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Aims High-risk cardiac surgery is commonly complicated by low cardiac output syndrome (LCOS), which is associated with high mortality. There are limited data derived from multi-centre studies with adjudicated endpoints describing factors associated with LCOS and its downstream clinical outcomes. Methods and results The Levosimendan in Patients with Left Ventricular Systolic Dysfunction Undergoing Cardiac Surgery Requiring Cardiopulmonary Bypass (LEVO-CTS) trial evaluated prophylactic levosimendan vs. placebo in patients with a reduced ejection fraction undergoing coronary artery bypass grafting (CABG) and/or valve surgery. We conducted a pre-specified analysis on LCOS, which was characterized by a four-part definition. We constructed a multivariable logistical regression model to evaluate risk factors associated with LCOS and performed Cox proportional hazards modelling to determine the association of LCOS with 90-day mortality. A total of 186 (22%) of 849 patients in the LEVO-CTS trial developed LCOS. The factors most associated with a higher adjusted risk of LCOS were pre-operative ejection fraction [odds ratio (OR) 1.26; 95% confidence interval (CI): 1.08–1.46 per 5% decrease] and age (OR 1.13; 95% CI: 1.04–1.24 per 5-year increase), whereas isolated CABG surgery (OR 0.44, 95% CI: 0.31–0.64) and levosimendan use (OR 0.65; 95% CI: 0.46–0.92) were associated with a lower risk of LCOS. Patients with LCOS had worse outcomes, including renal replacement therapy at 30-day (10 vs. 1%) and 90-day mortality (16 vs. 3%, adjusted hazard ratio of 5.04, 95% CI: 2.66–9.55). Conclusion Low cardiac output syndrome is associated with a high risk of post-operative mortality in high-risk cardiac surgery.

We describe variables and outcomes associated with peri-operative mechanical circulatory support (MCS) utilization among patients enrolled in the Levosimendan in patients with Left Ventricular Systolic Dysfunction Undergoing Cardiac Surgery Requiring Cardiopulmonary Bypass (LEVO-CTS) trial.In the LEVO-CTS trial, MCS utilization (defined as intra-aortic balloon pump, extracorporeal membrane oxygenation, or surgical ventricular assist device) within 5 days of surgery was examined. The association between MCS use and outcomes including 90-day mortality, 30-day renal-replacement therapy, and hospital and critical stay length of stay were determined.Among the 849 patients from 70 centers randomized to levosimendan or placebo, 85 (10.0%) patients were treated with MCS (71 intra-aortic balloon pump, 7 extracorporeal membrane oxygenation, 7 ventricular assist device); with 89.4% started on post-operative day 0. Inter-institutional use ranged from 0% to 100%. Variables independently associated with MCS utilization included combined coronary artery bypass grafting and valve surgery (adjusted odds ratio [OR] 2.73, 95% confidence interval [CI] 1.70-4.37, P.001), history of lung disease (OR 1.70, 95% CI 1.06-2.70, P = .029), and history of heart failure (OR 2.44, 95% CI 1.10-5.45, P = .027). Adjusted 90-day mortality (22.4% vs 4.1%, hazard ratio 6.11, 95% CI 3.95-9.44, P.001) was higher, and median critical care length of stay (8.0 vs 4.0 days, P.001) was longer in patients managed with MCS.In a randomized controlled trial of high-risk cardiac surgical patients in North America, we observed patient, and surgical variables associated with MCS utilization. MCS use was associated with a higher risk of post-operative mortality.

Background: In the VICTORIA trial (Vericiguat Global Study in Patients with Heart Failure with Reduced Ejection Fraction), anemia occurred more often in patients treated with vericiguat (7.6%) than with placebo (5.7%). We explored the association between vericiguat, randomization hemoglobin, development of anemia, and whether the benefit of vericiguat related to baseline hemoglobin. Methods: Anemia was defined as hemoglobin Results: At baseline, 1719 (35.7%) patients had World Health Organization anemia; median hemoglobin was 13.4 g/L (25th, 75th percentile: 12.1, 14.7 g/dL). At 16 weeks from randomization, 1643 patients had World Health Organization anemia (284 new for vericiguat and 219 for placebo), which occurred more often with vericiguat than placebo ( P Conclusions: Anemia was common at randomization and lower hemoglobin was associated with a greater frequency of clinical events. Although vericiguat modestly lowered hemoglobin by 16 weeks, this effect did not further progress nor was it related to the treatment benefit of vericiguat. Registration: URL: https://www.clinicaltrials.gov : Unique identifier: NCT02861534.

ObjectivesRemote ischaemic conditioning (RIC) has been tested as a possible strategy for mitigating reperfusion injury in ST elevation myocardial infarction (STEMI) with primary percutaneous coronary intervention (PPCI). However, surrogate outcomes have shown inconsistent effects with lack of clinical correlation.MethodsWe performed a registry-based randomised study of patients with STEMI allocated to RIC (4 cycles of blood pressure cuff inflation to 200 mm Hg for 5 min of ischaemia followed by 5 min of reperfusion) or standard of care (SOC) during PPCI. We examined the associations of RIC on core laboratory measurements of myocardial perfusion, infarct size (IS), left ventricular (LV) performance and clinical outcomes.ResultsA total of 252 patients were enrolled. The median age was 61 (IQR: 55–70) years and 72.8% were male. Sum ST segment deviation resolution ≥50% was similar between RIC and SOC (65.2% vs 55.7%, p=0.269). In those with 3-day cardiovascular MRI (n=88), no difference in median (25th, 75th percentiles) IS (14.9% (4.5%, 23.1%) vs 16.1% (3.3%, 22.0%), p=0.980), LV dimensions (LV end-diastolic volume index: 78.7 (71.1, 91.2) mL/m2 vs 79.9 (71.2, 88.8) mL/m2, p=0.630; LV end-systolic volume index: 48.8 (35.7, 51.4) mL/m2 vs 37.9 (31.8, 47.5) mL/m2, p=0.551) or ejection fraction (50.0% (41.0%–55.0%) vs 50.0% (43.0%–56.0%), p=0.554) was demonstrated. Similar results were observed with 90-day cardiovascular MRI. At 1 year, the clinical composite of death, congestive heart failure, cardiogenic shock and recurrent myocardial infarction was similar in RIC and SOC (21.7% vs 13.3%, p=0.110).ConclusionsIn a contemporary registry-based randomised study of patients with STEMI undergoing PPCI, adjunctive therapy with RIC did not improve myocardial perfusion, reduce IS or alter LV performance. Consequently, there was no difference in clinical outcomes within 1 year.Trial registration numberNCT03930589.

