Dual antiplatelet therapy reduces non-fatal ischaemic events after acute coronary syndrome (ACS) but increases bleeding to a similar extent. We sought to determine the prognostic impact of myocardial ...infarction (MI) vs. bleeding during an extended follow-up period to gain insight into the trade-off between efficacy and safety among patients after ACS.
In 12 944 patients with non-ST-segment elevation ACS from the Thrombin Receptor Antagonist for Clinical Event Reduction in Acute Coronary Syndrome (TRACER) trial, we investigated the relative impact of MI and bleeding occurring >30 days post-ACS and subsequent all-cause mortality. Bleeding was graded according to Bleeding Academic Research Consortium (BARC) criteria. MI was associated with a five-fold increase in mortality. BARC type 2 and 3, but not type 1, bleeding had a significant impact on mortality. MI was associated with a greater risk of mortality compared with BARC 2 relative risk (RR) 3.5; 95% confidence interval (CI) 2.08-4.77; P < 0.001 and BARC 3a bleeding (RR 2.23; 95% CI 1.36-3.64; P = 0.001), and a risk similar to BARC 3b bleeding (RR 1.37; 95% CI 0.81-2.30; P = 0.242). Risk of death after MI was significantly lower than after BARC 3c bleeding (RR 0.22; 95% CI 0.13-0.36; P < 0.001). MI and bleeding had similar time-associations with mortality, which remained significant for several months, still being higher early after the event.
In patients treated with antiplatelet therapy after ACS, both MI and bleeding significantly impacted mortality with similar time-dependency. Although BARC 2 and 3a bleeding were less prognostic for death than MI, the risk of mortality was equivalent between BARC 3b bleeding and MI, and was higher following BARC 3c bleeding.
This Viewpoint discusses the rising tide of medical misinformation and its adverse effects on global health, and suggests ways in which medical journals can collaborate with health professionals, ...organizations, institutions, and mainstream media to counteract such misinformation.
Abstract
Randomized clinical trials initially used heart failure (HF) patients with low left ventricular ejection fraction (LVEF) to select study populations with high risk to enhance statistical ...power. However, this use of LVEF in clinical trials has led to oversimplification of the scientific view of a complex syndrome. Descriptive terms such as ‘HFrEF’ (HF with reduced LVEF), ‘HFpEF’ (HF with preserved LVEF), and more recently ‘HFmrEF’ (HF with mid-range LVEF), assigned on arbitrary LVEF cut-off points, have gradually arisen as separate diseases, implying distinct pathophysiologies. In this article, based on pathophysiological reasoning, we challenge the paradigm of classifying HF according to LVEF. Instead, we propose that HF is a heterogeneous syndrome in which disease progression is associated with a dynamic evolution of functional and structural changes leading to unique disease trajectories creating a spectrum of phenotypes with overlapping and distinct characteristics. Moreover, we argue that by recognizing the spectral nature of the disease a novel stratification will arise from new technologies and scientific insights that will shape the design of future trials based on deeper understanding beyond the LVEF construct alone.
Advances in cardiovascular medicine fueled by innovative clinical trials have dramatically improved the lives of patients worldwide. Commensurate with this progress has been a decline in morbid and ...mortal events. Accordingly, an increased propensity to collate patient outcomes in clinical trials has emerged that combines death and nonfatal complications into a single composite event. Despite the acknowledged benefits in trial efficiency from such an approach, this method assumes uniform directionality of each component, does not distinguish the relative clinical significance of each, and counts only the first occurrence of any event in the final tally within a conventional time to first event analysis. In this article, we evaluate the criticisms that have been leveled at this approach and provide an overview of recently published phase III cardiovascular trials using primary composite end points. We then explore what to anticipate from the large cohort of as-yet unpublished clinical trials in this arena. Last, we propose a variety of novel approaches that use composite end points and suggest a path forward to enhancing their use in future clinical trials.
Uncertainty exists as to which reperfusion strategy for ST-elevation myocardial infarction (MI) is optimal. We evaluated whether optimal pharmacologic therapy at the earliest point of care, ...emphasizing pre-hospital randomization and treatment was non-inferior to expeditious primary percutaneous coronary intervention (PCI).
Which Early ST-elevation myocardial infarction Therapy (WEST) was a four-city Canadian, open-label, randomized, feasibility study of 304 STEMI patients (> 4 mm ST-elevation/deviation) within 6 h of symptom onset, emphasizing pre-hospital ambulance treatment and participation of community and tertiary care centres. All received aspirin, subcutaneous enoxaparin (1 mg/kg), and were randomized to one of three groups: (A) tenecteplase (TNK) and usual care, (B) TNK and mandatory invasive study < or = 24 h, including rescue PCI for reperfusion failure, and (C) primary PCI with 300 mg loading dose of clopidogrel. Time from symptom onset to treatment was rapid (to TNK for A = 113 and B = 130 min and for PCI in C = 176 min). The primary outcome, a composite of 30-day death, re-infarction, refractory ischaemia, congestive heart failure, cardiogenic shock, and major ventricular arrhythmia, was 25% (Group A), 24% (Group B), and 23% (Group C), respectively. However, there was a higher frequency of the combination of death and recurrent MI in Group A vs. Group C (13.0 vs. 4.0%, respectively, P-logrank = 0.021), yet no difference between Group B (6.7%, P-logrank = 0.378) and C.
These data suggest that a contemporary pharmacologic regimen rapidly delivered, coupled with a strategy of regimented rescue and routine coronary intervention within 24 h of initial treatment, may not be different from timely expert PCI.
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