Karolina Szummer

Ticagrelor Versus Clopidogrel in Acute Coronary Syndromes in Relation to Renal Function Results From the Platelet Inhibition and Patient Outcomes (PLATO) Trial

Background— Reduced renal function is associated with a poorer prognosis and increased bleeding risk in patients with acute coronary syndromes and may therefore alter the risk-benefit ratio with antiplatelet therapies. In the Platelet Inhibition and Patient Outcomes (PLATO) trial, ticagrelor compared with clopidogrel reduced the primary composite end point of cardiovascular death, myocardial infarction, and stroke at 12 months but with similar major bleeding rates. Methods and Results— Central laboratory serum creatinine levels were available in 15 202 (81.9%) acute coronary syndrome patients at baseline, and creatinine clearance, estimated by the Cockcroft Gault equation, was calculated. In patients with chronic kidney disease (creatinine clearance <60 mL/min; n=3237), ticagrelor versus clopidogrel significantly reduced the primary end point to 17.3% from 22.0% (hazard ratio [HR], 0.77; 95% confidence interval [CI], 0.65 to 0.90) with an absolute risk reduction greater than that of patients with normal renal function (n=11 965): 7.9% versus 8.9% (HR, 0.90; 95% CI, 0.79 to 1.02). In patients with chronic kidney disease, ticagrelor reduced total mortality (10.0% versus 14.0%; HR, 0.72; 95% CI, 0.58 to 0.89). Major bleeding rates, fatal bleedings, and non–coronary bypass–related major bleedings were not significantly different between the 2 randomized groups (15.1% versus 14.3%; HR, 1.07; 95% CI, 0.88 to 1.30; 0.34% versus 0.77%; HR, 0.48; 95% CI, 0.15 to 1.54; and 8.5% versus 7.3%; HR, 1.28; 95% CI, 0.97 to 1.68). The interactions between creatinine clearance and randomized treatment on any of the outcome variables were nonsignificant. Conclusions— In acute coronary syndrome patients with chronic kidney disease, ticagrelor compared with clopidogrel significantly reduces ischemic end points and mortality without a significant increase in major bleeding but with numerically more non–procedure-related bleeding. Clinical Trial Registration— URL:http://www.clinicatrials.gov. Unique identifier: NCT00391872.

Influence of Renal Function on the Effects of Early Revascularization in Non-ST-Elevation Myocardial Infarction Data From the Swedish Web-System for Enhancement and Development of Evidence-Based Care in Heart Disease Evaluated According to Recommended Therapies (SWEDEHEART)

Background— It is unknown whether patients with non–ST-elevation myocardial infarction derive a similar benefit from an early invasive therapy at different levels of renal function. Methods and Results— A total of 23 262 consecutive non–ST-elevation myocardial infarction patients ≤80 years old were included in a nationwide coronary care unit register between 2003 and 2006. Glomerular filtration rate (eGFR) was estimated with the Modification of Diet in Renal Disease Study formula. Patients were divided into medically or invasively treated groups if revascularized within 14 days of admission. A propensity score for the likelihood of invasive therapy was calculated. A Cox regression model with adjustment for propensity score and discharge medication was used to assess the association between early revascularization and 1-year mortality across renal function stages. There was a gradient, with significantly fewer patients treated invasively with declining renal function: eGFR ≥90 mL · min−1 · 1.73 m−2, 62%; eGFR 60 to 89 mL · min−1 · 1.73 m−2, 55%; eGFR 30 to 59 mL · min−1 · 1.73 m−2, 36%; eGFR 15 to 29 mL · min−1 · 1.73 m−2, 14%; and eGFR <15 mL · min−1 · 1.73 m−2/dialysis, 15% (P<0.001). After adjustment, the overall 1-year mortality was 36% lower (hazard ratio 0.64, 95% confidence interval 0.56 to 0.73, P<0.001) with an invasive strategy. The magnitude of survival difference was similar in normal-to-moderate renal function groups. The lower mortality observed with invasive therapy declined with lower renal function, with no difference in mortality in patients with kidney failure (eGFR <15 mL · min−1 · 1.73 m−2) or in those receiving dialysis (hazard ratio 1.61, 95% confidence interval 0.84 to 3.09, P=0.15). Conclusions— Early invasive therapy is associated with greater 1-year survival in patients with non–ST-elevation myocardial infarction and mild-to-moderate renal insufficiency, but the benefit declines with lower renal function, and is less certain in those with renal failure or on dialysis.

