Prevalence and Impact of Frailty in Patients ≥70 Years Old with Acute Coronary Syndrome Referred for Coronary Angiography.

INTRODUCTION: Elderly patients with acute coronary syndrome (ACS) have a higher risk of adverse cardiovascular events and may be frail but are underrepresented in clinical trials. Previous studies have proposed that frailty assessment is a better tool than chronological age, in assessing older patients' biological age, and may exceed conventional risk scores in predicting the prognosis. Therefore, we wanted to investigate the prevalence and impact on 12-month outcomes of frailty in patients ≥70 years with ACS referred for coronary angiography (CAG). METHODS: Patients ≥70 years with ACS referred for CAG underwent frailty scoring with the clinical frailty scale (CFS). Patients were divided into three groups depending on their CFS: robust (1-3), vulnerable (4), and frail (5-9) and followed for 12 months. RESULTS: Of 455 patients, 69 (15%) patients were frail, 79 (17%) were vulnerable, and 307 (68%) were robust. Frail patients were older (frail: 80.9 ± 5.7 years, vulnerable: 78.5 ± 5.5 years, and robust: 76.6 ± 4.9 years, p < 0.001) and less often treated with percutaneous coronary intervention (frail: 56.5%, vulnerable: 53.2%, and robust: 68.6%, p = 0.014). 12-month mortality was higher among frail patients (frail: 24.6%, vulnerable: 21.8%, and robust: 6.2%, p < 0.001). Frailty was associated with a higher mortality after adjustment for age, sex, comorbidities, the Global Registry of Acute Coronary Events (GRACE) score, and revascularisation (HR 2.67, 95% CI 1.30-5.50, p = 0.008). There was no difference between GRACE and CFS in predicting 12-month mortality (p = 0.893). CONCLUSIONS: Fifteen percent of patients ≥70 years old with ACS referred for CAG are frail. Frail patients have significantly higher 12-month mortality. GRACE and CFS are similar in predicting 12-month mortality.

Angiographic and Procedural Characteristics in Frail Older Patients with Non-ST Elevation Acute Coronary Syndrome.

Background: Angiographic and procedural characteristics stratified by frailty status are not known in older patients with non-ST elevation acute coronary syndrome (NSTEACS). We evaluated angiographic and procedural characteristics in older adults with NSTEACS by frailty category, as well as associations of baseline and residual SYNTAX scores with long-term outcomes. Methods: In this study, 271 NSTEACS patients aged ≥75 years underwent coronary angiography. Frailty was assessed using the Fried criteria. Angiographic analysis was performed using QAngio® XA Medis in a core laboratory. Major adverse cardiovascular events (MACE) consisted of all-cause mortality, MI, stroke or transient ischaemic attack, repeat unplanned revascularisation and significant bleeding. Results: Mean (±SD) patient age was 80.5 ± 4.9 years. Compared with robust patients, patients with frailty had more severe culprit lesion calcification (OR 5.40; 95% CI [1.75-16.8]; p=0.03). In addition, patients with frailty had a smaller mean improvement in culprit lesion stenosis after percutaneous coronary intervention (50.6%; 95% CI [45.7-55.6]) than robust patients (58.6%; 95% CI [53.5-63.7]; p=0.042). There was no association between frailty phenotype and completeness of revascularisation (OR 0.83; 95% CI [0.36-1.93]; p=0.67). A high baseline SYNTAX score (≥33) was associated with adjusted (age and sex) 5-year MACE (HR 1.40; 95% CI [1.08-1.81]; p=0.01), as was a high residual SYNTAX score (≥8; adjusted HR 1.22; 95% CI [1.00-1.49]; p=0.047). Conclusion: Frail adults presenting with NSTEACS have more severe culprit lesion calcification. Frail adults were just as likely as robust patients to receive complete revascularisation. Baseline and residual SYNTAX score were associated with MACE at 5 years.

Sex-based Differences in Percutaneous Coronary Intervention Outcomes in Patients with Ischaemic Heart Disease.

