Clopidogrel induced reduction in neutrophil count: An overlooked beneficial effect?

Complement-stimulated neutrophils are able to adhere to the endothelium and damage endothelial cells both in vitro and in vivo. These blood cells participate in the early stages, growth and complications of atherosclerotic plaques. Recent findings, based on mendelian randomization analysis, support the concept that high neutrophil counts are a causal risk factor for ischemic heart disease and myocardial infarction . Clopidogrel decreases leukocyte count and inflammatory markers in patients with acute coronary syndromes; this off-target effect, which is independent of the antiplatelet action, may help explaining secondary prevention data showing a superiority of clopidogrel over aspirin in reducing new cardiovascular events.

Invasive vs. conservative management of older patients with non-ST-elevation acute coronary syndrome: individual patient data meta-analysis.

BACKGROUND AND AIMS: Older patients with non-ST-elevation acute coronary syndrome (NSTEACS) are less likely to receive guideline-recommended care including coronary angiography and revascularization. Evidence-based recommendations regarding interventional management strategies in this patient cohort are scarce. This meta-analysis aimed to assess the impact of routine invasive vs. conservative management of NSTEACS by using individual patient data (IPD) from all available randomized controlled trials (RCTs) including older patients. METHODS: MEDLINE, Web of Science and Scopus were searched between 1 January 2010 and 11 September 2023. RCTs investigating routine invasive and conservative strategies in persons >70 years old with NSTEACS were included. Observational studies or trials involving populations outside the target range were excluded. The primary endpoint was a composite of all-cause mortality and myocardial infarction (MI) at 1 year. One-stage IPD meta-analyses were adopted by use of random-effects and fixed-effect Cox models. This meta-analysis is registered with PROSPERO (CRD42023379819). RESULTS: Six eligible studies were identified including 1479 participants. The primary endpoint occurred in 181 of 736 (24.5%) participants in the invasive management group compared with 215 of 743 (28.9%) participants in the conservative management group with a hazard ratio (HR) from random-effects model of 0.87 (95% CI 0.63-1.22; P = .43). The hazard for MI at 1 year was significantly lower in the invasive group compared with the conservative group (HR from random-effects model 0.62, 95% CI 0.44-0.87; P = .006). Similar results were seen for urgent revascularization (HR from random-effects model 0.41, 95% CI 0.18-0.95; P = .037). There was no significant difference in mortality. CONCLUSIONS: No evidence was found that routine invasive treatment for NSTEACS in older patients reduces the risk of a composite of all-cause mortality and MI within 1 year compared with conservative management. However, there is convincing evidence that invasive treatment significantly lowers the risk of repeat MI or urgent revascularisation. Further evidence is needed from ongoing larger clinical trials.

Current Spectrum and Outcomes of Infarct-Related Cardiogenic Shock: Insights from the CULPRIT-SHOCK Registry and RCT.

BACKGROUND: We analysed consecutive patients with acute myocardial infarction complicated by cardiogenic shock (CS) who were enrolled into the CULPRIT-SHOCK randomized controlled trial (RCT) and those with exclusion criteria who were included into the accompanying registry. METHODS: In total, 1,075 patients with infarct-related CS were screened for CULPRIT-SHOCK in 83 specialised centres in Europe; 369 of them had exclusion criteria for the RCT and were enrolled into the registry. Patients were followed over 1-year. RESULTS: Mean age was 68 years and 260 (25 %) were women. 13.5 %, 30.9 %, and 55.6 % had 1-vessel, 2-vessel, and 3-vessel coronary artery disease (CAD), respectively. Significant left main (LM) coronary artery stenosis was present in 8.0 %. 54.2 % of the patients had cardiac arrest before admission. TIMI 3 patency of the infarct vessel after PCI was achieved in 83.6 % of all patients. Mechanical circulatory support was applied in one third of patients. Total mortality after 30 days and one year was 47.6 % and 52.9 %. Mortality after one year was highest in patients with LM coronary artery stenosis (63.5 %), followed by 3-vessel- (56.6 %), 2-vessel- (49.8 %), and 1-vessel-CAD (38.6 %), respectively. Mechanical complications were rare (21/1008; 2.1 %) but associated with a high mortality of 66.7 % after 1 year. CONCLUSIONS: In specialised centres in Europe short- and long-term mortality of patients with infarct-related CS treated with an invasive strategy is still high and mainly depending on the extent of coronary artery disease. Therefore, there is still need for improvement of care to improve prognosis of infarct-related CS.

