Low-dose rivaroxaban plus aspirin in patients with polypharmacy and multimorbidity: an analysis from the COMPASS trial.

AIMS: To analyse whether the benefits and risks of rivaroxaban plus aspirin vary in patients with comorbidities and receiving multiple drugs. In patients with coronary or peripheral artery disease, adding low-dose rivaroxaban to aspirin reduces cardiovascular events and mortality. Polypharmacy and multimorbidity are frequent in such patients. METHODS AND RESULTS: We describe ischaemic events (cardiovascular death, stroke, or myocardial infarction) and major bleeding in participants from the randomized, double-blind COMPASS study by number of cardiovascular medications and concomitant medical conditions. We compared event rates and hazard ratios (HRs) for rivaroxaban plus aspirin vs. aspirin alone by the number of medications and concomitant conditions, and tested for interaction between polypharmacy or multimorbidity and the antithrombotic regimen. The risk of ischaemic events was higher in patients with more concomitant drugs (HR 1.7, 95% confidence interval 1.5-2.1 for >4 vs. 0-2) and with more comorbidities (HR 2.3, 1.8-2.1 for >3 vs. 0-1). Multimorbidity, but not polypharmacy, was associated with a higher risk of major bleeding. The relative efficacy, safety, and net clinical benefit of rivaroxaban were not affected by the number of drugs or comorbidities. Patients taking more concomitant medications derived the largest absolute reduction in the net clinical outcome with added rivaroxaban (1.1% vs. 0.4% reduction with >4 vs. 0-2 cardiovascular drugs, number needed to treat 91 vs. 250). CONCLUSION: Adding low-dose rivaroxaban to aspirin resulted in benefits irrespective of the number of concomitant drugs or comorbidities. Multiple comorbidities and/or polypharmacy should not dissuade the addition of rivaroxaban to aspirin in otherwise eligible patients.

A contemporary approach to a young female patient with Loeys-Dietz syndrome and an uncomplicated type B aortic dissection: a case report.

BACKGROUND: Aortic dissection is a relatively uncommon, but often catastrophic disease that requires early and accurate diagnosis. It often presents in patients with congenital connective tissue disorders. The current aortic surgical techniques are related with serious early and late complications. This case report emphasizes the importance of early diagnosis of aortic root dilatation and the risk of dissection, especially in patients with congenital connective tissue disorders. We present an alternative, contemporary and multidisciplinary approach based on the present state of knowledge. CASE PRESENTATION: We present a rare case of a young female patient with Loeys-Dietz syndrome who was admitted with an uncomplicated aortic dissection (Stanford type B / DeBakey type III) and a dilated aortic root. After a period of close surveillance and extensive vascular imaging, thoracic endovascular aortic repair was deemed to be technically not possible. Medical treatment was optimized and our patient successfully underwent a personalised external aortic root support procedure (PEARS) as a contemporary alternative to existing aortic root surgical techniques. CONCLUSIONS: This case highlights the importance of interdisciplinary approach, close follow-up and multimodality imaging. The decision to intervene in a chronic type B aortic dissection is still challenging and should be made in experienced centers by an interdisciplinary team. However, if an acute complication occurs, thoracic endovascular aortic repair TEVAR is the method of choice. In all cases optimal medical treatment is important. There is increasing evidence that personalized external aortic root support procedure PEARS is effective in stabilizing the aortic root and preventing its dilatation and dissection not only in patients with Marfan syndrome, but also in other cases of aortic root dilation of other etiologies. Moreover, many publications have reported the additional benefit of reduction or even eradication of aortic regurgitation by improving coaptation of the aortic valve leaflets in dilated aortas.

Risk factors and clinical outcomes in chronic coronary and peripheral artery disease: An analysis of the randomized, double-blind COMPASS trial.

