), active cancer, or any subgroup of cancer. However, cancer was associated with an increased risk of bleeding, although only in patients with active cancer (sHR, 1.42; 95%CI, 1.20-1.67) or prior radiotherapy (sHR, 1.40; 95%CI, 1.19-1.65). Both the CHA2DS2-VASc and HAS-BLED scores showed suboptimal performance to predict embolic and bleeding risk (c-statistic <0.50), respectively, in nonanticoagulated patients with active cancer. The ratio between the increase in bleeding and the decrease in embolisms with anticoagulation was similar in patients with and without cancer (5.6 vs 7.8; P <.001). CONCLUSIONS: Cancer was not associated with an increased risk of embolic events in AF patients, only with an increased risk of bleeding. However, active cancer worsened the ability of the CHA2DS2-VASc and HAS-BLED scores to predict embolic and bleeding events, respectively, in nonanticoagulated patients.

Validation of Embolic and Bleeding Risk Scores in Patients With Atrial Fibrillation and Cancer.

Little is known about the prediction of atrial fibrillation (AF) risk scores in patients with cancer. The aim of this study was to assess the predictive ability of the CHA2DS2-VASc and HAS-BLED scores in patients with AF and cancer. Overall, 16,056 patients with AF diagnosed between 2014 and 2018 from a Spanish health area, including 1,137 patients with cancer, were observed during a median follow-up of 4.9 years. Although discrimination was similar between patients with cancer and patients without cancer who were treated with anticoagulation therapy (0.56 and 0.58), in patients with cancer who were not treated with anticoagulation therapy, c-statistic of CHA2DS2-VASc was poor and significantly lower than in the patients without cancer (0.42 vs 0.65). The overall precision of the CHA2DS2-VASc score was good throughout the follow-up (Brier score < 0.1), in patients with and without cancer. Regarding the HAS-BLED score, calibration and discrimination were poor in patients with cancer (c-statistic 0.51), similar to those in patients without cancer (c-statistic 0.53). In patients with cancer who were not treated with anticoagulation therapy, the embolic risk CHA2DS2-VASc score = 1 was similar to CHA2DS2-VASc score ≥ 2. Only patients with AF and cancer and CHA2DS2-VASc score = 0 presented a low risk of embolic events (negative predictive value 100%). A HAS-BLED score > 3 was not associated with higher bleeding risk in patients with cancer (p > 0.05). In summary, in patients with cancer and with AF, neither the CHA2DS2-VASc score nor the HAS-BLED score was useful for predicting embolic and hemorrhagic events, respectively. However, a CHA2DS2-VASc score 0 is useful to identify patients with AF and cancer who are at low embolic risk.

A Score to Assess Mortality After Percutaneous Mitral Valve Repair.

BACKGROUND: Risk stratification for transcatheter edge-to-edge mitral valve repair (TEER) is paramount in the decision-making process for treating severe mitral regurgitation (MR). OBJECTIVES: This study sought to create and validate a user-friendly score (MitraScore) to predict the risk of mortality in patients undergoing TEER. METHODS: The derivation cohort was based on a multicentric international registry that included 1,119 patients referred for TEER between 2012 and 2020. Score discrimination was assessed using Harrell's c-statistic, and the calibration was evaluated with the Gronnesby and Borgan goodness-of-fit test. An external validation was carried out in 725 patients from the GIOTTO registry. RESULTS: After multivariate analysis, we identified 8 independent predictors of mortality during the follow-up (2.1 ± 1.8 years): age ≥75 years, anemia, glomerular filtrate rate <60 mL/min/1.73 m2, left ventricular ejection fraction <40%, peripheral artery disease, chronic obstructive pulmonary disease, high diuretic dose, and no therapy with renin-angiotensin system inhibitors. The MitraScore was derived by assigning 1 point to each independent predictor. The c-statistic was 0.70. Per each point of the MitraScore, the relative risk of mortality increased by 55% (HR: 1.55; 95% CI: 1.44-1.67; P < 0.001). The discrimination and calibration for mortality prediction was better than those of EuroSCORE II (c-statistic 0.61) or Society of Thoracic Surgeons score (c-statistic 0.57). The MitraScore maintained adequate performance in the validation cohort (c-statistic 0.66). The score was also predictive for heart failure rehospitalization and was correlated with the probability of clinical improvement. CONCLUSIONS: The MitraScore is a simple prediction algorithm for the prediction of follow-up mortality in patients treated with TEER.

