-
1.
Comparison of early clinical outcomes between dual antiplatelet therapy and triple antithrombotic therapy in patients with atrial fibrillation undergoing percutaneous coronary intervention.
Park, J, Jung, JH, Choi, EK, Lee, SW, Kwon, S, Lee, SR, Kang, J, Han, KD, Park, KW, Oh, S, et al
PloS one. 2022;(2):e0264538
Abstract
BACKGROUND AND OBJECTIVE Most Asian patients with atrial fibrillation (AF) who undergo percutaneous coronary intervention (PCI) receive only dual antiplatelet therapy (DAPT) without oral anticoagulants (vitamin K antagonists [VKA] or non-VKA oral anticoagulants [NOAC]). However, it has not been fully investigated whether the DAPT results in better clinical outcomes in the early period after PCI than the standard triple therapy with VKA or NOAC. METHODS We analyzed the claims records of 11,039 Korean AF population who had PCI between 2013 and 2018. Patients were categorized according to the post-PCI antithrombotic therapy as VKA-based triple therapy (VKA-TT), NOAC-based triple therapy (NOAC-TT), and DAPT groups. After baseline adjustment using inverse probability weighting, we compared the risks of ischemic endpoints (ischemic stroke, myocardial infarction, and all-cause mortality) and major bleeding at 3 months post-PCI. RESULTS Ischemic stroke, MI, and all-cause mortality occurred in 105, 423, and 379 patients, respectively, and 138 patients experienced major bleeding. The DAPT group was associated with a lower risk of ischemic stroke and major bleeding (hazard ratio [HR] 0.55, 95% confidence interval [CI] 0.37-0.84) compared to the VKA-TT group, despite no significant differences in the risks of MI and all-cause mortality. In contrast, the DAPT group demonstrated no significant difference in the risks for ischemic endpoints compared to the NOAC-TT group. Additionally, the DAPT group had a numerically lower risk of major bleeding than the NOAC-TT group but this was not statistically significant (HR 0.69, 95% CI 0.45-1.07). CONCLUSIONS An outcome benefit of DAPT was observed in the early period after PCI compared to the VKA-TT, but not against NOAC-TT users among the Asian AF population. Given the potential long-term benefits of NOACs, greater efforts should be made to increase compliance in clinical practice with proper combination therapy with NOAC after PCI.
-
2.
Asymptomatic peripheral artery disease: Silent but deadly.
Behroozian, AA, Beckman, JA
Progress in cardiovascular diseases. 2021;:2-8
Abstract
Peripheral Artery Disease (PAD) is a manifestation of atherosclerosis characterized by diminished perfusion of the limb and a state of dysmetabolism. The asymptomatic PAD phenotype is a relatively recent classification. It is unknown how many people currently live with asymptomatic PAD because there are no universal screening recommendations for patients at risk for PAD. Patients with asymptomatic PAD suffer from a similar risk profile of morbidity and mortality as their counterparts with claudication. Despite this increased risk, there is a dearth of clinical investigations into therapies that specifically benefit the asymptomatic PAD population. At present, current pharmacotherapies that have been studied in PAD patient populations do not stratify by symptom status. We believe that further investigation of the impact of existing therapies in this unique population presents an opportunity to reduce morbidity and mortality due to PAD. This can only be achieved in combination with wide-spread adoption of screening for asymptomatic PAD.
-
3.
Risk Factors for Severe Bleeding Complications in Vitreoretinal Surgery and the Role of Antiplatelet or Anticoagulant Agents.
