Angiotensin Receptor-Neprilysin Inhibition in Patients With STEMI vs NSTEMI.

BACKGROUND: Patients who sustain an acute myocardial infarction (AMI), including ST-segment elevation myocardial infarction (STEMI) and non-ST-segment elevation myocardial infarction (NSTEMI), remain at high risk for heart failure (HF), coronary events, and death. Angiotensin-converting enzyme inhibitors have been shown to significantly decrease the risk for cardiovascular events in both STEMI and NSTEMI patients. OBJECTIVES: The objectives were to determine whether angiotensin-receptor blockade and neprilysin inhibition with sacubitril/valsartan, compared with ramipril, has impact on reducing cardiovascular events according to the type of AMI. METHODS: The PARADISE-MI (Prospective ARNI versus ACE inhibitor trial to DetermIne Superiority in reducing heart failure Events after Myocardial Infarction) trial enrolled patients with AMI complicated by left ventricular dysfunction and/or pulmonary congestion and at least 1 risk-enhancing factor. Patients were randomized to either sacubitril/valsartan or ramipril. The primary endpoint was death from cardiovascular causes or incident HF. In this prespecified analysis, we stratified patients according to AMI type. RESULTS: Of 5,661 enrolled patients, 4,291 (75.8%) had STEMI. These patients were younger and had fewer comorbidities and cardiovascular risk factors than NSTEMI patients. After adjustment for potential confounders, the risk for the primary outcome was marginally higher in NSTEMI vs STEMI patients (adjusted HR: 1.19; 95% CI: 1.00-1.41), with borderline statistical significance (P = 0.05). The primary composite outcome occurred at similar rates in patients randomized to sacubitril/valsartan vs ramipril in STEMI (10% vs 12%; HR: 0.87; 95% CI: 0.73-1.04; P = 0.13) and NSTEMI patients (17% vs 17%; HR: 0.97; 95% CI: 0.75-1.25; P = 0.80; P interaction = 0.53). CONCLUSIONS: Compared with ramipril, sacubitril/valsartan did not significantly decrease the risk for cardiovascular death and HF in patients with AMI complicated by left ventricular dysfunction, irrespective of the type of AMI. (Prospective ARNI vs ACE Inhibitor Trial to Determine Superiority in Reducing Heart Failure Events After MI; NCT02924727).

The Evaluation and Management of Coronary Artery Disease in the Lung Transplant Patient.

Lung transplantation can greatly improve quality of life and extend survival in those with end-stage lung disease. In order to derive the maximal benefit from such a procedure, patients must be carefully selected and be otherwise healthy enough to survive a high-risk surgery and sometimes prolonged immunosuppressive therapy following surgery. Patients therefore must be critically assessed prior to being listed for transplantation with close attention paid towards assessment of cardiovascular health and operative risk. One of the biggest dictators of this is coronary artery disease. In this review article, we discuss the assessment and management of coronary artery disease in the potential lung transplant candidate.

Personalized Approaches to Antiplatelet Treatment for Cardiovascular Diseases: An Umbrella Review.

Antiplatelet therapy is the cornerstone of antithrombotic prevention in patients with established atherosclerosis, since it has been proven to reduce coronary, cerebrovascular, and peripheral thrombotic events. However, the protective effect of antiplatelet agents is counterbalanced by an increase of bleeding events that impacts on patients' mortality and morbidity. Over the last years, great efforts have been made toward personalized antithrombotic strategies according to the individual bleeding and ischemic risk profile, aiming to maximizing the net clinical benefit. The development of risk scores, consensus definitions, and the new promising artificial intelligence tools, as well as the assessment of platelet responsiveness using platelet function and genetic testing, are now part of an integrated approach to tailored antithrombotic management. Moreover, novel strategies are available including dual antiplatelet therapy intensity and length modulation in patients undergoing myocardial revascularization, the use of P2Y12 inhibitor monotherapy for long-term secondary prevention, the implementation of parenteral antiplatelet agents in high-ischemic risk clinical settings, and combination of antiplatelet agents with low-dose factor Xa inhibitors (dual pathway inhibition) in patients suffering from polyvascular disease. This review summarizes the currently available evidence and provides an overview of the principal risk-stratification tools and antiplatelet strategies to inform treatment decisions in patients with cardiovascular disease.

