Joakim Alfredsson

Frailty Is Independently Associated With Short-Term Outcomes for Elderly Patients With Non–ST-Segment Elevation Myocardial Infarction

Background— For the large and growing population of elderly patients with cardiovascular disease, it is important to identify clinically relevant measures of biological age and their contribution to risk. Frailty is an emerging concept in medicine denoting increased vulnerability and decreased physiological reserves. We analyzed the manner in which the variable frailty predicts short-term outcomes for elderly non–ST-segment elevation myocardial infarction patients. Methods and Results— Patients aged ≥75 years, with diagnosed non–ST-segment elevation myocardial infarction were included at 3 centers, and clinical data including judgment of frailty were collected prospectively. Frailty was defined according to the Canadian Study of Health and Aging Clinical Frailty Scale. The impact of the comorbid conditions on risk was quantified by the coronary artery disease–specific index. Of 307 patients, 149 (48.5%) were considered frail. By multiple logistic regression, frailty was found to be strongly and independently associated with risk for the primary composite outcome (death from any cause, myocardial reinfarction, revascularization due to ischemia, hospitalization for any cause, major bleeding, stroke/transient ischemic attack, and need for dialysis up to 1 month after inclusion) (odds ratio, 2.2; 95% confidence interval, 1.3–3.7), in-hospital mortality (odds ratio, 4.6; 95% confidence interval, 1.3–16.8), and 1-month mortality (odds ratio, 4.7; 95% confidence interval, 1.7–13.0). Conclusions— Frailty is strongly and independently associated with in-hospital mortality, 1-month mortality, prolonged hospital care, and the primary composite outcome. The combined use of frailty and comorbidity may constitute an ultimate risk prediction concept in regard to cardiovascular patients with complex needs. Clinical Trial Registration— http://www.clinicaltrials.gov. Unique identifier: NCT01049997.

Gender differences in management and outcome in non-ST-elevation acute coronary syndrome

Objective: To study gender differences in management and outcome in patients with non-ST-elevation acute coronary syndrome. Design, setting and patients: Cohort study of 53 781 consecutive patients (37% women) from the Register of Information and Knowledge about Swedish Heart Intensive care Admissions (RIKS-HIA), with a diagnosis of either unstable angina pectoris or non-ST-elevation myocardial infarction. All patients were admitted to intensive coronary care units in Sweden, between 1998 and 2002, and followed for 1 year. Main outcome measures: Treatment intensity and in-hospital, 30-day and 1-year mortality. Results: Women were older (73 vs 69 years, p<0.001) and more likely to have a history of hypertension and diabetes, but less likely to have a history of myocardial infarction or revascularisation. After adjustment, there were no major differences in acute pharmacological treatment or prophylactic medication at discharge. Revascularisation was, however, even after adjustment, performed more often in men (OR 1.15; 95% CI, 1.09 to 1.21). After adjustment, there was no significant difference in in-hospital (OR 1.03; 95% CI, 0.94 to 1.13) or 30-days (OR 1.07; 95% CI, 0.99 to 1.15) mortality, but at 1 year being male was associated with higher mortality (OR 1.12; 95% CI, 1.06 to 1.19). Conclusion: Although women are somewhat less intensively treated, especially regarding invasive procedures, after adjustment for differences in background characteristics, they have better long-term outcomes than men.

Time trends in STEMI—improved treatment and outcome but still a gender gap: a prospective observational cohort study from the SWEDEHEART register

Objective In ST elevation myocardial infarction women received less evidence-based medicine and had worse outcome during the fibrinolytic era. With the shift to primary percutaneous coronary intervention (pPCI) as preferred reperfusion strategy, the authors aimed to investigate whether these gender differences has diminished. Design, setting and participants Cohort study including consecutive ST elevation myocardial infarction patients registered 1998–2000 (n=15 697) and 2004–2006 (n=14 380) in the Register of Information and Knowledge about Swedish Heart Intensive care Admissions. Outcome measures 1. Use of evidence-based medicine such as reperfusion therapy (pPCI or fibrinolysis) and evidence-based drugs at discharge. 2. Inhospital and 1-year mortality. Results Of those who got reperfusion therapy, pPCI was the choice in 9% in the early period compared with 68% in the late period. In the early period, reperfusion therapy was given to 63% of women versus 71% of men, p<0.001. Corresponding figures in the late period were 64% vs 75%, p<0.001. After multivariable adjustments, the ORs (women vs men) were 0.86 (95% CI 0.78 to 0.94) in the early and 0.80 (95% CI 0.73 to 0.89) in the late period. As regards evidence-based secondary preventive drugs at discharge in hospital survivors (platelet inhibitors, statins, ACE inhibitors/angiotensin receptor blockers and β-blockers), there were small gender differences in the early period. In the late period, women had 14%–25% less chance of receiving these drugs, OR 0.75 (95% CI 0.68 to 0.81) through 0.86 (95% CI 0.73 to 1.00). In both periods, multivariable-adjusted inhospital mortality was higher in women, OR 1.18 (95% CI 1.02 to 1.36) and 1.21 (1.00 to 1.46). One-year mortality was gender equal, HR 0.95 (95% CI 0.87 to 1.05) and 0.96 (0.86 to 1.08), after adding evidence-based medicine to the multivariable adjustments. Conclusion In spite of an intense gender debate, focus on guideline adherence and the change in reperfusion strategy, the last decade gender differences in use of reperfusion therapy and evidence-based therapy at discharge did not decline during the study period, rather the opposite. Moreover, higher mortality in women persisted.