Impact of age on the predictive value of NT-proBNP in patients with diabetes mellitus stabilised after an acute coronary syndrome.

AIMS: To assess the impact of age on the prognostic value of NT-proBNP concentration in patients with type-2 diabetes mellitus (T2DM) stabilised after an Acute Coronary Syndrome (ACS). METHODS: The AleCardio study compared aleglitazar with placebo in 7226 patients with T2DM and recent ACS. Patients with heart failure were excluded. Median follow-up was 104 weeks. Baseline NT-proBNP plasma concentration was measured centrally. Multivariable Cox regression was used to determine the mortality predictive information provided by NT-proBNP across age groups. RESULTS: Median age was 61y (IQR 54, 67). NT-proBNP concentration increased by quartile (Q) of age (median 264, 318, 391, and 588 pg/ml). Compared to Q1, patients in Q4 of NT-proBNP had higher (p < 0.001) adjusted HR for all-cause (aHR 6.9; 95 % CI 4.0-12) and cardiovascular (11; 5.4-23) death. Within each age Q, baseline NT-proBNP in patients who died was 3 times higher than in survivors (all p < 0.001). When age and NT-proBNP levels were modeled as continuous variables, their interaction term was nonsignificant. The relative prognostic information provided by NT-proBNP (percent of total X2) increased from 38 % in age Q1 to 75 % in age Q4 for mortality, and from 50 % to 88 % for CV death. CONCLUSIONS: Among patients with T2DM stabilised after an ACS, NT-proBNP level predicts death irrespective of age.

[The heart patient at high altitude: not just thin air]. / Il cardiopatico ad alta quota: non solo aria sottile.

The exposure to high altitude, with its inherent hypobaric hypoxia, elicits transient compensatory physiological responses of the cardiovascular and respiratory system which, however, do not preclude a safe sojourn at least up to 3500 m to the vast majority of well compensated patients with heart disease on stable drug therapy. Existing scientific statements of the European and American Societies of Cardiovascular and High-Mountain Medicine have released specific and helpful recommendations, though mostly based on expert consensus rather than solid evidence. The risk of cardiac events has been recorded only during sports activities, does not seem to depend on altitude and is similar to what is observed during intense exercise at sea level. Besides altitude itself, other aspects of the mountain environment should be considered, such as lower temperature, wind and dehydration which all require careful planning and equipment typical of the alpine sports. The distance of most mountain areas from medical centers able to provide effective care in time-dependent emergencies, and the lack in most cases of dedicated protocols, should also be considered as an important, most likely the most important limiting factor in high-risk patients.

Two Myocardial Infarctions and Five 8,000-m Peaks.

We report the case of a male smoker who is overweight and has no leisure time physical activity until a first acute inferolateral myocardial infarction at the age of 44 years, which was treated using coronary stenting of the left circumflex artery. He was discharged with an ejection fraction of 0.45 and the indication to quit smoking and initiate regular aerobic physical activity. After that episode, he started regular mountain hiking in the Alps, Andes, and, finally, in the Himalayas and Karakorum, where, up to the age of 65 years, he climbed 5 peaks of altitude >8,000 m, always solo and without oxygen, despite a recurrent myocardial infarction because of occlusion at the distal edge of the previously implanted stent. This case supports the indication that high-altitude per se is not contraindicated in patients with well-compensated coronary artery disease, even after an acute MI.

Hospital-Acquired Anemia in Patients with Acute Coronary Syndrome: Epidemiology and Potential Impact on Long-Term Outcome.