Predictors of All-Cause Mortality After Successful Transcatheter Aortic Valve Implantation in Patients With Atrial Fibrillation.

Prevalent and incident atrial fibrillation are common in patients who undergo transcatheter aortic valve implantation and are associated with impaired postprocedural outcomes, including mortality. We determined predictors of long-term mortality in patients with atrial fibrillation after successful transcatheter aortic valve implantation. The EdoxabaN Versus standard of care and theIr effectS on clinical outcomes in pAtients havinG undergonE Transcatheter Aortic Valve Implantation-Atrial Fibrillation (ENVISAGE-TAVI AF) trial (NCT02943785) was a multicenter, prospective, randomized controlled trial in patients with prevalent or incident atrial fibrillation after successful transcatheter aortic valve implantation who received edoxaban or vitamin K antagonists. A Cox proportional hazard model was performed to identify predictors of all-cause mortality using a stepwise approach for multiple regression analysis. In addition, we assessed the performance of different risk scores and prediction models using ENVISAGE-TAVI AF data. Of 1,426 patients in ENVISAGE-TAVI AF, 178 (12.5%) died during the follow-up period (median 548 days). Our stepwise approach identified greater risk of mortality with older age, impaired renal function, nonparoxysmal atrial fibrillation, excessive alcohol use, New York Heart Association heart failure class III/IV, peripheral artery disease, and history of major bleeding or predisposition to bleeding. The present model (concordance statistic [c-statistic] 0.67) was a better discriminator than were other frequently used risk scores, such as the Society of Thoracic Surgeons score (c-statistic 0.56); Congestive heart failure, Hypertension, Age ≥75, Diabetes, Stroke, Vascular disease, Age 65 to 74 years, and Sex category (CHA2DS2-VASc) score (c-statistic 0.54); or Hypertension, Abnormal renal/liver function, Stroke, Bleeding history or predisposition, Labile international normalized ratio, Elderly, and Drugs/alcohol concomitantly (HAS-BLED) score (c-statistic 0.58). In ENVISAGE-TAVI AF, several modifiable and nonmodifiable clinical characteristics were significantly associated with greater long-term all-cause mortality. Improved risk stratification to estimate the probability of mortality after successful transcatheter aortic valve implantation in patients with atrial fibrillation may improve long-term patient prognosis.

Impact of chronic kidney disease and diabetes on clinical outcomes in women undergoing PCI.

BACKGROUND: For women undergoing drug-eluting stent (DES) implantation, the individual and combined impact of chronic kidney disease (CKD) and diabetes mellitus (DM) on outcomes is uncertain. AIMS: We sought to assess the impact of CKD and DM on prognosis in women after DES implantation. METHODS: We pooled patient-level data on women from 26 randomised controlled trials comparing stent types. Women receiving DES were stratified into 4 groups based on CKD (defined as creatine clearance <60 mL/min) and DM status. The primary outcome at 3 years after percutaneous coronary intervention was the composite of all-cause death or myocardial infarction (MI); secondary outcomes included cardiac death, stent thrombosis and target lesion revascularisation. RESULTS: Among 4,269 women, 1,822 (42.7%) had no CKD/DM, 978 (22.9%) had CKD alone, 981 (23.0%) had DM alone, and 488 (11.4%) had both conditions. The risk of all-cause death or MI was not increased in women with CKD alone (adjusted hazard ratio [adj. HR] 1.19, 95% confidence interval [CI]: 0.88-1.61) nor DM alone (adj. HR 1.27, 95% CI: 0.94-1.70), but was significantly higher in women with both conditions (adj. HR 2.64, 95% CI: 1.95-3.56; interaction p-value <0.001). CKD and DM in combination were associated with an increased risk of all secondary outcomes, whereas alone, each condition was only associated with all-cause death and cardiac death. CONCLUSIONS: Among women receiving DES, the combined presence of CKD and DM was associated with a higher risk of the composite of death or MI and of any secondary outcome, whereas alone, each condition was associated with an increase in all-cause and cardiac death.