Lauermann, P, Klingelhöfer, A, Mielke, D, van Oterendorp, C, Hoerauf, H, Striebe, NA, Storch, MW, Pfeiffer, S, Koscielny, J, Sucker, C, et al
Ophthalmology. Retina. 2021;(8):e23-e29
Abstract
PURPOSE To evaluate the influences and risk factors for severe bleeding complications during vitreoretinal surgery and to investigate the role of antiplatelet and anticoagulant agents. DESIGN Prospective trial. PARTICIPANTS Patients undergoing vitreoretinal surgery. METHODS The procedures included were pars plana vitrectomy and scleral buckling. We developed a uniform classification to grade the bleeding severity. Bleeding was graded on an ordinal scale ranging from 0 to 5. Immediately after surgery and 1 day later, the incidence and the severity of bleeding events was documented on a standardized form. A grade of 3 or more was defined as severe bleeding. Furthermore, the influence of known systemic disorders before surgery, the type of anesthesia, type of surgical procedure, intraoperative blood pressure, and the use or change of antiplatelet or anticoagulant agents on intraoperative bleeding was analyzed. MAIN OUTCOME MEASURES Incidence and risk factors for severe intraoperative bleeding events. RESULTS Data from 374 eyes undergoing vitreoretinal procedures were included in our study (mean age, 67.6 ± 12.9 years). A severe intraoperative bleeding event was observed in 15 eyes (4%). We found that concomitant diseases such as diabetes mellitus and carotid artery stenosis, the presence of diabetic retinopathy, younger age, and scleral buckling combined with a transscleral puncture were associated significantly with severe bleeding events. By contrast, use of antiplatelet or anticoagulant agents, or both, had no significant influence on severe intraoperative bleeding events. CONCLUSIONS Although external manipulations during buckling surgery (e.g., drainage of subretinal fluid) and concomitant diseases such as diabetes mellitus and carotid artery stenosis influences the risk of severe intraoperative bleeding events, we did not detect an increased risk related to coexisting antiplatelet or anticoagulant medication use, or both.
-
4.
Details on the effect of very short dual antiplatelet therapy after drug-eluting stent implantation in patients with high bleeding risk: insight from the STOPDAPT-2 trial.
Watanabe, H, Domei, T, Morimoto, T, Natsuaki, M, Shiomi, H, Toyota, T, Ohya, M, Suwa, S, Takagi, K, Nanasato, M, et al
Cardiovascular intervention and therapeutics. 2021;(1):91-103
-
-
Free full text
-
Abstract
Previously we briefly reported the effect of 1-month dual antiplatelet therapy (DAPT) for patients with high bleeding risk (HBR) receiving percutaneous coronary intervention (PCI) in the STOPDAPT-2 trial, but full analysis data have not been available. We conducted post hoc subgroup analysis regarding the effect of very short DAPT for HBR patients in STOPDAPT-2 trial. The primary endpoint was a 1-year composite of cardiovascular (cardiovascular death, myocardial infarction, definite stent thrombosis, or stroke) and bleeding (TIMI major/minor bleeding) outcomes. Major secondary endpoints were 1-year cardiovascular composite endpoint and bleeding endpoint. HBR was defined by the academic research consortium (ARC) HBR criteria. Among the 3009 study patients, 1054 (35.0%) were classified as HBR and 1955 (65.0%) were as non-HBR. There were no significant interactions between HBR/non-HBR subgroups and the assigned DAPT group on the primary endpoint (HBR; 3.48% vs. 5.98%, HR 0.57, 95% CI 0.32-1.03, and non-HBR; 1.81% vs. 2.36%, HR 0.78, 95% CI 0.42-1.45; P for interaction = 0.48), the major secondary cardiovascular endpoint (HBR; 3.07% vs. 4.03%, HR 0.77, 95% CI 0.40-1.48, and non-HBR; 1.41% vs. 1.61%, HR 0.89, 95% CI 0.43-1.84; P for interaction = 0.77), and the major secondary bleeding endpoint (HBR; 0.41% vs. 2.71%, HR 0.15, 95% CI 0.03-0.65, and non-HBR; 0.40% vs. 0.85%, HR 0.48, 95% CI 0.14-1.58; P for interaction = 0.22). In conclusion, the effects of 1-month DAPT for the primary and major secondary endpoints were consistent in HBR and non-HBR patients without any significant interactions. The benefit of 1-month DAPT in reducing major bleeding was numerically greater in HBR patients.Clinical trial registration Short and optimal duration of dual antiplatelet therapy after everolimus-eluting cobalt-chromium stent-2 [STOPDAPT-2]; NCT02619760.
-
5.
Polypill with or without Aspirin in Persons without Cardiovascular Disease.