AIMS: Secondary prevention in patients with coronary artery disease and peripheral artery disease involves antithrombotic therapy and optimal control of cardiovascular risk factors. In the Cardiovascular Outcomes for People Using Anticoagulation Strategies (COMPASS) study, adding low-dose rivaroxaban on top of aspirin lowered cardiovascular events, but there is limited data about risk factor control in secondary prevention. We studied the association between risk factor status and outcomes, and the impact of risk factor status on the treatment effect of rivaroxaban, in a large contemporary population of patients with coronary artery disease or peripheral artery disease. METHODS AND RESULTS: We reported ischemic events (cardiovascular death, stroke, or myocardial infarction) in participants from the randomized, double-blind COMPASS study by individual risk factor (blood pressure, smoking status, cholesterol level, presence of diabetes, body mass index, and level of physical activity), and by number of risk factors. We compared rates and hazard ratios of patients treated with rivaroxaban plus aspirin vs aspirin alone within each risk factor category and tested for interaction between risk factor status and antithrombotic regimen. Complete baseline risk factor status was available in 27,117 (99%) patients. Status and number of risk factors were both associated with increased risk of ischemic events. Rates of ischemic events (hazard ratio 2.2; 95% confidence interval 1.8-2.6) and cardiovascular death (hazard ratio 2.0; 1.5-2.7) were more than twofold higher in patients with 4-6 compared with 0-1 risk factors (p < 0.0001 for both). Rivaroxaban reduced event rates independently of the number of risk factors (p interaction 0.93), with the largest absolute benefit in patients with the highest number of risk factors. CONCLUSION: More favorable risk factor status and low-dose rivaroxaban were independently associated with lower risk of cardiovascular events.

Bleeding and New Cancer Diagnosis in Patients With Atherosclerosis.

BACKGROUND: Patients treated with antithrombotic drugs are at risk of bleeding. Bleeding may be the first manifestation of underlying cancer. METHODS: We examined new cancers diagnosed in relation to gastrointestinal or genitourinary bleeding among patients enrolled in the COMPASS trial (Cardiovascular Outcomes for People Using Anticoagulation Strategies) and determined the hazard of new cancer diagnosis after bleeding at these sites. RESULTS: Of 27 395 patients enrolled (mean age, 68 years; women, 21%), 2678 (9.8%) experienced any (major or minor) bleeding, 713 (2.6%) experienced major bleeding, and 1084 (4.0%) were diagnosed with cancer during a mean follow-up of 23 months. Among 2678 who experienced bleeding, 257 (9.9%) were subsequently diagnosed with cancer. Gastrointestinal bleeding was associated with a 20-fold higher hazard of new gastrointestinal cancer diagnosis (7.4% versus 0.5%; hazard ratio [HR], 20.6 [95% CI, 15.2-27.8]) and 1.7-fold higher hazard of new nongastrointestinal cancer diagnosis (3.8% versus 3.1%; HR, 1.70 [95% CI, 1.20-2.40]). Genitourinary bleeding was associated with a 32-fold higher hazard of new genitourinary cancer diagnosis (15.8% versus 0.8%; HR, 32.5 [95% CI, 24.7-42.9]), and urinary bleeding was associated with a 98-fold higher hazard of new urinary cancer diagnosis (14.2% versus 0.2%; HR, 98.5; 95% CI, 68.0-142.7). Nongastrointestinal, nongenitourinary bleeding was associated with a 3-fold higher hazard of nongastrointestinal, nongenitourinary cancers (4.4% versus 1.9%; HR, 3.02 [95% CI, 2.32-3.91]). CONCLUSIONS: In patients with atherosclerosis treated with antithrombotic drugs, any gastrointestinal or genitourinary bleeding was associated with higher rates of new cancer diagnosis. Any gastrointestinal or genitourinary bleeding should prompt investigation for cancers at these sites. CLINICAL TRIAL REGISTRATION: URL: https://www.clinicaltrials.gov. Unique identifier: NCT01776424.

Clinical Features and Outcomes of Patients With Malignancy and Takotsubo Syndrome: Observations From the International Takotsubo Registry.

Background Clinical characteristics and outcomes of takotsubo syndrome (TTS) patients with malignancy have not been fully elucidated. This study sought to explore differences in clinical characteristics and to investigate short- and long-term outcomes in TTS patients with or without malignancy. Methods and Results TTS patients were enrolled from the International Takotsubo Registry. The TTS cohort was divided into patients with and without malignancy to investigate differences in clinical characteristics and to assess short- and long-term mortality. A subanalysis was performed comparing long-term mortality between a subset of TTS patients with or without malignancy and acute coronary syndrome (ACS) patients with or without malignancy. Malignancy was observed in 16.6% of 1604 TTS patients. Patients with malignancy were older and more likely to have physical triggers, but less likely to have emotional triggers compared with those without malignancy. Long-term mortality was higher in patients with malignancy (P<0.001), while short-term outcome was comparable (P=0.17). In a subanalysis, long-term mortality was comparable between TTS patients with malignancies and ACS patients with malignancies (P=0.13). Malignancy emerged as an independent predictor of long-term mortality. Conclusions A substantial number of TTS patients show an association with malignancy. History of malignancy might increase the risk for TTS, and therefore, appropriate screening for malignancy should be considered in these patients. Clinical Trial Registration URL: http://www.clinicaltrial.gov. Unique identifier: NCT01947621.