Prognostic value of high-sensitivity C-reactive protein among chronic kidney disease patients undergoing percutaneous coronary intervention.

BACKGROUND: Data on the prognostic value of high-sensitivity C-reactive protein (hs-CRP) levels in patients with chronic kidney disease (CKD) undergoing percutaneous coronary intervention (PCI) are limited. METHODS: Patients undergoing PCI at a tertiary center from January 2012 to December 2019 were included. CKD was defined as a glomerular filtration rate (GFR) <60 mL/min/1.73m2 and elevated hs-CRP was defined as >3 mg/L. Acute myocardial infarction (MI), acute heart failure, neoplastic disease, patients undergoing hemodialysis, or hs-CRP >10 mg/L were exclusion criteria. The primary outcome was major adverse cardiac events (MACE), a composite of all-cause death, MI, and target vessel revascularization at 1-year after PCI. RESULTS: Out of 12,410 patients, 3029 (24.4 %) had CKD. Elevated hs-CRP levels were found in 31.8 % of CKD and 25.8 % of no-CKD patients. At 1 year, MACE occurred in 87 (11.0 %) CKD patients with elevated hs-CRP and 163 (9.5 %) with low hs-CRP (adj. HR 1.26, 95 % CI 0.94-1.68); among no-CKD patients, in 200 (10 %) and 470 (8.1 %), respectively (adj. HR 1.21, 95 % CI 1.00-1.45). Hs-CRP was associated with an increased risk of all-cause death in both CKD (Adj. HR 1.92, 95 % CI 1.07-3.44) and no-CKD patients (adj. HR 3.02, 95 % CI 1.74-5.22). There was no interaction between hs-CRP and CKD status. CONCLUSIONS: Among patients undergoing PCI without acute MI, elevated hs-CRP values were not associated with a higher risk of MACE at 1 year, but with increased mortality hazards consistently in patients with or without CKD.

Impact of coronary artery disease on clinical outcomes after TAVR: Insights from the BRAVO-3 randomized trial.

OBJECTIVE: To determine the prognostic impact of coronary artery disease (CAD) in patients randomized to bivalirudin or unfractionated heparin (UFH) during transcatheter aortic valve replacement (TAVR). BACKGROUND: CAD is a common comorbidity among patients undergoing TAVR and studies provide conflicting data on its prognostic impact. METHODS: The Bivalirudin on Aortic Valve Intervention Outcomes-3 (BRAVO-3) randomized trial compared the use of bivalirudin versus UFH in 802 high-surgical risk patients undergoing transfemoral TAVR for severe symptomatic aortic stenosis. Patients were stratified according to the presence or absence of history of CAD as well as periprocedural anticoagulation. The coprimary endpoints were net adverse cardiac events (NACE; a composite of all-cause mortality, myocardial infarction, stroke, or major bleeding) and major Bleeding Academic Research Consortium (BARC) bleeding ≥3b at 30 days postprocedure. RESULTS: Among 801 patients, 437 (54.6%) had history of CAD of whom 223 (51.0%) received bivalirudin. There were no significant differences in NACE (adjusted odds ratio [OR]: 1.04; 95% confidence interval [CI]: 0.69-1.58) or BARC ≥ 3b bleeding (adjusted OR: 0.84; 95% CI: 0.51-1.39) in patients with vs without CAD at 30 days. Among CAD patients, periprocedural use of bivalirudin was associated with similar NACE (OR: 0.80; 95% CI: 0.47-1.35) and BARC ≥ 3b bleeding (OR: 0.64; 95% CI: 0.33-1.25) compared with UFH, irrespective of history of CAD (p-interaction = 0.959 for NACE; p-interaction = 0.479 for major bleeding). CONCLUSION: CAD was not associated with a higher short-term risk of NACE or major bleeding after TAVR. Periprocedural anticoagulation with bivalirudin did not show any advantage over UFH in patients with and without CAD.

Fatal, ischemic and bleeding risk of patients meeting the selection criteria of the TWILIGHT trial: Insights from a large PCI registry.