Yusuf, S, Joseph, P, Dans, A, Gao, P, Teo, K, Xavier, D, López-Jaramillo, P, Yusoff, K, Santoso, A, Gamra, H, et al
The New England journal of medicine. 2021;(3):216-228
-
-
Free full text
-
Abstract
BACKGROUND A polypill comprising statins, multiple blood-pressure-lowering drugs, and aspirin has been proposed to reduce the risk of cardiovascular disease. METHODS Using a 2-by-2-by-2 factorial design, we randomly assigned participants without cardiovascular disease who had an elevated INTERHEART Risk Score to receive a polypill (containing 40 mg of simvastatin, 100 mg of atenolol, 25 mg of hydrochlorothiazide, and 10 mg of ramipril) or placebo daily, aspirin (75 mg) or placebo daily, and vitamin D or placebo monthly. We report here the outcomes for the polypill alone as compared with matching placebo, for aspirin alone as compared with matching placebo, and for the polypill plus aspirin as compared with double placebo. For the polypill-alone and polypill-plus-aspirin comparisons, the primary outcome was death from cardiovascular causes, myocardial infarction, stroke, resuscitated cardiac arrest, heart failure, or revascularization. For the aspirin comparison, the primary outcome was death from cardiovascular causes, myocardial infarction, or stroke. Safety was also assessed. RESULTS A total of 5713 participants underwent randomization, and the mean follow-up was 4.6 years. The low-density lipoprotein cholesterol level was lower by approximately 19 mg per deciliter and systolic blood pressure was lower by approximately 5.8 mm Hg with the polypill and with combination therapy than with placebo. The primary outcome for the polypill comparison occurred in 126 participants (4.4%) in the polypill group and in 157 (5.5%) in the placebo group (hazard ratio, 0.79; 95% confidence interval [CI], 0.63 to 1.00). The primary outcome for the aspirin comparison occurred in 116 participants (4.1%) in the aspirin group and in 134 (4.7%) in the placebo group (hazard ratio, 0.86; 95% CI, 0.67 to 1.10). The primary outcome for the polypill-plus-aspirin comparison occurred in 59 participants (4.1%) in the combined-treatment group and in 83 (5.8%) in the double-placebo group (hazard ratio, 0.69; 95% CI, 0.50 to 0.97). The incidence of hypotension or dizziness was higher in groups that received the polypill than in their respective placebo groups. CONCLUSIONS Combined treatment with a polypill plus aspirin led to a lower incidence of cardiovascular events than did placebo among participants without cardiovascular disease who were at intermediate cardiovascular risk. (Funded by the Wellcome Trust and others; TIPS-3 ClinicalTrials.gov number, NCT01646437.).
-
6.
Risk Factors Control and Early Recurrent Cerebral Infarction in Patients with Symptomatic Intracranial Atherosclerotic Disease.
Del Brutto, VJ, Liebeskind, DS, Romano, JG, Campo-Bustillo, I, Cotsonis, G, Nizam, A, Prabhakaran, S, ,
Journal of stroke and cerebrovascular diseases : the official journal of National Stroke Association. 2021;(9):105914
-
-
Free full text
-
Abstract
BACKGROUND The risk of early recurrent cerebral infarction (RCI) is high in patients with symptomatic intracranial atherosclerotic disease (IAD). We sought to determine the relationship between risk factor control and early RCI risk among patients with symptomatic IAD. METHODS We analyzed participants with symptomatic IAD in the multi-center prospective observational MYRIAD study. Risk factor control was assessed at 6-8-week follow-up. Optimal risk factor control was defined by target systolic blood pressure, being non-smoker, target physical activity, and antiplatelet and antilipidemic therapy compliance. Age-adjusted associations were calculated between risk factor control and RCI determined by MRI-evident new infarcts in the territory of the stenotic vessel at 6-8 weeks from the index event. RESULTS Among 82 participants with clinical and brain MRI information available 6-8 weeks after the index event (mean age 63.5 ±12.5 years, 62.2% men), RCI occurred in 21 (25.6%) cases. At 6-8-week follow-up, 37.8% had target systolic blood pressure, 92.7% were non-smokers, 51.2% had target physical activity, and 98.8% and 86.6% were compliant with antiplatelet and antilipidemic therapy, respectively. Optimal risk factor control increased from 4.9% at baseline to 19.5% at 6-8-week follow-up (p=0.01). None of the participants with optimal risk factor control at follow-up had RCI (0% vs. 31.8%, p<0.01). CONCLUSIONS Only one-fifth of MYRIAD participants had optimal risk factor control during early follow-up. Approximately half and two-thirds had physical inactivity and uncontrolled systolic blood pressure, respectively. These risk factors may represent important therapeutic targets to prevent early RCI in patients with symptomatic IAD.
-
7.
Aspirin in Primary Prevention: What Changed? A Critical Appraisal of Current Evidence.