Incidence and Predictors of Bleeding in Patients With Cancer and Atrial Fibrillation.

Despite patients with cancer having a higher incidence of atrial fibrillation (AF), little is known about the predictors of outcomes in this population. This study aimed to assess the incidence and predictors of bleeding in patients with AF and cancer. The study population comprised 16,056 patients from a Spanish health area diagnosed with AF between 2014 and 2018 (1,137 with cancer). Competing risk analysis were used to evaluate the association of cancer and bleeding. Discrimination and calibration of bleeding risk scores were assessed by the concordance statistic and the Brier score, respectively. During a median follow-up of 4.9 years, the incidence of bleeding in patients with cancer was 13.2 per 100 patients/year. After multivariate adjustment, a significant association between cancer and bleeding was detected (subdistribution hazard ratio [sHR] 1.18, 95% CI 1.07 to 1.30, p = 0.001), specifically in patients with active cancer or previous radiotherapy. Early age, male gender, diabetes, and anticoagulation were independent predictors of bleeding. However, only anticoagulation with vitamin K antagonist (sHR 1.36, 95% CI 1.03 to 1.78, p = 0.026), not with direct oral anticoagulants (sHR 1.25, 95% CI 0.84 to 1.85, p = 0.270), was associated with bleeding. Discrimination and calibration of Hypertension, Abnormal renal/liver function, Stroke, Bleeding history or predisposition, Labile INR, Elderly, and Drugs/alcohol concomitantly (HAS-BLED), AnTicoagulation and Risk factors In Atrial fibrillation (ATRIA), and Hepatic or renal disease, Ethanol abuse, Malignancy, Older (age ≥75 years), Reduced platelet count or function, Rebleeding risk, Hypertension, Anaemia, Genetic factors, Excessive fall risk and Stroke (HEMORR2HAGES) scores were poor in patients with cancer (concordance statistic <0.6 and Brier score >0.1). In summary, cancer was associated with an increased risk of bleeding in patients with AF. The predictive ability of bleeding risk scores was poor in this population. Anticoagulation with vitamin K antagonist but not with direct oral anticoagulants, was an independent predictor of bleeding in patients with cancer.

Safety and efficacy of different P2Y12 inhibitors in patients with acute coronary syndromes stratified by the PRAISE risk score: a multicentre study.

AIMS: To establish the safety and efficacy of different dual antiplatelet therapy (DAPT) combinations in patients with acute coronary syndrome (ACS) according to their baseline ischaemic and bleeding risk estimated with a machine learning derived model [machine learning-based prediction of adverse events following an acute coronary syndrome (PRAISE) score]. METHODS AND RESULTS: Incidences of death, re-acute myocardial infarction (re-AMI), and Bleeding Academic Research Consortium 3-5 bleeding with aspirin plus different P2Y12 inhibitors (clopidogrel or potent P2Y12 inhibitors: ticagrelor or prasugrel) were appraised among patients of the PRAISE data set grouped in four subcohorts: low-to-moderate ischaemic and bleeding risk; low-to-moderate ischaemic risk and high bleeding risk; high ischaemic risk and low-to-moderate bleeding risk; and high ischaemic and bleeding risk. Hazard ratios (HRs) for the outcome measures were derived with inverse probability of treatment weighting adjustment. Among patients with low-to-moderate bleeding risk, clopidogrel was associated with higher rates of re-AMI in those at low-to-moderate ischaemic risk [HR 1.69, 95% confidence interval (CI) 1.16-2.51; P = 0.006] and increased risk of death (HR 3.2, 1.45-4.21; P = 0.003) and re-AMI (HR 2.23, 1.45-3.41; P < 0.001) in those at high ischaemic risk compared with prasugrel or ticagrelor, without a difference in the risk of major bleeding. Among patients with high bleeding risk, clopidogrel showed comparable risk of death, re-AMI, and major bleeding vs. potent P2Y12 inhibitors, regardless of the baseline ischaemic risk. CONCLUSION: Among ACS patients with non-high risk of bleeding, the use of potent P2Y12 inhibitors is associated with a lower risk of death and recurrent ischaemic events, without bleeding excess. Patients deemed at high bleeding risk may instead be safely addressed to a less intensive DAPT strategy with clopidogrel.