Objectives To describe and evaluate outcomes in STEMI patients sustained on clopidogrel compared to those switched to ticagrelor following fibrinolysis. Background World‐wide, many STEMI patients cannot achieve timely PCI and therefore require fibrinolysis. Although comparable 30‐day and 1‐year safety was shown with clopidogrel or ticagrelor in the TREAT study, there is paucity of long‐term outcomes in pharmacoinvasive treated STEMI. Methods We conducted an observational cohort study evaluating consecutive pharmacoinvasive STEMI patients treated in a network, comparing those switched to ticagrelor to those sustained on clopidogrel. The primary efficacy composite was one‐year all‐cause death, recurrent myocardial infarction, and stroke with major bleeding and intracranial hemorrhage (ICH) as the safety outcomes. Multivariable Cox regression model was used to examine the association between P2Y12 inhibitor and outcomes with inverse probability weighting. Results Of 1426 pharmacoinvasive STEMI patients, 28% (n = 396) were converted to ticagrelor at a mean of 9.9 h after fibrinolysis with comparable GRACE Risk Scores (median; 158 vs 157, p0.352). The primary composite occurred in 3.5% of ticagrelor and 7.0% of clopidogrel treated patients (p0.014). Following adjustment, ticagrelor was associated with a 54% lower composite outcome (adjusted HR 0.46, 95% confidence interval 0.26–0.84). Major bleeding 6.3% vs 6.1% (NS) and ICH 0.0% vs 0.2% (NS) were similar. Conclusions In a prospective STEMI cohort, switching to ticagrelor compared with sustaining clopidogrel following fibrinolysis pharmacoinvasive reperfusion reduced recurrent ischemic events at 1‐year with no differences in major bleeding or ICH. Aligned with randomized data, these findings provide support to switch pharmaco‐invasively treated STEMI patients.

Aims Whether glycaemic control is associated with cardiovascular outcomes in patients with type 2 diabetes (T2D) is unclear. Consequently, we assessed the relationship between glycated haemoglobin (HbA1c ) and cardiovascular outcomes in a placebo-controlled randomized trial which demonstrated no cardiovascular effect of sitagliptin in patients with T2D and atherosclerotic vascular disease. Methods and results Secondary analysis of 14 656 TECOS participants with time to event analyses using multivariable Cox proportional hazard models. During a median 3.0 (interquartile range 2.3-3.8) year follow-up, 456 (3.1% of 14 656) patients had first hospitalization for heart failure (HF), 1084 (11.5%) died, 1406 (9.6%) died or were hospitalized for HF, and 1689 (11.5%) had a non-HF cardiovascular event (cardiovascular death, non-fatal stroke, non-fatal myocardial infarction, or hospitalization for unstable angina). Associations between baseline or time-varying HbA1c and cardiovascular outcomes were U-shaped, with the lowest risk when HbA1c was around 7%. Each one-unit increase in the time-varying HbA1c above 7% was associated with an adjusted hazard ratio (HR) of 1.21 [95% confidence interval (CI) 1.11-1.33] for first HF hospitalization, 1.11 (1.03-1.21) for all-cause death, 1.18 (1.09-1.26) for death or HF hospitalization, and 1.10 (1.02-1.17) for non-HF cardiovascular events. Each one-unit decrease in the time-varying HbA1c below 7% was associated with an adjusted HR of 1.35 (95% CI 1.12-1.64) for first HF hospitalization, 1.37 (1.16-1.61) for death, 1.42 (1.23-1.64) for death or HF hospitalization, and 1.22 (1.06-1.41) for non-HF cardiovascular events. Conclusion Glycated haemogobin exhibits a U-shaped association with cardiovascular outcomes in patients with T2D and atherosclerotic vascular disease, with nadir around 7%. Clinical trial registration ClinicalTrials.gov Identifier: NCT00790205.

Background Obesity is a risk factor for type 2 diabetes (T2D) and cardiovascular disease (CVD). Whether obesity affects outcomes among those with T2D and atherosclerotic CVD (ASCVD) remains uncertain. Our objective was to investigate the relationship between body mass index (BMI) and ASCVD outcomes among TECOS participants with T2D and ASCVD. Methods BMI categories were defined as underweight/normal weight (BMI 2 ), overweight (25-29.9 kg/m 2 ), obese class I (30-34.9 kg/m 2 ), obese class II (35-39.9 kg/m 2 ), and obese class III (≥ 40 kg/m 2 ). Asian-specific BMI categories were applied to Asian participants. Kaplan-Meier survival analysis and Cox proportional hazards models were used to examine associations between baseline BMI and a composite CV outcome (CV death, nonfatal myocardial infarction, nonfatal stroke, or hospitalization for unstable angina). Results For 14,534 TECOS patients with available BMI, mean age was 65.5 years; 29.3% were female, 32.0% non-White, and 23.1% insulin-treated, with median 3 years' follow-up. At baseline, 11.6% (n = 1686) were underweight/normal weight, 38.1% (n = 5532) overweight, 32.2% (n = 4683) obese class I, 12.4% (n = 1806) obese class II, and 5.7% (n = 827) obese class III. The composite CV outcome occurred in 11.4% (n = 1663) of participants; the outcome risk was lower, compared with under/normal weight, in overweight (HR 0.83, 95% CI 0.71-0.98) and obese class I (HR 0.79, 95% CI 0.67-0.93) individuals. Obesity was not associated with worse glycemic control. Conclusions The majority of TECOS participants with ASCVD and T2D were overweight or obese, yet overweight or obese class I individuals had lower CV risk than those who were under/normal weight. These results suggest the presence of an obesity paradox, but this paradox may reflect an epidemiological artifact rather than a true negative association between normal weight and clinical outcomes.