BACKGROUND: The TWILIGHT trial (NCT02270242) demonstrated that in selected high-risk patients undergoing percutaneous coronary intervention (PCI) ticagrelor monotherapy significantly reduced bleeding complications without ischemic harm as compared to ticagrelor plus aspirin after 3-month of dual antiplatelet therapy. The aim of this analysis was to assess the applicability of the findings TWILIGHT trial to a real-world population. METHODS: Patients undergoing PCI at a tertiary center between 2012 and 2019 and not meeting any TWILIGHT exclusion criterion (oral anticoagulation treatment, ST-segment elevation myocardial infarction [MI], cardiogenic shock, dialysis, prior stroke, or thrombocytopenia) were included. Patients were stratified into 2 groups based on whether they fulfilled the TWILIGHT inclusion criteria (high-risk) or not (low-risk). The primary outcome was all-cause death; the key secondary outcomes were MI and major bleeding at 1 year after PCI. RESULTS: Out of 13,136 included patients, 11,018 (83%) were at high risk. At 1-year, these patients had an approximately 3 folds greater hazard of death (1.4% vs 0.4%, HR 3.63, 95% CI 1.70-7.77) and MI (1.8% vs 0.6%, HR 2.81, 95% CI 1.56-5.04) and a nearly 2 folds higher risk of major bleeding (3.3% vs 1.8%, HR 1.86, 95% CI 1.32-2.62) as compared to low-risk patients. CONCLUSION: Among patients not meeting the TWILIGHT exclusion criteria from a large PCI registry, the high-risk inclusion criteria of the TWILIGHT trial were met by the majority of patients and were associated with an increased risk of mortality and MI and a moderately elevated risk of bleeding.

Outcomes in Patients With Early Menopause Who Underwent Transcatheter Aortic Valve Implantation.

Early menopause is associated with an increased risk of cardiovascular diseases, including aortic stenosis (AS). We sought to investigate the prevalence and impact of early menopause on clinical outcomes in patients who underwent transcatheter aortic valve implantation (TAVI) for severe symptomatic AS. Women's International TAVI is a multinational, prospective, observational registry of women who underwent TAVI for severe symptomatic AS (n = 1,019). Patients were divided into 2 groups based on age of menopause: early menopause (age ≤45 years) and regular menopause (age >45 years). The primary outcome of interest was Valve Academic Research Consortium 2 efficacy end point, a composite of mortality, stroke, myocardial infarction, hospitalization for valve-related symptoms, or heart failure or valve-related dysfunction at 1-year follow-up. Of 732 patients with available data on menopause age, 173 (23.6%) were classified as having early menopause. These patients presented for TAVI at a younger age (81.6 ± 6.9 vs 82.7 ± 5.9, p = 0.05) and had a significantly lower Society of Thoracic Surgeons score (6.6 ± 4.8 vs 8.2 ± 7.1, p = 0.03) than those with regular menopause. However, the total valve calcium volume was smaller among patients with early versus regular menopause (731.8 ± 850.9 mm3 vs 807.6 ± 633.8 mm3, p = 0.002). Other co-morbidities were similar between the 2 groups. At 1-year follow-up, there were no significant differences in clinical outcomes between patients with early versus regular menopause (hazard ratio 1.00, 95% confidence interval 0.61 to 1.63, p = 1.00). In conclusion, despite presenting for TAVI at a younger age, patients with early menopause had a similar risk of adverse events as patients with regular menopause at 1 year after TAVI.

Impact of complex percutaneous coronary intervention features on clinical outcomes in patients with or without chronic kidney disease.

