Eva Swahn

Outcome at 1 year after an invasive compared with a non-invasive strategy in unstable coronary-artery disease: the FRISC II invasive randomised trial

BACKGROUND The Fragmin and Fast Revascularisation during Instability in Coronary artery disease II trial (FRISC II) compared an early invasive with an early non-invasive strategy in unstable coronary-artery disease. We report outcome at 1 year. METHODS 2457 patients were randomly assigned invasive or non-invasive treatment and 3 months of dalteparin or placebo. Complete information at 1 year was available for 1222 in the invasive group and 1234 in the non-invasive group. Analyses were by intention to treat. FINDINGS Revascularisation was done within the first 10 days in 71% of the invasive group and 9% of the non-invasive group and within the first year in 78% and 43%. During the first year, 27 (2.2%) patients in the invasive group and 48 (3.9%) in the non-invasive group died (risk ratio 0.57 [95% CI 0.36-0.90], p=0.016). 105 (8.6%) versus 143 (11.6%) had myocardial infarction (0.74 [0.59-0.94], p=0.015). The composite of death or myocardial infarction occurred in 127 (10.4%) versus 174 (14.1%) patients (0.74 [0.60-0.92], p=0.005). There were also reductions in readmission (451 [37%] vs 704 [57%]; 0.67 [0.62-0.72]), and revascularisation after the initial admission (92 [7.5%] vs 383 [31%]; 0.24 [0.20-0.30]). The results did not interact with the dalteparin/placebo allocation. INTERPRETATION After 1 year in 100 patients, an invasive strategy saves 1.7 lives, prevents 2.0 non-fatal myocardial infarctions and 20 readmissions, and provides earlier and better symptom relief at the cost of 15 more patients with coronary-artery bypass grafting and 21 more with percutaneous transluminal angioplasty. Therefore, an invasive approach should be the preferred strategy in patients with unstable coronary-artery disease and signs of ischaemia on electrocardiography or raised levels of biochemical markers of myocardial damage.

Early Invasive vs Conservative Treatment Strategies in Women and Men With Unstable Angina and Non–ST-Segment Elevation Myocardial Infarction: A Meta-analysis

CONTEXT Although an invasive strategy is frequently used in patients with non-ST-segment elevation acute coronary syndromes (NSTE ACS), data from some trials suggest that this strategy may not benefit women. OBJECTIVE To conduct a meta-analysis of randomized trials to compare the effects of an invasive vs conservative strategy in women and men with NSTE ACS. DATA SOURCES Trials were identified through a computerized literature search of the MEDLINE and Cochrane databases (1970-April 2008) using the search terms invasive strategy, conservative strategy, selective invasive strategy, acute coronary syndromes, non-ST-elevation myocardial infarction, and unstable angina. STUDY SELECTION Randomized clinical trials comparing an invasive vs conservative treatment strategy in patients with NSTE ACS. DATA EXTRACTION The principal investigators for each trial provided the sex-specific incidences of death, myocardial infarction (MI), and rehospitalization with ACS through 12 months of follow-up. DATA SYNTHESIS Data were combined across 8 trials (3075 women and 7075 men). The odds ratio (OR) for the composite of death, MI, or ACS for invasive vs conservative strategy in women was 0.81 (95% confidence interval [CI], 0.65-1.01; 21.1% vs 25.0%) and in men was 0.73 (95% CI, 0.55-0.98; 21.2% vs 26.3%) without significant heterogeneity between sexes (P for interaction = .26). Among biomarker-positive women, an invasive strategy was associated with a 33% lower odds of death, MI, or ACS (OR, 0.67; 95% CI, 0.50-0.88) and a nonsignificant 23% lower odds of death or MI (OR, 0.77; 95% CI, 0.47-1.25). In contrast, an invasive strategy was not associated with a significant reduction in the triple composite end point in biomarker-negative women (OR, 0.94; 95% CI, 0.61-1.44; P for interaction = .36) and was associated with a nonsignificant 35% higher odds of death or MI (OR, 1.35; 95% CI, 0.78-2.35; P for interaction = .08). Among men, the OR for death, MI, or ACS was 0.56 (95% CI, 0.46-0.67) if biomarker-positive and 0.72 (95% CI, 0.51-1.01) if biomarker-negative (P for interaction = .09). CONCLUSIONS In NSTE ACS, an invasive strategy has a comparable benefit in men and high-risk women for reducing the composite end point of death, MI, or rehospitalization with ACS. In contrast, our data provide evidence supporting the new guideline recommendation for a conservative strategy in low-risk women.

