The Effect of the Timing of Invasive Management on Cardiac Function in Patients with NSTE-ACS, Insights from the OPTIMA-2 Randomized Controlled Trial.

The timing of coronary angiography in patients with non-ST-elevation acute coronary syndrome (NSTE-ACS) remains a matter of debate. The relationship between the timing of invasive management and left ventricular function (LVF) is largely unknown. The An Immediate or Early Invasive Strategy in Non-ST-Elevation Acute Coronary Syndrome trial (OPTIMA-2) was a randomized controlled prospective open-label multicenter trial that randomized 249 NSTE-ACS patients to either an immediate (<3 h) invasive treatment strategy or an early strategy (12-24 h). Patients were pre-treated with a combination of aspirin, ticagrelor and fondaparinux. The aim of this prespecified sub-analysis was to assess (the recovery of) left ventricular function by analysing echocardiography data obtained <72 h after admission and at 30-day follow-up, for patients with a confirmed diagnosis of acute coronary syndrome. LVF was determined using ejection fraction (EF) and global longitudinal strain (GLS). Inter-observer variability was tested. No difference in the recovery of EF was found between an immediate and early strategy if the follow-up echocardiograms were compared to baseline: 2.5% (standard deviation (SD): 7.9) and 3.3% (SD: 8.5), p = 0.51, nor was there any difference in GLS recovery between the study groups: -0.8% (SD: 2.5) vs. -0.7% (SD 2.8) p = 0.82. If baseline and follow-up echocardiograms were compared, there was a similar but significant improvement in both EF and GLS in both separate study groups. An immediate invasive strategy in NSTE-ACS patients did not result in an improved left ventricular EF or GLS recovery compared with an early strategy.

One-year mortality in NSTEMI patients is unaffected by timing of PCI within the first week of admission: Results of a real-world cohort analysis.

OBJECTIVES: We aimed to explore the impact of time to percutaneous coronary intervention (PCI) (T2P) on 1-year mortality in non-ST-elevation myocardial infarction (NSTEMI) patients. BACKGROUND: The current guidelines recommend an early invasive strategy for NSTEMI patients. However, impact of an early invasive strategy on mortality is a matter of debate. For that reason, real world data are of great value to determine the optimal treatment window. METHODS: This retrospective single center cohort study was performed in a high-volume PCI center in Amsterdam, The Netherlands. Intermediate- and high-risk NSTEMI patients undergoing PCI were included. The main discriminant was timing of PCI after admission (T2P), stratified according to different time windows (<24 h, 24-72 h, 72 h-7 days or >7 days). We analyzed 1-year mortality and the time distribution of overall survival. RESULTS: In total, 848 patients treated between January 1, 2016 and January 1, 2018 were included in the analysis. T2P was <24 h in 145 patients, 24-72 h in 192 patients, 72 h-7 days in 275 patients, and >7 days in 236 patients. The mean GRACE-risk score was 127.1 (SD 28.7), 130.0 (33.1), 133.8 (32.1), and 148.7 (34.6) respectively, p = <0.001. After adjusting for confounders, 1-year mortality in patients with T2P <24 h did not significantly differ when compared with T2P 24-72 h (OR = 1.08; 95% CI = 0.33-3.51) and T2P 72 h-7 days (OR 1.72; 95% CI = 0.57-5.21) but was significantly higher in T2P >7 days (OR = 3.20; 95% CI = 1.06-9.68). CONCLUSIONS: In an unselected cohort of patients with NSTEMI, treatment by PCI <24 h did not lead to improved survival as compared to aT2P <7 days strategy. Delay in PCI >7 days after admission resulted in worse outcome.

An immediate or early invasive strategy in non-ST-elevation acute coronary syndrome: The OPTIMA-2 randomized controlled trial.

BACKGROUND: In intermediate- and high-risk non-ST elevated acute coronary syndrome (NSTE-ACS) patients, a routine invasive approach is recommended. The timing of coronary angiography remains controversial. To assess whether an immediate (<3 hours) invasive treatment strategy would reduce infarct size and is safe, compared with an early strategy (12-24 hours), for patients admitted with NSTE-ACS while preferably treated with ticagrelor. METHODS: In this single-center, prospective, randomized trial an immediate or early invasive strategy was randomly assigned to patients with NSTE-ACS. At admission, the patients were preferably treated with a combination of aspirin, ticagrelor and fondaparinux. The primary endpoint was the infarct size as measured by area under the curve (AUC) of CK-MB in 48 hours. Secondary endpoints were bleeding outcomes and major adverse cardiac events (MACE): composite of all-cause death, MI and unplanned revascularization. Interim analysis showed futility regarding the primary endpoint and trial inclusion was terminated. RESULTS: In total 249 patients (71% of planned) were included. The primary endpoint of in-hospital infarct size was a median AUC of CK-MB 186.2 ng/mL in the immediate group (IQR 112-618) and 201.3 ng/mL in the early group (IQR 119-479). Clinical follow-up was 1-year. The MACE-rate was 10% in the immediate and 10% in the early group (hazard ratio [HR] 1.13, 95% CI: 0.52-2.49). CONCLUSIONS: In NSTE-ACS patients randomized to either an immediate or an early-invasive strategy the observed median difference in the primary endpoint was about half the magnitude of the expected difference. The trial was terminated early for futility after 71% of the projected enrollment had been randomized into the trial.

Paclitaxel-Coated Balloon Angioplasty Versus Drug-Eluting Stent in Acute Myocardial Infarction: The REVELATION Randomized Trial.