Safety of Proton Pump Inhibitors Based on a Large, Multi-Year, Randomized Trial of Patients Receiving Rivaroxaban or Aspirin.

BACKGROUND & AIMS: Proton pump inhibitors (PPIs) are effective at treating acid-related disorders. These drugs are well tolerated in the short term, but long-term treatment was associated with adverse events in observational studies. We aimed to confirm these findings in an adequately powered randomized trial. METHODS: We performed a 3 × 2 partial factorial double-blind trial of 17,598 participants with stable cardiovascular disease and peripheral artery disease randomly assigned to groups given pantoprazole (40 mg daily, n = 8791) or placebo (n = 8807). Participants were also randomly assigned to groups that received rivaroxaban (2.5 mg twice daily) with aspirin (100 mg once daily), rivaroxaban (5 mg twice daily), or aspirin (100 mg) alone. We collected data on development of pneumonia, Clostridium difficile infection, other enteric infections, fractures, gastric atrophy, chronic kidney disease, diabetes, chronic obstructive lung disease, dementia, cardiovascular disease, cancer, hospitalizations, and all-cause mortality every 6 months. Patients were followed up for a median of 3.01 years, with 53,152 patient-years of follow-up. RESULTS: There was no statistically significant difference between the pantoprazole and placebo groups in safety events except for enteric infections (1.4% vs 1.0% in the placebo group; odds ratio, 1.33; 95% confidence interval, 1.01-1.75). For all other safety outcomes, proportions were similar between groups except for C difficile infection, which was approximately twice as common in the pantoprazole vs the placebo group, although there were only 13 events, so this difference was not statistically significant. CONCLUSIONS: In a large placebo-controlled randomized trial, we found that pantoprazole is not associated with any adverse event when used for 3 years, with the possible exception of an increased risk of enteric infections. ClinicalTrials.gov Number: NCT01776424.

Five-year outcomes in cardiac surgery patients with atrial fibrillation undergoing concomitant surgical ablation versus no ablation. The long-term follow-up of the PRAGUE-12 Study.

BACKGROUND: The long-term effect of concomitant surgical ablation (SA) on clinical outcomes in an unselected population of patients has not been sufficiently reported in randomized studies. OBJECTIVE: The aim of this study was to assess clinical outcomes of the SA after 5 years of follow-up. METHODS: The PRAGUE-12 study was a prospective, randomized clinical trial assessing cardiac surgery with ablation for AF vs cardiac surgery alone. Patients with AF who were also indicated for cardiac surgery (coronary artery disease [CAD], valve surgery) were randomized to SA or control (no ablation) group. All patients were followed for 5 years. The primary endpoint was a composite of cardiovascular death, stroke, hospitalization for heart failure, or severe bleeding. Secondary endpoint was a recurrence of AF. RESULTS: A total of 207 patients were analyzed (SA group = 108 patients, control group = 99 patients). Both groups were similar relative to important clinical characteristics except for CAD, which was more common in the control group. Cumulative incidence curves showed a higher incidence of the primary endpoint in the control group (P = .024, Gray's test). However, after adjusting for all covariables, the difference between groups was not significant (subhazard ratio [SHR] 0.69 [0.47-1.02], P = .068). The incidence of stroke and AF recurrences were significantly reduced in the SA group, and remained significant even after adjustment for all covariables, including CAD (stroke: SHR 0.32 [0.12-0.84], P = .02, AF recurrences: SHR 0.44 [0.31-0.62], P < .001). CONCLUSIONS: Concomitant SA of AF is associated with a greater likelihood of maintaining sinus rhythm and a decreased risk of stroke.

Hyperuricemia treatment in acute heart failure patients does not improve their long-term prognosis: A propensity score matched analysis from the AHEAD registry.