Early invasive compared with a selective invasive strategy in women with non-ST-elevation acute coronary syndromes: a substudy of the OASIS 5 trial and a meta-analysis of previous randomized trials

AIMS The aim of this study was to compare benefits and risks of a routine invasive compared with a selective invasive strategy in women with non-ST-elevation acute coronary syndromes. METHODS AND RESULTS We randomly assigned 184 women, either to a routine or to a selective invasive strategy as a substudy to the OASIS 5 trial, who were followed for 2 years. Meta-analysis of data from previous randomized trials was also done. There were no significant differences between the two treatment strategies in the primary outcome death/myocardial infarction (MI)/stroke [21.0 vs. 15.4%, HR = 1.46, 95% CI (0.73-2.94)], in the secondary outcome death/MI [18.8 vs. 14.3%, HR = 1.39, 95% CI (0.67-2.88)], or separately analysed outcomes MI [12.9 vs. 13.3%, HR = 0.95, 95% CI (0.42-2.19)] or stroke [2.3 vs. 4.4%, HR = 0.67, 95% CI (0.12-3.70)]. However, there were significantly more deaths after 1 year (8.8 vs. 1.1%, HR = 9.01, 95% CI (1.11-72.90) and a higher rate of major bleeding at 30 days [8.8 vs. 1.1%, HR = 11.45, 95% CI (1.43-91.96)] in the routine invasive strategy group. A meta-analysis including 2692 women in previous randomized trials, with a gender perspective, showed no significant difference in the composite outcome death/MI, OR = 1.18, 95% CI (0.92-1.53) but a higher mortality with a routine invasive strategy for women, OR = 1.51, 95% CI (1.00-2.29). CONCLUSION The rate of death, MI, or stroke in women was not different in patients treated with a routine invasive strategy compared with a selective invasive strategy, but there was a concerning trend towards higher mortality. When combined with data from previous trials, there does not appear to be a benefit of an early invasive strategy in women with ACS, which differs from the results in men. These data emphasize the lack of clear evidence in favour of an invasive strategy in women and suggest caution in extrapolating the results from men to women.

An Invasive or Conservative Strategy in Patients With Diabetes Mellitus and Non-ST-Segment Elevation Acute Coronary Syndromes A Collaborative Meta-Analysis of Randomized Trials

OBJECTIVES The purpose of this study was to conduct a meta-analysis to examine an invasive or conservative strategy in diabetic versus nondiabetic patients. BACKGROUND Diabetic patients are at increased risk of cardiovascular events after an acute coronary syndrome, yet it remains unknown whether they derive enhanced benefit from an invasive strategy. METHODS Randomized trials comparing an invasive versus conservative treatment strategy were identified. The prevalence of cardiovascular events through 12 months was reported for each trial, stratified by diabetes mellitus status and randomized treatment strategy. Relative risk (RR) ratios and absolute risk reductions were combined using random-effects models. RESULTS Data were combined across 9 trials comprising 9,904 subjects of whom 1,789 (18.1%) had diabetes mellitus. The RRs for death, nonfatal myocardial infarction (MI), or rehospitalization with an acute coronary syndrome for an invasive versus conservative strategy were similar between diabetic patients (RR: 0.87; 95% confidence interval [CI]: 0.73 to 1.03) and nondiabetic patients (RR: 0.86; 95% CI: 0.70 to 1.06; p interaction = 0.83). An invasive strategy reduced nonfatal MI in diabetic patients (RR: 0.71; 95% CI: 0.55 to 0.92), but not in nondiabetic patients (RR: 0.98; 95% CI: 0.74 to 1.29; p interaction = 0.09). The absolute risk reduction in MI with an invasive strategy was greater in diabetic than nondiabetic patients (absolute risk reduction: 3.7% vs. 0.1%; p interaction = 0.02). There were no differences in death or stroke between groups (p interactions 0.68 and 0.20, respectively). CONCLUSIONS An early invasive strategy yielded similar RR reductions in overall cardiovascular events in diabetic and nondiabetic patients. However, an invasive strategy appeared to reduce recurrent nonfatal MI to a greater extent in diabetic patients. These data support the updated guidelines that recommend an invasive strategy for patients with diabetes mellitus and non-ST-segment elevation acute coronary syndromes.