The effect of vericiguat on sequential N-terminal pro-B-type natriuretic peptide (NT-proBNP) levels and influence of this relationship on clinical outcomes is unknown.This study assessed the relationship between changes in NT-proBNP and the primary outcome (cardiovascular death or heart failure hospitalization); evaluated the effect of vericiguat on changes in NT-proBNP; and explored the association between the efficacy of vericiguat and changes in NT-proBNP.NT-proBNP was measured at randomization and at 16, 32, 48, and 96 weeks in 4,805 of 5,050 patients. The association between NT-proBNP change at week 16 and the primary outcome was assessed. The relationship between changes in NT-proBNP and the primary outcome according to treatment group was assessed by using joint modeling and mediation analysis.A significant and sustained decline in NT-proBNP levels was seen in both treatment groups. After week 16, NT-proBNP levels decreased more with vericiguat vs placebo (any reduction: odds ratio [OR]: 1.45 [95% CI: 1.28-1.65]; P 0.001; ≥50% reduction: OR: 1.27 [95% CI: 1.10-1.47]; P = 0.001) and were less likely to increase (≥20% increase: OR: 0.68 [95% CI: 0.59-0.78]; P 0.001; ≥50% increase: OR: 0.70 [95% CI: 0.59-0.82]; P 0.001). The treatment effect related to serial NT-proBNP on the primary composite outcome was HR: 0.96 (95% CI: 0.95-0.99) at week 16, which increased to HR: 0.90 (95% CI: 0.85-0.96) at week 48; the average extent of mediation of the composite outcome related to NT-proBNP was 45%.In patients with worsening HFrEF, vericiguat significantly decreased NT-proBNP levels compared with placebo. This change appeared associated with a modest relative improvement in the primary outcome of cardiovascular death or heart failure hospitalization. (Vericiguat Global Study in Subjects With Heart Failure With Reduced Ejection Fraction [VICTORIA]; NCT02861534).

OBJECTIVE Phenotypic heterogeneity among patients with type 2 diabetes mellitus (T2DM) and atherosclerotic cardiovascular disease (ASCVD) is ill defined. We used cluster analysis machine-learning algorithms to identify phenotypes among trial participants with T2DM and ASCVD. RESEARCH DESIGN AND METHODS We used data from the Trial Evaluating Cardiovascular Outcomes with Sitagliptin (TECOS) study (n = 14,671), a cardiovascular outcome safety trial comparing sitagliptin with placebo in patients with T2DM and ASCVD (median follow-up 3.0 years). Cluster analysis using 40 baseline variables was conducted, with associations between clusters and the primary composite outcome (cardiovascular death, nonfatal myocardial infarction, nonfatal stroke, or hospitalization for unstable angina) assessed by Cox proportional hazards models. We replicated the results using the Exenatide Study of Cardiovascular Event Lowering (EXSCEL) trial. RESULTS Four distinct phenotypes were identified: cluster I included Caucasian men with a high prevalence of coronary artery disease; cluster II included Asian patients with a low BMI; cluster III included women with noncoronary ASCVD disease; and cluster IV included patients with heart failure and kidney dysfunction. The primary outcome occurred, respectively, in 11.6%, 8.6%, 10.3%, and 16.8% of patients in clusters I to IV. The crude difference in cardiovascular risk for the highest versus lowest risk cluster (cluster IV vs. II) was statistically significant (hazard ratio 2.74 [95% CI 2.29–3.29]). Similar phenotypes and outcomes were identified in EXSCEL. CONCLUSIONS In patients with T2DM and ASCVD, cluster analysis identified four clinically distinct groups. Further cardiovascular phenotyping is warranted to inform patient care and optimize clinical trial designs.

Background There are limited data to inform policy mandating primary percutaneous coronary intervention ( PPCI ) volume benchmarks for catheterization laboratories in low‐ and middle‐income countries. Methods and Results This prospective state‐wide registry included ST‐segment–elevation myocardial infarction patients with symptoms of PPCI . From June 2013 to March 2016, we recruited 5560 consecutive patients. We categorized hospitals on the basis of annual PPCI volumes into low, medium, and high volume (PPCI volume and 1‐year mortality. Among 42 recruiting hospitals, there were 24 (57.2%) low‐volume, 8 (19%) medium‐volume, and 10 (23.8%) high‐volume hospitals. The median (25th–75th percentile) TIMI (Thrombolysis in Myocardial Infarction) ST‐segment–elevation myocardial infarction risk score was 3 (2–5). Cardiac arrest before admission occurred in 4.2%, 2.1%, and 2.9% of cases at low‐, medium‐, and high‐volume hospitals, respectively ( P =0.02). Total ischemic time differed significantly among low‐volume (median [25th–75th percentile], 3.5 [2.4–5.5] hours), medium‐volume (median, 3.8 [25th–75th percentile, 2.58–6.05] hours), and high‐volume hospitals (median, 4.16 [25th–75th percentile 2.8–6.3] hours) ( P =0.01). Vascular access was radial in 61.5%, 71.3%, and 63.2% of cases at low‐, medium‐, and high‐volume hospitals, respectively ( P =0.01). The observed 1‐year mortality rate was 6.5%, 3.4%, and 8.6% at low‐, medium‐ and high‐volume hospitals, respectively ( P CI ], 1.80 [1.12–2.90]; high versus medium: hazard ratio [95% CI ], 2.53 [1.78–3.58]) ( P Conclusions Low‐ and middle‐income countries, like India, may have a nonlinear relationship between institutional PPCI volume and outcomes, partly driven by procedural variations and inequalities in access to care.

Aims:The STREAM study randomly assigned ST-elevation myocardial infarction (STEMI) patients to receive a pharmacoinvasive versus primary percutaneous coronary intervention reperfusion strategy. We assessed whether there was an association between outcomes based on randomisation at a community hospital versus a prehospital location.Methods/results:Community hospital patients (358/1866 (19.2%)) were compared to prehospital patients and their outcomes categorised into pharmacoinvasive according to their treatment assignment. Compared to prehospital patients, community hospital patients had more diabetes (17.8% vs. 11.5%, P=0.001), higher Killip Class >1 (9.4% vs. 5.0%, P=0.002) and thrombolysis in myocardial infarction risk scores ⩾5 (18.2% vs. 12.4%, P=0.005). The 30-day primary endpoint (death, shock, congestive heart failure and re-infarction) for community hospital patients was 14.9% versus 13.2% for prehospital patients ( P=0.403). Community hospital pharmacoinvasive patients tended to receive less rescue (35.1% vs. 42.8%, P=0.062); when deployed their rescue was delayed 43 minutes. Community hospital patients undergoing primary percutaneous coronary intervention experienced a delay of 31 minutes versus prehospital patients. Pharmacoinvasive patients receiving scheduled angiography from a community hospital and prehospital patients had comparable times to angiography (17.7 vs. 18.7 hours) and low event rates (6.2% vs. 8.0%). Although the interaction between randomisation location and treatment received on the primary endpoint was not significant ( Pinteraction=0.065) those pharmacoinvasive patients requiring rescue from community hospitals had worse outcomes than prehospital rescue patients (odds ratio 2.28, 95% confidence interval 1.16–4.49).Conclusion:Within STREAM, STEMI patients randomly assigned at community hospitals had a higher baseline risk but similar outcomes compared to those studied prehospital patients irrespective of successful pharmacoinvasive therapy or primary percutaneous coronary intervention. However, worse outcomes in the pharmacoinvasive patients requiring rescue in community hospitals emphasises their need for immediate transfer to a percutaneous coronary intervention-capable hospital.

