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Radiostereometric analysis (RSA) has evolved as gold standard in the evaluation of wear and especially as regards novel hip implant materials. However, several cup shell materials and articulation types used in total hip arthroplasty (THA) cannot be studied due to poor radiographic visibility of the femoral head (FH). We addressed this problem with use of a point transfer function in the RSA software to indirectly measure FH translations with use of stem markers. In a base examination, the stem marker segment and cup center, as an approximation for the FH center position, were mathematically coupled. Thereafter, in subsequent examinations, we used the point transfer function to calculate FH positions from stem marker positions. To determine the variance of the difference of directly and indirectly measured FH positions, four stem marker configurations were studied in THAs with radiographically visible FHs. For the axis with least variance we also compared directly and indirectly measured translation up to 7 years. Finally, we applied the method in a ceramic‐on‐ceramic (COC) articulation and measured proximal translation up to 7 years and also estimated precision. Vertical translations had the smallest variation between measured and calculated FH position. Directly and indirectly measured vertical FH translation correlated well but indirect measurements had increased variance. Proximal steady‐state penetration rate in uncemented COC THA was −0.003 (SD 0.021) mm/year with 99% precision along the vertical axis measuring 0.34 mm. The point transfer function can be used to measure proximal FH penetration, but with less precision than direct RSA. [ABSTRACT FROM AUTHOR]

Background: In an earlier study with a 2-year follow-up of uncemented cups, we had reported low femoral-head penetration of vitamin E-infused highly cross-linked polyethylene liners (E1) compared with highly cross-linked liners without vitamin E (ArComXL). We studied the penetration rate of E1 compared with that of ArComXL, with a focus on changes occurring between 2 and 5 years after total hip arthroplasty.Methods: In this randomized controlled study, we performed radiostereometric analysis of the penetration rate up to 5 years in 63 hips.Results: During the total period of observation, the median proximal penetration for E1, 0.13 mm (mean, 0.11 mm [95% confidence interval (CI), 0.08 to 0.14 mm]), was lower than that for ArComXL, 0.20 mm (mean, 0.22 mm [95% CI, 0.17 to 0.26 mm]). The median proximal penetration rate between 2 and 5 years was 0.02 mm/yr (mean, 0.01 mm/yr [95% CI, 0.01 to 0.02 mm/yr]) for E1 and 0.04 mm/yr (mean, 0.04 mm/yr [95% CI, 0.03 to 0.05 mm/yr) for ArComXL. The corresponding median total (i.e., 3-dimensional resultant) penetration rates were 0.04 mm/yr (mean, 0.04 mm/yr [95% CI, 0.03 to 0.05 mm/yr]) for E1 and 0.07 mm/yr (mean, 0.08 mm/yr [95% CI, 0.06 to 0.10 mm/yr]) for ArComXL.Conclusions: From years 2 to 5, we observed increased penetration in both groups. The penetration rate was higher for ArComXL, resulting in more proximal and total penetration at 5 years than for E1.Level Of Evidence: Therapeutic Level I. See Instructions for Authors for a complete description of levels of evidence. [ABSTRACT FROM AUTHOR]

Background and purpose — Most registry studies regarding highly crosslinked polyethylene (XLPE) have focused on the overall revision risk. We compared the risk of cup and/or liner revision for specific cup and liner designs made of either XLPE or conventional polyethylene (CPE), regarding revision for any reason and revision due to aseptic loosening and/or osteolysis. Patients and methods — Using the Nordic Arthroplasty Register Association (NARA) database, we identified cup and liner designs where either XLPE or CPE had been used in more than 500 THAs performed for primary hip osteoarthritis. We assessed risk of revision for any reason and for aseptic loosening using Cox regression adjusted for age, sex, femoral head material and size, surgical approach, stem fixation, and presence of hydroxyapatite coating (uncemented cups). Results — The CPE version of the ZCA cup had a risk of revision for any reason similar to that of the XLPE version (p = 0.09), but showed a 6-fold higher risk of revision for aseptic loosening (p < 0.001). The CPE version of the Reflection All Poly cup had an 8-fold elevated risk of revision for any reason (p < 0.001) and a 5-fold increased risk of revision for aseptic loosening (p < 0.001). The Charnley Elite Ogee/Marathon cup and the Trilogy cup did not show such differences. Interpretation — Whether XLPE has any advantage over CPE regarding revision risk may depend on the properties of the polyethylene materials being compared, as well as the respective cup designs, fixation type, and follow-up times. Further research is needed to elucidate how cup design factors interact with polyethylene type to affect the risk of revision. [ABSTRACT FROM PUBLISHER]

ABSTRACT In conventional Radiostereometric analysis (RSA) implants with attached tantalum markers are frequently used, which may be difficult to visualize. This problem can be avoided with model-based RSA (MBRSA), but it is uncertain if this method has the same precision as marker-based RSA. We evaluated the influence of cup design for the precision of MBRSA in four uncemented cups to study if the design had any influence on the precision. Stereo radiographs were analyzed postoperatively (double-examinations) and after 2 years (single examinations). The difference between the double-examinations was used to compute the precision for the methods and for each type of implant. Femoral head penetration and cup translation up to 2 years were compared using marker-based RSA as reference. The precision of proximal penetration and migration measurements did not differ between the methods for Trilogy, TMT and ABG. For Ringloc design a poorer precision was observed using MBRSA. Comparison between the methods regarding proximal penetration and cup migration at 2 years did not differ for three of the designs ( p = 0.12-0.91). However, for the group with porous plasma sprayed surface (Ringloc) a significant difference between the methods was observed ( ppenetration <0.01 and pmigration <0.01). Poorer precision, different penetration and migration values at 2 years for one of the designs indicate that the resolution of MBRSA might vary depending on surface coating and implant geometry. Therefore, we conclude that the resolution of MBRSA has to be studied for each type of basic cup design. © 2016 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 35:760-767, 2017. [ABSTRACT FROM AUTHOR]