In high-income countries, ischaemic heart disease is the leading cause of death in women and men, accounting for more than 20% of deaths in both sexes. However, women are less likely to receive guideline-recommended percutaneous coronary intervention (PCI) than men. Women undergoing PCI have poorer unadjusted outcomes because they are older and have greater comorbidity than men, but uncertainty remains whether sex affects outcome after these differences in clinical characteristics are considered. In this paper, we review recent published evidence comparing outcomes between men and women undergoing PCI. We focus on the sex differences in PCI outcomes in different scenarios: acute coronary syndromes, stable angina and complex lesions, including the approach of left main coronary artery. We also review how gender is considered in recent guidelines and offer a common clinical scenario to illustrate the contemporary management strategies an interventional cardiologist should consider when performing PCI on a female patient.

Sex differences in treatment and outcomes amongst myocardial infarction patients presenting with and without obstructive coronary arteries: a prospective multicentre study.

Aims: Women have an increased prevalence of myocardial infarction (MI) with non-obstructive coronary arteries (MINOCA). Whether sex differences exist in the outcomes of patients with MI and obstructive coronary arteries (MIOCA) vs. MINOCA remains unclear. We describe sex-based differences in diagnosis, treatment, and clinical outcomes of patients with MINOCA vs. MIOCA. Methods and results: A large-scale cohort study of patients with ST/non-ST elevation MI undergoing coronary angiography (01/2015-12/2019). Patient demographics, diagnosis, prescribed discharge medications, in-hospital complications, and follow-up data were prospectively collected. A total of 13 202 participants were included (males 68.2% and females 31.8%). 10.9% were diagnosed with MINOCA. Median follow-up was 4.62 years. Females (44.8%) were as commonly diagnosed with MINOCA as males (55.2%), unlike the male preponderance in MIOCA (male, 69.8%; female, 30.2%). Less secondary prevention medications were prescribed at discharge for MINOCA than MIOCA. There was no difference in mortality risk between MINOCA and MIOCA [in-hospital: adjusted odds ratio (OR) 1.32, 95% confidence interval (CI) 0.74-2.35, P = 0.350; long term: adjusted hazard ratio (HR) 1.03, 95% CI 0.81-1.31, P = 0.813]. MINOCA patients had reduced mortality at long-term follow-up if prescribed secondary prevention medications (aHR 0.64, 95% CI 0.47-0.87, P = 0.004). Females diagnosed with MIOCA had greater odds of in-hospital and 1-year mortality than males (aOR 1.50, 95% CI 1.09-2.07, P = 0.014; aHR 1.18, 95% CI 1.01-1.38, P = 0.048). Conclusion: MINOCA patients have similar mortality rates as MIOCA patients. MINOCA patients were less likely than those with MIOCA to be discharged with guideline-recommended secondary prevention therapy; however, those with MINOCA who received secondary prevention survived longer. Females with MIOCA experienced higher mortality rates vs. males.

Coronary CT and timing of invasive coronary angiography in patients ≥75 years old with non-ST segment elevation acute coronary syndromes.

BACKGROUND: The ability of coronary CT angiography (cCTA) to rule out significant coronary artery disease (CAD) in older patients with non-ST segment elevation acute coronary syndromes (NSTEACS) is unclear since valid cCTA analysis may be limited by extensive coronary artery calcification. In addition, the effect of very early invasive coronary angiography (ICA) with possible revascularisation is debated. METHODS: This is a posthoc analysis of patients ≥75 years included in the Very Early vs Standard Care Invasive Examination and Treatment of Patients with Non-ST-Segment Elevation Acute Coronary Syndrome Trial. cCTA was performed prior to the ICA. The diagnostic accuracy of cCTA was investigated. Presence of a coronary artery stenosis ≥50% by subsequent ICA was used as reference. Patients were randomised to a very early (within 12 hours of diagnosis) or a standard ICA (within 48-72 hours of diagnosis). The primary composite endpoint was 5-year all-cause mortality, non-fatal recurrent myocardial infarction or hospital admission for refractory myocardial ischaemia or heart failure. RESULTS: Of 452 (21%) patients ≥75 years, 161 (35.6%) underwent cCTA. 19% of cCTAs excluded significant CAD. The negative predictive value (NPV) of cCTA was 94% (95% CI 79 to 99) and the sensitivity 98% (95% CI 94 to 100). No significant differences in the frequency of primary endpoints were seen in patients randomised to very early ICA (at 5-year follow-up, n=100 (46.9%) vs 122 (51.0%), log-rank p=0.357). CONCLUSION: In patients ≥75 years with NSTEACS, cCTA before ICA showed a high NPV. A very early ICA <12 hours of diagnosis did not significantly improve long-term clinical outcomes.