Background: Recent clinical trial data support a pharmacoinvasive strategy as an alternative to primary percutaneous coronary intervention (pPCI) in ST-segment elevation myocardial infarction. We evaluated whether this is true in a real-world prehospital ST-segment elevation myocardial infarction network using ECG assessment of reperfusion coupled with clinical outcomes within 1 year. Methods: Of the 5583 ST-segment elevation myocardial infarction patients in the Alberta Vital Heart Response Program (Cohort 1 [2006–2011]: n=3593; Cohort 2 [2013–2016]: n=1990), we studied 3287 patients who received a pharmacoinvasive strategy with tenecteplase (April 2013: half-dose tenecteplase was employed in prehospital patients ≥75 years) or pPCI. ECGs were analyzed within a core laboratory; sum ST-segment deviation resolution ≥50% was defined as successful reperfusion. The primary composite was all-cause death, congestive heart failure, cardiogenic shock, and recurrent myocardial infarction within 1 year. Results: The pharmacoinvasive approach was administered in 1805 patients (54.9%), (493 [27.3%] underwent rescue/urgent percutaneous coronary intervention and 1312 [72.7%] had scheduled angiography); pPCI was performed in 1482 patients (45.1%). There was greater ST-segment resolution post-catheterization/percutaneous coronary intervention with a pharmacoinvasive strategy versus pPCI (75.8% versus 64.3%, IP-weighted odds ratio, 1.59; 95% CI, 1.33–1.90; P P =0.033). Major bleeding and intracranial hemorrhage were similar between a pharmacoinvasive strategy and pPCI (7.6% versus 7.5%, P =0.867; 0.6% versus 0.6%; P =0.841, respectively). In the 82 patients ≥75 years with a prehospital pharmacoinvasive strategy, similar ST-segment resolution and rescue rates were observed with full-dose versus half-dose tenecteplase (75.8% versus 88.9%, P =0.259; 31.0% versus 29.2%, P =0.867) with no difference in the primary composite (31.0% versus 25.0%, P =0.585). Conclusions: In this large Canadian ST-segment elevation myocardial infarction registry, a pharmacoinvasive strategy was associated with improved ST-segment resolution and enhanced outcomes within 1 year compared with pPCI. Our findings support the application of a selective pharmacoinvasive reperfusion strategy when delay to pPCI exists.

Contains fulltext : 215191.pdf (Publisher’s version ) (Closed access) BACKGROUND: The effects of beta-blocker therapy in patients with type 2 diabetes (T2D) and established atherosclerotic cardiovascular disease (ASCVD) are unclear. We sought to evaluate associations between beta-blocker use in T2D with ASCVD and cardiovascular (CV) outcomes. METHODS: In patients with T2D and ASCVD enrolled in the Trial Evaluating Cardiovascular Outcomes with Sitagliptin (TECOS), an inverse probability of treatment-weighted Cox proportional hazards model was used to examine the association between baseline beta-blocker therapy (at randomization) and the primary CV composite (defined as CV death, non-fatal myocardial infarction [MI], non-fatal stroke, or hospitalization for unstable angina), including in subgroups with prior MI and heart failure (HF); other outcomes evaluated included individual components of the primary composite, hospitalization for HF, and severe hypoglycemic events. RESULTS: Of the 14,671 patients randomized, 9322 (64%) were on a beta-blocker at baseline; these patients were more likely to have prior MI or HF. Over a median 3.0 (25th, 75th percentile: 2.2, 3.6) years, the risk of the primary CV composite was significantly higher with baseline beta-blocker use versus no beta-blocker use (4.5 vs. 3.4 events/100-patient years, adjusted hazard ratio [HR] 1.17, 95% confidence interval [CI] 1.05-1.29); no significant interaction was noted for patients with versus without prior MI or HF. Baseline beta-blocker use was not associated with risks for severe hypoglycemic events (HR 1.14, 95% CI 0.88-1.48). CONCLUSIONS: In this observational analysis of T2D and ASCVD, baseline beta-blocker use was not associated with risks for severe hypoglycemia yet also was not associated with CV risk reduction over 3 years of follow-up, supporting a randomized examination of chronic beta-blocker therapy in this patient population. (TECOS ClinicalTrials.gov number, NCT00790205).

Objective Uncertainty exists concerning the relative merits of pharmacological versus mechanical coronary reperfusion in patients presenting early with ST-elevation myocardial infarction (STEMI) with extensive myocardium at risk. Accordingly, we investigated whether the extent of baseline ST-segment shift was related to the response of either reperfusion modality in patients with STEMI presenting within 3 h of symptoms. Methods We analysed baseline ECGs from 1859 patients enrolled in the STrategic Reperfusion Early After Myocardial Infarction (STREAM) trial. The sum of ST-segment elevation (∑STE) and ST-segment deviation (∑STD) was categorised into quartiles and associations with the primary endpoint (30-day death/shock/congestive heart failure/re-myocardial infarction) for each reperfusion strategy (early fibrinolysis vs primary percutaneous coronary intervention) were explored. Results Overall, there was a progressive rise in the 30-day primary endpoint according to quartiles of baseline ∑STE (10.3% (0–5 mm), 12.4% (5.5–8.5 mm), 12.1% (9–13.5 mm), 17.6% (>14.0 mm), p=0.008) and ∑STD (9.0% (0–9 mm), 13.5% (9.5–14 mm), 14.7% (14.5–20 mm), 15.3% (>20 mm), p=0.019). Both ∑STE and ∑STD were associated with the primary endpoint (∑STE: p=0.071; ∑STD: p=0.024). However, there was no interaction between quartiles of baseline ∑STE or ∑STD and efficacy of either reperfusion strategy on the 30-day clinical outcomes (∑STE: p (interaction)=0.696; ∑STD: p (interaction)=0.542). Conclusions These data demonstrate an association between ∑STE or ∑STD on the baseline ECG and clinical events at 30 days following reperfusion therapy in STEMI. More importantly, the response to different reperfusion strategies was not influenced by the extent of jeopardised myocardium. Trial registration number NCT00623623; Post-results.