Background: Radiostereometry (RSA) measurements of early micromotion can predict later failure in hip and knee prostheses. In hip implants, RSA has been particularly helpful in the evaluation of composite-beam stem designs. The Spectron EF Primary stem (Smith & Nephew, London, UK) has shown inferior performance compared with its predecessors in both clinical studies and registry reports. Early RSA studies have shown somewhat greater subsidence for the Spectron EF Primary stem compared with the earlier Spectron EF, but still within boundaries considered to be safe.Questions/purposes: Our primary research question was whether stem subsidence and rotation for this stem design measured with RSA at 2 years can predict later stem failure. A secondary question was whether high femoral stem offset and small stem sizes, both features specific to the Spectron EF Primary stem compared with its predecessors, are associated with stem failure rate.Methods: Two hundred forty-seven hips (209 patients with median age 63 years [range, 29-80 years], 65% female, and 77% primary osteoarthritis) with a valid RSA examination at 2 years were selected from four different RSA studies (totaling 279 hips in 236 patients) in our department. The studies were primarily aimed at evaluating cup fixation, bone cement, and polyethylene types. All study patients received a cemented Spectron EF Primary stem. The selected hips had complete followup until stem failure, death, or the end of the followup period. Stem failure was defined as revision of a loose femoral stem or radiological failure with significant osteolysis in Gruen zones 2 to 6. Cox regression analyses were performed to evaluate if stem subsidence and rotation after 2 years, adjusted for age, sex, stem size, standard/high stem offset, and conventional/highly crosslinked polyethylene, could predict later clinical aseptic failure of the stem. We identified 32 stem failures (27 revisions, five radiological failures) at 14 years median followup (range, 3-18 years). Ten-year stem survival was 94% (95% confidence interval [CI], 90%-96%).Results: Stem subsidence at 2 years (adjusted hazard ratio [HR], 6.0; 95% CI, 2.5-15; p < 0.001) and retrotorsion of the stem (adjusted HR, 1.7; 95% CI, 1.1-2.5; p = 0.018) were associated with later stem failure. Further risk factors were male sex (subsidence analysis HR, 6.9; p > 0.001), use of the two smallest stem sizes (HRsize 1, 8.0; p > 0.001, HRsize 2, 1 [reference], HRsize 3+, 0.06; p = 0.035), and the high offset option (HR, 3.1; p = 0.005).Conclusions: Stem subsidence and retrotorsion at 2 years can predict later failure in the Spectron EF Primary stem, consistent with earlier findings on composite-beam cemented stems. Small stem size and high-offset stems comprise the main group of underperforming stems. We recommend that premarket small-scale RSA studies be performed after any design change to a THA femoral component, because even seemingly minor design changes may unexpectedly result in inferior performance.Level Of Evidence: Level III, therapeutic study. [ABSTRACT FROM AUTHOR]

Background: Highly cross-linked polyethylene infused with vitamin E (E-poly) was developed to increase oxidative resistance without affecting mechanical properties. We evaluated this type of polyethylene in a randomized clinical study that used radiostereometric analysis. Our objective was to compare the early-term femoral head penetration of an E-poly liner with that of a heat-treated polyethylene liner, ArComXL. We hypothesized that the clinical outcome at two years following total hip arthroplasty would be unaffected by the choice of polyethylene.Methods: In this prospective study, sixty-one patients (seventy hips) with noninflammatory hip osteoarthritis and a median age of fifty-eight years were randomized to receive either an implant with an E-Poly or a heat-treated highly cross-linked polyethylene liner. The patients were followed for two years and evaluated at three time points (three months, one year, and two years).Results: The median proximal penetration in the E-poly group increased from 0.04 mm at three months to 0.06 mm at two years of follow-up. Corresponding values for the ArComXL group were 0.03 mm and 0.10 mm. In both groups, significantly increased penetration was observed between three months and two years (E-poly, p = 0.02; ArComXL, p < 0.001), but between one and two years, the increase was significant only in the control group (E-poly, p = 0.23; ArComXL, p = 0.002).Conclusions: The femoral head penetration of E-poly was very low at two years. Whether the increase observed between three months and two years was caused by creep, deformation, wear, or a combination of these cannot be determined by our study. There were no significant differences observed in femoral head penetration rates between E-poly and ArComXL. Currently, the theoretical advantages of E-poly remain to be confirmed. [ABSTRACT FROM AUTHOR]

Background: Highly cross-linked polyethylene infused with vitamin E (E-poly) was developed to increase oxidative resistance without affecting mechanical properties. We evaluated this type of polyethylene in a randomized clinical study that used radiostereometric analysis. Our objective was to compare the early-term femoral head penetration of an E-poly liner with that of a heat-treated polyethylene liner, ArComXL. We hypothesized that the clinical outcome at two years following total hip arthroplasty would be unaffected by the choice of polyethylene. Methods: In this prospective study, sixty-one patients (seventy hips) with noninflammatory hip osteoarthritis and a median age of fifty-eight years were randomized to receive either an implant with an E-Poly or a heat-treated highly crosslinked polyethylene liner. The patients were followed for two years and evaluated at three time points (three months, one year, and two years). Results: The median proximal penetration in the E-poly group increased from 0.04 mm at three months to 0.06 mm at two years of follow-up. Corresponding values for the ArComXL group were 0.03 mm and 0.10 mm. In both groups, significantly increased penetration was observed between three months and two years (E-poly, p = 0.02; ArComXL, p < 0.001), but between one and two years, the increase was significant only in the control group (E-poly, p = 0.23; ArComXL, p = 0.002). Conclusions: The femoral head penetration of E-poly was very low at two years. Whether the increase observed between three months and two years was caused by creep, deformation, wear, or a combination of these cannot be determined by our study. There were no significant differences observed in femoral head penetration rates between E-poly and ArComXL. Currently, the theoretical advantages of E-poly remain to be confirmed. [ABSTRACT FROM AUTHOR]

Background: Polyethylene (PE) wear particles are believed to cause aseptic loosening and thereby impair function in hip arthroplasty. Highly crosslinked polyethylene (XLPE) has low short- and medium-term wear rates. However, the long-term wear characteristics are unknown and it is unclear whether reduced wear particle burden improves function and survival of cemented hip arthroplasty. Questions/purposes: We asked whether XLPE wear rates remain low up to 10 years and whether this leads to improved implant fixation, periprosthetic bone quality, and clinical function compared to conventional PE. Methods: We randomized 60 patients (61 hips) to receive either PE or XLPE cemented cups combined with a cemented stem. At 10 years postoperatively, 51 patients (52 hips) were evaluated for polyethylene wear and component migration estimation by radiostereometry, for radiolucent lines, bone densitometry, and Harris hip and pain scores. Revisions were recorded. Results: XLPE cups had a lower mean three-dimensional wear rate between 2 and 10 years compared to conventional PE hips: 0.005 mm/year versus 0.056 mm/year. We found no differences in cup migration, bone mineral density, radiolucencies, functional scores, and revision rate. There was a trend toward improved stem fixation in the XLPE group. The overall stem failure rate was comparably high, without influencing wear rate in XLPE hips. Conclusions: XLPE displayed a low wear rate up to 10 years when used in cemented THA, but we found no clear benefits in any other parameters. Further research is needed to determine whether cemented THA designs with XLPE are less prone to stem loosening. Level of Evidence: Level I, therapeutic study. See the Instructions for Authors for a complete description of levels of evidence. [ABSTRACT FROM AUTHOR]

The article discusses a study on the relationship between the adoption of evidence-based treatment and survival of patients with ST-elevation myocardial infarction (STEMI). The study involves the use of mortality data from the Register of Information and Knowledge About Swedish Heart Intensive Admissions (RIKS-HIA) database in Sweden. Analysis of evidence-based in-hospital treatments shows that reperfusion treatment posted an increase to 79% while primary percutaneous coronary intervention (PCI) rose to 61%. Results indicate that the implementation of new treatment strategies on STEMI patients supported by the registry leads to an increased use of evidence-based treatments, better adherence to treatment guidelines and a decrease in variation across hospitals.

