Background: Conflicting evidence is available on the efficacy and safety of early intravenous beta-blockers before primary percutaneous coronary intervention for ST-segment elevation myocardial infarction. We performed a patient-pooled meta-analysis of trials comparing early intravenous beta-blockers with placebo or routine care in ST-segment elevation myocardial infarction patients undergoing primary percutaneous coronary intervention. Aim: The aim of this study was to evaluate the clinical and safety outcomes of intravenous beta-blockers in ST-segment elevation myocardial infarction patients undergoing primary percutaneous coronary intervention. Methods: Four randomized trials with a total of 1150 patients were included. The main outcome was one-year death or myocardial infarction. Secondary outcomes included biomarker-based infarct size, left ventricular ejection fraction during follow-up, ventricular tachycardia, and a composite safety outcome (cardiogenic shock, symptomatic bradycardia, or hypotension) during hospitalization. Results: One-year death or myocardial infarction was similar among beta-blocker (4.2%) and control patients (4.4%) (hazard ratio: 0.96 (95% confidence interval: 0.53–1.75, p=0.90, I2=0%). No difference was observed in biomarker-based infarct size. One-month left ventricular ejection fraction was similar, but left ventricular ejection fraction at six months was significantly higher in patients treated with early intravenous beta-blockade (52.8% versus 50.0% in the control group, p=0.03). No difference was observed in the composite safety outcome or ventricular tachycardia during hospitalization. Conclusion: In ST-segment elevation myocardial infarction patients undergoing primary percutaneous coronary intervention, the administration of early intravenous beta-blockers was safe. However, there was no difference in the main outcome of one-year death or myocardial infarction with early intravenous beta-blockers. A larger clinical trial is warranted to confirm the definitive efficacy of early intravenous beta-blockers.
Unlike neighboring countries, the Netherlands does not have a national acute coronary syndrome (ACS) registry to evaluate quality of care. We conducted a pilot registry in two hospitals to assess the prescription of guideline-recommended therapies in Dutch patients with ACS. We included all consecutive patients with ST-elevation myocardial infarction (STEMI) and non-STEMI (NSTEMI) (n = 1309) admitted to two Dutch percutaneous coronary intervention centers between March 2015 and February 2016. We collected follow-up medication use and reasons for discontinuation at discharge and 1, 6, and 12 months post-discharge. We assessed the use of optimal medical therapy (OMT), defined as the combined prescription of aspirin, P2Y12 inhibitors, statins, β-blockers, and angiotensin-converting enzyme inhibitors or angiotensin-receptor blockers. OMT prescription was 43.2% at discharge, 60.1% at 1 month, and 28.7% at 12 months. At 1 month, OMT prescription was significantly lower in patients with NSTEMI (51.8 vs. 65.7% for STEMI; p < 0.001). OMT prescription was lower in women (6 months: 55.4 vs. 62.0%, p = 0.036) and in elderly patients. In this pilot study that aimed to extend a national Dutch ACS registry to patients with STEMI and NSTEMI, OMT prescription was comparable to that in other local registries, was lower in women and patients with NSTEMI, and decreased with increasing age.
Optimal medical therapy (OMT) is recommended in acute coronary syndrome (ACS) patients. Few studies present temporal trends of OMT prescription and its impact on outcomes in a real-world setting. We aimed to evaluate OMT prescription in a real-world ACS population and its relation to mortality during almost a decade.Consecutive ST-elevation myocardial infarction and non-ST-elevation myocardial infarction (NSTEMI) patients (n = 9202) admitted to a single Dutch tertiary hospital between 2006 and 2014 were included and followed for drug prescription and mortality up to 1 year. Optimal medical therapy was defined as prescription of aspirin, P2Y12inhibitors, statin, beta-blockers, and angiotensin converting enzyme inhibitors or angiotensin receptor blockers (ACEi/ARB). Optimal medical therapy prescription was 43.7% at discharge, 46.6% at 30-days, and 25.5% at 1-year. Optimal medical therapy prescription at discharge was lower among NSTEMI patients (34.5% vs. 49.2%, P < 0.001). Optimal medical therapy prescription at discharge, 30-days and 1-year and mortality outcomes did not change during the study period. After adjustment for baseline and admission characteristics, OMT at discharge was associated with a reduction in mortality in patients who survived hospitalization for the index event [adjusted hazard ratio: 0.66, 95% confidence interval (0.46-0.93)].In this single-centre observational registry with >9000 patients reflecting almost a decade of ACS care, <50% of patients were on OMT at discharge. Prescription of OMT and mortality outcomes remained stable during the study period. After adjustment, OMT prescription at discharge was associated with reduced mortality in ACS survivors. Further contemporary randomized studies are warranted to determine the role of beta-blockers and ACEi/ARBs in ACS patients with preserved left ventricular ejection fraction.