Is early invasive treatment of unstable Coronary artery disease equally effective for both women and men

BACKGROUND The Fragmin and fast Revascularization during InStability in Coronary artery disease (FRISC II) trial compared the effectiveness of an early invasive versus a noninvasive strategy in terms of the incidence of death and myocardial infarction (MI) in patients with unstable coronary artery disease (CAD). OBJECTIVES In this subanalysis, we sought to evaluate gender differences in the effect of these different strategies. METHODS The patients (749 women and 1,708 men) were randomized to early invasive or noninvasive strategies. Coronary angiography was performed within the first 7 days in 96% and 10% of the invasive and noninvasive groups, respectively, and revascularization was performed within the first 10 days in 71% and 9% of the invasive and noninvasive groups, respectively. RESULTS Women presenting with unstable CAD were older, but fewer had previous infarctions, left ventricular dysfunction and elevated troponin T levels. Women had fewer angiographic changes. There was no difference in MI or death at 12 months among women in the invasive and noninvasive groups (12.4% vs. 10.5%, respectively), in contrast to the favorable effect in the invasively treated group of men (9.6% vs. 15.8%, p < 0.001). In an interaction analysis, there was a different effect of the early invasive strategy for the two genders (p = 0.008). CONCLUSIONS Women with symptoms and/or signs of unstable CAD are older, but still have less severe CAD and a better prognosis compared with men. In contrast to its beneficial effect in men, an early invasive strategy did not reduce the risk of future events among women. Further research is warranted to identify the most appropriate treatment strategy in women with unstable CAD.

5-year outcomes in the FRISC-II randomised trial of an invasive versus a non-invasive strategy in non-ST-elevation acute coronary syndrome: a follow-up study

BACKGROUND The FRISC-II invasive trial compared an early invasive with a non-invasive strategy in terms of death and myocardial infarction in non-ST-elevation acute coronary syndrome. We present 5-year follow-up results, overall and in subgroups based on recommended risk stratification criteria. METHODS In the FRISC-II trial, 2457 patients with non-ST-elevation acute coronary syndrome were randomised to early invasive strategy (coronary angiography and, if appropriate, revascularisation, within 7 days from admission) or non-invasive primarily medical strategy. Risk stratification was done on the basis of risk indicators at randomisation: age older than 65 years, male sex, diabetes mellitus, previous myocardial infarction, ST-segment depression, raised troponin concentration (>0.03 mug/L), and raised C-reactive protein or interleukin 6. Information on events after 24 months was taken from national registries. Analyses were done on an intention-to-treat basis. FINDINGS At 5 years the groups differed in terms of the primary composite endpoint of death, myocardial infarction, or both (invasive 217, 19.9 %; noninvasive 270, 24.5 %; risk ratio 0.81; 95% CI 0.69-0.95; p=0.009). 5-year mortality was 117 (9.7%) in the invasive group compared with 124 (10.1%) in the noninvasive group (0.95; 0.75 -1.21; p=0.693). Rates of myocardial infarction were 141 (12.9 %) in the invasive and 195 (17.7%) in the non-invasive group (0.73; 0.60-0.89; p=0.002). The benefit of the invasive strategy was confined to male patients, non-smokers, and patients with two or more risk indicators. INTERPRETATION The 5-year outcome of this trial indicates sustained benefit of an early invasive strategy in patients with non-ST-elevation acute coronary syndrome at moderate to high risk.

