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Whether a conservative strategy of medical therapy alone or a strategy of medical therapy plus invasive treatment is more beneficial in older adults with non-ST-segment elevation myocardial infarction (NSTEMI) remains unclear. We conducted a prospective, multicenter, randomized trial involving patients 75 years of age or older with NSTEMI at 48 sites in the United Kingdom. The patients were assigned in a 1:1 ratio to a conservative strategy of the best available medical therapy or an invasive strategy of coronary angiography and revascularization plus the best available medical therapy. Patients who were frail or had a high burden of coexisting conditions were eligible. The primary outcome was a composite of death from cardiovascular causes (cardiovascular death) or nonfatal myocardial infarction assessed in a time-to-event analysis. A total of 1518 patients underwent randomization; 753 patients were assigned to the invasive-strategy group and 765 to the conservative-strategy group. The mean age of the patients was 82 years, 45% were women, and 32% were frail. A primary-outcome event occurred in 193 patients (25.6%) in the invasive-strategy group and 201 patients (26.3%) in the conservative-strategy group (hazard ratio, 0.94; 95% confidence interval [CI], 0.77 to 1.14; P = 0.53) over a median follow-up of 4.1 years. Cardiovascular death occurred in 15.8% of the patients in the invasive-strategy group and 14.2% of the patients in the conservative-strategy group (hazard ratio, 1.11; 95% CI, 0.86 to 1.44). Nonfatal myocardial infarction occurred in 11.7% in the invasive-strategy group and 15.0% in the conservative-strategy group (hazard ratio, 0.75; 95% CI, 0.57 to 0.99). Procedural complications occurred in less than 1% of the patients. In older adults with NSTEMI, an invasive strategy did not result in a significantly lower risk of cardiovascular death or nonfatal myocardial infarction (the composite primary outcome) than a conservative strategy over a median follow-up of 4.1 years. (Funded by the British Heart Foundation; BHF SENIOR-RITA ISRCTN Registry number, ISRCTN11343602.).

In a randomized trial, patients with chest pain underwent a standard diagnostic evaluation with or without coronary CT angiography (CTA). The group assigned to CTA had a lower rate of death from coronary heart disease or nonfatal myocardial infarction at 5 years.

Non-ST-elevation myocardial infarction (NSTEMI) and unstable angina pectoris are frequent causes of hospital admission in the elderly. However, clinical trials targeting this population are scarce, and these patients are less likely to receive treatment according to guidelines. We aimed to investigate whether this population would benefit from an early invasive strategy versus a conservative strategy. In this open-label randomised controlled multicentre trial, patients aged 80 years or older with NSTEMI or unstable angina admitted to 16 hospitals in the South-East Health Region of Norway were randomly assigned to an invasive strategy (including early coronary angiography with immediate assessment for percutaneous coronary intervention, coronary artery bypass graft, and optimum medical treatment) or to a conservative strategy (optimum medical treatment alone). A permuted block randomisation was generated by the Centre for Biostatistics and Epidemiology with stratification on the inclusion hospitals in opaque concealed envelopes, and sealed envelopes with consecutive inclusion numbers were made. The primary outcome was a composite of myocardial infarction, need for urgent revascularisation, stroke, and death and was assessed between Dec 10, 2010, and Nov 18, 2014. An intention-to-treat analysis was used. This study is registered with ClinicalTrials.gov, number NCT01255540. During a median follow-up of 1·53 years of participants recruited between Dec 10, 2010, and Feb 21, 2014, the primary outcome occurred in 93 (40·6%) of 229 patients assigned to the invasive group and 140 (61·4%) of 228 patients assigned to the conservative group (hazard ratio [HR] 0·53 [95% CI 0·41–0·69], p=0·0001). Five patients dropped out of the invasive group and one from the conservative group. HRs for the four components of the primary composite endpoint were 0·52 (0·35–0·76; p=0·0010) for myocardial infarction, 0·19 (0·07–0·52; p=0·0010) for the need for urgent revascularisation, 0·60 (0·25–1·46; p=0·2650) for stroke, and 0·89 (0·62–1·28; p=0·5340) for death from any cause. The invasive group had four (1·7%) major and 23 (10·0%) minor bleeding complications whereas the conservative group had four (1·8%) major and 16 (7·0%) minor bleeding complications. In patients aged 80 years or more with NSTEMI or unstable angina, an invasive strategy is superior to a conservative strategy in the reduction of composite events. Efficacy of the invasive strategy was diluted with increasing age (after adjustment for creatinine and effect modification). The two strategies did not differ in terms of bleeding complications. Norwegian Health Association (ExtraStiftelsen) and Inger and John Fredriksen Heart Foundation.