BACKGROUND: Hyperuricemia is associated with a poorer prognosis in heart failure (HF) patients. Benefits of hyperuricemia treatment with allopurinol have not yet been confirmed in clinical practice. The aim of our work was to assess the benefit of allopurinol treatment in a large cohort of HF patients. METHODS: The prospective acute heart failure registry (AHEAD) was used to select 3160 hospitalized patients with a known level of uric acid (UA) who were discharged in a stable condition. Hyperuricemia was defined as UA ≥500 µmoL/L and/or allopurinol treatment at admission. The patients were classified into three groups: without hyperuricemia, with treated hyperuricemia, and with untreated hyperuricemia at discharge. Two- and five-year all-cause mortality were defined as endpoints. Patients without hyperuricemia, unlike those with hyperuricemia, had a higher left ventricular ejection fraction, a better renal function, and higher hemoglobin levels, had less frequently diabetes mellitus and atrial fibrillation, and showed better tolerance to treatment with angiotensin-converting enzyme inhibitors/angiotensin receptor blockers and/or beta-blockers. RESULTS: In a primary analysis, the patients without hyperuricemia had the highest survival rate. After using the propensity score to set up comparable groups, the patients without hyperuricemia had a similar 5-year survival rate as those with untreated hyperuricemia (42.0% vs 39.7%, P = 0.362) whereas those with treated hyperuricemia had a poorer prognosis (32.4% survival rate, P = 0.006 vs non-hyperuricemia group and P = 0.073 vs untreated group). CONCLUSION: Hyperuricemia was associated with an unfavorable cardiovascular risk profile in HF patients. Treatment with low doses of allopurinol did not improve the prognosis of HF patients.

Prevalence and predictors of coronary artery disease in patients undergoing carotid artery stenting.

INTRODUCTION: A relationship between carotid stenosis and coronary arterial disease (CAD) is widely accepted; however, data on the exact prevalence of coronary disease in patients with severe carotid stenosis are lacking. Information on the prevalence and predictors of CAD among these patients could impact diagnostic and treatment approaches. AIM: The primary aim of this study was to determine the prevalence of significant CAD among patients referred for carotid artery revascularization. The secondary objectives included characterizing the association between the level of advancement of carotid stenosis and the presence of CAD, and between atherosclerotic risk factors and the presence of CAD in patients with carotid stenosis, and also to determine whether there was a difference in the prevalence of CAD between patients with symptomatic versus asymptomatic carotid stenosis. PATIENTS AND METHODS: We included 200 patients with severe carotid stenosis, of whom 77 (38.5%) had symptomatic stenosis. All patients underwent coronary angiography no more than 6 months before the scheduled carotid revascularization. Of the 200 total of patients, 192 underwent carotid stenting, six underwent carotid endarterectomy, and two were treated conservatively. CAD was defined as stenosis of at least 50% on recent coronary angiography or a history of previous percutaneous coronary intervention and/or coronary aortic bypass graft; the prevalence was 77.5% among our patients. There was no statistically significant difference in the prevalence of CAD between patients with unilateral versus bilateral carotid stenosis or contralateral carotid occlusion. The difference in the severity of coronary disease, which was given by the SYNTAX score, was not significant between these groups. Factors associated with the presence of CAD were male sex, a history of smoking, and global or regional wall motion disorder on echocardiography. We did not find any significant difference in the prevalence of CAD between patients with symptomatic versus asymptomatic carotid stenosis. CONCLUSION: We observed a very high prevalence of concomitant CAD in patients with severe carotid stenosis. The results of our study suggest that routine preprocedural screening for CAD in patients with carotid artery stenosis could identify a large proportion of patients with silent CAD; whether treatment for CAD before carotid revascularization can prevent periprocedural myocardial infarction should be addressed in a randomized-controlled trial.

Rivaroxaban, Aspirin, or Both to Prevent Early Coronary Bypass Graft Occlusion: The COMPASS-CABG Study.