New Cancer Diagnosis After Bleeding in Anticoagulated Patients With Atrial Fibrillation.

Background Bleeding is frequent in patients with atrial fibrillation (AF) treated with oral anticoagulant therapy, and may be the first manifestation of underlying cancer. We sought to investigate to what extent bleeding represents the unmasking of an occult cancer in patients with AF treated with oral anticoagulants. Methods and Results Using data from CardioCHUVI-AF (Retrospective Observational Registry of Patients With Atrial Fibrillation From Vigo's Health Area), 8753 patients with AF aged ≥75 years with a diagnosis of AF between 2014 and 2017 were analyzed. Of them, 2171 (24.8%) experienced any clinically relevant bleeding, and 479 (5.5%) were diagnosed with cancer during a follow-up of 3 years. Among 2171 patients who experienced bleeding, 198 (9.1%) were subsequently diagnosed with cancer. Patients with bleeding have a 3-fold higher hazard of being subsequently diagnosed with new cancer compared with those without bleeding (4.7 versus 1.4 per 100 patient-years; adjusted hazard ratio [HR], 3.2 [95% CI, 2.6-3.9]). Gastrointestinal bleeding was associated with a 13-fold higher hazard of new gastrointestinal cancer diagnosis (HR, 13.4; 95% CI, 9.1-19.8); genitourinary bleeding was associated with an 18-fold higher hazard of new genitourinary cancer diagnosis (HR, 18.1; 95% CI, 12.5-26.2); and bronchopulmonary bleeding was associated with a 15-fold higher hazard of new bronchopulmonary cancer diagnosis (HR, 15.8; 95% CI, 6.0-41.3). For other bleeding (nongastrointestinal, nongenitourinary, nonbronchopulmonary), the HR for cancer was 2.3 (95% CI, 1.5-3.6). Conclusions In patients with AF treated with oral anticoagulant therapy, any gastrointestinal, genitourinary, or bronchopulmonary bleeding was associated with higher rates of new cancer diagnosis. These bleeding events should prompt investigation for cancers at those sites.

The impact of optimal medical therapy on patients with recurrent acute myocardial infarction: Subanalysis from the BleeMACS study.

BACKGROUND: Acute myocardial infarction (AMI) recurrence is still high despite great progress in secondary prevention. Patients with recurrent AMI suffer worse prognosis compared to those with first AMI. The objective was to evaluate the effect of optimal medical therapy (OMT) on these patients with recurrent AMI. METHODS AND RESULTS: Sub-analysis was performed including 13,343 patients with AMI from the international multicenter Bleeding complications in a Multicenter registry of patients discharged with diagnosis of Acute Coronary Syndrome (BleeMACS) registry. OMT was defined as the combination of aspirin, any P2Y12 inhibitor, statin, angiotensin converting enzyme inhibitor/angiotensin receptor blocker, and beta-blocker. Among 1285 patients with prior AMI, 56.8% received OMT prescription. Patients receiving OMT suffered from less congestive heart failure, peripheral artery disease, malignancy, and bleeding history. Kaplan-Meier survival estimates revealed that OMT was strongly related to decreased in all-cause death (4.2% vs. 10.1%, p < .001) and the composite endpoint of death/re-AMI (11.1% vs. 16.9%, p = .005) at 1-year follow-up. OMT was the independent protect factor of primary endpoint even after adjusting for multiple possible confounders (HR, 0.46; 95% CI, 0.27-0.78; p = .004). However, no significant difference was observed regarding re-AMI between OMT and non-OMT groups. OMT also reduced all-cause death in patients with recurrent AMI after propensity score matching. CONCLUSIONS: The prescription of OMT was seriously insufficient in patients with recurrent AMI, especially high-risk patients, even though OMT was associated with improved prognosis. Further improvements in pharmacological therapy are needed to reduce subsequent recurrent events.