Background and purpose The reported outcomes of hip resurfacing arthroplasty (HRA) vary. The frequency of this procedure in Denmark, Norway, and Sweden is low. We therefore determined the outcome of HRA in the NARA database, which is common to all 3 countries, and compared it to the outcome of conventional total hip arthroplasty (THA). Methods The risk of non-septic revision within 2 years was analyzed in 1,638 HRAs and compared to that for 172,554 conventional total hip arthroplasties (THAs), using Cox regression models. We calculated relative risk (RR) of revision and 95% confidence interval. Results HRA had an almost 3-fold increased revision risk compared to THA (RR = 2.7, 95% CI: 1.9-3.7). The difference was even greater when HRA was compared to the THA subgroup of cemented THAs (RR = 3.8, CI: 2.7-5.3). For men below 50 years of age, this difference was less pronounced (HRA vs. THA: RR = 1.9, CI: 1.0-3.9; HRA vs. cemented THA: RR = 2.4, CI: 1.1-5.3), but it was even more pronounced in women of the same age group (HRA vs. THA: RR = 4.7, CI: 2.6-8.5; HRA vs. cemented THA: RR = 7.4, CI: 3.7-15). Within the HRA group, risk of non-septic revision was reduced in hospitals performing ≥ 70 HRAs annually (RR = 0.3, CI: 0.1-0.7) and with use of Birmingham hip resurfacing (BHR) rather than the other designs as a group (RR = 0.3, CI: 0.1-0.7). Risk of early revision was also reduced in males (RR = 0.5, CI: 0.2-0.9). The femoral head diameter alone had no statistically significant influence on the early revision rate, but it eliminated the significance of male sex in a combined analysis. Interpretation In general, our results do not support continued use of hip resurfacing arthroplasty. Men had a lower early revision rate, which was still higher than observed for all-cemented hips. Further follow-up is necessary to determine whether HRA might be useful as an alternative in males. [ABSTRACT FROM AUTHOR]

Acute ST-segment elevation myocardial infarction requires prompt restoration of myocardial perfusion to salvage myocardium at risk of ischemic necrosis and improve clinical outcome. Early resolution of ST-segment elevation during the time after reperfusion has been associated with both these end points. From the ASsessment of the Safety and Efficacy of a New Thrombolytic regimen (ASSENT) 3 trial, 3,425 patients were analyzed to investigate whether the amount of ST-segment resolution, divided into 3 groups (complete, >70%; partial, 30% to 70%; and no resolution, <30%), in the first hour after initiation of therapy was a predictor of final infarct size, estimated by peak creatine kinase and Selvester QRS score on the discharge electrocardiogram. Complete compared with partial and no ST resolution resulted in significantly (p <0.001) smaller infarct sizes of 10.5%, 13.2%, and 15.0% of the left ventricle and significantly (p = 0.001) fewer patients with peak creatine >5 times the upper reference level at 50.3%, 71.8%, and 76.3%, respectively. In conclusion, our findings supported previous smaller studies suggesting that early resolution of ST elevation, as a sign of early myocardial reperfusion, resulted in less myocardial damage and preservation of left ventricular function. [Copyright &y& Elsevier]

We compared combination fibrinolytic plus glycoprotein IIb/IIIa inhibitor therapy with stand-alone fibrinolysis with respect to speed and stability of reperfusion in patients who had acute ST-segment elevation myocardial infarction; data were obtained from 654 patients in 4 trials (Integrilin to Manage Platelet Aggregation to Combat Thrombosis in Acute Myocardial Infarction, Platelet Aggregation Receptor Antagonist Dose Investigation and Reperfusion Gain in Myocardial Infarction, Integrilin and Tenecteplase in Acute Myocardial Infarction, and the Fifth Global Use of Strategies to Open Occluded Coronary Arteries) that compared thrombolytics plus lamifiban, eptifibatide, or abciximab with standard thrombolysis. We found significantly faster and more stable ST-segment recovery with combination therapy starting at 60 minutes (56.7% vs 48.0% with ≥50% ST-segment resolution, p = 0.03) and sustained over 180 minutes after drug administration; this transient benefit may suggest a time frame when more optimal percutaneous coronary intervention can be performed. [Copyright &y& Elsevier]

Introduction: Cardiovascular outcome trials (CVOTs) are essential to explore the long term cardiovascular effects of medicines, and since 2008 it is also mandatory for all new antidiabetic drugs, targeting T2DM, to demonstrate CV no harm. Since CVOTs normally recruit thousands of patients and are running for many years, trial design is extra important since an incorrect estimate of the expected event rate can generate unwelcome costs and delays. Hypothesis: In this work, we investigate the prevalence and rate of over optimistic event rate estimation when designing outcomes trials and its potential impact on chance of successful trials. Methods: In this systematic review, we compare predicted event rate, extracted from earliest available study protocol, to reported event rate, from main publication in NEJM or Lancet, in all CVOTs with at least 1000 subjects published between start of 2010 and end of 2016. A linear regression model was used estimate relation between predicted and observed event rate. A model weighted on planned follow-up (patient years) as well as sensitivity analyses on several covariates were also performed. Logistic regression was used to test covariate influence on likelihood of trial success. Results: Out of 2205 articles, 173 trials were identified and 78 were eligible for the analysis. On average, the observed event rate was 14 percent lower (slope=0.86, p<0.0001) than what was originally predicted in the study protocol. In the model weighted on planned patient years, the overestimation was 24 percent. Publication year, journal, Industry or non-industry sponsor, active comparator or primary endpoint (MACE, MACE+ or other) did not affect the predictability. Thirty of the 78 trials (38 percent) met their primary objective. Most variables did not influence likelihood of success, but non-inferiority trials were more likely to succeed than superiority studies, 76.9% vs 30.8%, respectively. Conclusions: In CVOTs reported during 2010-2016, the estimation of event rate in general was significantly over-optimistic. The consequences of such mispredictions normally result in prolonged study duration, increased sample size or a decreased power. To decrease the risk when investments are made in CVOTs, the identification of highly relevant source data is critical. [ABSTRACT FROM AUTHOR]