BACKGROUND: Patients with recent coronary artery bypass graft (CABG) surgery are at risk for early graft failure, which is associated with a risk of myocardial infarction and death. In the COMPASS (Cardiovascular OutcoMes for People Using Anticoagulation StrategieS) trial, rivaroxaban 2.5 mg twice daily plus aspirin 100 mg once daily compared with aspirin 100 mg once daily reduced the primary major adverse cardiovascular events (MACE) outcome of cardiovascular death, stroke, or myocardial infarction. Rivaroxaban 5 mg twice daily alone did not significantly reduce MACE. OBJECTIVES: This pre-planned substudy sought to determine whether the COMPASS treatments are more effective than aspirin alone for preventing graft failure and MACE after CABG surgery. METHODS: The substudy randomized 1,448 COMPASS trial patients 4 to 14 days after CABG surgery to receive the combination of rivaroxaban plus aspirin, rivaroxaban alone, or aspirin alone. The primary outcome was graft failure, diagnosed by computed tomography angiogram 1 year after surgery. RESULTS: The combination of rivaroxaban and aspirin and the regimen of rivaroxaban alone did not reduce the graft failure rates compared with aspirin alone (combination vs. aspirin: 113 [9.1%] vs. 91 [8.0%] failed grafts; odds ratio [OR]: 1.13; 95% confidence interval [CI]: 0.82 to 1.57; p = 0.45; rivaroxaban alone vs. aspirin: 92 [7.8%] vs. 92 [8.0%] failed grafts; OR: 0.95; 95% CI: 0.67 to 1.33; p = 0.75). Compared with aspirin, the combination was associated with fewer MACE (12 [2.4%] vs. 16 [3.5%]; hazard ratio [HR]: 0.69; 95% CI: 0.33 to 1.47; p = 0.34), whereas rivaroxaban alone was not (16 [3.3%] vs. 16 [3.5%]; HR: 0.99, CI: 0.50 to 1.99; p = 0.98). There was no fatal bleeding or tamponade within 30 days of randomization. CONCLUSIONS: The combination of rivaroxaban 2.5 mg twice daily plus aspirin or rivaroxaban 5 mg twice daily alone compared with aspirin alone did not reduce graft failure in patients with recent CABG surgery, but the combination of rivaroxaban 2.5 mg twice daily plus aspirin was associated with similar reductions in MACE, as observed in the larger COMPASS trial. (Cardiovascular OutcoMes for People Using Anticoagulation StrategieS [COMPASS]; NCT01776424).

Rivaroxaban with or without aspirin in patients with stable coronary artery disease: an international, randomised, double-blind, placebo-controlled trial.

BACKGROUND: Coronary artery disease is a major cause of morbidity and mortality worldwide, and is a consequence of acute thrombotic events involving activation of platelets and coagulation proteins. Factor Xa inhibitors and aspirin each reduce thrombotic events but have not yet been tested in combination or against each other in patients with stable coronary artery disease. METHODS: In this multicentre, double-blind, randomised, placebo-controlled, outpatient trial, patients with stable coronary artery disease or peripheral artery disease were recruited at 602 hospitals, clinics, or community centres in 33 countries. This paper reports on patients with coronary artery disease. Eligible patients with coronary artery disease had to have had a myocardial infarction in the past 20 years, multi-vessel coronary artery disease, history of stable or unstable angina, previous multi-vessel percutaneous coronary intervention, or previous multi-vessel coronary artery bypass graft surgery. After a 30-day run in period, patients were randomly assigned (1:1:1) to receive rivaroxaban (2·5 mg orally twice a day) plus aspirin (100 mg once a day), rivaroxaban alone (5 mg orally twice a day), or aspirin alone (100 mg orally once a day). Randomisation was computer generated. Each treatment group was double dummy, and the patients, investigators, and central study staff were masked to treatment allocation. The primary outcome of the COMPASS trial was the occurrence of myocardial infarction, stroke, or cardiovascular death. This trial is registered with ClinicalTrials.gov, number NCT01776424, and is closed to new participants. FINDINGS: Between March 12, 2013, and May 10, 2016, 27 395 patients were enrolled to the COMPASS trial, of whom 24 824 patients had stable coronary artery disease from 558 centres. The combination of rivaroxaban plus aspirin reduced the primary outcome more than aspirin alone (347 [4%] of 8313 vs 460 [6%] of 8261; hazard ratio [HR] 0·74, 95% CI 0·65-0·86, p<0·0001). By comparison, treatment with rivaroxaban alone did not significantly improve the primary outcome when compared with treatment with aspirin alone (411 [5%] of 8250 vs 460 [6%] of 8261; HR 0·89, 95% CI 0·78-1·02, p=0·094). Combined rivaroxaban plus aspirin treatment resulted in more major bleeds than treatment with aspirin alone (263 [3%] of 8313 vs 158 [2%] of 8261; HR 1·66, 95% CI 1·37-2·03, p<0·0001), and similarly, more bleeds were seen in the rivaroxaban alone group than in the aspirin alone group (236 [3%] of 8250 vs 158 [2%] of 8261; HR 1·51, 95% CI 1·23-1·84, p<0·0001). The most common site of major bleeding was gastrointestinal, occurring in 130 [2%] patients who received combined rivaroxaban plus aspirin, in 84 [1%] patients who received rivaroxaban alone, and in 61 [1%] patients who received aspirin alone. Rivaroxaban plus aspirin reduced mortality when compared with aspirin alone (262 [3%] of 8313 vs 339 [4%] of 8261; HR 0·77, 95% CI 0·65-0·90, p=0·0012). INTERPRETATION: In patients with stable coronary artery disease, addition of rivaroxaban to aspirin lowered major vascular events, but increased major bleeding. There was no significant increase in intracranial bleeding or other critical organ bleeding. There was also a significant net benefit in favour of rivaroxaban plus aspirin and deaths were reduced by 23%. Thus, addition of rivaroxaban to aspirin has the potential to substantially reduce morbidity and mortality from coronary artery disease worldwide. FUNDING: Bayer AG.