Background Postoperative clinical outcomes associated with the preoperative continuation or discontinuation of angiotensin‐converting enzyme inhibitors ( ACEIs ) or angiotensin receptor blockers ( ARBs ) before cardiac surgery remain unclear. Methods and Results In a single‐center, open‐label, randomized, registry‐based clinical trial, patients undergoing nonemergent cardiac surgery were assigned to ACEI / ARB continuation or discontinuation 2 days before surgery. Among the 584 patients screened, 261 met study criteria and 126 (48.3%) patients were enrolled. In total,121 patients (96% adherence; 60 to continuation and 61 to ACEI / ARB discontinuation) underwent surgery and completed the study protocol, and follow‐up was 100% complete. Postoperative intravenous vasopressor use (78.3% versus 75.4%, P =0.703), vasodilator use (71.7% versus 80.3%, P =0.265), vasoplegic shock (31.7% versus 27.9%, P =0.648), median duration of vasopressor (10 versus 5 hours, P =0.494), and vasodilator requirements (10 versus 9 hours, P =0.469) were not significantly different between the continuation and discontinuation arms. No differences were observed in the incidence of acute kidney injury (1.7% versus 1.6%, P =0.991), stroke (no events, mortality (1.7% versus 1.6%, P =0.991), median duration of mechanical ventilation (6 versus 6 hours, P =0.680), and median intensive care unit length of stay (43 versus 27 hours, P =0.420) between the treatment arms. Conclusions A randomized study evaluating the routine continuation or discontinuation of ACEIs or ARB s before cardiac surgery was feasible, and treatment assignment was not associated with differences in postoperative physiological or clinical outcomes. These preliminary findings suggest that preoperative ACEI / ARB management strategies did not affect the postoperative course of patients undergoing cardiac surgery. Clinical Trial Registration URL : https://www.clinicaltrials.gov . Unique identifier: NCT 02096406.

Background: Adjudication by an adjudication committee in clinical trials plays an important role in the assessment of outcomes. Controversy exists regarding the utility of adjudication committee versus site-based assessments and their relationship to subsequent clinical events. Methods: This study is a secondary analysis of the Providing Rapid Out of Hospital Acute Cardiovascular Treatment-3 trial, which randomized patients with chest pain or shortness of breath for biomarker testing in the ambulance. The emergency department physician diagnosis at the time of emergency department disposition was compared with an adjudicated diagnosis assigned by an adjudication committee. The level of agreement between emergency department and adjudication committee diagnosis was evaluated using kappa coefficient and compared to clinical outcomes (30-day re-hospitalization, 30-day and 1-year mortality). Results: Of the 477 patients, 49.3% were male with a median age of 70 years; hospital admission rate was 31.2%. The emergency department physicians and the adjudication committee disagreed in 55 cases (11.5%) with a kappa of 0.71 (95% confidence interval: 0.64, 0.78). The 30-day re-hospitalization, 30-day mortality, and 1-year mortality were 22%, 1.9%, and 9.4%, respectively. Although there were similar rates of re-hospitalization irrespective of adjudication, in cases of disagreement compared to agreement between adjudication committee and emergency department diagnosis, there was a higher 30-day (7.3% vs 1.2%, p = 0.002) and 1-year mortality (27.3% vs 7.1%, p Conclusion: Despite substantial agreement between the diagnosis of emergency department physicians and adjudication committee, in the subgroup of patients where there was disagreement, there was significantly worse short-term and long-term mortality.

Background— Using a comprehensive ST-segment–elevation myocardial infarction registry, we evaluated the relationships of baseline Q waves, time from symptom onset, and reperfusion strategy with in-hospital clinical outcomes. Methods and Results— Consecutive ST-segment–elevation myocardial infarction patients from a defined health region were classified by the presence of baseline Q waves and additionally into primary percutaneous coronary intervention, fibrinolysis, or no reperfusion. ECGs were collected at baseline, after reperfusion, and analyzed for the presence of Q waves using Selvester criteria. Among 2290 ST-segment–elevation myocardial infarction patients, 36.9% had Q waves on their baseline ECG. Patients with Q waves were older (median age, 59 versus 57), were more often male (82.0% versus 75.4%), had higher heart rate (80 versus 72), had higher Global Registry of Acute Coronary Events risk score (129 versus 127), and were with longer time to reperfusion (42 minutes longer). They had higher composite end points (16.3% versus 10.0%), consistent across times from symptom onset to presentation (15.4% versus 9.9% ≤3 hours; 18.5% versus 8.9% >3 to ≤6 hours; 15.9% versus 11.3% >6 hours; Q and no Q, respectively). Baseline Q waves, but not time to reperfusion, were associated with an increased odds of the in-hospital composite end point of death, congestive heart failure, cardiogenic shock, and reinfarction (adjusted odds ratio, 1.65; 95% confidence interval, 1.18–2.30; P =0.003). Type of reperfusion did not modify the association of baseline Q waves and in-hospital outcomes ( P interaction=0.918). Conclusions— The presence of baseline Q waves, rather than time to treatment, was significantly associated with adverse in-hospital events in real-world patients, regardless of reperfusion strategy used.

Objectives We evaluated inter-reader agreement of the ST-segment between two electrocardiogram (ECG) core laboratories. Background Accurate measurement of the ST-segment is key to diagnosis and management of acute coronary syndromes (ACS). Clinical trials also rely on adherence to the pre-specified ECG eligibility criteria. Methods 150 patients (100 ST-segment elevation (STE)-ACS, 50 non-STE-ACS) were selected. An experienced ECG reader from each laboratory measured ST-segment deviation on the baseline ECGs (nearest 0.1 mm). Results ∑ ST-segment deviation showed excellent inter-reader agreement (R = 0.965, intraclass correlation coefficient (ICC) 0.949, 95% CI (0.930–0.963)). Similar agreement was observed when ∑ ST-segment elevation (∑ STE) and ∑ ST-segment depression (∑ STD) were assessed separately. Better agreement was evident in STE-ACS cohort (ICC (95% CI): 0.968 (0.953–0.978, 0.969 (0.954–0.979), 0.931 (0.899–0.953)) compared to NSTE-ACS patients (ICC (95% CI): 0.860 (0.768–0.917), 0.816 (0.699–0.890), 0.753 (0.605–0.851) across measurement of ∑ ST-segment deviation, ∑ STE, and ∑ STD. Conclusions We demonstrated excellent agreement on ST-segment measurements between two experienced readers from two ECG core laboratories.