Abstract: Background: We wanted to evaluate predictors of direct admittance to a coronary care unit (CCU) and predictors of death in patients with suspected acute coronary syndromes (ACS). Methods: During 2004–2007, all consecutive prehospitally triaged patients with suspected ACS were prospectively included. Prehospital and emergency data were collected at point of care. Data from medical records, ECG-, echocardiography- and laboratory databases was collected retrospectively. Results: In all, 2757 patients were included. Out of these 858 were directly admitted to the CCU or cath/lab. Predictors for direct admittance to the CCU were ST-segment elevation on the initial ECG; odds ratio (OR) 46.11, left bundle branch block; OR 3.30, ongoing symptoms; OR 2.90, current smoking; OR 2.18 and ST-segment depression; OR 2.05. Independent predictors for 1-year mortality were cardiogenic shock; OR 14.40, increasing age OR (per year) 1.08, diabetes; OR 2.09 and chronic heart failure; OR 1.67. ST-segment elevation was associated with a lower 1-year mortality rate; OR 0.52. Conclusions: Among patients with a suspected ACS, prehospital ECG-signs indicating an acute coronary occlusion were not only a predictor for direct admission to acute coronary care but also a predictor for increased survival. To improve future outcome in acute ischemic heart diseases we must find and treat not only the STEMI's but also the high-risk NSTEMIs that otherwise would have a poor prognosis. [Copyright &y& Elsevier]

Objectives: The purpose of this study was to examine the extent of change in troponin T levels in patients with non-ST-segment elevation myocardial infarction (NSTEMI).Background: Changes in cardiac troponin T (cTnT) levels are required for the diagnosis of NSTEMI, according to the new universal definition of acute myocardial infarction. A relative change of 20% to 230% and an absolute change of 7 to 9 ng/l have been suggested as cutoff points.Methods: In a clinical setting, where a change in cTnT was not mandatory for the diagnosis of NSTEMI, serial samples of cTnT were measured with a high-sensitivity cTnT (hs-cTnT) assay, and 37 clinical parameters were evaluated in 1,178 patients with a final diagnosis of NSTEMI presenting <24 h after symptom onset.Results: After 6 h of observation, the relative change in the hs-cTnT level remained <20% in 26% and the absolute change <9 ng/l in 12% of the NSTEMI patients. A relative hs-cTnT change <20% was linked to higher long-term mortality across quartiles (p = 0.002) and in multivariate analyses (hazard ratio: 1.61 [95% confidence interval: 1.17 to 2.21], p = 0.004), whereas 30-day mortality was similar across quartiles of relative hs-cTnT change.Conclusions: Because stable hs-TnT levels are common in patients with a clinical diagnosis of NSTEMI in our hospital, a small hs-cTnT change may not be useful to exclude NSTEMI, particularly as these patients show both short-term and long-term mortality at least as high as patients with large changes in hs-cTnT. [ABSTRACT FROM AUTHOR]

Objectives: The purpose of this study was to examine the extent of change in troponin T levels in patients with non–ST-segment elevation myocardial infarction (NSTEMI). Background: Changes in cardiac troponin T (cTnT) levels are required for the diagnosis of NSTEMI, according to the new universal definition of acute myocardial infarction. A relative change of 20% to 230% and an absolute change of 7 to 9 ng/l have been suggested as cutoff points. Methods: In a clinical setting, where a change in cTnT was not mandatory for the diagnosis of NSTEMI, serial samples of cTnT were measured with a high-sensitivity cTnT (hs-cTnT) assay, and 37 clinical parameters were evaluated in 1,178 patients with a final diagnosis of NSTEMI presenting <24 h after symptom onset. Results: After 6 h of observation, the relative change in the hs-cTnT level remained <20% in 26% and the absolute change <9 ng/l in 12% of the NSTEMI patients. A relative hs-cTnT change <20% was linked to higher long-term mortality across quartiles (p = 0.002) and in multivariate analyses (hazard ratio: 1.61 [95% confidence interval: 1.17 to 2.21], p = 0.004), whereas 30-day mortality was similar across quartiles of relative hs-cTnT change. Conclusions: Because stable hs-TnT levels are common in patients with a clinical diagnosis of NSTEMI in our hospital, a small hs-cTnT change may not be useful to exclude NSTEMI, particularly as these patients show both short-term and long-term mortality at least as high as patients with large changes in hs-cTnT. [Copyright &y& Elsevier]

In patients with ST-segment elevation myocardial infarction treated with fibrinolytics, electrocardiogram-derived measures of ST-segment recovery guide therapy decisions and predict infarct size. The comprehension of these relationships in patients undergoing mechanical reperfusion is limited. We studied 144 patients treated with primary percutaneous coronary intervention. We aimed to define the association between infarct size as determined by cardiac magnetic resonance imaging and different metrics of ST-segment recovery. Electrocardiograms were assessed at baseline and 90 minutes after primary percutaneous coronary intervention. Three methods for calculating and categorizing ST-segment recovery were used: (1) summed ST-segment deviation (STD) resolution analyzed in 3 categories (≥70%, ≥30% to <70%, and <30%); (2) single-lead STD resolution analyzed in the same 3 categories; (3) worst-lead residual STD analyzed in 3 categories (<1 mm, 1 to <2 mm, and ≥2 mm). Infarct size and ejection fraction were assessed at 4 months by cardiac magnetic resonance imaging. All 3 ST-segment recovery algorithms predicted the final infarct size and cardiac function. Worst-lead residual STD performed the same as, or better than, the more complex methods and identified large subgroups at either end of the risk spectrum (median infarct size from the lowest to highest risk category (percentage of left ventricle: 7.7% [interquartile range 10.8], 13.1% [interquartile range 13.6]; 24.6% [interquartile range 21.1]); with adjusted odds ratios for infarct size greater than the median (reference <1 mm): 1 to <2 mm, odds ratio 2.3 (95% confidence interval 0.8 to 5.9); ≥2 mm, odds ratio 6.3 (95% confidence interval 1.7 to 23.7; c-index 0.781). In conclusion, an electrocardiogram obtained early after primary percutaneous coronary intervention analyzed by a simple algorithm provided prognostic information on the final infarct size and cardiac function. [Copyright &y& Elsevier]