Proton-pump inhibitors (PPIs) are commonly prescribed in acute coronary syndrome (ACS) patients on antiplatelet therapy. We studied PPI prescription in ACS patients in the era of novel P2Y12 inhibitors and assessed the association between PPI use and clinical outcomes. Between 2010 and 2014, we included all consecutive ACS patients admitted to a Dutch tertiary hospital. The main outcome was PPI prescription at discharge. Additionally, we present 1-year mortality and 30-day cardiovascular and bleeding outcomes. Of 4595 ACS patients with known discharge medication, 63.9% received a PPI. PPI-treated patients were older (67.1 ± 12.5 vs. 63.0 ± 13.3, P < 0.001). PPI treatment at discharge increased from 34.7% in 2010 to 88.7% in 2014 (P < 0.001). Concurrently, ticagrelor prescription at discharge increased from 0.0% to 48.6% in 2014 (P < 0.001), while clopidogrel prescription decreased from 78.6% in 2010 to 28.7% in 2014 (P < 0.001). PPI treatment was associated with reductions in death or myocardial infarction (MI) [adjusted hazard ratio (HR) 0.27, 95% confidence interval (CI) 0.10–0.76] and death, MI or stroke (adjusted HR 0.33, 95% CI 0.14–0.81) at 30-days post-discharge. However, this association was not present in subgroup analyses of patients treated with clopidogrel or ticagrelor. In this single-centre registry, PPI prescription in ACS patients doubled between 2010 and 2014. PPI treatment at discharge was associated with a reduction in death, MI, or stroke at 30-days post-discharge, mainly driven by a reduction in MI. There were no differences gastrointestinal bleeding between patients treated with or without a PPI. PPI treatment may serve as a marker of improved therapies and outcome, rather than causing a reduction in cardiovascular events.
The ICTUS (Invasive Versus Conservative Treatment in Unstable Coronary Syndromes) trial compared early invasive strategy with a selective invasive strategy in patients with non-ST-segment elevation acute coronary syndrome (NSTE-ACS) and an elevated cardiac troponin T. No long-term benefit of an early invasive strategy was found at 1 and 5 years.The aim of this study was to determine the 10-year clinical outcomes of an early invasive strategy versus a selective invasive strategy in patients with NSTE-ACS and an elevated cardiac troponin T.The ICTUS trial was a multicenter, randomized controlled clinical trial that included 1,200 patients with NSTE-ACS and an elevated cardiac troponin T. Enrollment was from July 2001 to August 2003. We collected 10-year follow-up of death, myocardial infarction (MI), and revascularization through the Dutch population registry, patient phone calls, general practitioners, and hospital records. The primary outcome was the 10-year composite of death or spontaneous MI. Additional outcomes included the composite of death or MI, death, MI (spontaneous and procedure-related), and revascularization.Ten-year death or spontaneous MI was not statistically different between the 2 groups (33.8% vs. 29.0%, hazard ratio [HR]: 1.12; 95% confidence interval [CI]: 0.97 to 1.46; p = 0.11). Revascularization occurred in 82.6% of the early invasive group and 60.5% in the selective invasive group. There were no differences in additional outcomes, except for a higher rate of death or MI in the early invasive group compared with the rates for the selective invasive group (37.6% vs. 30.5%; HR: 1.30; 95% CI: 1.07 to 1.58; p = 0.009), driven by a higher rate of procedure-related MI in the early invasive group (6.5% vs. 2.4%; HR: 2.82; 95% CI: 1.53 to 5.20; p = 0.001).In patients with NSTE-ACS and elevated cardiac troponin T levels, an early invasive strategy has no benefit over a selective invasive strategy in reducing the 10-year composite outcome of death or spontaneous MI, and a selective invasive strategy may be a viable option in selected patients.
This thesis concerns the invasive and pharmacological treatment of acute coronary syndrome (ACS). In the last 30 years the development of the treatment of patients with an acute coronary syndrome has improved outcomes. In Part A we discuss care for ACS patients in the Netherlands. In Part B we describe the 10-year outcome of an early or selective invasive strategy in patients with non-ST-segment elevation acute coronary syndrome. Finally in Part C we report the use of pharmacological therapies during and after hospitalization for acute coronary syndrome. A national registry for acute coronary syndrome patients in the Netherlands remains highly warranted.