Sex differences in long-term outcomes in older adults undergoing invasive treatment for non-ST elevation acute coronary syndrome: An ICON-1 sub-study.

Background: Cardiovascular disease is the leading cause of mortality for females globally, yet females are underrepresented in studies of acute coronary syndrome (ACS). Studies investigating sex-related differences in clinical outcomes of patients with non-ST elevation ACS (NSTEACS) have reported divergent results, and it is unknown whether long-term outcomes for older people with NSTEACS differ between males and females. Methods: The multi-centre prospective cohort study, ICON-1, consisted of patients aged ≥75 years undergoing coronary angiography following NSTEACS. The primary composite endpoint was all-cause mortality, myocardial infarction, unplanned revascularisation, stroke, and bleeding. We report outcomes at five-years by sex. Results: Of 264 patients, 102 (38.6%) females and 162 (61.4%) males completed the five-year follow-up and were included in the analytic cohort. At admission, females were older than males (82 ± 4.3 years vs 80.0 ± 4.1 years p = 0.018). Co-morbidity profile and GRACE score were similar between the groups. There were no differences in the provision of invasive or pharmacological treatments between sexes. At five-years, there were no association between sex and the primary outcome. Conclusion: In older adults with invasive treatment of NSTEACS, provision of guideline-indicated care and long-term clinical outcomes were similar between males and females.

Five-year clinical outcomes in patients with frailty aged ≥75 years with non-ST elevation acute coronary syndrome undergoing invasive management.

Aim: Frailty is associated with adverse outcomes in older patients with acute coronary syndrome (ACS). The impact of frailty on long-term clinical outcomes following invasive management of non-ST elevation ACS (NSTEACS) is unknown. Methods and results: The multi-centre Improve Clinical Outcomes in high-risk patieNts with ACS 1 (ICON-1) prospective cohort study consisted of patients aged >75 years undergoing coronary angiography following NSTEACS. Patients were categorized by frailty assessed by Canadian Study of Health and Ageing Clinical Frailty Scale (CFS) and Fried criteria. The primary composite endpoint was all-cause mortality, unplanned revascularization, myocardial infarction, stroke, and bleeding. Of 263 patients, 33 (12.5%) were frail, 152 (57.8%) were pre-frail, and 78 (29.7%) were robust according to CFS. By Fried criteria, 70 patients (26.6%, mean age 82.1 years) were frail, 147 (55.9%, mean age 81.3 years) were pre-frail, and 46 (17.5%, mean age 79.9 years) were robust. The composite endpoint was more common at 5 years among patients with frailty according to CFS (frail: 22, 66.7%; pre-frail: 81, 53.3%; robust: 27, 34.6%, P = 0.003), with a similar trend when using Fried criteria (frail: 39, 55.7%; pre-frail: 72, 49.0%; robust: 16, 34.8%, P = 0.085). Frailty measured with both CFS and Fried criteria was associated with the primary endpoint [age and sex-adjusted hazard ratio (HR) compared with robust groups. CFS: 2.22, 95% confidence interval (CI) 1.23-4.02, P = 0.008; Fried: HR 1.81, 95% CI 1.00-3.27, P = 0.048]. Conclusion: In older patients who underwent angiography following NSTEACS, frailty is associated with an increased risk of the primary composite endpoint at 5 years. Registration: Clinicaltrials.gov NCT01933581.

Is the contemporary care of the older persons with acute coronary syndrome evidence-based?

Globally, ischaemic heart disease is the leading cause of death, with a higher mortality burden amongst older adults. Although advancing age is associated with a higher risk of adverse outcomes following acute coronary syndrome (ACS), older patients are less likely to receive evidence-based medications and coronary angiography. Guideline recommendations for managing ACS are often based on studies that exclude older patients, and more contemporary trials have been underpowered and produced inconsistent findings. There is also limited evidence for how frailty and comorbidity should influence management decisions. This review focuses on the current evidence base for the medical and percutaneous management of ACS in older patients and highlights the distinct need to enrol older patients with ACS into well-powered, large-scale randomized trials.