Objective: Heart failure (HF) is an impactful complication of type 2 diabetes mellitus (T2DM). We aimed to develop and validate a risk score for hospitalization for HF (HHF) incorporating biomarkers and clinical factor(s) in patients with T2DM.Research Design and Methods: We derived a risk score for HHF using clinical data, high-sensitivity troponin T (hsTnT), and N-terminal prohormone of B-type natriuretic peptide (NT-proBNP) from 6,106 placebo-treated patients with T2DM in SAVOR-TIMI 53 (Saxagliptin Assessment of Vascular Outcomes Recorded in Patients with Diabetes Mellitus-Thrombolysis in Myocardial Infarction 53). Candidate variables were assessed using Cox regression. The strongest indicators of HHF risk were included in the score using integer weights. The score was externally validated in 7,251 placebo-treated patients in DECLARE-TIMI 58 (Dapagliflozin Effect on CardiovascuLAR Events-Thrombolysis in Myocardial Infarction 58). The effect of dapagliflozin on HHF was assessed by risk category in DECLARE-TIMI 58.Results: The strongest indicators of HHF risk were NT-proBNP, prior HF, and hsTnT (each P < 0.001). A risk score using these three variables identified a gradient of HHF risk (P-trend <0.001) in the derivation and validation cohorts, with C-indices of 0.87 (95% CI, 0.84-0.89) and 0.84 (0.81-0.86), respectively. Whereas there was no significant effect of dapagliflozin versus placebo on HHF in the low-risk group (hazard ratio [HR] 0.98 [95% CI 0.50-1.92]), dapagliflozin significantly reduced HHF in the intermediate-, high-, and very-high-risk groups (HR 0.64 [0.43-0.95], 0.63 [0.43-0.94], and 0.72 [0.54-0.96], respectively). Correspondingly, absolute risk reductions (95% CI) increased across these latter 3 groups: 1.0% (0.0-1.9), 3.0% (0.7-5.3), and 4.4% (-0.2 to 8.9) (P-trend <0.001).Conclusions: We developed and validated a risk score for HHF in T2DM that incorporated NT-proBNP, prior HF, and hsTnT. The risk score identifies patients at higher risk of HHF who derive greater absolute benefit from dapagliflozin. [ABSTRACT FROM AUTHOR]

A letter to the editor is presented in response to the article "Association Between Adoption of Evidence-Based Treatment and Survival for Patients With ST-Elevation Myocardial Infarction," by Tomas Jernberg and colleagues which appeared in a previous issue.

Background: In the DAPA-HF trial (Dapagliflozin and Prevention of Adverse Outcomes in Heart Failure), dapagliflozin, added to guideline-recommended therapies, reduced the risk of mortality and heart failure (HF) hospitalization. We examined the frequency and significance of episodes of outpatient HF worsening, requiring the augmentation of oral therapy, and the effects of dapagliflozin on these additional events.Methods: Patients in New York Heart Association functional class II to IV, with a left ventricular ejection fraction ≤40% and elevation of NT-proBNP (N-terminal pro-B-type natriuretic peptide), were eligible. The primary outcome was the composite of an episode of worsening HF (HF hospitalization or an urgent HF visit requiring intravenous therapy) or cardiovascular death, whichever occurred first. An additional prespecified exploratory outcome was the primary outcome plus worsening HF symptoms/signs leading to the initiation of new, or the augmentation of existing, oral treatment.Results: Overall, 36% more patients experienced the expanded, in comparison with the primary, composite outcome. In the placebo group, 684 of 2371 (28.8%) patients and, in the dapagliflozin group, 527 of 2373 (22.2%) participants experienced the expanded outcome (hazard ratio, 0.73 [95% CI, 0.65-0.82]; P<0.0001). Each component of the composite was reduced significantly by dapagliflozin. Over the median follow-up of 18.2 months, the number of patients needed to treat with dapagliflozin to prevent 1 experiencing an episode of fatal or nonfatal worsening was 16. Among the 4744 randomly assigned patients, the first episode of worsening was outpatient augmentation of treatment in 407 participants (8.6%), an urgent HF visit with intravenous therapy in 20 (0.4%), HF hospitalization in 489 (10.3%), and cardiovascular death in 295 (6.2%). The adjusted risk of death from any cause (in comparison with no event) after an outpatient worsening was hazard ratio, 2.67 (95% CI, 2.03-3.52); after an urgent HF visit, the adjusted risk of death was hazard ratio, 3.00 (95% CI, 1.39-6.48); and after a HF hospitalization, the adjusted risk of death was hazard ratio, 6.21 (95% CI, 5.07-7.62).Conclusion: In DAPA-HF, outpatient episodes of HF worsening were common, were of prognostic importance, and were reduced by dapagliflozin. Registration: URL: https://www.clinicaltrials.gov; Unique Identifier: NCT03036124. [ABSTRACT FROM AUTHOR]

Background: Patients with peripheral artery disease (PAD) are at heightened risk of cardiovascular complications. The sodium-glucose cotransporter 2 inhibitor dapagliflozin reduces the risk for hospitalization for heart failure (HHF) and kidney events in patients with type 2 diabetes mellitus. An increased risk of amputation has been observed with canagliflozin in 1 previous trial. We examined cardiovascular and kidney efficacy and the risk of limb-related events in patients with and without PAD in an exploratory analysis.Methods: A total of 17 160 patients with type 2 diabetes mellitus, including 1025 (6%) with PAD, were randomized. Key efficacy outcomes were MACE (cardiovascular [CV] death, myocardial infarction, stroke), CV death/HHF, and progression of kidney disease. Amputations, peripheral revascularization, and limb ischemic adverse events were site-reported and categorized by a blinded reviewer.Results: Patients in the placebo arm with PAD versus those without tended to have higher adjusted risk of CV death, myocardial infarction, or stroke (adjusted hazard ratio [HR], 1.23 [95% CI, 0.97-1.56], P=0.094) and significantly higher adjusted risk of CV death/HHF (adjusted HR, 1.60 [95% CI, 1.21-2.12], P=0.0010) and progression of kidney disease (adjusted HR, 1.51 [95% CI, 1.13 - 2.03], P=0.0058), and limb adverse events (adjusted HR, 8.37, P<0.001). The relative risk reductions with dapagliflozin for CV death/HHF (HR, 0.86, PAD; HR, 0.82, no-PAD; P-interaction=0.79) and progression of kidney disease (HR, 0.78, PAD; HR, 0.76, no-PAD; P-interaction=0.84) were consistent regardless of PAD. There were 560 patients who had at least 1 limb ischemic event, 454 patients with at least 1 peripheral revascularization, and 236 patients with at least 1 amputation, with a total of 407 amputations reported. Overall, there were no significant differences in any limb outcome with dapagliflozin versus placebo including limb ischemic adverse events (HR, 1.07 [95% CI, 0.90-1.26]) and amputation (HR, 1.09 [95% CI, 0.84-1.40]), with no significant interactions by a history of PAD versus not (P-interactions=0.30 and 0.093, respectively).Conclusions: Patients with versus without PAD are at a higher risk of CV death of CV death, HHF, and kidney outcomes, and have a consistent benefits for CV death/HHF and progression of kidney disease with dapagliflozin. Patients with PAD had a higher risk of limb events, with no consistent pattern of incremental risk observed with dapagliflozin. Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT01730534. [ABSTRACT FROM AUTHOR]