Warfarin, Kidney Dysfunction, and Outcomes Following Acute Myocardial Infarction in Patients With Atrial Fibrillation

IMPORTANCE Conflicting evidence exists regarding the association between warfarin treatment, death, and ischemic stroke incidence in patients with advanced chronic kidney disease (CKD) and atrial fibrillation. OBJECTIVE To study outcomes associated with warfarin treatment in relation to kidney function among patients with established cardiovascular disease and atrial fibrillation. DESIGN, SETTING, AND PARTICIPANTS Observational, prospective, multicenter cohort study from the Swedish Web-System for Enhancement and Development of Evidence-Based Care in Heart Disease Evaluated According to Recommended Therapies (SWEDEHEART) registry (2003-2010), which includes all Swedish hospitals that provide care for acute cardiac diseases. Participants included consecutive survivors of an acute myocardial infarction (MI) with atrial fibrillation and known serum creatinine (N = 24,317), including 21.8% who were prescribed warfarin at discharge. Chronic kidney disease stages were classified according to estimated glomerular filtration rate (eGFR). MAIN OUTCOMES AND MEASURES (1) Composite end point analysis of death, readmission due to MI, or ischemic stroke; (2) bleeding (composite of readmission due to hemorrhagic stroke, gastrointestinal bleeding, bleeding causing anemia, and others); or (3) the aggregate of these 2 outcomes within 1 year from discharge date. RESULTS A total of 5292 patients (21.8%) were treated with warfarin at discharge, and 51.7% had manifest CKD (eGFR <60 mL/min/1.73 m2 [eGFR<60]). Compared with no warfarin use, warfarin was associated with a lower risk of the first composite outcome (n = 9002 events) in each CKD stratum for event rates per 100 person-years: eGFR>60 event rate, 28.0 for warfarin vs 36.1 for no warfarin; adjusted hazard ratio (HR), 0.73 (95% CI, 0.65 to 0.81); eGFR>30-60: event rate, 48.5 for warfarin vs 63.8 for no warfarin; HR, 0.73 (95% CI, 0.66 to 0.80); eGFR>15-30: event rate, 84.3 for warfarin vs 110.1 for no warfarin; HR, 0.84 (95% CI, 0.70-1.02); eGFR≤15: event rate, 83.2 for warfarin vs 128.3 for no warfarin; HR, 0.57 (95% CI, 0.37-0.86). The risk of bleeding (n = 1202 events) was not significantly higher in patients treated with warfarin in any CKD stratum for event rates per 100 person-years: eGFR>60 event rate, 5.0 for warfarin vs 4.8 for no warfarin; HR, 1.10 (95% CI, 0.86-1.41); eGFR>30-60 event rate, 6.8 for warfarin vs 6.3 for no warfarin; HR, 1.04 (95% CI, 0.81-1.33); eGFR>15-30 event rate, 9.3 for warfarin vs 10.4 for no warfarin; HR, 0.82 (95% CI, 0.48-1.39); eGFR≤15 event rate, 9.1 for warfarin vs 13.5 for no warfarin; HR, 0.52 (95% CI, 0.16-1.65). Warfarin use in each CKD stratum was associated with lower hazards of the aggregate outcome (n = 9592 events) for event rates per 100 person-years: eGFR>60 event rate, 32.1 for warfarin vs 40.0 for no warfarin; HR, 0.76 (95% CI, 0.69-0.84); eGFR>30-60 event rate, 53.6 for warfarin vs 69.0 for no warfarin; HR, 0.75 (95% CI, 0.68-0.82); eGFR>15-30 event rate, 90.2 for warfarin vs 117.7 for no warfarin; HR, 0.82 (95% CI, 0.68-0.99); eGFR≤15 event rate, 86.2 for warfarin vs 138.2 for no warfarin; HR, 0.55 (95% CI, 0.37-0.83). CONCLUSIONS AND RELEVANCE Warfarin treatment was associated with a lower 1-year risk for the composite outcome of death, MI, and ischemic stroke without a higher risk of bleeding in consecutive acute MI patients with atrial fibrillation. This association was not related to the severity of concurrent CKD.

Relation between renal function, presentation, use of therapies and in-hospital complications in acute coronary syndrome: data from the SWEDEHEART register.

Abstract.  Szummer K, Lundman P, Jacobson SH, Schön S, Lindbäck J, Stenestrand U, Wallentin L, Jernberg T, for SWEDEHEART. (Karolinska Institute, Karolinska University Hospital, Stockholm; Karolinska Institute, Danderyd Hospital, Danderyd; Ryhov County Hospital, Jönköping; University Hospital, Uppsala and University Hospital, Linköping; Sweden) Relation between renal function, presentation, use of therapies and in‐hospital complications in acute coronary syndrome: data from the SWEDEHEART register. J Intern Med 2010; 268:40–49.