BACKGROUND: Patients with chronic kidney disease (CKD) are at higher risk of ischemic and bleeding events after percutaneous coronary intervention (PCI). Complex PCI (CPCI) is associated with higher rates of ischemic complications. Whether CPCI confers an additive risk of adverse events in CKD patients is unclear. METHODS: Patients who underwent PCI at a single tertiary-care-center between 2012 and 2019 were stratified by CKD status and CPCI. The primary outcome was major adverse cardiac events (MACE), a composite of all-cause death, myocardial infarction (MI), and target-vessel revascularization (TVR) at 1-year follow-up. Secondary outcomes included the individual components of the primary outcome and major bleeding. RESULTS: Out of 15,071 patients, 4537 (30.1%) had CKD and 10,534 (69.9%) had no CKD. Patients undergoing CPCI were 1151 (25.4%) and 2983 (28.3%) in the two cohorts, respectively. At one year, CPCI compared with no CPCI was associated with higher risk of MACE in both CKD (Adj. HR 1.72, 95% confidence interval [CI] 1.45-2.06, p < 0.001) and no-CKD patients (Adj. hazard ratios [HR] 2.19, 95% CI 1.91-2.51, p < 0.001; p of interaction 0.057), determined by an excess of death, MI and TVR in CKD patients and of TVR and MI only in no-CKD. CPCI was related with a consistent increase of major bleeding in the CKD (Adj. HR 1.49, 95% CI 1.18-1.87, p < 0.001) and no-CKD group (Adj. HR 1.23, 95% CI 0.98-1.54, p = 0.071, p of interaction 0.206). CONCLUSION: At 1-year follow-up, CPCI was associated with higher risk of MACE and major bleeding irrespective of concomitant CKD. CPCI predicted mortality in CKD patients only.

The mega COMBO collaboration: An individual patient data pooled analysis of patients undergoing PCI with COMBO stent.

BACKGROUND: COMBO (OrbusNeich Medical, Hong Kong) is a dual-therapy coronary stent featuring sirolimus as antiproliferative drug and an anti-CD34+ antibody coating to attract endothelial progenitor cells favoring rapid stent re-endothelization. The Mega COMBO collaboration aimed to evaluate the performance of the COMBO stent in a large contemporary cohort of patients undergoing percutaneous coronary intervention (PCI). METHODS: Patient-level data of subjects undergoing PCI with the COMBO stent from the REMEDEE-Trial, REMEDEE-OCT, HARMONEE, REDUCE, SORT OUT X, REMEDEE-Registry and MASCOT studies were pooled together. The primary endpoint was 1-year target lesion failure (TLF), a composite of cardiovascular death, target vessel myocardial infarction (TV-MI) or clinically driven target lesion revascularization (CD-TLR). Secondary outcomes were the individual components of the primary endpoint and stent thrombosis (ST). Endpoints were evaluated against performance goals based on the EAPCI (the European Association of Percutaneous Coronary Intervention) recommendations for new drug-eluting stents. RESULTS: A total of 6753 patients (mean age 63.7 ± 11.4 years, 23% women) were included. At 1-year follow-up, TLF occurred in 303 (4.6%) patients. The rates of cardiovascular death, TV-MI, and CD-TLR were 1.3%, 1.8%, and 2.5%, respectively. The rate of definite/probable ST was 0.73%, early ST (<1 month) was 0.48%, while late ST (1-12 months) was 0.26%. The performance goals were met for all of the evaluated endpoints. CONCLUSIONS: This large patient-level pooled analysis provides a comprehensive outline of the performance of the dual-therapy COMBO stent. The low rates of primary and secondary endpoints suggest that this stent technology may be a good alternative to other contemporary drug eluting coronary stent platforms.

New Criteria to Identify Patients at Higher Risk for Cardiovascular Complications After Percutaneous Coronary Intervention.

A universal definition to identify patients at higher risk of complications after percutaneous coronary intervention (PCI) is lacking. We aimed to validate a recently developed score to identify patients at increased risk of all-cause death after PCI. All consecutive patients from a large PCI registry not presenting with ST-elevation myocardial infarction or cardiogenic shock were included. Each patient was assigned a score obtained by summing the points associated with the following variables: age >80 years (3 points), dialysis (6 points), left ventricular ejection fraction <30% (2 points), and multivessel PCI (2 points). Patients were stratified in 3 groups: low risk (score 0), intermediate risk (score 2 to 3), or high risk (score ≥4). The primary outcome was all-cause death, and the secondary outcomes were major adverse cardiovascular events and major bleeding. Events were assessed at 1 year after PCI. Between January 2014 and December 2019, 12,689 patients underwent PCI. Compared with the 9,884 patients at low risk, those at intermediate and high risk had a fourfold (hazard ratio 3.99, 95% confidence interval 2.95 to 5.38) and ninefold (hazard ratio 9.55, 95% confidence interval 6.89 to 13.2) higher hazard for all-cause death at 1 year, respectively. The score had a good predictive value for all-cause death at 1 year (area under the curve 0.70). The risk of major adverse cardiovascular events and major bleeding increased consistently from the low- to the high-risk group. In conclusion, in patients who underwent PCI for stable ischemic heart disease or non-ST-elevation acute coronary syndrome, a score based on 4 variables well predicted the risk of all-cause death at 1 year.