Objective Type 2 diabetes is associated with increased fracture risk, further elevated by treatments such as thiazolidinediones and sodium-glucose co-transporter-2 inhibitors. As data regarding dipeptidyl peptidase-4 inhibitors are mixed, we examined fracture incidence in the Trial Evaluating Cardiovascular Outcomes with Sitagliptin (TECOS). Research Design and Methods We used data from 14,671 TECOS patients randomized double-blind to sitagliptin (n=7332) or placebo (n=7339). Cumulative fracture incidence rates were calculated and their association with study treatment assignment examined using multivariable Cox proportional hazards regression. Results Baseline mean (SD) age was 65.5 (8.0) years, diabetes duration 11.6 (8.1) years, HbA1c 7.2% (0.5%) (55.2 mmol/mol [5.5]), with 29.3% of participants women and 32.1% non-White. During 43,222 person-years’ follow-up, 375 (2.6%; 8.7 per 1000 person-years) had a fracture; 146 were major osteoporotic fractures (hip [n=34], upper extremity [n=81], and clinical spine [n=31]). Adjusted analyses showed fracture risk increased independently with older age (p Conclusion Fractures were common among TECOS patients with diabetes, but not related to sitagliptin therapy. Insulin and metformin treatment were associated with increased and decreased fracture risks, respectively.

Coronary plaque rupture mediating acute ST segment elevation myocardial infarction (STEMI) is associated with a systemic inflammatory response. Whether early temporal changes in inflammatory biomarkers are associated with angiographic and electrocardiographic markers of reperfusion and subsequent clinical outcomes is unclear. In the APEX-AMI biomarker substudy, 376 patients with STEMI had inflammatory biomarkers measured at the time of hospital presentation and 24 h later. The primary outcome was the 90-day composite of death, shock, or heart failure. Secondary reperfusion outcomes were (1) worst least residual ST segment elevation (ST-E

Background Whether prehospital point‐of‐care ( POC ) troponin further accelerates the time to diagnosis in patients with chest pain ( CP ) is unknown. We conducted a randomized trial of POC ‐Troponin testing in the ambulance. Methods and Results Patients with chest pain presenting by ambulance were randomized to usual care ( UC ) or POC ‐Troponin; ST ‐elevation myocardial infarction patients or those with noncardiovascular symptoms were excluded. Pre‐hospital high‐sensitivity troponin was analyzed on a POC device and available to the paramedic and emergency department ( ED ) staff. The final diagnosis was centrally adjudicated. The primary endpoint was time from first medical contact to discharge from ED or admission to hospital. We randomized 601 patients in 19 months; 296 to UC and 305 to POC ‐Troponin. After ambulance arrival, the first troponin was available in 38 minutes in POC ‐Troponin and 139 minutes in UC . In POC ‐Troponin, the troponin was >0.01 ng/mL in 17.4% and >0.03 ng/mL in 9.8%. Patients spent a median of 9.0 hours from first medical contact to final disposition, and 165 (27.4%) were admitted to the hospital. The primary endpoint was shorter in patients randomized to POC ‐Troponin (median 8.8 hours [6.2–10.8] compared to UC (median 9.1 hours [6.7–11.2]; P =0.05). There was no difference in the secondary endpoint of repeat ED visits, hospitalizations, or death in the next 30 days. Conclusions In this broad population of patients with CP , ambulance POC ‐Troponin accelerated the time to final disposition. Enhanced and more cost‐effective early ED discharge of the majority of patients with CP calling 911 is an unrealized opportunity. Clinical Trial Registration URL : https://www.ClinicalTrials.gov/ . Unique identifier: NCT 01634425.

Background A pharmacoinvasive ( PI ) strategy for early presenting ST ‐segment elevation myocardial infarction nominally reduced 30‐day cardiogenic shock and congestive heart failure compared with primary percutaneous coronary intervention ( PPCI ). We evaluated whether infarct size ( IS ) was related to this finding. Methods and Results Using the peak cardiac biomarker in patients randomized to PI versus PPCI within the Strategic Reperfusion Early After Myocardial Infarction ( STREAM ) trial, IS was divided into 3 groups: small (≤2 times the upper limit normal [ ULN ]), medium (>2 to ≤5 times the upper limit normal) and large (>5 times the upper limit normal). The association between IS and 30‐day shock and congestive heart failure was subsequently examined. Data on 1701 of 1892 (89.9%) patients randomized to PI (n=853, 50.1%) versus PPCI (n=848, 49.9%) within STREAM were evaluated. A higher proportion of PPCI patients had a large IS ( PI versus PPCI : small, 49.8% versus 50.2%; medium, 56.9% versus 43.1%; large, 48.4% versus 51.6%; P =0.035), despite comparable intergroup ischemic times for each reperfusion strategy. As IS increased, a parallel increment in shock and congestive heart failure occurred in both treatment arms, except for the small IS group. The difference in shock and congestive heart failure in the small IS group (4.4% versus 11.6%, P =0.026) in favor of PI likely relates to higher rates of aborted myocardial infarction with the PI strategy (72.7% versus 54.3%, P =0.005). After adjustment, a trend favoring PI persisted in this subgroup (relative risk 0.40, 95% CI 0.15 to 1.06, P =0.064); no difference in treatment‐related outcomes was evident in the other 2 groups. Conclusion A PI strategy appears to alter the pattern of IS after ST ‐segment elevation myocardial infarction, resulting in more medium and fewer large infarcts compared with PPCI . Despite a comparable number of small infarcts, PI patients in this group had more aborted myocardial infarctions and less 30‐day shock and congestive heart failure. Clinical Trial Registration URL : http://ClinicalTrials.gov . Unique identifier: NCT 00623623.

Summary Background & aims Concerns have been raised about the impact of dietary sodium restriction on the overall dietary intake and nutritional status in patients with heart failure (HF). The objective of this study was to evaluate the association between a significant reduction in sodium intake and dietary changes and nutritional status in patients with chronic HF. Methods This is a secondary analysis of 38 patients enrolled in a pilot study of dietary sodium reduction. Patients were classified into two groups according to a level of sodium reduction achieved (≥25% [n = 21 patients] and Results Patients had a median age of 65 years, 51% were male, median body mass index was 30.7 kg/m2 and median ejection fraction was 39%. Over 6 months, the group with ≥25% sodium reduction exhibited a greater increase in folate intake [median change 50 mcg/day (25th–75th percentiles: −101, 167) vs. −31 mcg/day (25th–75th percentiles: −221, 51), p = 0.04 between groups] and a larger reduction in calcium intake [median change −262 (25th–75th percentiles: −585, −9) vs. 91 (25th–75th percentiles: −114, 210), p = 0.01 between groups], and were more likely to meet the parameters of the DASH diet compared to the Conclusions Dietary sodium reduction may be achieved without compromising overall dietary intake and nutritional status in patients with HF when an individualized and comprehensive dietary approached is used. Clinical Trial Identifier : Clinicaltrials.gov identifier: NCT01480401 .