Clinical ResearchInterventional CardiologyTranscatheter Aortic Valve Replacement With the St. Jude Medical Portico Valve: First-in-Human Experience

OBJECTIVES The purpose of this study was to demonstrate the feasibility and procedural outcomes with a new self-expanding and repositionable transcatheter heart valve. BACKGROUND Transcatheter aortic valve replacement is a viable option for selected patients with severe symptomatic aortic stenosis. However, suboptimal prosthesis positioning may contribute to paravalvular regurgitation, atrioventricular conduction block, and mitral or coronary compromise. METHODS The repositionable Portico valve (St. Jude Medical, Minneapolis, Minnesota) was implanted in 10 patients with severe aortic stenosis utilizing percutaneous femoral arterial access. Patients underwent transthoracic and transesophageal echocardiography and multidetector computed tomography before and after valve implantation. Clinical and echocardiographic follow-up was obtained at 30 days. RESULTS Device implantation was successful in all patients. Prosthesis recapture and repositioning was performed in 4 patients. Intermittent prosthetic leaflet dysfunction in 1 patient required implantation of a second transcatheter valve. There was 1 minor stroke. At 30-day follow-up, echocardiographic mean transaortic gradient was reduced from 44.9 ± 16.7 mm Hg to 10.9 ± 3.8 mm Hg (p < 0.001), and valve area increased from 0.6 ± 0.1 cm(2) to 1.3 ± 0.2 cm(2) (p < 0.001). Paravalvular regurgitation was mild or less in 9 patients (90%) and moderate in 1 patient (10%). There were no major strokes, major vascular complications, major bleeds, or deaths. No patient required pacemaker implantation. All patients were in New York Heart Association functional class II or less. CONCLUSIONS Transcatheter aortic valve replacement with the repositionable Portico transcatheter heart valve is feasible, with good short-term clinical and hemodynamic outcomes.

Associations with and prognostic impact of chronic kidney disease in heart failure with preserved, mid-range, and reduced ejection fraction

As the role of chronic kidney disease (CKD) in different types of heart failure (HF) is poorly understood, our aim was to compare CKD in HF with preserved (HFpEF), mid‐range (HFmrEF), and reduced ejection fraction (HFrEF) with regard to prevalence, associations and prognostic role.

Improved outcomes in patients with ST-elevation myocardial infarction during the last 20 years are related to implementation of evidence-based treatments : experiences from the SWEDEHEART registry 1995-2014

Abstract Aims Impact of changes of treatments on outcomes in ST-elevation myocardial infarction (STEMI) patients in real-life health care has not been documented. Methods and results All STEMI cases (n = 105.674) registered in the nation-wide SWEDEHEART registry between 1995 and 2014 were included and followed for fatal and non-fatal outcomes for up to 20 years. Most changes in treatment and outcomes occurred from 1994 to 2008. Evidence-based treatments increased: reperfusion from 66.2 to 81.7%; primary percutaneous coronary intervention: 4.5 to 78.0%; dual antiplatelet therapy from 0 to 89.6%; statin: 14.1 to 93.6%; beta-blocker: 78.2 to 91.0%, and angiotensin-converting-enzyme/angiotensin-2-receptor inhibitors: 40.8 to 85.2% (P-value for-trend <0.001 for all). One-year mortality decreased from 22.1 to 14.1%. Standardized incidence ratio compared with the general population decreased from 5.54 to 3.74 (P < 0.001). Cardiovascular (CV) death decreased from 20.1 to 11.1%, myocardial infarction (MI) from 11.5 to 5.8%; stroke from 2.9 to 2.1%; heart failure from 7.1 to 6.2%. After standardization for differences in demography and baseline characteristics, the change of 1-year CV-death or MI corresponded to a linear trend of 0.915 (95% confidence interval: 0.906–0.923) per 2-year period which no longer was significant, 0.997 (0.984–1.009), after adjustment for changes in treatment. The changes in treatment and outcomes were most pronounced from 1994 to 2008. Conclusion Gradual implementation of new and established evidence-based treatments in STEMI patients during the last 20 years has been associated with prolonged survival and lower risk of recurrent ischaemic events, although a plateauing is seen since around 2008.