Impact of multimorbidity on long-term outcomes in older adults with non-ST elevation acute coronary syndrome in the North East of England: a multi-centre cohort study of patients undergoing invasive care.

OBJECTIVES: Older adults have a higher degree of multimorbidity, which may adversely affect longer term outcomes from non-ST elevation acute coronary syndrome (NSTE-ACS). We investigated the impact of multimorbidity on cardiovascular outcomes 5 years after invasive management of NSTE-ACS. DESIGN: Prospective cohort study. SETTING: Multicentre study conducted in the north of England. PARTICIPANTS: 298 patients aged ≥75 years with NSTE-ACS and referred for coronary angiography, with 264 (88.0%) completing 5-year follow-up. MAIN OUTCOME MEASURES: Multimorbidity was evaluated at baseline with the Charlson comorbidity index (CCI). The primary composite outcome was all-cause mortality, myocardial infarction, stroke, urgent repeat revascularisation or significant bleeding. RESULTS: Mean age was 80.9 (±6.1) years. The cohort median CCI score was 5 (IQR 4-7). The primary composite outcome occurred in 48.1% at 5 years, at which time 31.0% of the cohort had died. Compared with those with few comorbidities (CCI score 3-5), a higher CCI score (≥6) was positively associated with the primary composite outcome (adjusted HR (aHR) 1.64 (95% CI 1.14 to 2.35), p=0.008 adjusted for age and sex), driven by an increased risk of death (aHR 2.20 (1.38 to 3.49), p=0.001). For each additional CCI comorbidity, on average, there was a 20% increased risk of the primary composite endpoint at 5 years (aHR 1.20 (1.09 to 1.33), p<0.001). CONCLUSIONS: In older adults with NSTE-ACS referred for coronary angiography, the presence of multimorbidity is associated with an increased risk of long-term adverse cardiovascular events, driven by a higher risk of all-cause mortality. TRIAL REGISTRATION NUMBER: NCT01933581; ClinicalTrials.gov.

Evidence base for the management of women with non-ST elevation acute coronary syndrome.

According to the Global Burden of Disease study, in 2019, there were an estimated 275.2 million cases of cardiovascular disease (CVD) in women worldwide. Although there was a decrease in the global age-standardised prevalence of CVD in women between 1990 and 2010 (-5.8%), there has been a slight increase (1.0%) since 2010. There were an estimated 6.10 million deaths from CVD in women in 1990, rising to 8.94 million in 2019. Hospital admissions of young women with acute myocardial infarction (AMI) steadily increased from 27% in 1995-1999 to 32% in 2010-2014. Women with AMI compared with men are less likely to receive guideline-indicated pharmacological (aspirin 93.4% vs 94.7%, P2Y12 inhibitors 79.3% vs 86.1% and statins 73.7% vs 77.5%) and revascularisation treatments (angiography (adjusted OR (aOR) 0.71), percutaneous coronary intervention (aOR 0.73)). Women represent <39% of clinical cardiovascular trial participants between 2010 and 2017. Major factors of under-representation in studies included concerns about the burden of participation on health and time. Women were more likely than men to document caring responsibilities as reasons for not participating in a clinical trial. Current clinical practice guidelines recommending risk stratification to guide the appropriateness of an invasive strategy in the context of acute coronary syndrome (ACS) may not be applicable to women given lack of studies specifically evaluating women using contemporary treatment strategies. In our review, we identify significant limitations in the evidence base for the best care of women with ACS, emphasising the need for well-designed clinical trials specifically recruiting women.

Outcome in Elderly Patients With Cardiogenic Shock Complicating Acute Myocardial Infarction.

