AIMS Chronic kidney disease (CKD) is associated with increased thrombotic events and seems to influence platelet reactivity. Conflicting results have been published on platelet response in CKD patients with stable coronary artery disease. The aim of our study was to investigate the impact of CKD on platelet aggregation in acute coronary syndrome (ACS) patients receiving dual antiplatelet therapy, included the more potent P2Y12 inhibitors. METHODS We enrolled 206 patients with ACS, divided in two groups, according to the presence or the absence of moderate/severe CKD. Platelet aggregation was performed with light transmission aggregometry and results are expressed as percentage of maximum platelet aggregation. High residual platelet reactivity (HRPR) was defined as maximum platelet aggregation more than 59%. RESULTS Patients with CKD [estimate glomerular filtration rate (eGFR) < 60 ml/min/1.73 m, n = 28] were prevalent older, diabetic, had previous coronary revascularization. In these patients, platelet aggregation was significantly higher than in those with eGFR ≥ 60 ml/min/1.73 m (ADP 10 μmol/l: 28.46 ± 26.19 vs. 16.64 ± 12.79, P < 0.001; ADP 20 μmol/l: 30.07 ± 25.89 vs. 17.46 ± 12.82, P < 0.001). HRPR was observed in 4.4% of patients, with higher prevalence in those with eGFR less than 60 ml/min/1.73 m [21.4 vs. 1.7%, P < 0.001, odds ratio (OR) [95% confidence interval (CI)] = 15.91 (3.71-68.17), P < 0.001]. At multivariate analysis, after correction for baseline confounders, eGFR [adjusted OR (95% CI) = 0.95 (0.91-0.98), P = 0.007], together with the use of clopidogrel [adjusted OR (95% CI) = 23.59 (4.01-138.82), P < 0.001], emerged as determinants of HRPR. CONCLUSION In patients with ACS receiving dual antiplatelet therapy, CKD is associated with an increasing ADP-induced platelet aggregation and higher prevalence of HRPR, which is mainly correlated to clopidogrel use.

Impact of chronic kidney disease on platelet aggregation in patients with acute coronary syndrome.

The optimal antiplatelet therapy of patients with non-ST-segment elevation acute coronary syndromes (NSTE-ACS) and chronic kidney disease (CKD) remains unknown. This study included 2,364 patients with NSTE-ACS undergoing predominantly percutaneous coronary intervention (PCI), who were randomized to ticagrelor or prasugrel in the ISAR-REACT 5 trial. Estimated glomerular filtration rate (eGFR) was calculated using the Chronic Kidney Disease Epidemiology Collaboration equation. The primary end point was 1-year mortality. Overall, there were 85 deaths (3.6%): 6 deaths (17.1%) in patients with eGFR <30, 31 deaths (6.9%) in patients with eGFR 30 to <60, 34 deaths (3.0%) in patients with eGFR 60 to <90, and 14 deaths (2.0%) in patients with eGFR ≥90 ml/min/1.73 m2; adjusted hazard ratio (HR)=1.15, 95% confidence interval (CI) 1.01 to 1.31; p = 0.033 for 10 ml/min/1.73 m2 decrement in the eGFR. Bleeding occurred in 129 patients (5.5%): 7 bleeds (20.2%) in patients with eGFR <30, 36 bleeds (8.0%) in patients with eGFR 30 to <60, 64 bleeds (5.6%) in patients with eGFR 60 to <90, and 22 bleeds (3.1%) in patients with eGFR ≥90 ml/min/1.73 m2; adjusted HR=1.11 (1.01 to 1.23); p = 0.045 for 10 ml/min/1.73 m2 decrement in the eGFR. One-year mortality and bleeding did not differ significantly between ticagrelor and prasugrel in all categories of impaired renal function. In conclusion, in patients with NSTE-ACS undergoing PCI with drug-eluting stents and third-generation antiplatelet drugs, impaired renal function was independently associated with higher risk of 1-year mortality and bleeding. The ischemic and bleeding risks appear to differ little between ticagrelor and prasugrel in all categories of impaired renal function. 

One-Year Ischemic and Bleeding Events According to Renal Function in Patients With Non-ST-Segment Elevation Acute Coronary Syndromes Treated With Percutaneous Coronary Intervention and Third-Generation Antiplatelet Drugs.

Aim: Patients with chronic kidney disease (CKD) are at increased cardiovascular risk. Methods: Patients with acute coronary syndrome were retrospectively allocated to three groups (stage 3A, stage 3B or stage 4) based on the Kidney Disease Improving Global Outcomes classification formulas: the CKD Epidemiology Collaboration (CKD-EPI; N = 401) and the modification of diet in renal disease (n = 355). The primary end point was all-cause mortality (median follow-up time, 32 months [15-70]). Results: Study results showed decreased median survival was associated with poor renal function for both the CKD-EPI (78 vs 61 vs 40 months, p = 0.014) and modification of diet in renal disease groups (68 vs 57 vs 32 months, p = 0.006). After adjustment, age (OR: 1.07; 95% CI: 1.01-1.14) and pulmonary artery systolic pressure (OR: 1.08; 95% CI: 1.03-1.14), but not estimated glomerular filtration rate, were associated with decreased survival. Conclusion: Study results suggest that poor outcomes after an acute coronary syndrome were associated with comorbidities rather than estimated glomerular filtration rate level.