Evolution of drug-eluting coronary stents: a back-and-forth journey from the bench to bedside.

Coronary stents have revolutionized the treatment of coronary artery disease. Compared with balloon angioplasty, bare-metal stents (BMSs) effectively prevented abrupt vessel closure but were limited by in-stent restenosis (ISR) due to smooth muscle cell proliferation and neointimal hyperplasia. The first-generation drug-eluting stent (DES), with its antiproliferative drug coating, offered substantial advantages over BMSs as it mitigated the risk of ISR. Nonetheless, they had several design limitations that increased the risk of late stent thrombosis. Significant advances in stent design, including thinner struts, enhanced polymers' formulation, and more potent antiproliferative agents, have led to the introduction of new-generation DES with a superior safety profile. Cardiologists have over 20 different DES types to choose from, each with its unique features and characteristics. This review highlights the evolution of stent design and summarizes the clinical data on the different stent types. We conclude by discussing the clinical implications of stent design in high-risk subsets of patients.

Efficacy and safety of P2Y12 inhibitor monotherapy after complex PCI: a collaborative systematic review and meta-analysis.

AIMS: Complex percutaneous coronary intervention (C-PCI) is associated with an increased risk of ischaemic and bleeding complications. We aimed to assess the safety and efficacy of a 1-3-month dual antiplatelet therapy (DAPT) regimen followed by P2Y12 inhibitor monotherapy after C-PCI. METHODS AND RESULTS: We conducted a meta-analysis of randomized trials comparing a 1-3-month DAPT regimen followed by P2Y12 inhibitor monotherapy with standard (≥12 months) DAPT in patients undergoing C-PCI. C-PCI criteria and the co-primary bleeding and ischaemic outcomes were determined according to each trial. Secondary outcomes included major bleeding, all-cause death, myocardial infarction, and stent thrombosis. All outcomes were evaluated at 12 months after randomization. We used hazard ratios (HRs) and 95% confidence interval (CI) as a metric of choice for treatment effects with random-effects models. Among 8299 screened studies, five randomized trials fulfilled the eligibility criteria. In the pooled population of 34 615 patients, 8818 (25.5%) underwent C-PCI. As compared with standard DAPT, a 1-3-month DAPT regimen followed by P2Y12 inhibitor monotherapy reduced the bleeding risk in C-PCI (HR:0.66, 95% CI:0.44-0.98) and non-C-PCI (HR:0.60, 95% CI:0.45-0.79) patients (P-interaction = 0.735). Furthermore, the risk for the primary ischaemic endpoint was similar in patients randomized to either arm, with significant effect modification by PCI complexity showing an enhanced benefit of 1-3-month DAPT in patients undergoing C-PCI (C-PCI, HR:0.69, 95% CI:0.48-1.00; non-C-PCI, HR:1.04, 95% CI:0.84-1.30; P-interaction = 0.028). CONCLUSION: As compared with a standard DAPT, a 1-3-month DAPT regimen followed by P2Y12 inhibitor monotherapy reduced bleeding complications after C-PCI without increasing the risk of ischaemic events.PROSPERO-registered (CRD42021259271).

Recent Advances in Antiplatelet Therapy in Complex Percutaneous Coronary Intervention.

Antithrombotic therapy is the cornerstone of secondary cardiovascular prevention after percutaneous coronary intervention (PCI). Improvements in drug-eluting stent (DES) design and materials over the last 2 decades have prompted the development of new antithrombotic strategies. Current guidelines recommend to tailor dual antiplatelet therapy (DAPT) according to clinical presentation and individual ischemic and bleeding risk. Given the growing number of complex PCI procedures performed nowadays, it is a priority to define the optimal antithrombotic treatment in this challenging patient subset. In this review article, we sought to summarize and discuss the current evidence on antiplatelet therapy in patients undergoing complex PCI.