Double-Dose Versus Standard-Dose Clopidogrel According to Smoking Status Among Patients With Acute Coronary Syndromes Undergoing Percutaneous Coronary Intervention.

BACKGROUND: Prior Studies have suggested better outcomes in smokers compared with nonsmokers receiving clopidogrel ("smoker's paradox"). The impact of a more intensive clopidogrel regimen on ischemic and bleeding risks in smokers with acute coronary syndromes requiring percutaneous coronary interventions remains unclear. METHODS AND RESULTS: We analyzed 17 263 acute coronary syndrome patients undergoing percutaneous coronary intervention from the CURRENT-OASIS 7 (Clopidogrel and Aspirin Optimal Dose Usage to Reduce Recurrent Events-Seventh Organization to Assess Strategies in Ischemic Symptoms) trial, which compared double-dose (600 mg day 1;150 mg days 2-7; then 75 mg daily) versus standard-dose (300 mg day 1; then 75 mg daily) clopidogrel in acute coronary syndrome patients. The primary outcome was cardiovascular death, myocardial infarction, or stroke at 30 days. Interactions between treatment allocation and smoking status (current smokers versus nonsmokers) were evaluated. Overall, 6394 patients (37.0%) were current smokers. For the comparison of double- versus standard-dose clopidogrel, there were significant interactions in smokers and nonsmokers for the primary outcome (P=0.031) and major bleeding (P=0.002). Double- versus standard-dose clopidogrel reduced the primary outcome among smokers by 34% (hazard ratio [HR] 0.66, 95% confidence interval [CI], 0.50-0.87, P=0.003), whereas in nonsmokers, there was no apparent benefit (HR 0.96, 95% CI, 0.80-1.14, P=0.61). For major bleeding, there was no difference between the groups in smokers (HR 0.77, 95% CI, 0.48-1.24, P=0.28), whereas in nonsmokers, the double-dose clopidogrel regimen increased bleeding (HR 1.89, 95% CI, 1.37-2.60, P<0.0001). Double-dose clopidogrel reduced the incidence of definite stent thrombosis in smokers (HR 0.41, 95% CI, 0.24-0.71) and nonsmokers (HR 0.63, 95% CI, 0.42-0.93; P for interaction=0.19). CONCLUSIONS: In smokers, a double-dose clopidogrel regimen reduced major cardiovascular events and stent thrombosis after percutaneous coronary intervention, with no increase in major bleeding. This suggests that clopidogrel dosing in patients with acute coronary syndromes should be personalized, taking into consideration both ischemic and bleeding risk. CLINICAL TRIAL REGISTRATION: URL: https://www.clinicaltrials.gov. Unique identifier: NCT00335452.

Antithrombotic therapy of patients with atrial fibrillation discharged after major non-cardiac surgery. 1-year follow-up. Sub-analysis of PRAGUE 14 study.