Chronic kidney disease in acute coronary syndromes: real-world data of long-term outcomes

The increasing prevalence of patients with the dual burden of heart and kidney disease has resulted in the rapid growth and diversification of several diagnostic and therapeutic strategies, within both the specialties of cardiology and nephrology. The spectrum of hospital based care for these patients extends from peri-procedural optimization of hemodynamics in acute severe cardio-renal syndromes, management of acute heart failure with emphasis on delivering goal directed medical therapies and reduction of hospitalizations, implementing nephro-protective strategies in patients undergoing complex cardiovascular percutaneous and surgical interventions and delivering renal replacement therapies, when appropriate. Given the high cardiovascular disease burden in patients with chronic kidney disease and end stage kidney disease, it is critical to customize medical and interventional therapies for cardiovascular disease in these patients towards minimizing nephrotoxicity and optimizing outcomes in the backdrop of higher complication rates, bleeding, clotting and alterations in pharmacokinetics unique to the milieu of chronic kidney disease. The nephrologist plays a pivotal role in co-managing several aspects of decision making in these contexts, and plays a key role in delivering evidence based best clinical practices in subjects with cardiac and kidney disease, along with the cardiologist. The implementation of joint cardiology and nephrology care teams in the future, along with collaborative research and educational opportunities in the cardio-nephrology interface will help create health care delivery model unique to needs of patients with cardio-renal disease, and thus optimize outcomes in these subjects in a precise and cost effective manner.

Nephrology Inpatient Consultative Approach in Patients with Cardiovascular Disease

/pdf/the-effects-of-renal-insufficiency-and-age-on-mortality-in-32vewlggn5.pdf

The Effects of Renal Insufficiency and Age on Mortality in Geriatric Patients with Non-ST-Segment Elevation Myocardial Infarction

Chronic renal failure (CRF) impairs prognosis in patients with acute coronary syndromes (ACS); the differential impact of CRF on ischemic and bleeding events in the setting of ACS is unclear. We explored the predictive role of CRF, identified by different equations for the glomerular filtration rate estimation, on the occurrence of the composite end point, including both ischemic cardiovascular and major bleeding (major adverse cardiovascular and bleeding events [MACBE]) at 1 year, and its components. We accessed each patients data from 718 participants in the prospective, multicenter, and START ANTIPLATELET registry, performed on patients with ACS. The ability to predict the risk of MACBE was modest and similar for Cockcroft-Gault, MDRD, and CKD-EPI equations (area under the curves: 0.55, 95% confidence interval [CI] 0.47 to 0.63; 0.53, 95% CI 0.45 to 0.61; 0.54, 95% CI 0.46 to 0.62; respectively, overall p = 0.63). The incidence of MACBE in patients with CRF was 12.6 versus 7.4 per 100 patients/year in those with preserved renal function (adjusted odds ratio [OR] 1.80, 1.02 to 3.20, p = 0.045); the absolute excess in events rate due to CRF was higher for ischemic events (3.5%) than for major bleeding (2.6%). The increased occurrence of MACBE was even greater in patients with CRF and concomitant anemia (OR 2.16) and in patients with severe CRF (OR 2.78). In conclusion, our study indicates that, in patients with ACS, CRF impairs the clinical outcome at 1 year, especially when severe and when is concomitant with anemia. CRF is associated with greater absolute increase of ischemic events than major bleeding.

Impact of Chronic Renal Failure on Ischemic and Bleeding Events at 1 Year in Patients With Acute Coronary Syndrome (from the Multicenter START ANTIPLATELET Registry).

Antithrombotic treatment of frail patients with AF presents various challenges. The fear of bleeding often leds to a large underuse of anticoagulant agents in these patients, although more recent data indicate that oral anticoagulation  (especially with the newer, direct anticoagulants) is increasingly used. While there is a need for more real world data, available evidence suggests that non-vitamin K antagonist oral anticoagulants (NOACs) are an effective alternative to warfarin in frail patients with AF for preventing thromboembolic events, with a better safety profile. Logical considerations and evidence-base data related to the reduced bleeding risk (also including major bleeding and intracranial bleeding) of NOACs make these drugs the anticoagulant agents of choice in frail patients; however, in this setting an individualised approach should be taken, taking into consideration the risk of thromboembolic and bleeding events, other comorbidities and patient-related factors, rather than a generalised "one drug fits all" approach.

/pdf/efficacy-and-safety-of-oral-anticoagulant-therapy-in-frail-mqnpkbjstw.pdf

Efficacy and safety of oral anticoagulant therapy in frail patients with atrial fibrillation.

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Impact of Chronic Renal Failure on Ischemic and Bleeding Events at 1 Year in Patients With Acute Coronary Syndrome (from the Multicenter START ANTIPLATELET Registry).

Efficacy and safety of oral anticoagulant therapy in frail patients with atrial fibrillation.