Background The prognostic value of time from symptom onset to reperfusion may be enhanced by the identification of Q waves on the presenting electrocardiogram (ECG) in patients with ST-segment elevation myocardial infarction (STEMI). We evaluated whether the relative prognostic utility of these 2 metrics was altered by sex. Methods Q waves in the distribution of the ST-segment elevation on the baseline ECG were evaluated by a blinded core laboratory in 2838 STEMI patients (2163 men and 675 women) from the PLATelet inhibition and patient Outcomes (PLATO) trial who underwent percutaneous coronary intervention (PCI) within 12 hours of symptom onset. Results Women were older (median 63 vs 57 years), more likely to be diabetic (24.1% vs 15.5%), hypertensive (69.2% vs 50.9%), and a higher Killip class > I (8.6% vs 5.9%), as compared with men. Whereas the Q waves frequency rose progressively over time to ECG in men, this relationship was attenuated in women ( P = .057). Q waves on the baseline ECG were associated with a higher excess hazard of 1-year vascular death in men (hazard ratio [HR] 2.03; 95% confidence interval [CI], 1.13-3.72), and a similar trend existed in women (HR 1.97; 95% CI, 0.86-4.51). Women with baseline Q waves tended to have higher risk of 1-year vascular death than men as continuous time from symptom onset to PCI increased ( P [interaction] = .182). Conclusions These differences in the evolution of baseline Q waves and relationship between time from symptom onset and vascular death in women and men deserve recognition in future studies of STEMI.

Aims Several methods provide new insights into understanding clinical trial composite endpoints, using both conventional and novel methods. The TRILOGY ACS trial is used as a contemporary example to prospectively compare these methods side by side. Methods and results The traditional time-to-first-event, Andersen–Gill recurrent events method, win ratio, and a weighted composite endpoint (WCE) are compared using the randomized, active-control TRILOGY ACS trial. This trial had a neutral result and randomized 9326 patients managed without coronary revascularization within 10 days of their acute coronary syndrome to receive either prasugrel or clopidogrel and followed them for up to 30 months. The traditional composite, win ratio, and WCE demonstrated no significant survival advantage for prasugrel, whereas the Andersen–Gill method demonstrated a statistical advantage for prasugrel [hazard ratio (HR), 0.86 (95% CI, 0.72–0.97)]. The traditional composite used 73% of total patient events; 40% of these were derived from the death events. The win ratio used 66% of total events; deaths comprised 57% of these. Both Andersen–Gill and WCE methods used all events in all participants; however, with the Andersen–Gill method, death comprised 41% of the proportion of events, whereas with the WCE method, death comprised 64% of events. Conclusion This study addresses the relative efficiency of various methods for assessing clinical trial events comprising the composite endpoint. The methods accounting for all events, in particular those incorporating their clinical relevance, appear most advantageous, and may be useful in interpreting future trials. This clinical and statistical advantage is especially evident with long-term follow-up where multiple non-fatal events are more common. Clinical Trial Registration NCT00699998.

We evaluated the prespecified endpoint, aborted myocardial infarction (AbMI), according to the use of a pharmacoinvasive (PI) strategy versus primary percutaneous coronary intervention (PCI) in 1754 patients randomised within 3 h of symptom onset in the STrategic Reperfusion Early After Myocardial infarction (STREAM) trial.Based on sequential ECG's and biomarkers, AbMI was defined as ST-elevation resolution ≥50% (90 min posttenecteplase (TNK) in the PI arm or 30 min postprimary PCI) with minimal biomarker rise.In the PI arm 11.1% (n=99) had AbMI versus 6.9% (n=59) in primary PCI arm (p0.01). In a multivariable model, AbMI patients overall had less baseline ΣST-deviation, fewer baseline Q-waves and shorter total ischaemic times. PI AbMI patients had faster time to TNK (90 vs 100 min, p=0.015): total ischaemic time was 100 min longer in primary PCI AbMI patients and no difference in ischaemic time existed between AbMI and non-AbMI patients within this group. Although no significant interaction between treatment and AbMI on the composite endpoint of death/shock/congestive heart failure/recurrent MI occurred (p=0.292), PI AbMI patients had a lower incidence in this endpoint than non-AbMI patients (5.1 vs 12%, p=0.038); this was not evident in primary PCI patients. Forty-five patients (ie, 2.5%) had masquerading MI with minimal biomarker elevation and no evolution in baseline ST-elevation.A PI strategy of early fibrinolysis more frequently aborts MI than primary PCI. Such PI patients had more favourable outcomes as compared with non-AbMIs. Diligent review of ECG evolution in STEMI distinguishes AbMI from infarct masquerade. ClinicalTrials.gov ID: NCT00623623.

To evaluate quantitative relationships between baseline Q-wave width and 90-day outcomes in ST-segment elevation myocardial infarction (STEMI).Baseline Q-waves are useful in predicting clinical outcomes after MI.3589 STEMI patients were assessed from a multi-centre study.1156 patients of the overall cohort had pathologic Q-waves. The 90-day mortality and the composite of mortality, congestive heart failure (CHF), or cardiogenic shock (p0.001 for both outcomes) rose as Q-wave width increased. After adapting a threshold ≥40ms for inferior and ≥20ms for lateral/apical MI in all patients (n=3065) with any measureable Q-wave we found hazard ratios (HR) for mortality (HR: 2.44, 95% confidence interval (CI) (1.54-3.85), p0.001) and the composite (HR: 2.32, 95% CI (1.70-3.16), p0.001). This improved reclassification of patients experiencing the composite endpoint versus the conventional definition (net reclassification index (NRI): 0.23, 95% CI (0.09-0.36), p0.001) and universal MI definition (NRI: 0.15, 95% CI (0.02-0.29), p=0.027).The width of the baseline Q-wave in STEMI adds prognostic value in predicting 90-day clinical outcomes. A threshold of ≥40ms in inferior and ≥20ms for lateral/apical MI enhances prognostic insight beyond current criteria.