BACKGROUND: Anemia (either pre-existing or hospital-acquired) is considered an independent predictor of mortality in acute coronary syndromes. However, it is still not clear whether anemia should be considered as a marker of worse health status or a therapeutic target. We sought to investigate the relationship between hospital-acquired anemia and clinical and laboratory findings and to assess the association with mortality and major cardiovascular events at long-term follow-up. METHODS: Patients consecutively admitted at Niguarda Hospital between February 2014 and November 2020 for an acute coronary syndrome were included in this cohort analysis and classified as anemic at admission (group A), with normal hemoglobin at admission but developing anemia during hospitalization (hospital-acquired anemia) (group B); and with normal hemoglobin levels throughout admission (group C). RESULTS: Among 1294 patients included, group A included 353 (27%) patients, group B 468 (36%), and group C 473 patients (37%). In terms of cardiovascular burden and incidence of death, major cardiovascular events and bleeding at 4.9-year median follow-up, group B had an intermediate risk profile as compared with A and C. Baseline anemia was an independent predictor of death (hazard ratio 1.51; 95% confidence interval, 1.02-2.25; P = .04) along with frailty, Charlson comorbidity Index, estimated glomerular filtration rate, previous myocardial infarction, and left ventricular ejection fraction. Conversely, hospital-acquired anemia was not associated with increased mortality (hazard ratio 1.18; 95% confidence interval, 0.8-1.75; P = .4). CONCLUSIONS: Hospital-acquired anemia affects one-third of patients hospitalized for acute coronary syndrome and is associated with age, frailty, and comorbidity burden, but was not found to be an independent predictor of long-term mortality.

Prognostic Impact of Percutaneous Coronary Intervention in Older Patients Hospitalized with Acute Myocardial Infarction: Real-World Findings from the Lombardy Health Database.

BACKGROUND: Older patients are less likely to receive percutaneous coronary intervention (PCI) for acute myocardial infarction (AMI) compared to younger patients. We investigated the prognostic impact of PCI in a large population of patients hospitalized with AMI in the period 2003-2018 by using the administrative Lombardy Health Database (Italy). METHODS: We considered all patients aged ≥75 years hospitalized with AMI (either STEMI or NSTEMI) from 2003 to 2018 in Lombardy. Patients were grouped according to whether they were treated or not with PCI during the index hospitalization. The primary outcome was in-hospital mortality. The secondary endpoints were 1-year mortality and 1-year re-hospitalization for acute heart failure (AHF) or AMI. RESULTS: 116,063 patients aged ≥75 years (mean age 83 ± 6; 48% males; 46% STEMI) were hospitalized with a primary diagnosis of AMI. Thirty-seven percent of them (n = 42,912) underwent PCI. The in-hospital mortality rate was significantly lower in PCI-treated patients (6% vs. 15%; p < 0.0001). One-year mortality and 1-year re-hospitalization for AHF/AMI were less frequent in PCI-treated patients (16% vs. 41% and 15% vs. 21%, respectively; p < 0.0001). The adjusted risks of the study endpoints were lower in PCI-treated patients: OR 0.37 (95% CI 0.36-0.39) for in-hospital mortality; HR 0.37 (95% CI 0.36-0.38) for 1-year mortality; HR 0.74 (95% CI 0.71-0.77) for 1-year re-hospitalization for AHF/AMI. Similar results were found in STEMI and NSTEMI patients considered separately. CONCLUSIONS: Our real-world data showed that in patients with AMI ≥ 75 years of age, PCI use is associated with lower in-hospital and 1-year mortality.

[The fact about e-cigarettes and cardiovascular risk]. / Il punto su sigarette elettroniche e rischio cardiovascolare.

Electronic cigarettes (e-cigarettes) are battery-powered devices containing a liquid based on propylene glycol or vegetable glycerin. These compounds, when vaporized, act as a vehicle for nicotine, flavors, and other chemical components. These devices have been marketed without clear evidence of risks, long-term safety, and efficacy. Toxicological data show lower plasma concentrations of carbon monoxide and other cancer-inducing substances as compared to traditional smoking. However, several studies have highlighted an increase in sympathetic tone, vascular stiffness, and endothelial dysfunction, all factors associated with cardiovascular risk that, however, is largely inferior to the cardiovascular risk related to traditional smoking. Recent clinical studies have shown how the use of e-cigarettes, combined with adequate psychological support, can be effective in reducing traditional smoking but not nicotine addiction. New policy directives are focusing on the possibility to ban some deleterious products in favor of the use of low-nicotine devices able to promote smoking cessation and reducing the risk of addiction, especially in young people. The use of e-cigarettes among smokers might be promoted with the specific aim of facilitating smoke cessation, but non-smokers and adolescents should be warned against using such devices. Finally, particular attention should be paid to smokers so that the combined use of electronic and traditional cigarettes can be limited as much as possible.

Antiplatelet Strategies for Older Patients with Acute Coronary Syndromes: Finding Directions in a Low-Evidence Field.