BACKGROUND: The study investigated the discharge antithrombotic medication in patients with atrial fibrillation (AF) after major non-cardiac surgery and the impact on one-year outcomes. METHODS: A subgroup of 366 patients (mean age 75.9±10.5 years, women 42.3%, acute surgery 42.9%) undergoing major non-cardiac surgery and having any form of AF (30.6% of the total population enrolled in the PRAGUE-14 study) was followed for 1 year. RESULTS: Antithrombotics (interrupted due to surgery) were resumed until discharge in 51.8% of patients; less frequently in men (OR 0.6 (95% CI 0.95 to 0.35); p = 0.029), and in patients undergoing elective surgery (OR 0.6 (95% CI 0.91 to 0.33); p = 0.021). Dual antiplatelet therapy was resumed more often (91.7%) in comparison to aspirin monotherapy (57.3%; p = 0.047), and vitamin K antagonist (56.3%; p = 0.042). Patients with AF had significantly higher one-year mortality (22.1%) than patients without AF (14.1%, p = 0.001). The causes of death were: ischaemic events (32.6% of deaths), bleeding events (8.1%), others (N = 51; 59.3%, 20 of them died due to cancer). Non-reinstitution of aspirin until discharge was associated with higher one-year mortality (17.6% vs. 34.8%; p = 0.018). CONCLUSION: Preoperatively interrupted antithrombotics were re-administrated at discharge only in half of patients with AF, less likely in male patients and those undergoing elective surgery. The presence of AF was recognized as a predictor of one-year mortality, especially if aspirin therapy was not resumed until discharge. TRIAL REGISTRATION: ClinicalTrials.gov NCT01897220.

Diabetic patients with acute coronary syndromes in contemporary European registries: characteristics and outcomes.

Aims: Among patients with acute coronary syndromes (ACS), those with diabetes mellitus (DM) are at particularly high risk of recurrent cardiovascular events and premature death. We aimed to provide a descriptive overview of unadjusted analyses of patient characteristics, ACS management, and outcomes up to 1 year after hospital admission for an ACS/index-ACS event, in patients with DM in contemporary registries in Europe. Methods and results: A total of 10 registries provided data in a systematic manner on ACS patients with DM (total n =28 899), and without DM (total n= 97 505). In the DM population, the proportion of patients with ST-Segment Elevation Myocardial Infarction (STEMI) ranged from 22.1% to 64.6% (other patients had non-ST-Segment Elevation Myocardial Infarction (NSTEMI-ACS) or unstable angina). All-cause mortality in the registries ranged from 1.4% to 9.4% in-hospital; 2.8% to 7.9% at 30 days post-discharge; 5.1% to 10.7% at 180 days post-discharge; and 3.3% to 10.5% at 1 year post-discharge. Major bleeding events were reported in up to 3.8% of patients while in hospital (8 registries); up to 1.3% at 30 days (data from two registries only), and 2.0% at 1 year (one registry only). Registries differed substantially in terms of study setting, site, patient selection, definition and schedule of endpoints, and use of various P2Y12 inhibitors. In most, but not all, registries, event rates in DM patients were higher than in patients without DM. Pooled risk ratios comparing cohorts with DM vs. no DM were in-hospital significantly higher in DM for all-cause death (1.66; 95% CI 1.42-1.94), for cardiovascular death (2.33; 1.78 - 3.03), and for major bleeding (1.35; 1.21-1.52). Conclusion: These registry data from real-life clinical practice confirm a high risk for recurrent events among DM patients with ACS, with great variation across the different registries.

Degenerative changes and immune response after transcatheter aortic valve implantation. Comparison with surgical aortic valve replacement.

BACKGROUND: Little is known about the valve degeneration process after transcutaneous aortic valve implantations (TAVI) that can have an important impact on patients' long-term prognosis. AIM: To evaluate degenerative changes of TAVI using computed tomography (CT) compared to findings in patients that underwent surgical aortic valve replacement (SAVR). Subsequently, to compare the level of immune and inflammatory markers in both groups and test their possible role in the valve degeneration process. METHODS AND RESULTS: 49 patients after TAVI and 29 patients in the control group after SAVR underwent 2 years of follow-up and 8 patients from the TAVI group and 7 patients after SAVR underwent five years of follow-up. CT was performed in all patients and calcifications on prosthesis cusps in both groups were measured using Agatson calcium score. TAVI patients were older compared to patients who underwent SAVR [82 (62;86) vs. 74 (64;84) years, p<0.001], and had more comorbidities - higher EuroScore I [21.0 (5.0;46.0) vs. 6.15 (2.54;11.17), p<0.001]. TAVI patients had more often concomitant coronary artery disease (69.4% vs. 13.8%, p<0.001) and previous history of cardiac surgery (32.7% vs. 0.0%, p<0.001). Slight calcifications (mean Agatson score 50.76) on prosthetic cusps were found in 2 patients 4-5 years after TAVI and in 1 patient 2 years after SAVR (p=NS). Even though significant differences were found in values of tumor necrosis factor-α and E-selectin before, 1 year, and 2 years after implantation, no significant changes in values of inflammatory markers were observed during follow-up period in both groups of patients. Detailed analysis revealed no significant difference between values of inflammatory markers of patients with and without calcifications present on CT. CONCLUSION: Minimal degenerative changes on TAVI prosthesis were observed in mid- and long-term follow-up. Systemic immune response did not differ between patients after TAVI and SAVR.