OBJECTIVES: This study sought to assess the efficacy and safety of a drug-coated balloon (DCB) strategy versus drug-eluting stent (DES) in primary percutaneous coronary intervention for ST-segment elevation myocardial infarction (STEMI). BACKGROUND: In primary percutaneous coronary intervention for STEMI, stenting has proved to be beneficial with regard to repeat revascularization, but not recurrent myocardial infarction or death, compared with balloon angioplasty alone. A strategy of DCB angioplasty without stenting might abolish the potential disadvantages of stent implantation while reducing the probability of restenosis observed in plain old balloon angioplasty. METHODS: In the prospective, randomized, single-center REVELATION trial, we compared DCB with DES in patients presenting with STEMI. Patients with a new, nonseverely calcified culprit lesion in a native coronary artery and a residual stenosis of <50% after pre-dilatation were randomized to treatment with a DCB or DES. The primary endpoint was fractional flow reserve at 9 months, allowing for a functional measurement of the infarct-related lesion. RESULTS: A total of 120 patients were included. At 9 months after enrolment, the mean fractional flow reserve value was 0.92 ± 0.05 in the DCB group (n = 35) and 0.91 ± 0.06 in the DES group (n = 38) (p = 0.27). One abrupt vessel closure requiring treatment occurred after treatment with DCB. Up to 9-months follow-up, 2 patients required nonurgent target lesion revascularization (1 in each group). CONCLUSIONS: In the setting of STEMI, the DCB strategy was noninferior to DES in terms of fractional flow reserve assessed at 9 months. Furthermore, it seemed to be a safe and feasible strategy. (Revascularization With Paclitaxel-Coated Balloon Angioplasty Versus Drug-Eluting Stenting in Acute Myocardial Infarction [REVELATION]; NCT02219802).

Effects of a nurse-coordinated prevention programme on health-related quality of life and depression in patients with an acute coronary syndrome: results from the RESPONSE randomised controlled trial.

BACKGROUND: Improvement of health-related quality of life (HRQOL) is an important goal in preventive cardiology. HRQOL is also related to depressive symptoms, which represent a common co-morbidity and risk factor in patients with an acute coronary syndrome (ACS). Comprehensive nurse-coordinated prevention programmes (NCPP) in secondary care have been shown to reduce cardiovascular risk, however their effects on HRQOL and depressive symptoms have not been evaluated. We therefore investigated HRQOL and depressive symptoms in a secondary analysis in the RESPONSE trial, evaluating the effect of a NCPP on cardiovascular risk. METHODS: RESPONSE was a multicentre (n = 11) randomised controlled trial in ACS-patients in secondary and tertiary healthcare settings evaluating a NCPP. The intervention consisted of four outpatient nurse clinic visits in the first 6 months after the index event, focusing on healthy lifestyles, biometric risk factors and medication adherence, in addition to usual care. The control group received usual care only. The outcome was change in HRQOL as measured by the MacNew questionnaire and change in depressive symptoms as measured by Beck's Depression Inventory (BDI) questionnaire at 12-months follow-up relative to baseline. RESULTS: Of 754 patients randomised, 615 were analysed for HRQOL; 120 for depressive symptoms. At baseline, HRQOL was 5.17 (SD 1.09) and 5.20 (SD1.04) (scale range 1.0 to 7.0) in the intervention and control group, respectively. At 12 months follow-up, HRQOL increased by 0.57 (SD 0.89) in the intervention group as compared with 0.42 (SD 0.90) in the control group (p = 0.03). This increase was observed across all relevant subscales. The BDI decreased by 1.9 in the intervention group as compared with 0.03 in the control group (p = 0.03) (scale range 1.0 to 63). CONCLUSION: Participation in a NCPP is associated with a modest but statistically significant increase in HRQOL, and a decrease of depressive symptoms, both of which are highly relevant to patients. A reduction in depressive symptoms may in addition contribute to a reduction in the overall risk of recurrent events. TRIAL REGISTRATION: Dutch trials register: NTR1290 . Registered 24 April 2008.

Effect of colchicine compared with placebo on high sensitivity C-reactive protein in patients with acute coronary syndrome or acute stroke: a pilot randomized controlled trial.

There is a need for more effective therapies to reduce morbidity and mortality from cardiovascular disease. Inflammation plays a central role in the pathogenesis of atherosclerosis but no randomized studies have evaluated anti-inflammatory therapy in patients with acute coronary or cerebrovascular disease. We performed a pilot randomized controlled trial comparing the effect of colchicine 1 mg per day with placebo on high sensitivity C-reactive protein (CRP) levels and platelet function in 80 patients with acute coronary syndrome or acute ischemic stroke who were followed for 30 days. Clinical status was ascertained for 74 (92.5%) patients and CRP levels were obtained in 68 (85%) of patients at follow up. Colchicine did not significantly reduce absolute hs-CRP at 30 days [median 1.0 mg/l (range 0.2, 162.0) versus 1.5 mg/l (0.2, 19.8), P = 0.22] or difference in CRP from baseline to 30 days [absolute difference 7.0 mg/l (-61.0, 87.8) vs. 7.1 mg/l (-1.0, 144), P = 0.64]. The proportion of patients with CRP <2 mg/l at follow up did not differ according to treatment allocation (77% vs. 62%, X (2) 1.84, P = 0.18). There was also no difference in platelet function assessed using platelet aggregation with ADP (5 µmol), arachidonic acid (0.5 mmol), collagen (1 µg/ml) and collagen (5 µg/ml) (P = 0.86, P = 0.64, P = 0.76, P = 0.20, respectively), and urine dehydrothromboxane B2 (P = 0.54). Colchicine was associated with an excess of diarrhoea (X(2) 4.14, P = 0.04). In conclusion, our pilot study provided no evidence that colchicine 1 mg daily for 30 days compared with placebo suppresses inflammation in patients with acute coronary syndrome or acute ischemic stroke.