Usefulness of Bleeding After Acute Coronary Syndromes for Unmasking Silent Cancer.

There is a growing body of evidence on the incidence and negative prognostic impact of postdischarge hemorrhagic complications after an acute coronary syndrome (ACS). However, the risk of subsequent cancer after postdischarge bleeding in these patients is currently poorly known. The aim of this study was to assess the association of postdischarge bleeding with newly diagnosed cancers after an ACS. Data from a single-center registry of 3,644 ACS patients, who were discharged with dual antiplatelet therapy and treated with percutaneous coronary intervention, were used to investigate the association between postdischarge bleeding and diagnosis of cancer. During a median follow-up of 56.2 months, bleeding events were documented in 1,216 patients and newly diagnosed cancers in 227 patients. Postdischarge bleeding was associated with cancer diagnosis (adjusted hazard ratio [HR] 3.43, 95% confidence interval [CI] 2.62 to 4.50), but only spontaneous bleeding (adjusted HR 4.38, 95% CI 3.31 to 5.79). This association was stronger as the severity of the bleeding increased (HR 1.52, 4.88, 7.30, and 12.29, for BARC type 1, 2, 3a, and 3b bleeding, respectively). Positive predictive values for cancer diagnosis of postdischarge bleeding was 7.7%. Median time from bleeding to cancer was 4.6 months. In conclusion, spontaneous postdischarge bleeding in ACS patients is strongly associated with subsequent cancer diagnosis within the first 6 months. A prompt evaluation of bleeding could be useful for enabling an early detection of cancer in these patients.

P2Y12 inhibitors in acute coronary syndrome patients with renal dysfunction: an analysis from the RENAMI and BleeMACS projects.

AIMS: The aim of the present study was to establish the safety and efficacy profile of prasugrel and ticagrelor in real-life acute coronary syndrome (ACS) patients with renal dysfunction. METHODS AND RESULTS: All consecutive patients from RENAMI (REgistry of New Antiplatelets in patients with Myocardial Infarction) and BLEEMACS (Bleeding complications in a Multicenter registry of patients discharged with diagnosis of Acute Coronary Syndrome) registries were stratified according to estimated glomerular filtration rate (eGFR) lower or greater than 60 mL/min/1.73 m2. Death and myocardial infarction (MI) were the primary efficacy endpoints. Major bleedings (MBs), defined as Bleeding Academic Research Consortium bleeding types 3 to 5, constituted the safety endpoint. A total of 19 255 patients were enrolled. Mean age was 63 ± 12; 14 892 (77.3%) were males. A total of 2490 (12.9%) patients had chronic kidney disease (CKD), defined as eGFR <60 mL/min/1.73 m2. Mean follow-up was 13 ± 5 months. Mortality was significantly higher in CKD patients (9.4% vs. 2.6%, P < 0.0001), as well as the incidence of reinfarction (5.8% vs. 2.9%, P < 0.0001) and MB (5.7% vs. 3%, P < 0.0001). At Cox multivariable analysis, potent P2Y12 inhibitors significantly reduced the mortality rate [hazard ratio (HR) 0.82, 95% confidence interval (CI) 0.54-0.96; P = 0.006] and the risk of reinfarction (HR 0.53, 95% CI 0.30-0.95; P = 0.033) in CKD patients as compared to clopidogrel. The reduction of risk of reinfarction was confirmed in patients with preserved renal function. Potent P2Y12 inhibitors did not increase the risk of MB in CKD patients (HR 1.00, 95% CI 0.59-1.68; P = 0.985). CONCLUSION: In ACS patients with CKD, prasugrel and ticagrelor are associated with lower risk of death and recurrent MI without increasing the risk of MB.