Angina might persist or reoccur despite successful revascularisation with percutaneous coronary intervention (PCI) and antianginal therapy. Additionally, PCI in stable patients has not been shown to improve survival compared with optimal medical therapy. Trimetazidine is an antianginal agent that improves energy metabolism of the ischaemic myocardium and might improve outcomes and symptoms of patients who recently had a PCI. In this study, we aimed to assess the long-term potential benefits and safety of trimetazidine added to standard evidence-based medical treatment in patients who had a recent successful PCI. We did a randomised, double-blind, placebo-controlled, event-driven trial of trimetazidine added to standard background therapy in patients who had undergone successful PCI at 365 centres in 27 countries across Europe, South America, Asia, and north Africa. Eligible patients were aged 21–85 years and had had either elective PCI for stable angina or urgent PCI for unstable angina or non-ST segment elevation myocardial infarction less than 30 days before randomisation. Patients were randomly assigned by an interactive web response system to oral trimetazidine 35 mg modified-release twice daily or matching placebo. Participants, study investigators, and all study staff were masked to treatment allocation. The primary efficacy endpoint was a composite of cardiac death; hospital admission for a cardiac event; recurrence or persistence of angina requiring an addition, switch, or increase of the dose of at least one antianginal drug; or recurrence or persistence of angina requiring a coronary angiography. Efficacy analyses were done according to the intention-to-treat principle. Safety was assessed in all patients who had at least one dose of study drug. This study is registered with the EU Clinical Trials Register (EudraCT 2010-022134-89). From Sept 17, 2014, to June 15, 2016, 6007 patients were enrolled and randomly assigned to receive either trimetazidine (n=2998) or placebo (n=3009). After a median follow-up of 47·5 months (IQR 42·3–53·3), incidence of primary endpoint events was not significantly different between the trimetazidine group (700 [23·3%] patients) and the placebo group (714 [23·7%]; hazard ratio 0·98 [95% CI 0·88–1·09], p=0·73). When analysed individually, there were no significant differences in the incidence of the components of the primary endpoint between the treatment groups. Similar results were obtained when patients were categorised according to whether they had an elective or urgent PCI. 1219 (40·9%) of 2983 patients in the trimetazidine group and 1230 (41·1%) of 2990 patients in the placebo group had serious treatment-emergent adverse events. Frequencies of adverse events of interest were similar between the groups. Our results show that the routine use of oral trimetazidine 35 mg twice daily over several years in patients receiving optimal medical therapy, after successful PCI, does not influence the recurrence of angina or the outcome; these findings should be taken into account when considering the place of trimetazidine in clinical practice. However, the long-term prescription of this treatment does not appear to be associated with any statistically significant safety concerns in the population studied. Servier.

Heterogeneity is observed in the care of patients with chest pain. We investigate the association of physician specialty and diagnostic testing among patients admitted for suspected acute coronary syndrome (ACS). This is a secondary analysis of the CMR-IMPACT multicenter randomized controlled trial in which patients with suspected ACS were admitted and randomized to undergo invasive angiography or non-invasive CMR stress imaging. Admitting physician was dichotomized to interventional cardiologist (IC) or not (e.g. hospitalist). We describe adherence to protocol and angiography during the index visit by treatment arm and admitting physician specialty. A generalized estimating equation accounting for clustering within physician was used to evaluate significance and adjusted for randomization arm. The 258 enrolled patients from 2013 to 2018 had a mean age of 60.7 (SD ± 10.9) years, 40.3 % (104/258 were female), and 64.7 % (167/258) were white race. ICs were the admitting physicians for 50.4 % (130/258) of the patients. Index angiography was performed more often among patients admitted by IC versus other physicians, 65.4 % (85/130) versus 53.1 % (68/128), respectively; aOR 1.75 (95 % CI 1.14–2.68). Among patients randomized to an invasive strategy, higher protocol adherence was observed in those admitted by IC [85.3 % (58/68)] versus other physicians [64.5 % (40/62)]; OR 2.82 (95 % CI 1.08–7.38). For patients randomized to the CMR-based strategy, adherence to protocol was similar for IC [67.7 % (42/62)] and other physicians [66.7 % (44/66)]; OR 0.82 (95 % CI 0.35–1.94). Invasive angiography was more frequent among patients admitted by interventional cardiologists compared to other physicians.