To continue or discontinue aspirin in the perioperative period: a randomized, controlled clinical trial

BACKGROUND Major adverse cardiac events (MACEs) are a common cause of death after non-cardiac surgery. Despite evidence for the benefit of aspirin for secondary prevention, it is often discontinued in the perioperative period due to the risk of bleeding. METHODS We conducted a randomized, double-blind, placebo-controlled trial in order to compare the effect of low-dose aspirin with that of placebo on myocardial damage, cardiovascular, and bleeding complications in high-risk patients undergoing non-cardiac surgery. Aspirin (75 mg) or placebo was given 7 days before surgery and continued until the third postoperative day. Patients were followed up for 30 days after surgery. RESULTS A total of 220 patients were enrolled, 109 patients received aspirin and 111 received placebo. Four patients (3.7%) in the aspirin group and 10 patients (9.0%) in the placebo group had elevated troponin T levels in the postoperative period (P=0.10). Twelve patients (5.4%) had an MACE during the first 30 postoperative days. Two of these patients (1.8%) were in the aspirin group and 10 patients (9.0%) were in the placebo group (P=0.02). Treatment with aspirin resulted in a 7.2% absolute risk reduction [95% confidence interval (CI), 1.3-13%] for postoperative MACE. The relative risk reduction was 80% (95% CI, 9.2-95%). Numbers needed to treat were 14 (95% CI, 7.6-78). No significant differences in bleeding complications were seen between the two groups. CONCLUSIONS In high-risk patients undergoing non-cardiac surgery, perioperative aspirin reduced the risk of MACE without increasing bleeding complications. However, the study was not powered to evaluate bleeding complications.

Red alert for women's heart: the urgent need for more research and knowledge on cardiovascular disease in women

A recent report of the EuroHeart project has shown that women are still underrepresented in many cardiovascular clinical trials, while important gender differences are present within most areas of heart disease. As the burden of cardiovascular disease is increasing in middle-aged women relative to men, a more profound understanding is needed of the fundamental biological differences that exist between men and women. In the current review, we aim to address the need for more explanatory sex-specific cardiovascular research to be able to adapt existing guidelines for a better heart health in women.

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.

Very early risk stratification by electrocardiogram at rest in men with suspected unstable coronary heart disease

Abstract. Objectives. To determine the possibility of very early prognostic stratification based on electrocardiograms (ECGs) at rest and/or cardiac enzyme levels after an episode of suspected unstable coronary heart disease.

A long-term perspective on the protective effects of an early invasive strategy in unstable coronary artery disease: Two-year follow-up of the FRISC-II invasive study

OBJECTIVES We sought to report the first and repeat events and to separate spontaneous and procedure-related events over two years in the Fast Revascularization during InStability in Coronary artery disease (FRISC-II) invasive trial. BACKGROUND The FRISC-II invasive trial compared the long-term effects of an early invasive versus noninvasive strategy, in terms of death and myocardial infarction (MI) and the need for repeat hospital admissions and late revascularization procedures in patients with coronary artery disease (UCAD). METHODS In the FRISC-II trial, 2,457 patients with UCAD were randomized to an early invasive or noninvasive strategy. RESULTS At 24 month follow-up, there were reductions in mortality (n = 45 [3.7%] vs. 67 [5.4%]; risk ratio 0.68 [95% confidence interval (CI) 0.47 to 0.98]; p = 0.038), MI (n = 111 [9.2%] vs. 156 [12.7%]; risk ratio 0.72 [95% CI 0.57 to 0.91]; p = 0.005), and the composite end point of death or MI (n = 146 [12.1%] vs. 200 [16.3%]; risk ratio 0.74 [95% CI 0.61 to 0.90]; p = 0.003) in the invasive compared with the noninvasive group. Procedure-related MIs were two to three times more common, but spontaneous ones were three times less common in the invasive than in the noninvasive group. After the first year, there was no difference in mortality (n = 20 [1.7%]) between the two groups and fewer MIs in the invasive group (p = 0.031). CONCLUSIONS In UCAD, the early invasive approach leads to a sustained reduction in mortality, cardiac morbidity, and the need for repeat hospital admissions and late revascularization procedures. Although the benefits are greatest during the first months, during the second year, cardiac morbidity is lower and the need for hospital care is less in the invasive group.

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.