Risk of cancer after an acute coronary syndrome according to the type of P2Y12 inhibitor.

INTRODUCTION: There are conflicting clinical and laboratory data about the effect of dual antiplatelet therapy (DAPT) on cancer incidence, including analysis suggesting an increased cancer risk. This study aims to analyze if there are differences in the incidence of cancer according to the type of P2Y12 inhibitor prescribed (clopidogrel, prasugrel, or ticagrelor), among a population of acute coronary syndrome (ACS) survivors treated with DAPT. MATERIAL AND METHODS: A retrospective study was conducted among 4229 consecutive ACS patients discharged from a tertiary hospital with DAPT from 2010 to 2016. Cox regression, propensity score, and survival-time inverse probability analysis were done. RESULTS: A total of 311 were diagnosed of cancer during a median follow-up of 46.2 months. The cumulative incidence function (CIF) of cancer (per 100 patients/year) was 2.2 for clopidogrel, 1.6 for prasugrel, and 0.3 for ticagrelor. After multivariate analysis, we have found that ticagrelor resulted associated with lower cancer risk than clopidogrel (sHR 0.20: 95% CI 0.05-0.84; p = 0.028), without differences between prasugrel and clopidogrel. After propensity score matching, ticagrelor was also associated with lower incidence of cancer than clopidogrel/prasugrel (sHR 0.22; 95% CI 0.05-0.90; p = 0.036), regardless of DAPT duration. CONCLUSION: DAPT with ticagrelor could be associated with lower follow-up cancer incidence than DAPT with clopidogrel or prasugrel after an ACS.

Assessing the performance of the PRECISE-DAPT and PARIS risk scores for predicting one-year out-of-hospital bleeding in acute coronary syndrome patients.

AIMS: The PRECISE-DAPT and PARIS risk scores (RSs) were recently developed for bleeding risk assessment in percutaneous coronary intervention (PCI) patients treated with dual antiplatelet therapy (DAPT). We aimed to assess the performance of these RSs for predicting out-of-hospital bleeding in patients with acute coronary syndrome (ACS). METHODS AND RESULTS: Retrospectively, we studied 1,926 consecutive ACS patients treated with PCI and DAPT. The performance of RSs for predicting one-year BARC type 2, 3 or 5 bleeding and BARC type 3 or 5 bleeding was assessed and compared. Both RSs were effective for the prediction of bleeding events. For BARC type 2, 3 or 5 bleeding, the c-statistic values for PRECISE-DAPT and PARIS were 0.61 and 0.63 (p=0.29), respectively. The two scores displayed equal c-statistics of 0.73 for predicting BARC type 3 or 5 bleeding. PARIS significantly outperformed PRECISE-DAPT in terms of indices of categoryless net reclassification improvement and integrated discrimination. Decision curve analyses also favoured PARIS. CONCLUSIONS: Within our cohort, PARIS and PRECISE-DAPT were fairly to moderately effective for the prediction of bleeding. Their predictiveness varies according to the bleeding severity. PARIS-derived bleeding risk assessment was associated with a higher net benefit compared to PRECISE-DAPT-based bleeding risk assessment.

Association Between Ischemic and Bleeding Risk Scores and the Use of New P2Y12 Inhibitors in Patients With Acute Coronary Syndrome.