Oxygen Therapy in Suspected Acute Myocardial Infarction

BACKGROUND The clinical effect of routine oxygen therapy in patients with suspected acute myocardial infarction who do not have hypoxemia at baseline is uncertain. METHODS In this registry‐based randomized clinical trial, we used nationwide Swedish registries for patient enrollment and data collection. Patients with suspected myocardial infarction and an oxygen saturation of 90% or higher were randomly assigned to receive either supplemental oxygen (6 liters per minute for 6 to 12 hours, delivered through an open face mask) or ambient air. RESULTS A total of 6629 patients were enrolled. The median duration of oxygen therapy was 11.6 hours, and the median oxygen saturation at the end of the treatment period was 99% among patients assigned to oxygen and 97% among patients assigned to ambient air. Hypoxemia developed in 62 patients (1.9%) in the oxygen group, as compared with 254 patients (7.7%) in the ambient‐air group. The median of the highest troponin level during hospitalization was 946.5 ng per liter in the oxygen group and 983.0 ng per liter in the ambient‐air group. The primary end point of death from any cause within 1 year after randomization occurred in 5.0% of patients (166 of 3311) assigned to oxygen and in 5.1% of patients (168 of 3318) assigned to ambient air (hazard ratio, 0.97; 95% confidence interval [CI], 0.79 to 1.21; P=0.80). Rehospitalization with myocardial infarction within 1 year occurred in 126 patients (3.8%) assigned to oxygen and in 111 patients (3.3%) assigned to ambient air (hazard ratio, 1.13; 95% CI, 0.88 to 1.46; P=0.33). The results were consistent across all predefined subgroups. CONCLUSIONS Routine use of supplemental oxygen in patients with suspected myocardial infarction who did not have hypoxemia was not found to reduce 1‐year all‐cause mortality. (Funded by the Swedish Heart–Lung Foundation and others; DETO2X‐AMI ClinicalTrials.gov number, NCT01787110.)

Similar outcome with an invasive strategy in men and women with non-ST-elevation acute coronary syndromes

AIMS To assess gender differences in outcome with an early invasive or non-invasive strategy in patients with non-ST-elevation acute coronary syndromes (NSTE ACS). METHODS AND RESULTS We included 46,455 patients [14 819 women (32%) and 31,636 men (68%)] from the SWEDEHEART register, with NSTE ACS, between 2000 and 2006, and followed them for 1 year. In the non-invasive strategy arm, the relative risk (RR) of death was (women vs. men) 1.02 [95% confidence interval (CI), 0.94-1.11] and in the invasive strategy arm 1.12 (95% CI, 0.96-1.29). After adjustment for baseline differences between the genders, with propensity score and discharge medication, there was a similar trend towards better outcome among women in both the early non-invasive cohort [RR 0.90 (95% CI, 0.82-0.99)] and the early invasive cohort [RR 0.90 (95% CI, 0.76-1.06)], although it did not reach statistical significance in the early invasive cohort. Results were similar with the combined endpoint death/myocardial infarction. An early invasive treatment was associated with a marked, and similar, mortality reduction in women [RR 0.46 (95% CI, 0.38-0.55)] and men [RR 0.45 (95% CI, 0.40-0.52)], without interaction with gender. CONCLUSION In this large cohort of patients with NSTE ACS, reflecting real-life management, women and men had similar and better outcome associated with an invasive strategy.