Time in Therapeutic Range and Outcomes After Warfarin Initiation in Newly Diagnosed Atrial Fibrillation Patients With Renal Dysfunction

Background It is unknown whether renal dysfunction conveys poor anticoagulation control in warfarin‐treated patients with atrial fibrillation and whether poor anticoagulation control associates with the risk of adverse outcomes in these patients. Methods and Results This was an observational study from the Stockholm CREatinine Measurements (SCREAM) cohort including all newly diagnosed atrial fibrillation patients initiating treatment with warfarin (n=7738) in Stockholm, Sweden, between 2006 and 2011. Estimated glomerular filtration rate (eGFR; mL/min per 1.73 m2) was calculated from serum creatinine. Time‐in‐therapeutic range (TTR) was assessed from international normalized ratio (INR) measurements up to warfarin cessation, adverse event, or end of follow‐up (2 years). Adverse events considered a composite of intracranial hemorrhage, ischemic stroke, myocardial infarction, or death. During median 254 days, TTR was 83%, based on median 21 INR measurements per patient. TTR was 70% among patients with eGFR <30, around 10% lower than in those with normal renal function. During observation, adverse events occurred in 4.0% of patients, and those with TTR ≤75% were at higher adverse event risk. This was independent of patient characteristics, comorbidities, number of INR tests, days exposed to warfarin, and, notably, independent of eGFR: adjusted odds ratio (OR) 1.84 (95% CI, 1.41–2.40) for TTR 75% to 60% and adjusted OR 2.09 (1.59–2.74) for TTR <60%. No interaction was observed between eGFR and TTR in association to adverse events (P=0.2). Conclusion Severe chronic kidney disease (eGFR <30) patients with atrial fibrillation have worse INR control while on warfarin. An optimal TTR (>75%) is associated with lower risk of adverse events, independently of underlying renal function.

Association between statin treatment and outcome in relation to renal function in survivors of myocardial infarction

As statins are recommended at discharge to all patients following myocardial infarction (MI), we studied their use and efficacy in renal disease by analyzing the data, in the nationwide SWEDEHEART registry, of 42,814 consecutive survivors of MI with available creatinine/dialysis data but without statin therapy on admission. The estimated glomerular filtration rate (eGFR) was determined by the Modification of Diet in Renal Disease Study formula and the patients classified into the five traditional stages of kidney disease. The 1-year survival in relation to prescription of statin at discharge was assessed in a Cox regression analysis adjusted by a propensity score that described each individuals likelihood of being treated with a statin, established by 36 baseline characteristics and in-hospital therapies. Statin use at discharge decreased with increased renal impairment from 81% in eGFR stage 1 to 31% in eGFR stage 5. After adjusting for the propensity score and discharge medication, statin use was associated with a significant reduction in overall risk of death (hazard ratio 0.63), with a statistically significant interaction between statin therapy and the stage of renal function. Thus, statin use at discharge was associated with improved 1-year survival of patients in stages 2-4 (mild-to-severe) of renal insufficiency. This effect appears attenuated in those with stage 5 renal failure.

Association between the use of fondaparinux vs low-molecular-weight heparin and clinical outcomes in patients with non-ST-segment elevation myocardial infarction.

IMPORTANCE Fondaparinux was associated with reduced major bleeding events and improved survival compared with low-molecular-weight heparin (LMWH) in a large randomized clinical trial involving patients with non-ST-segment elevation myocardial infarction (NSTEMI). Large-scale experience of the use of fondaparinux vs LMWH in a nontrial setting is lacking. OBJECTIVE To study the association between the use of fondaparinux vs LMWH and outcomes in patients with NSTEMI in Sweden. DESIGN, SETTING, AND PATIENTS Prospective multicenter cohort study from the Swedish Web-System for Enhancement and Development of Evidence-Based Care in Heart Disease Evaluated According to Recommended Therapies registry involving 40,616 consecutive patients with NSTEMI who received fondaparinux or LMWH between September 1, 2006, through June 30, 2010, with the last follow-up on December 31, 2010. EXPOSURES In-hospital treatment with fondaparinux or LMWH during the hospital stay. MAIN OUTCOMES AND MEASURES In-hospital severe bleeding events and death and 30- and 180-day death, MI, stroke, and major bleeding events. Logistic regression models adjusted for calendar time, admitting hospital, baseline characteristics, and in-hospital revascularization. RESULTS In total, 14,791 patients (36.4%) were treated with fondaparinux and 25,825 (63.6%) with LMWH. One hundred sixty-five patients (1.1%) in the fondaparinux group vs 461 patients (1.8%) in the LMWH group experienced in-hospital bleeding events (adjusted odds ratio [OR], 0.54; 95% CI, 0.42-0.70). A total of 394 patients (2.7%) in the fondaparinux group died while in the hospital vs 1022 (4.0%) in the LMWH group (adjusted OR, 0.75; 95% CI, 0.63-0.89). The differences in major bleeding events and mortality between the 2 treatments were similar at 30 and 180 days. There were no significant differences in the number of recurrent MI and stroke events at 30 or 180 days among the 2 treatment groups. CONCLUSIONS AND RELEVANCE In routine clinical care of patients with NSTEMI, fondaparinux was associated with lower odds than LMWH of major bleeding events and death both in-hospital and up to 180 days afterward.