INTRODUCTION: Despite advances in treatment of patients with cardiogenic shock following acute myocardial infarction (AMICS) in-hospital mortality remains around 50%. Outcome varies among patient subsets and the elderly often have a poor a priori prognosis. We sought to investigate outcome among elderly AMICS patients referred to evaluation and treatment at a tertiary university hospital. METHODS: Current analysis was based on the RETROSHOCK registry comprising consecutive AMICS patients admitted to tertiary care. Patients in the registry were individually identified and validated. RESULTS: Of 1,716 admitted patients, 496 (28.9%) patients were ≥75 years old. Older patients were less likely to be admitted directly to a tertiary centre (59.4% vs. 69.9%, P = 0.003), receive mechanical support devices (i.e., Impella® (8.9% vs. 15.0%, P = 0.003), and undergo revascularization attempt (76.8% vs. 90.2%, P < 0.001). Thirty-day survivors ≥75 years were characterized by having higher left ventricular ejection fraction (30.2% ±â€Š12.5% vs. 26.5% ±â€Š11.8%, P = 0.004) and lower arterial lactate (3.2[2.2-5.2] mmol/L vs. 5.5[3.3-8.2] mmol/L, P < 0.001) at admission. In a multivariable analysis of patients ≥75 years, higher age (HR 1.09, 95% CI 1.05-1.14, P < 0.001), higher heart rate (HR 1.01, 95% CI 1.001-1.014, P = 0.03), and higher lactate (HR 1.11, 95% CI 1.07-1.16, P < 0.001) at admission were associated with an increased risk of 30-day mortality. CONCLUSION: Among patients ≥75 years with AMICS referred for tertiary specialized treatment, 30-day mortality was 73.4%. Survivors were characterized by lower arterial lactate and heart rate at admission.

Incidence, Predictors, and Outcome of In-Hospital Bleeding in Patients With Cardiogenic Shock Complicating Acute Myocardial Infarction.

Bleeding after acute myocardial infarction (AMI) is associated with an increased morbidity and mortality. The frequency and consequences of bleeding events in patients with AMICS are not well described. The objective was to investigate incidence and outcome of bleeding complications among unselected patients with AMI complicated by cardiogenic shock (AMICS) and referred for immediate revascularization. Bleeding events were assessed by review of medical records in consecutive AMICS patients admitted between 2010 and 2017. Bleedings during admission were classified according to Bleeding Academic Research Consortium classification. Patients who did not survive to admission in the intensive care unit were excluded. Of the 1,716 patients admitted with AMICS, 1,532 patients (89%) survived to ICU admission. At 30 days, mortality was 48%. Severe bleedings classified as BARC 3/5 were seen in 87 non-coronary bypass grafting patients (6.1%). Co-morbidity did not differ among patients; however, patients who had a BARC 3/5 bleeding had significantly higher lactate and lower systolic blood pressure at admission, indicating a more severe state of shock. The use of mechanical assist devices was significantly associated with severe bleeding events. Univariable analysis showed that patients with a BARC 3/5 bleeding had a significantly higher 30-day mortality hazard compared with patients without severe bleedings. The association did not sustain after multivariable adjustment (hazard ratio 0.90, 95% confidence interval 0.64; 1.26, p = 0.52). In conclusion, severe bleeding events according to BARC classification in an all-comer population of patients with AMICS were not associated with higher mortality when adjusting for immediate management, hemodynamic, and metabolic state. This indicates that mortality in these patients is primarily related to other factors.

The effect of TIcagrelor administered through a nasogastric tube to COMAtose patients undergoing acute percutaneous coronary intervention: the TICOMA study.

AIMS: Patients in a coma after cardiac arrest may have adversely affected drug absorption and metabolism. This study, the first of its kind, aimed to investigate the early pharmacokinetic and pharmacodynamic effects of ticagrelor administered through a nasogastric tube (NGT) to patients resuscitated after an out of hospital cardiac arrest (OHCA) and undergoing primary percutaneous coronary intervention (pPCI). METHODS AND RESULTS: Blood samples were drawn at baseline and at two, four, six, eight, 12, and 24 hours and then daily for up to five days after administration of a 180 mg ticagrelor loading dose (LD), followed by 90 mg twice daily in 44 patients. The primary endpoint was the occurrence of high platelet reactivity (HPR) 12 hours after the LD. Assessment by VerifyNow (VFN) showed 96 (15.25-140.5) platelet reactivity units (PRU), and five (12%) patients exhibited HPR. Multiplate analysis showed 19 (12-29) units (U) at twelve hours, and three patients (7%) had HPR. Ticagrelor and its main metabolite AR-C124910XX concentrations were 85.2 (37.2-178.5) and 18.3 (6.4-52.4) ng/mL. Median times to sufficient platelet inhibition below the HPR limit were 3 (2-6) hours (VFN) and 4 (2-8) hours (Multiplate). CONCLUSIONS: Ticagrelor, administered as crushed tablets through a nasogastric tube, leads to sufficient platelet inhibition after 12 hours, and in many cases earlier, in the vast majority of patients undergoing pPCI and subsequent intensive care management after an OHCA.

