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.

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.