The relationship of metabolic syndrome and its individual components (obesity, hypertension, glucose intolerance, high triglycerides, and low high-density lipoprotein cholesterol) with 1-year mortality in non-ST-segment elevation acute coronary syndromes (NSTE ACS) patients is not known.The association of metabolic syndrome (and its individual components) with all-cause mortality within 1 year was assessed in NSTE ACS patients enrolled in the EARLY ACS trial. Adjusted hazard ratio (HR) and 95% CIs are reported.Of 9,406 patients, 2,596 (27.6%) had metabolic syndrome. Compared with those without metabolic syndrome, patients with this syndrome were younger, were more often female, and had a higher prevalence of comorbid conditions and higher-risk presenting features. Metabolic syndrome was not associated with increased 1-year mortality (HR 1.20, 95% CI 0.97-1.47; P = .09). The risk of 1-year mortality varied across the individual components: high-density lipoprotein40 mg/dL (men)/50 mg/dL (women; or dyslipidemia) was associated with higher risk (HR 1.52, 95% CI 1.15-2.02), and triglycerides150 mg/dL (or dyslipidemia) was associated with lower risk (HR 0.66, 95% CI 0.54-0.81), whereas the other components (ie, body mass index30 kg/m(2), fasting plasma glucose100 mg/dL or diabetes, systolic blood pressure130 mm Hg or diastolic85 mm Hg [or hypertension]) were associated with neutral risk of this event.The individual components of metabolic syndrome had varying associations with 1-year mortality, and as an integrated diagnosis, metabolic syndrome was not significantly associated with 1-year mortality. Thus, patient case-mix of the studied NSTE ACS population may influence the observed relationship of metabolic syndrome with subsequent cardiovascular events.

Objectives The aim of this study was to compare clinical outcomes, resource utilization, and health-related quality of life between Canadian and U.S. patients enrolled in ASCEND-HF (Acute Study of Clinical Effectiveness of Nesiritide in Decompensated Heart Failure). A further aim was to supplement the within-trial analysis with a contemporaneous population-based comparison of all patients hospitalized with primary diagnoses of heart failure (HF) in the 2 countries. Background Little is known about intercountry differences in outcomes of patients with HF in Canada and the United States. Methods Trial patients consisted of 465 Canadian and 2,684 U.S. patients enrolled in ASCEND-HF. Population-level cohorts consisted of 1.9 million U.S. and 81,016 Canadians hospitalized for HF in 2007 and 2008. Results Canadian patients in ASCEND-HF were older, were more likely to be white, and had lower body weights and blood pressures than U.S. patients. Canadians also had lower baseline-adjusted odds of 30-day mortality (odds ratio: 0.46; 95% confidence interval: 0.23 to 0.92) and better health-related quality of life than U.S. patients. In both countries, trial patients differed significantly from population-level cohorts. In contrast to ASCEND-HF, unadjusted in-hospital mortality at the population level was significantly lower in the United States (3.4%) compared with Canada (11.1%) (p Conclusions Intercountry differences in outcomes of patients hospitalized with HF differed significantly between trial and population cohorts. Further study on how cardiac care is delivered in the 2 countries and how it influences the results of clinical trials and population-level outcomes, especially in the long term, is warranted. (A Study Testing the Effectiveness of Nesiritide in Patients With Acute Decompensated Heart Failure; NCT00475852 )

Background Information on practice patterns and outcomes in patients with ST-elevation myocardial infarction undergoing primary percutaneous coronary interventions (PCIs) in Canada vs United States is limited. Methods We evaluated differences in clinical and angiographic features, practice patterns, and outcomes between Canada and United States in 2,086 patients with ST-elevation myocardial infarction undergoing primary PCI in the APEX AMI trial. Results Of 2,086 patients, 335 (19%) were enrolled in Canada. Compared with US patients, Canadians were older with lower body mass index and creatinine clearance and less likely to have history of hypertension, smoking, or prior revascularization. Baseline infarct artery patency was higher, and the use of intra-aortic balloon pump and drug-eluting stents was lower in Canadian patients. Median door-to-PCI time was significantly shorter among Canadian patients (0.9 hours [interquartile range 0.6-1.3] vs 1.2 hours [interquartile range 0.8-1.7]). Clinical outcomes at 90 days were lower among Canadian patients, including shock (2.7% vs 4.2%), heart failure (3.6% vs 5.6%), bleeding (3.6% vs 9.6%), and atrial (3.6% vs 7.4%) and ventricular (3.0% vs 6.4%) arrhythmias. However, 90-day mortality (2.7% vs 4.8%, adjusted hazard ratio 0.62, 95% CI 0.47-1.28) and composite of death, shock, or heart failure (6.8% vs 11.5%, adjusted hazard ratio 0.77, 95% CI 0.47-1.27) were similar in the 2 cohorts. Conclusions Compared with US patients, Canadian patients had shorter door-to-PCI time but similar 90-day outcomes. These data suggest an opportunity for US sites to examine and learn from the Canadian systems of processes of care and implement changes so as to improve the timeliness of primary PCI.

Background Elderly patients with ST-segment elevation myocardial infarction (STEMI) have worse outcomes and a greater risk of intracranial bleeding than nonelderly patients. Baseline characteristics, clinical outcomes, and the relationship of the tenecteplase (TNK) dose reduction to the efficacy, safety, and electrocardiographic indicators of reperfusion efficacy were evaluated in STEMI patients ≥75 years. Methods The STREAM trial evaluated early presenting STEMI patients who could not undergo primary percutaneous coronary intervention within 1 hour of first medical contact. Because of excess intracranial hemorrhage (ICH) in patients ≥75 years, the dose of TNK was reduced by 50%. Results Before dose amendment, there were 3 (7.1%) of 42 elderly patients with ICH; 2 of these were fatal, whereas no ICH occurred in the 93 elderly patients who received half-dose TNK postamendment. The median extent of ST-segment elevation resolution (≥50%) and proportion of patients with ≥2 mm in the electrocardiogram lead with greatest ST-segment elevation was comparable in elderly patients preamendment and postamendment (63.2% vs 56.0% and 43.6% vs 40.0%, respectively). Patients requiring rescue coronary intervention after TNK was also similar (42.9% vs 44.1%). The primary composite end point (30-day all-cause death, cardiogenic shock, congestive heart failure, and reinfarction) was 31.0% before versus 24.7% postamendment. Conclusions Our data, from a modest-sized population of elderly STEMI patients, indicate that half-dose TNK reduces the likelihood of ICH without compromising reperfusion efficacy. These observations are hypothesis generating and warrant further confirmation in randomized clinical trials in the elderly.