INTRODUCTION AND OBJECTIVES: Acute coronary syndrome (ACS) guidelines recommend the use of newer P2Y12 inhibitors (prasugrel and ticagrelor) over clopidogrel in patients with moderate-to-high ischemic risk, unless they have an increased bleeding risk. The aim of our study was to assess the GRACE risk score and the CRUSADE bleeding risk score relative to prescription of newer P2Y12 inhibitors at discharge in ACS patients. METHODS: Retrospective analysis of a multicenter ACS registry; 3515 consecutive patients were included. The association between risk scores and prescription of newer P2Y12 inhibitors was assessed by binary logistic regression analysis. RESULTS: A total of 1021 patients (29%) were treated with prasugrel or ticagrelor. On multivariate analyses, both GRACE (OR per 10 points, 0.89; 95%CI, 0.86-0.92; P < .001) and CRUSADE (OR per 10 points, 0.96; 95%CI, 0.94-0.98; P < .001) risk scores were inversely associated with the use of newer P2Y12 inhibitors. Moreover, other factors not included in these scores (revascularization approach, in-hospital stent thrombosis, major bleeding, and concomitant indication for anticoagulation therapy) also predicted the use of newer P2Y12 inhibitors. CONCLUSIONS: New P2Y12 inhibitors were more frequently prescribed among ACS patients with lower CRUSADE bleeding risk. However, an ischemic risk paradox was found, with higher use of these agents in patients with lower ischemic risk based on GRACE risk score estimates. These results underscore the importance of risk stratification to safely deliver optimal therapies.

Prevalence and outcome of patients with cancer and acute coronary syndrome undergoing percutaneous coronary intervention: a BleeMACS substudy.

BACKGROUND: The prevalence and outcome of patients with cancer that experience acute coronary syndrome (ACS) have to be determined. METHODS AND RESULTS: The BleeMACS project is a multicentre observational registry enrolling patients with acute coronary syndrome undergoing percutaneous coronary intervention worldwide in 15 hospitals. The primary endpoint was a composite event of death and re-infarction after one year of follow-up. Bleedings were the secondary endpoint. 15,401 patients were enrolled, 926 (6.4%) in the cancer group and 14,475 (93.6%) in the group of patients without cancer. Patients with cancer were older (70.8±10.3 vs. 62.8±12.1 years, P<0.001) with more severe comorbidities and presented more frequently with non-ST-segment elevation myocardial infarction compared with patients without cancer. After one year, patients with cancer more often experienced the composite endpoint (15.2% vs. 5.3%, P<0.001) and bleedings (6.5% vs. 3%, P<0.001). At multiple regression analysis the presence of cancer was the strongest independent predictor for the primary endpoint (hazard ratio (HR) 2.1, 1.8-2.5, P<0.001) and bleedings (HR 1.5, 1.1-2.1, P=0.015). Despite patients with cancer generally being undertreated, beta-blockers (relative risk (RR) 0.6, 0.4-0.9, P=0.05), angiotensin-converting enzyme inhibitors/angiotensin receptor blockers (RR 0.5, 0.3-0.8, P=0.02), statins (RR 0.3, 0.2-0.5, P<0.001) and dual antiplatelet therapy (RR 0.5, 0.3-0.9, P=0.05) were shown to be protective factors, while proton pump inhibitors (RR 1, 0.6-1.5, P=0.9) were neutral. CONCLUSION: Cancer has a non-negligible prevalence in patients with acute coronary syndrome undergoing percutaneous coronary intervention, with a major risk of cardiovascular events and bleedings. Moreover, these patients are often undertreated from clinical despite medical therapy seems to be protective. Registration:The BleeMACS project (NCT02466854).

Tobacco, illicit drugs use and risk of cardiovascular disease in patients living with HIV.

PURPOSE OF REVIEW: There is a strong link between HIV, smoking and illicit drugs. This association could be clinically relevant as it may potentiate the risk of cardiovascular diseases (CVD). The purpose of this review is to bring readers up to date on issues concerning the cardiovascular risk associated with tobacco and illicit drugs in patients living with HIV (PLHIV), examining the studies related to this topic published in the last year. RECENT FINDINGS: There is a strong association between smoking and atherosclerotic disease in PLHIV, reducing life expectancy secondary to CVD by up to 6 years. Illicit drugs were associated with increased risk of atherosclerotic problems but to a lesser extent than smoking. A significant association of drugs such as cocaine with subclinical coronary atherosclerosis been demonstrated. The relation of marijuana, heroin and amphetamines with atherosclerosis generates more controversy. However, those drugs are associated with cardiovascular morbidity, independently of smoking and other traditional risk factors. SUMMARY: Tobacco and illicit drugs are linked to CVD in HIV patients. This leads to the need to create special programs to address the addiction to smoking and illicit drugs, in order to mitigate their consequences and reduce cardiovascular risk.