Background: Patients with type 2 diabetes mellitus (T2DM) are at increased risk of developing heart failure. Sodium-glucose cotransporter-2 inhibitors reduce the risk of hospitalization for heart failure (HHF) in patients with T2DM. We aimed to develop and validate a practical clinical risk score for HHF in patients with T2DM and assess whether this score can identify high-risk patients with T2DM who have the greatest reduction in risk for HHF with a sodium-glucose cotransporter-2 inhibitor.Methods: We developed a clinical risk score for HHF in 8212 patients with T2DM in the placebo arm of SAVOR-TIMI 53 (Saxagliptin Assessment of Vascular Outcomes Recorded in Patients With Diabetes Mellitus-Thrombolysis in Myocardial Infarction 53). Candidate variables were assessed using multivariable Cox regression, and independent clinical risk indicators achieving statistical significance of P<0.001 were included in the risk score. We externally validated the score in 8578 patients with T2DM in the placebo arm of DECLARE-TIMI 58 (Dapagliflozin Effect on Cardiovascular Events-Thrombolysis in Myocardial Infarction 58). The relative and absolute risk reductions in HHF with the sodium-glucose cotransporter-2 inhibitor dapagliflozin were assessed by baseline HHF risk.Results: Five clinical variables were independent risk predictors of HHF: prior heart failure, history of atrial fibrillation, coronary artery disease, estimated glomerular filtration rate, and urine albumin-to-creatinine ratio. A simple integer-based score (0-7 points) using these predictors identified a >20-fold gradient of HHF risk (P for trend <0.001) in both the derivation and validation cohorts, with C indices of 0.81 and 0.78, respectively. Although relative risk reductions with dapagliflozin were similar for patients across the risk scores (25%-34%), absolute risk reductions were greater in those at higher baseline risk (1-sided P for trend=0.04), with high-risk (2 points) and very-high-risk (≥3 points) patients having 1.5% and 2.7% absolute reductions in Kaplan-Meier estimates of HHF risk at 4 years, respectively.Conclusions: Risk stratification using a novel clinical risk score for HHF in patients with T2DM identifies patients at higher risk for HHF who derive greater absolute benefit from sodium-glucose cotransporter-2 inhibition.Clinical Trial Registration: URL: https://www.clinicaltrials.gov. Unique identifiers: NCT01107886 and NCT01730534. [ABSTRACT FROM AUTHOR]

Background and Objective: Ticagrelor is a P2Y12 receptor inhibitor approved as an antiplatelet drug for patients with acute coronary syndrome or a history of myocardial infarction. Ticagrelor is also being investigated for the reduction of vaso-occlusive crises in pediatric patients with sickle cell disease. A pediatric formulation suitable for this age range was developed; the development strategy is described. Primary objectives were determining the relative bioavailability of ticagrelor pediatric tablets and granules for oral suspension to the adult immediate-release tablet, and the pediatric tablets taken whole and dispersed/suspended in water to the granules for oral suspension. Bioequivalence between the pediatric tablet taken whole or suspended in water was also assessed. Secondary objectives were comparing the formulations' safety and tolerability. Methods: We conducted a randomized, four-period, cross-over, single-dose study. Pharmacokinetic parameters were assessed for ticagrelor and its active metabolite AR-C124910XX. Bioequivalence was concluded if the 90% confidence intervals of the maximum plasma concentration and area under the plasma concentration–time curve ratios were contained completely within the 80.00–125.00% limits for ticagrelor/AR-C124910XX. Results: Forty-four healthy adults (95% white; 57% male) were included. Similar bioavailability of ticagrelor (and AR-C124910XX) was demonstrated for all comparisons tested. Ticagrelor pediatric tablets taken whole were bioequivalent to pediatric tablets suspended in water. The plasma concentration–time profiles for ticagrelor and AR-C124910XX were similar, showing rapid ticagrelor absorption and AR-C124910XX formation. All formulations were well tolerated. Conclusion: Similar bioavailability of a new pediatric dispersible tablet formulation of ticagrelor for use across a wide age range of pediatric patients was demonstrated compared with other oral ticagrelor formulations. ClinicalTrials.gov Identifier: NCT03126695. EudraCT: 2017-000371-93. [ABSTRACT FROM AUTHOR]

Background: In DECLARE-TIMI 58 (Dapagliflozin Effect on Cardiovascular Events-Thrombolysis in Myocardial Infarction 58), the sodium-glucose cotransporter 2 inhibitor dapagliflozin reduced the composite end point of cardiovascular death/hospitalization for heart failure (HHF) in a broad population of patients with type 2 diabetes mellitus. However, the impact of baseline left ventricular ejection fraction (EF) on the clinical benefit of sodium-glucose cotransporter 2 inhibition is unknown.Methods: In the DECLARE-TIMI 58 trial, baseline heart failure (HF) status was collected from all patients, and EF was collected when available. HF with reduced EF (HFrEF) was defined as EF <45%. Outcomes of interest were the composite of cardiovascular death/HHF, its components, and all-cause mortality.Results: Of 17 160 patients, 671 (3.9%) had HFrEF, 1316 (7.7%) had HF without known reduced EF, and 15 173 (88.4%) had no history of HF at baseline. Dapagliflozin reduced cardiovascular death/HHF more in patients with HFrEF (hazard ratio [HR], 0.62 [95% CI, 0.45-0.86]) than in those without HFrEF (HR, 0.88 [95% CI, 0.76-1.02]; P for interaction=0.046), in whom the treatment effect of dapagliflozin was similar in those with HF without known reduced EF (HR, 0.88 [95% CI, 0.66-1.17]) and those without HF (HR, 0.88 [95% CI, 0.74-1.03]). Whereas dapagliflozin reduced HHF both in those with (HR, 0.64 [95% CI, 0.43-0.95]) and in those without HFrEF (HR, 0.76 [95% CI, 0.62-0.92]), it reduced cardiovascular death only in patients with HFrEF (HR, 0.55 [95% CI, 0.34-0.90]) but not in those without HFrEF (HR, 1.08 [95% CI, 0.89-1.31]; P for interaction=0.012). Likewise, dapagliflozin reduced all-cause mortality in patients with HFrEF (HR, 0.59 [95% CI, 0.40-0.88;) but not in those without HFrEF (HR, 0.97 [95% CI, 0.86-1.10]; P for interaction=0.016).Conclusions: In the first sodium-glucose cotransporter 2 inhibitor cardiovascular outcome trial to evaluate patients with type 2 diabetes mellitus stratified by EF, we found that dapagliflozin reduced HHF in patients with and without HFrEF and reduced cardiovascular death and all-cause mortality in patients with HFrEF.Clinical Trial Registration: URL: https://www.clinicaltrials.gov . Unique identifier: NCT01730534. [ABSTRACT FROM AUTHOR]