Although sex differences exist in the management of acute coronary syndromes, less is known about the management and outcomes of women and men with suspected coronary artery disease being evaluated with noninvasive testing (NIT). We investigated sex-based differences in NIT results and subsequent clinical management in 4,720 women and 4,246 men randomized to CT angiography versus stress testing in the PROMISE trial. Logistic regression models assessed relationships between sex and referral for catheterization, revascularization, and aspirin or statin use. Cox regression models assessed the relationship between sex and the composite of all-cause death, myocardial infarction, or unstable angina. Women more often had normal NITs than men (61.0% vs 49.6%, P < .001) and less often had mild (29.3% vs 35.4%, P < .001), moderate (4.0% vs 6.8%, P < .001), or severe abnormalities (5.7% vs 8.3%, P < .001) found on NIT. Women were less likely to be referred for catheterization than men (7.6% vs 12.6%, adjusted OR 0.75 [0.62-0.90]; P = .002). Of those who underwent catheterization within 90 days of randomization (358 women, 534 men), fewer women than men had obstructive coronary artery disease (40.8% vs 60.9%, P < .001). At a 60-day visit, women were significantly less likely than men to report statin use when indicated (adjusted OR 0.81 [0.73-0.91]; P < .001) but were similarly likely to report aspirin use when indicated (adjusted OR 0.78 [0.56-1.08]; P = .13). Over a median follow-up of 25 months, women had better outcomes than men (adjusted OR 0.73 [0.57-0.94]; P = .017). Although women more frequently had normal NITs compared with men, those with abnormalities on NIT were less likely to be referred for catheterization or to receive statin therapy. The high rates of negative NIT in women, coupled with the better outcomes compared with men, strongly support the need for a sex-specific algorithm to guide NIT and chest pain management.

Delayed admission of myocardial infarction (MI) patients is an important prognostic factor. In the present nationwide registry (TURKMI-2), we evaluated the treatment delays and outcomes of patients with acute MI during the Covid-19 pandemic and compaired with a recentpre-pandemic registry (TURKMI-1). The pandemic and pre-pandemic studies were conducted prospectively as 15-day snapshot registries in the same 48 centers. The inclusion criteria for both registries were aged ≥18 years and a final diagnosis of acute MI (AMI) with positive troponin levels. The only difference between the 2 registries was that the pre-pandemic (TURKMI-1) registry (n=1872) included only patients presenting within the first 48 hours after symptom-onset. TURKMI-2 enrolled all consecutive patients (n=1113) presenting with AMI during the pandemic period. A comparison of the patients with acute MI presenting within the 48-hour of symptom-onset in the pre-pandemic and pandemic registries revealed an overall 47.1% decrease in acute MI admissions during the pandemic. Median time from symptom-onset to hospital-arrival increased from 150 min to 185 min in patients with ST elevation MI (STEMI) and 295 min to 419 min in patients presenting with non-STEMI (NSTEMI) (p-values <0.001). Door-to-balloon time was similar in the two periods (37 vs. 40 min, p=0.448). In the pandemic period, percutaneous coronary intervention (PCI) decreased, especially in the NSTEMI group (60.3% vs. 47.4% in NSTEMI, p<0.001; 94.8% vs. 91.1% in STEMI, p=0.013) but the decrease was not significant in STEMI patients admitted within 12 hours of symptom-onset (94.9% vs. 92.1%; p=0.075). In-hospital major adverse cardiac events (MACE) were significantly increased during the pandemic period [4.8% vs. 8.9%; p<0.001; age- and sex-adjusted Odds ratio (95% CI) 1.96 (1.20-3.22) for NSTEMI, p=0.007; and 2.08 (1.38-3.13) for STEMI, p<0.001]. The present comparison of 2 nationwide registries showed a significant delay in treatment of patients presenting with acute MI during the COVID-19 pandemic. Although PCI was performed in a timely fashion, an increase in treatment delay might be responsible for the increased risk of MACE. Public education and establishing COVID-free hospitals are necessary to overcome patients' fear of using healthcare services and mitigate the potential complications of AMI during the pandemic. (Anatol J Cardiol 2020; 24: 334-42).