Patients ≥ 75 years of age account for about one third of hospitalizations for acute coronary syndromes (ACS). Since the latest European Society of Cardiology guidelines recommend that older ACS patients use the same diagnostic and interventional strategies used by the younger ones, most elderly patients are currently treated invasively. Therefore, an appropriate dual antiplatelet therapy (DAPT) is indicated as part of the secondary prevention strategy to be implemented in such patients. The choice of the composition and duration of DAPT should be tailored on an individual basis, after careful assessment of the thrombotic and bleeding risk of each patient. Advanced age is a main risk factor for bleeding. Recent data show that in patients of high bleeding risk short DAPT (1 to 3 months) is associated with decreased bleeding complications and similar thrombotic events, as compared to standard 12-month DAPT. Clopidogrel seems the preferable P2Y12 inhibitor, due to a better safety profile than ticagrelor. When the bleeding risk is associated with a high thrombotic risk (a circumstance present in about two thirds of older ACS patients) it is important to tailor the treatment by taking into account the fact that the thrombotic risk is high during the first months after the index event and then wanes gradually over time, whereas the bleeding risk remains constant. Under these circumstances, a de-escalation strategy seems reasonable, starting with DAPT that includes aspirin and low-dose prasugrel (a more potent and reliable P2Y12 inhibitor than clopidogrel) then switching after 2-3 months to DAPT with aspirin and clopidogrel for up to 12 months.

Non-ST-elevation acute coronary syndrome in chronic kidney disease: prognostic implication of an early invasive strategy.

BACKGROUND: The optimal timing of PCI for NSTE-ACS with CKD is unclear. The aim of our study was to assess whether early percutaneous coronary intervention (PCI) (within 24 hours from admission) is associated with improved in-hospital (mortality or acute kidney injury) and long-term events (composite of mortality, myocardial infarction, stroke and bleeding events) in patients with non-ST-elevation acute coronary syndromes (NSTE-ACS) with chronic kidney disease (CKD). METHODS: We retrospectively studied NSTE-ACS patients who underwent PCI in large tertiary centers. CKD was defined as estimated glomerular filtration rate (eGFR)<60 mL/min/1.73 m2. A propensity score for the likelihood of an early invasive strategy was calculated. Relative risks (RR) and adjusted hazard ratios (HR) were estimated for in-hospital and follow-up events. RESULTS: We included 821 patients, mean age was 69±12 years; 492 (60%) received an early PCI, and 273 (33%) had an eGFR <60. Median follow-up was 391 days. At univariate analysis, early treatment was associated with significantly lower in-hospital and follow-up events. However, after adjustment for major prognostic factors, there was no significant association with both in-hospital (RR=1.06; 95% CI 0.83-1.36) and follow-up events (RR=1.07; 95% CI 0.83-1.37). When the association was assessed in strata of CKD, lack of statistically significant association was confirmed, even if a trend emerged in patients with preserved renal function both on primary outcome (RR=0.47, 95% 0.18-1.22) and time to secondary outcome (HR=0.62, 95% CI 0.36-1.08). CONCLUSIONS: In conclusion in a cohort of NSTE-ACS patients, an early invasive strategy does not independently affect prognosis.

Acute, Prolonged, and Extensive Myocardial Ischemia in a Patient With Colorectal Cancer.

This case report describes a patient in their 60s with spontaneously subsiding and reoccurring severe acute chest pain that lasted for about 30 minutes as well as a recent diagnosis of colorectal cancer.

Tailoring oral antiplatelet therapy in acute coronary syndromes: from guidelines to clinical practice.

The assessment of bleeding and ischemic risk is a crucial step in establishing appropriate composition and duration of dual antiplatelet therapy (DAPT) in patients with acute coronary syndrome (ACS) treated with percutaneous coronary angioplasty. Evidence from recent randomized clinical trials led to some paradigm shifts in current guidelines recommendations. Options alternative to the standard 12-month DAPT duration include shorter periods of DAPT followed by single antiplatelet treatment with either aspirin or P2Y12 monotherapy, guided or unguided de-escalation DAPT, prolonged DAPT beyond the 12-month treatment period. Although DAPT composition and duration should be selected for each ACS patient on an individual basis weighing clinical and procedural variables, data from latest trials and meta-analyses may permit suggesting the most appropriate DAPT strategy according to the ischemic and bleeding risk assessed using validated tools and scores.

In-hospital outcomes in nonagenarian patients undergoing primary percutaneous coronary intervention.