Prasugrel Versus Ticagrelor in Patients With Acute Myocardial Infarction Treated With Primary Percutaneous Coronary Intervention: Multicenter Randomized PRAGUE-18 Study.

BACKGROUND: No randomized head-to-head comparison of the efficacy and safety of ticagrelor and prasugrel has been published in the 7 years since the higher efficacy of these newer P2Y12 inhibitors were first demonstrated relative to clopidogrel. METHODS: This academic study was designed to compare the efficacy and safety of prasugrel and ticagrelor in acute myocardial infarction treated with primary or immediate percutaneous coronary intervention. A total of 1230 patients were randomly assigned across 14 sites to either prasugrel or ticagrelor, which was initiated before percutaneous coronary intervention. Nearly 4% were in cardiogenic shock, and 5.2% were on mechanical ventilation. The primary end point was defined as death, reinfarction, urgent target vessel revascularization, stroke, or serious bleeding requiring transfusion or prolonging hospitalization at 7 days (to reflect primarily the in-hospital phase). This analysis presents data from the first 30 days (key secondary end point). The total follow-up will be 1 year for all patients and will be completed in 2017. RESULTS: The study was prematurely terminated for futility. The occurrence of the primary end point did not differ between groups receiving prasugrel and ticagrelor (4.0% and 4.1%, respectively; odds ratio, 0.98; 95% confidence interval, 0.55-1.73; P=0.939). No significant difference was found in any of the components of the primary end point. The occurrence of key secondary end point within 30 days, composed of cardiovascular death, nonfatal myocardial infarction, or stroke, did not show any significant difference between prasugrel and ticagrelor (2.7% and 2.5%, respectively; odds ratio, 1.06; 95% confidence interval, 0.53-2.15; P=0.864). CONCLUSIONS: This head-to-head comparison of prasugrel and ticagrelor does not support the hypothesis that one is more effective or safer than the other in preventing ischemic and bleeding events in the acute phase of myocardial infarction treated with a primary percutaneous coronary intervention strategy. The observed rates of major outcomes were similar but with broad confidence intervals around the estimates. These interesting observations need to be confirmed in a larger trial. CLINICAL TRIAL REGISTRATION: URL: http://www.ClinicalTrials.gov. Unique identifier: NCT02808767.

Use, patient selection and outcomes of P2Y12 receptor inhibitor treatment in patients with STEMI based on contemporary European registries.

AIMS: Among acute coronary syndromes (ACS), ST-segment elevation myocardial infarction (STEMI) has the most severe early clinical course. We aimed to describe the effectiveness and safety of P2Y12 receptor inhibitors in patients with STEMI based on the data from contemporary European ACS registries. METHODS AND RESULTS: Twelve registries provided data in a systematic manner on outcomes in STEMI patients overall, and seven of these also provided data for P2Y12 receptor inhibitor-based dual antiplatelet therapy. The registries were heterogeneous in terms of site, patient, and treatment selection, as well as in definition of endpoints (e.g. bleeding events). All-cause death rates based on the data from 84 299 patients (9612 patients on prasugrel, 11 492 on ticagrelor, and 27 824 on clopidogrel) ranged between 0.49 and 6.68% in-hospital, between 3.07 and 7.95% at 30 days (reported in 6 registries), between 8.15 and 9.13% at 180 days, and between 2.41 and 9.58% at 1 year (5 registries). Major bleeding rates were 0.09-3.55% in-hospital (8 registries), 0.09-1.65% at 30 days, and 1.96% at 1 year (only 1 registry). Fatal/life-threatening bleeding was rare occurring between 0.08 and 0.13% in-hospital (4 registries) and 1.96% at 1 year (1 registry). CONCLUSIONS: Real-world evidence from European contemporary registries shows that death, ischaemic events, and bleeding rates are lower than those reported in Phase III studies of P2Y12 inhibitors. Regarding individual P2Y12 inhibitors, patients on prasugrel, and, to a lesser degree, ticagrelor, had fewer ischaemic and bleeding events at all time points than clopidogrel-treated patients. These findings are partly related to the fact that the newer agents are used in younger and less ill patients.