Gait Speed Predicts 30-Day Mortality After Transcatheter Aortic Valve Replacement Results From the Society of Thoracic Surgeons/American College of Cardiology Transcatheter Valve Therapy Registry

Background— Surgical risk scores do not include frailty assessments (eg, gait speed), which are of particular importance for patients with severe aortic stenosis considering transcatheter aortic valve replacement. Methods and Results— We assessed the association of 5-m gait speed with outcomes in a cohort of 8039 patients who underwent transcatheter aortic valve replacement (November 2011–June 2014) and were included in the Society of Thoracic Surgeons/American College of Cardiology Transcatheter Valve Therapy Registry. We evaluated the association between continuous and categorical gait speed and 30-day all-cause mortality before and after adjustment for Society of Thoracic Surgeons–predicted risk of mortality score and key variables. Secondary outcomes included in-hospital mortality, bleeding, acute kidney injury, and stroke. The overall median gait speed was 0.63 m/s (25th–75th percentile, 0.47–0.79 m/s), with the slowest walkers (<0.5 m/s) constituting 28%, slow walkers (0.5–0.83 m/s) making up 48%, and normal walkers (>0.83 m/s) constituting 24% of the population. Thirty-day all-cause mortality rates were 8.4%, 6.6%, and 5.4% for the slowest, slow, and normal walkers, respectively (P<0.001). Each 0.2-m/s decrease in gait speed corresponded to an 11% increase in 30-day mortality (adjusted odds ratio, 1.11; 95% confidence interval, 1.01–1.22). The slowest walkers had 35% higher 30-day mortality than normal walkers (adjusted odds ratio, 1.35; 95% confidence interval, 1.01–1.80), significantly longer hospital stays, and a lower probability of being discharged to home. Conclusions— Gait speed is independently associated with 30-day mortality after transcatheter aortic valve replacement. Identification of frail patients with the slowest gait speeds facilitates preprocedural evaluation and anticipation of a higher level of postprocedural care. Clinical Trial Registration— URL: http://www.clinicaltrials.gov. Unique identifier: NCT01737528.

A gender perspective on short- and long term mortality in ST-elevation myocardial infarction — A report from the SWEDEHEART register

BACKGROUND Previous studies of patients admitted for ST-elevation myocardial infarction [STEMI] have indicated that women have a higher risk of early mortality than do men. These studies have presented limited information on gender related differences in the short term and almost no information on the long term. METHODS AND RESULTS We analysed a prospective, consecutively included STEMI population consisting of 54,146 patients (35% women). This population consists of almost all patients hospitalised in Sweden between January 1, 1995 and December 31, 2006 as recorded in the SWEDEHEART register (formerly RIKS-HIA). Follow-up time ranged from one to 13 years (mean 4.6). Women had a lower probability of being given reperfusion therapy, odds ratio [OR] 0.83 (95% confidence interval [CI] 0.79-0.88). During the time these STEMI patients were in the hospital, 13% of the women and 7% of men died, multivariable adjusted OR 1.21 (95% CI 1.11-1.32). During the follow up period, 46% of the women died as compared with 32% of the men. There was, however, no gender difference in age-adjusted risk of long term mortality (hazard ratio [HR] 0.98, 95% CI 0.95-1.01) whereas the multivariable adjusted risk was lower in women (HR 0.92, 95% CI 0.89-0.96). The long term risk of re-infarction was the same in men and women (HR 0.98, 95% CI 0.93-1.03) whereas men in the youngest group had a higher risk than women in that age group (HR 0.82, 95% CI 0.72-0.94). CONCLUSION In STEMI, women had a higher risk of in-hospital mortality but the long-term risk of death was higher in men. More studies are needed in the primary percutaneous coronary intervention (pPCI) era that are designed to determine why women fare worse than men after STEMI during the first phase when they are in hospital.

Frailty is independently associated with 1-year mortality for elderly patients with non-ST-segment elevation myocardial infarction

Background For the large population of elderly patients with cardiovascular disease, it is crucial to identify clinically relevant measures of biological age and their contribution to risk. Frailty is denoting decreased physiological reserves and increased vulnerability. We analysed the manner in which the variable frailty is associated with 1-year outcomes for elderly non-ST-segment elevation myocardial infarction (NSTEMI) patients. Methods and Results Patients aged 75 years or older, with diagnosed NSTEMI were included at three centres, and clinical data including judgment of frailty were collected prospectively. Frailty was defined according to the Canadian Study of Health and Aging Clinical Frailty Scale. Of 307 patients, 149 (48.5%) were considered frail. By Cox regression analyses, frailty was found to be independently associated with 1-year mortality after adjusting for cardiovascular risk and comorbid conditions (hazard ratio 4.3, 95% CI 2.4–7.8). The time to the first event was significantly shorter for frail patients than for nonfrail (34 days, 95% CI 10–58, p = 0.005). Conclusions Frailty is strongly and independently associated with 1-year mortality. The combined use of frailty and comorbidity may constitute an important risk prediction concept in regard to cardiovascular patients with complex needs.