Background: Ticagrelor reduces ischemic risk in patients with prior myocardial infarction (MI). It remains unclear whether ischemic risk and the benefits of prolonged P2Y12 inhibition in this population remain consistent over time.Objectives: The study sought to investigate the pattern of ischemic risk over time and whether the efficacy and safety of ticagrelor were similar early and late after randomization.Methods: The PEGASUS-TIMI (Prevention of Cardiovascular Events in Patients with Prior Heart Attack Using Ticagrelor Compared to Placebo on a Background of Aspirin-Thrombolysis In Myocardial Infarction) 54 trial randomized patients with prior MI (median 1.7 years prior) to ticagrelor 90 mg, ticagrelor 60 mg, or placebo on a background of aspirin. The rates of cardiovascular (CV) death, MI, and stroke as well as TIMI major bleeding were analyzed at yearly landmarks (years 1, 2, and 3).Results: A total of 21,162 patients were randomized and followed for 33 months (median), with 28% of patients ≥5 years from MI at trial conclusion. The risk of CV death, MI, or stroke in the placebo arm remained roughly constant over the trial at an ∼3% annualized rate. The benefit of ticagrelor 60 mg was consistent at each subsequent landmark (year 1 hazard ratio [HR]: 0.82; 95% confidence interval [CI]: 0.67 to 0.99; year 2 HR: 0.90; 95% CI: 0.74 to 1.11; and year 3 HR: 0.79; 95% CI: 0.62 to 1.00). TIMI major bleeding was increased with ticagrelor 60 mg at each landmark, but with the greatest hazard in the first year (year 1 HR: 3.22; year 2 HR: 2.07; year 3 HR: 1.65).Conclusions: Patients with a history of MI remain at persistent high risk for CVD, MI, and stroke as late as 5 years after MI. The efficacy of low-dose ticagrelor is consistent over time with a trend toward less excess bleeding. (Prevention of Cardiovascular Events in Patients with Prior Heart Attack Using Ticagrelor Compared to Placebo on a Background of Aspirin [PEGASUS]; NCT01225562). [ABSTRACT FROM AUTHOR]

Bone impaction grafting is a biologically and mechanically appealing option in acetabular revision surgery, allowing restitution of the bone stock and restoration of the biomechanics. We analysed differences in proximal migration of the revision acetabular components when bone impaction grafting is used together with a cemented or an uncemented cup.~Background~Background~43 patients (47 hips), revised due to acetabular loosening and judged to have less than 50% host bone-implant contact were included. The hips were randomised to either an uncemented (n = 20) or a cemented (n = 27) revision cup. Radiostereometry and radiography was performed postoperatively, at 3 and 6 months, 1, 2, 3, 5, 7, 10 and 13 and 17 years postoperatively. Clinical follow-up was performed at 1, 2 and 5 years postoperatively and thereafter at the same interval as in the radiographic follow-up.~Patients and Methods~Methods~There were no differences in the base line demographic data between the 2 groups. At the last follow-up (17 years) 14 hips (10 cemented, 4 uncemented) had been re-revised due to loosening. 3 additional cups (1 uncemented and 2 cemented) were radiographically loose. There was a higher early proximal migration in the cemented cups.~Results~Results~Cups operated on with cement showed a higher early migration measured with RSA and also a higher number of late revisions. The reason for this is not known, but factors such as inclusion of cases with severe bone defects, use of smaller bone chips and issues related to the impaction technique might have had various degrees of influence.~Discussion~Conclusions [ABSTRACT FROM AUTHOR]

Abstract: Objectives: To describe the differences in characteristics and outcome between two consecutive series of patients admitted to hospital with chest pain in a 20-year perspective. Particular emphasis is placed on changes in outcome in relation to the initial electrocardiogram (ECG). Subjects: In the two periods, 1986–1987 and 2008, all patients with chest pain admitted to the study hospitals in Gothenburg, Sweden, were included. Results: Five thousand and sixteen patients were registered in a period of 21months in 1986–1987 and 2287 patients were registered during 3months in 2008. In a comparison of the two time periods, the age of chest pain patients was not significantly different (mean age 60.1±17.8years in 1986–1987 and 59.8±19.1years in 2008, p=0.50). There was a lower prevalence of previous angina pectoris, congestive heart failure and current smoking in the second period, whereas a history of acute myocardial infarction, hypertension and diabetes mellitus had become more prevalent. The use of cardio-protective drugs increased and ECG changes indicating acute myocardial ischemia on admission to hospital decreased. Length of hospitalisation was reduced from a median of 5days to 3days (p<0.0001). A significant decrease in 30-day and 1-year mortality was found (3.8% in 1986–1987 vs 2.0% in 2008 and 9.9% vs 6.3% respectively, p<0.0001 for both comparisons). Conclusions: During a period of 20years, the characteristics and outcome of patients admitted to hospital with chest pain changed. The most important changes were a lower prevalence of ECG signs indicating acute myocardial ischemia on admission, shorter hospitalisation time and a lower 30-day and 1-year mortality. [Copyright &y& Elsevier]

Twelve-lead ST-segment monitoring is a widely used tool for capturing focal ischemia and transient intermittent episodes. However, continuous registration of all 10 electrodes is impractical in clinical settings. This study investigated the accuracy of 2 derived 12-lead strategies that required 6 electrodes, including all limb leads, and 2 precordial leads by using population-based (generalized) and individualized (patient-specific) reconstruction coefficients to derive the additional 4 chest leads. A total of 26,880 simultaneous digital conventional 12-lead generalized and patient-specific electrocardiograms were monitored over 112 hours in 39 patients during percutaneous coronary intervention, including 159 balloon occlusions in 63 arteries, to test accuracy at rest and during ischemia. Occlusion duration was 78 seconds (range 42 to 96) in the left main coronary in 2 patients, the left anterior descending artery in 15, the right coronary artery in 10, the circumflex artery in 2, and graft segments in 5 patients. Average summated 12-lead ST deviation over the study population at baseline was 377 μV (range 104 to 1,718), which increased at peak ischemia to an average of 1,086 μV (range 282 to 4,099). Median absolute differences at peak ischemic ST deviation were 25 μV in lead V1, 0 μV in lead V2, 35 μV in lead V3, 34 μV in lead V4, 0 μV in lead V5, 11 μV in lead V6, and 114 μV for summated 12-lead ST deviation with the generalized method and 7 μV in lead V1, 4 μV in lead V2, 1 μV in lead V3, 5μV in lead V4, 4 μV in lead V5, 9 μV in lead V6, and 83 μV for the summated 12-lead ST deviation with the patient-specific method. Limb leads (I, II, III, aVR, aVL, and aVF) were identical in all patients. Thus, generalized and patient-specific methods derived from 12-lead electrocardiography using actual limb and 2 precordial electrodes accurately derived the additional chest leads at rest and during ischemia. These approaches appear to be more practical than conventional 10-electrode monitoring but preserve high accuracy. [Copyright &y& Elsevier]