BackgroundThe HEART score, the T-MACS model and the GRACE score support early decision-making for acute chest pain, which could be complemented by CT coronary angiography (CTCA). However, their performance has not been directly compared.MethodsIn this secondary analysis of a multicentre randomised controlled trial of early CTCA in intermediate-risk patients with suspected acute coronary syndrome, C-statistics and performance metrics (using the predefined cut-offs) of clinical decision aids and CTCA, alone and then in combination, for the index hospital diagnosis of acute coronary syndrome and for 30-day coronary revascularisation were assessed in those who underwent CTCA and had complete data.ResultsAmong 699 patients, 358 (51%) had an index hospital diagnosis of acute coronary syndrome, for which the C-statistic was higher for CTCA (0.80), followed by the T-MACS model (0.78), the HEART score (0.74) and the GRACE score (0.60). The negative predictive value was higher for the absence of coronary artery disease on CTCA (0.90) or a T-MACS estimate of <0.05 (0.83) than a HEART score of <4 (0.81) and a GRACE score of <109 (0.55). For 30-day coronary revascularisation, CTCA had the greatest C-statistic (0.80) with a negative predictive value of 0.96 and 0.92 in the absence of coronary artery disease and obstructive coronary artery disease, respectively. The combination of the T-MACS estimates and the CTCA findings was most discriminative for the index hospital diagnosis of acute coronary syndrome (C-statistic, 0.88) and predictive of 30-day coronary revascularisation (C-statistic, 0.85). No patients with a T-MACS estimate of <0.05 and normal coronary arteries had acute coronary syndrome during index hospitalisation or underwent coronary revascularisation within 30 days.ConclusionsIn intermediate-risk patients with suspected acute coronary syndrome, the T-MACS model combined with CTCA improved discrimination of the index hospital diagnosis of acute coronary syndrome and prediction of 30-day coronary revascularisation.Trial registration number NCT02284191.

ObjectivesTo determine resource utilisation according to age and gender-specific subgroups in two large randomized diagnostic trials.MethodsWe pooled patient-specific data from ACRIN-PA 4005 and ROMICAT II that enrolled subjects with acute chest pain at 14 US sites. Subjects were randomized between a standard work-up and a pathway utilizing cardiac computed tomography angiography (CCTA) and followed for the occurrence of acute coronary syndrome (ACS) and resource utilisation during index hospitalisation and 1-month follow-up. Study endpoints included diagnostic accuracy of CCTA for the detection of ACS as well as resource utilisation.ResultsAmong 1240 patients who underwent CCTA, negative predictive value of CCTA to rule out ACS remained very high (≥99.4%). The proportion of patients undergoing additional diagnostic testing and cost increased with age for both sexes (p < 0.001), and was higher in men as compared to women older than 60 years (43.1% vs. 23.4% and $4559 ± 3382 vs. $3179 ± 2562, p < 0.01; respectively). Cost to rule out ACS was higher in men (p < 0.001) and significantly higher for patients older than 60 years ($2860–5935 in men, p < 0.001).ConclusionsCCTA strategy in patients with acute chest pain results in varying resource utilisation according to age and gender-specific subgroups, mandating improved selection for advanced imaging.Key Points• In this analysis, CAD and ACS increased with age and male gender.• CCTA in patients with acute chest pain results in varying resource utilisation.• Significant increase of diagnostic testing and cost with age for both sexes.• Cost to rule out ACS is higher in men and patients >60 years.• Improved selection of subjects for cardiac CTA result in more resource-driven implementation.

A number of investigative strategies exist for the diagnosis of coronary heart disease (CHD). Despite the widespread availability of noninvasive imaging, invasive angiography is commonly used early in the diagnostic pathway. Consequently, approximately 60% of angiograms reveal no evidence of obstructive coronary disease. Reducing unnecessary angiography has potential financial savings and avoids exposing the patient to unnecessary risk. There are no large-scale comparative effectiveness trials of the different diagnostic strategies recommended in international guidelines and none that have evaluated the safety and efficacy of cardiovascular magnetic resonance. CE-MARC 2 is a prospective, multicenter, 3-arm parallel group, randomized controlled trial of patients with suspected CHD (pretest likelihood 10%-90%) requiring further investigation. A total of 1,200 patients will be randomized on a 2:2:1 basis to receive 3.0-T cardiovascular magnetic resonance–guided care, single-photon emission computed tomography–guided care (according to American College of Cardiology/American Heart Association appropriate-use criteria), or National Institute for Health and Care Excellence guidelines–based management. The primary (efficacy) end point is the occurrence of unnecessary angiography as defined by a normal (>0.8) invasive fractional flow reserve. Safety of each strategy will be assessed by 3-year major adverse cardiovascular event rates. Cost-effectiveness and health-related quality-of-life measures will be performed. The CE-MARC 2 trial will provide comparative efficacy and safety evidence for 3 different strategies of investigating patients with suspected CHD, with the intension of reducing unnecessary invasive angiography rates. Evaluation of these management strategies has the potential to improve patient care, health-related quality of life, and the cost-effectiveness of CHD investigation.