BACKGROUND: The aim of the present analysis was to evaluate the incidence and predictors of in-hospital adverse outcomes in nonagenarian patients undergoing primary percutaneous coronary intervention (pPCI) for ST-segment elevation myocardial infarction (STEMI). METHODS: Consecutive nonagenarian patients undergoing pPCI for STEMI from 2009 to 2019 were retrospectively included in an international multicenter registry. In-hospital all-cause death was the primary outcome. RESULTS: A total of 308 patients were included (mean age 92.5±2.5 years, 65.6% female). Mean systolic blood pressure (SBP) at hospital admission was 130.7±33.5 mmHg, 46 (17%) patients presented with a Killip class III-IV, mean left ventricle ejection fraction (LVEF) was 40.0±11.5% and 147 (58%) patients were independent in everyday activities. In-hospital death occurred in 99 patients (32%). After multivariate adjustment, lower LVEF (OR per unit reduction 1.08, 95% CI: 1.03-1.11, P value <0.001), lower SBP (OR 1.02 per mmHg reduction, 95% CI: 1.01-1.03, P value 0.001) and being not independent at home (OR 2.56, 95% CI: 1.25-5.26, P value 0.01) resulted independent predictors of in-hospital mortality. A sensitivity analysis performed in final TIMI 3 flow population confirmed the prognostic role of LVEF and independency on in-hospital mortality. CONCLUSIONS: Nonagenarian patients presenting with STEMI and undergoing pPCI have high in-hospital mortality. Independency in everyday life is a strong independent predictor of survival to hospital discharge.

The point on the electronic cigarette more than 10 years after its introduction.

Electronic cigarettes (e-cigarettes) are battery-powered devices containing a liquid based on propylene glycol or vegetable glycerin, compounds which, when vaporized, act as a vehicle for nicotine, flavours, and other chemical components. These devices have been marketed without clear evidence of risks, long-term safety, and efficacy as a means of traditional smoking cessation. Recent clinical studies have shown how the use of the e-cigarette, combined with adequate psychological support, can be effective in reducing traditional smoking but not nicotine addiction. However, meta-analyses of observational studies have not confirmed this efficacy. Several studies have also highlighted an increase in sympathetic tone, vascular stiffness, and endothelial dysfunction, all factors associated with an increased cardiovascular risk. Clinicians, therefore, should carefully monitor the possible risks to public health deriving from the use of e-cigarettes and should discourage non-smokers and adolescents from using such devices. Finally, particular attention should be paid to smokers so that the combined use of electronic and traditional cigarettes can be limited as much as possible.

Multivessel vs. culprit-only percutaneous coronary intervention strategy in older adults with acute myocardial infarction.

BACKGROUND: The optima revascularization strategy for senior patients admitted with acute myocardial infarction (AMI) in the context of multivessel coronary artery disease (MVCAD) remains unclear. We aimed to compare a strategy of culprit-vessel (CV) vs. multi-vessel percutaneous coronary intervention (MV-PCI) in older adults (≥75 years) with AMI. METHODS: We analyzed four randomized controlled trials designed to include older adults with AMI. The primary endpoint was all-cause death. The secondary endpoint was the composite of all-cause death, myocardial infarction, stroke and major bleeding (Net Adverse Clinical Events, NACE). A non-parsimonious propensity score and nearest-neighbor matching was performed to account for bias. RESULTS: A total of 1,334 trial participants were included; of them, 770 (57.7%) underwent CV-PCI and 564 (42.3%) a MV-PCI strategy. After a median follow-up of 365 days, patients treated with MV-PCI experienced a lower rate of death (6.0% vs. 9.9%; p = 0.01) and of NACE (11.2% vs. 15.5%; p = 0.016). After multivariable analysis, MV-PCI was independently associated with a lower hazard of death (hazard ratio [HR]: 0.65; 95% confidence interval [CI]: 0.42-0.96; p = 0.03) and NACE (NACE 0.72[0.53-0.98]; p = 0.04). These results were confirmed in a matched propensity analysis, were consistent throughout the spectrum of older age and when analyzed by subgroups and when immortal-time bias was considered. CONCLUSIONS: In the setting of older adults with MVCAD who were managed invasively for AMI, a MV-PCI strategy to pursue complete revascularization was associated with better survival and lower risk of NACE compared to a CV-PCI. Adequately sized RCTs are required to confirm these findings.