Traditional clinical risk factors predict clopidogrel hypo-responsiveness in unselected patients undergoing non-emergent percutaneous coronary intervention.

High and low platelet reactivity, HPR and LPR respectively, to clopidogrel and aspirin have previously been associated with adverse events following percutaneous coronary intervention (PCI). The aim is to test the ability of a previously developed clinical risk-score, the PREDICT score, to identify patients with HPR and LPR. Nine hundred and twenty-three consecutive patients undergoing non-emergent PCI were enrolled. Platelet reactivity (PR) was determined using Multiplate assays. Patients were grouped into quintiles based on their PR values. Upper and lower quintiles defined HPR and LPR, respectively, whereas quintiles 2-4 defined normal responders. All patients were assigned PREDICT score points in clinical categories (age > 65, reduced left ventricular function, reduced kidney function, acute coronary syndrome (ACS) and diabetes). We found an association between the cumulative number of PREDICT score variables and the incidence of HPR for clopidogrel (HPR (ADP)) (p < 0.001) and aspirin (HPR (AA)) (p = 0.007). In addition, the higher the PREDICT score, the higher the risk of HPR (ADP) (1-3 points, odds ratio (OR) 3.82 (95% CI 1.5-9.73, p = 0.005); 4-6 points OR 4.11 (95% CI 1.61-10.52, p = 0.003); 7-9 points OR 9.84 (95% CI 3.49-27.7, p < 0.001); patients with 0 PREDICT points defined the reference population). The relation was reversed with regards to clopidogrel LPR (LPR (ADP)). On the other hand, there was no clear association between PREDICT score and AA response. The PREDICT score was able to identify patients with a high risk of HPR (ADP) but did not correlate well with PR to AA. In order to assure an optimal tailoring of antiplatelet therapy, costly platelet function tests (PFTs) could be reserved for patients with high clinical likelihood for HPR.

Prehospital administration of P2Y12 inhibitors and early coronary reperfusion in primary PCI: an observational comparative study.

The newer oral P2Y12 inhibitors prasugrel and ticagrelor have been reported to be more potent and faster-acting antiplatelet agents than clopidogrel. This study aimed to investigate whether prehospital loading with prasugrel or ticagrelor improves early coronary reperfusion as compared to prehospital loading with clopidogrel in a real-world ST-elevation myocardial infarction (STEMI) setting. Over a 70-month period, 3497 patients with on-going STEMI of less than 6 hours and without cardiac arrest or cardiogenic shock underwent primary percutaneous coronary intervention (PPCI) at our centre. The primary endpoint of this study was the proportion of patients who did not meet the criteria for TIMI (Thrombolysis In Myocardial Infarction) flow grade 3 in the infarct-related artery at initial angiography before PPCI. Prehospital loading with prasugrel (n = 883) or ticagrelor (n = 491) did not significantly improve coronary reperfusion as compared to prehospital loading with clopidogrel (n = 1,532) - a TIMI-flow 3 at initial angiography was absent in 71.7 %, 69.0 % and 71.5 % of patients, respectively. Major adverse cardiac event (MACE) rates were low at 30 days (3.4 % to 4.0 %) and did not significantly differ between the different P2Y12 inhibitor regimens. In conclusion, this large observational, non-randomised study is the first to show that prehospital loading with the newer P2Y12 inhibitors does not improve early coronary reperfusion as compared to prehospital loading with clopidogrel in a PPCI cohort excluding cardiac arrest and cardiogenic shock.