Introduction: Long-term treatment with ticagrelor 60 mg added to ASA reduces ischemic risk but increases bleeding in patients with prior MI. Hypothesis: Clinical characteristics predicting bleeding and ischemic risk respectively applied in PEGASUS-TIMI 54 (NCT01225562) will identify subgroups who derive greater benefit with lower risk Methods: Predictors of bleeding (anemia at baseline, prior hospitalization for bleeding) and subgroups associated with greater ischemic risk reduction were merged into a selection algorithm. Efficacy (PEP - CV death, MI or stroke), safety (TIMI major bleeding) and net outcomes (CV death, MI, stroke, ICH or fatal bleeding) of ticagrelor 60 mg were evaluated by risk group. Results: Patients (N=13938) were divided into 4 groups first by the presence of a bleeding predictor (High Bleeding Risk - HBR, N=2703, 19%) and then the remainder (Low Bleeding Risk - LBR, N=11235, 81%) divided by the number of ischemic risk factors. In those with HBR, ticagrelor did not reduce the PEP (ARD 0.0%) but did increase bleeding by 2.2%. Of those with LBR, 22% had only 0 or 1 ischemic risk indicators, and in this subgroup ticagrelor reduced PEP by 0.5%, but increased bleeding by 1.0%. The remaining 59% of patients had no bleeding risk indicators and at least 2 ischemic risk indicators, and in this subgroup ticagrelor significantly reduced the risk of the PEP by 1.9% (P=0.0024, NNT 52) and only increased bleeding by 1.0% (P<0.0001, NNH 102). In this latter subgroup, ticagrelor significantly reduced CV death (HR 0.66, 95% CI 0.50 - 87, p=0.0034, ARR 1.2%) and all-cause mortality (HR 0.75, 95% CI 0.61 - 0.95, p=0.018, ARR 1.1%) and the net outcomes (HR 0.80, 95% CI 0.68 - 0.93, p=0.0031, ARR 1.9%). Conclusions: A patient selection strategy first identifying those at low bleeding risk and then stratifying according to number of ischemic high-risk features identifies a population that derives significant ischemic benefit with reductions in all-cause mortality and net outcomes. [ABSTRACT FROM AUTHOR]

Introduction: Ticagrelor is associated with dyspnea with a potential mechanism being increased adenosine exposure. Studies have shown reductions in dyspnea from ticagrelor with theophylline. Caffeine shares similar properties to theophylline and could potentially attenuate dyspnea from ticagrelor. However, safety of caffeine in patients with prior MI is debated, especially regarding risk of arrhythmias. Hypothesis: We sought to investigate, in patients with prior MI, whether caffeine consumption at baseline: 1) modifies the risk of dyspnea with ticagrelor; and 2) is associated with cardiovascular risk. Methods: The effect of caffeine on dyspnea was a prespecified analysis from PEGASUS trial (NCT 01225562), which randomized 21,162 patients with prior MI to ticagrelor 60 mg, 90 mg or matching placebo (twice daily). When data regarding potential effect for caffeine on dyspnea related to ticagrelor were reported, a dedicated form was created, which collected caffeine intake at baseline as the number of caffeinated beverages in cups per week. Outcomes of interest were: dyspnea, death due to coronary heart disease, sudden cardiac death and atrial fibrillation. Results: Caffeine intake was recorded for 9,568 patients, with median of 10 cups per week. Patients with higher than median caffeine intake were younger and more commonly obese and smokers. After adjustment, there was no association between caffeine above the median with dyspnea (HR 1.05; 95 % CI 0.93 to 1.19) nor with death due to coronary heart disease (HR 0.72; 95 % CI 0.48 to 1.08), sudden cardiac death (HR 0.76; 95 % CI 0.49 to 1.19) or atrial fibrillation (HR 0.87; 95 % CI 0.56 to 1.35). Both ticagrelor doses increased dyspnea similarly regardless of caffeine intake at baseline (Figure). Conclusions: In high-risk patients with prior MI, caffeine intake did not modify dyspnea associated with ticagrelor. Besides that, there did not appear to be any increased cardiovascular risk associated with caffeine intake. [ABSTRACT FROM AUTHOR]

Introduction: Use of high-sensitivity troponin (hsTn) in stable patients (pts) with established ischemic heart disease (SIHD) is an emerging application to identify heightened risk of major cardiovascular (CV) events. However, appropriate decision-limits are not yet defined. Methods: We measured serum hsTnI (Abbott ARCHITECT, limit-of-detection 2 ng/L, MI cut-point 26 ng/L) in a prospective nested cohort of 8,635 pts enrolled in the PEGASUS-TIMI 54 trial. All patients had SIHD with a myocardial infarction (MI) 1-3 years prior to enrollment. Previous studies have proposed 6 ng/L as a decision-limit for risk stratification. Pts were categorized based on baseline hsTnI: undetectable (<2), low (2-6), and high (>6 ng/L). The primary endpoint (PEP) was a composite of CV death, MI, or stroke. Pts were followed for a median of 33 months. Results: The median value of hsTnI was 4.2 ng/L (25th, 75th: 2.7, 7.2 ng/L) and 89.3% of pts had detectable hsTnI (≥2 ng/L) with 31.1% >6 ng/L. The 3y PEP rates for the undetectable, low, and high hsTnI groups were 2.8, 6.0, and 13.5%, respectively (Fig). Adjusting for age, diabetes, smoking, hypertension, stroke, CABG, peripheral artery disease, history of heart failure and chronic kidney disease, there remained a 2 and 4-fold higher risk for the PEP in the low and high hsTnI groups(Fig). Rates of MI in the undetectable, low, and high groups were 2.5, 4.3, and 8.7%, respectively, with adjusted HRs of 1.9 (95% CI 1.2-3.2, p=0.009) in the low and 3.6 (95% CI 2.2-6.0, p<0.0001) in the high group. No CV deaths occurred in pts with undetectable troponin. There was no significant interaction with efficacy of ticagrelor. Conclusion: hsTn demonstrates a strong independent graded association with recurrent major cardiovascular events in pts with SIHD. The increased risk is present in the low detectable range and progresses with higher levels. A single hsTnI >6 ng/L was present in nearly 1/3 of patients, identifying a 4-fold higher risk of recurrent cardiac event. [ABSTRACT FROM AUTHOR]