Optimal Medical Therapy in Patients with Malignancy Undergoing Percutaneous Coronary Intervention for Acute Coronary Syndrome: a BleeMACS Sub-Study.

OBJECTIVE: Our objective was to define the most appropriate treatment for acute coronary syndrome (ACS) in patients with malignancy. METHODS AND RESULTS: The BleeMACS project is a worldwide multicenter observational prospective registry in 16 hospitals enrolling patients with ACS undergoing percutaneous coronary intervention. Primary endpoints were death, re-infarction, and major adverse cardiac events (MACE; composite of death and re-infarction) after 1 year of follow-up. The secondary endpoint was bleeding events during follow-up. We performed sub-study analyses according to whether ß-blockers (BBs), angiotensin-converting enzyme inhibitors (ACEIs) or angiotensin receptor blockers (ARBs), statins, or proton pump inhibitors (PPIs) were prescribed at discharge. We also calculated the propensity score for optimal medical therapy (OMT; combination of BB, ACEI/ARB, and statins). The study included 926 patients. According to the multivariate analysis, ACEIs/ARBs (hazard ratio [HR] 0.58, 95 % confidence interval [CI] 0.36-1.94; p = 0.03) and statins (HR 0.37, 95 % CI 0.23-0.61; p < 0.01) reduced the risk of MACE, while the effects of BBs (HR 0.85, 95 % CI 0.55-1.32; p = 0.48) and PPIs (HR 1.33, 95 % CI 0.83-2.12; p = 0.23) were not significant. OMT was prescribed at discharge in 300 (32.4 %) patients; after propensity score analysis, OMT showed a significant reduction in death (3 % vs. 12.5 %, HR 0.21, 95 % CI 0.1-0.4; log-rank p < 0.001) and MACE (6.7 vs. 15.2 %, log-rank p = 0.01). CONCLUSION: In patients with ACS and malignancy, OMT reduces the risk of adverse events at 1 year; in particular, ACEIs/ARBs and statins were the most protective drugs. (Clinical trials identifier: NCT02466854).

[Impact of concomitant use of P2Y12 inhibitors and proton pump inhibitors on ischemia events in patients with acute coronary syndrome in real world].

Objective: The study aimed to analyze the impact of concomitant administration of P2Y12 inhibitors and PPIs on ischemia events in patients with acute coronary syndrome (ACS) after percutaneous coronary intervention (PCI). Methods: We retrospectively analyzed data from a international, multi-center registry between 2003 and 2014 in patients with ACS after PCI, grouped the cohort into patients receiving PPIs or no PPIs and assessed 1-year clinical endpoint (all-cause death/re-infarction). Meanwhile, we grouped the cohort into patients receiving clopidogrel or ticagrelor, and compared the impact of concomitant administration of PPIs and clopidogrel or ticagrelor on 1-year clinical endpoint. Results: Of 9 429 patients in the final cohort, 54.8% (n=5 165) was prescribed a PPI at discharge. Patients receiving a PPI were more likely to have comorbidities. No association was observed between PPI use and the clinical endpoint (HR 1.00, 95% CI 0.86-1.18). Meanwhile, no association was found between PPI use and the clinical endpoint in patients receiving either clopidogrel or ticagrelor. And the clinical endpoint in patients administrated of clopidogrel and PPIs had no difference with that of ticagrelor and PPIs. Conclusions: In patients with ACS following PCI, increased risk of ischemia event was not found in the concomitant use of PPIs and P2Y12 inhibitors, and especially, compared with ticagrelor, clopidogrel was found no association with ischemia events when concomitant administrated with PPIs.