Dasa, O, Pepine, CJ, Pearson, TA
The American journal of cardiology. 2021;:38-48
Abstract
Aspirin has been the mainstay of both secondary and primary prevention of cardiovascular disease for half a century. In 2018, 3 trials showed a modest reduction in cardiovascular outcomes that appeared counterbalanced by the risk of clinically significant bleeding. The latest ACC/AHA primary prevention guidelines downgraded their recommendation for aspirin use in primary prevention to that of physician preference. Despite the consistent and robust evidence previously supporting the use of aspirin in cardiovascular disease prevention, little discussion has been given to mechanisms or analytic explanations for this revision of recommendations. In this review, we explore 3 possible mechanisms that may have contributed to the alteration of our perception of aspirin's role in primary prevention. These include changes in the population potentially using aspirin in primary prevention, changes in cardiovascular disease and its presentation, and changes in aspirin itself. Here we present a translational look at knowledge gaps that should be addressed to better guide contemporary aspirin use in primary prevention. In conclusion, based on these considerations, the current recommendations might be improved by recalibration of the cardiovascular risk threshold above which aspirin should be recommended for primary prevention, including the incorporation of newer risk assessment modalities such as calcium scoring. A second enhancement would be developing a bleeding risk calculator to support clinicians' assessment of risk vs benefit. The use of enteric-coated aspirin vs noncoated aspirin should also be reassessed.
-
8.
Creatine kinase and bleeding in patients with acute coronary syndromes.
Ndrepepa, G, Holdenrieder, S, Cassese, S, Kastrati, A
European journal of clinical investigation. 2021;(7):e13514
Abstract
BACKGROUND The association between elevated creatine kinase (CK) and bleeding in patients with acute coronary syndrome (ACS) remains incompletely investigated. We undertook this study to assess whether there is an association between elevated CK activity and the risk for bleeding in contemporary patients with ACS. MATERIALS AND METHODS This post hoc analysis of a randomized trial included 3368 patients with ACS undergoing percutaneous coronary intervention. CK was measured serially in all patients until hospital discharge. The main outcome was 30-day incidence of major bleeding (type 3 to 5 bleeding according to the Bleeding Academic Research Consortium criteria). RESULTS Patients were categorized in groups according to the peak CK tertiles: 1st tertile (CK ≤259 U/L; n = 1127 patients), 2nd tertile (CK ≥260 to 990 U/L; n = 1119 patients), and 3rd tertile (CK ≥ 991 U/L; n = 1122 patients). Peak CK activity was higher in patients with bleeding than those without bleeding (771 [316-1845] U/L vs. 496 [190-1357] U/L; P <.001). Bleeding occurred in 26 patients (2.3%) with peak CK within 1st tertile, 39 patients (3.5%) with peak CK within 2nd tertile, and 54 patients (4.8%) with peak CK within 3rd tertile (univariable hazard ratio [HR]=1.39, 95% confidence interval [CI] 1.08 to 1.81, P =.012, per tertile increment in CK values). After adjustment, peak CK activity remained significantly associated with the 30-day bleeding (HR = 1.67 [1.16-2.41]; P =.006 per unit increment in logarithmic CK values). The C statistic of the multivariable model with CK activity was 0.807 [0.770-0.842]. CONCLUSIONS In patients with ACS, peak CK activity was independently associated with increased 30-day incidence of bleeding.
-
9.
Prostacyclin analog beraprost sodium efficacy in primary glomerular disease or nephrosclerosis: Analysis of the Japanese subgroup in CASSIOPEIR study.
Kurumatani, H, Okada, K, Origasa, H, Fujita, T, Isono, M, Nakamoto, H
Therapeutic apheresis and dialysis : official peer-reviewed journal of the International Society for Apheresis, the Japanese Society for Apheresis, the Japanese Society for Dialysis Therapy. 2021;(5):551-564
-
-
Free full text
-
Abstract
We conducted a multicenter, randomized, double-blind, placebo-controlled, phase IIb/III study (CASSIOPEIR) using a renal composite endpoint (i.e., doubling of SCr or end-stage renal disease) in seven Asian countries/region. CASSIOPEIR compared TRK-100STP (120 μg and 240 μg) with placebo in patients with non-diabetic CKD patients with primary glomerular disease or nephrosclerosis (n = 892). However, the superiority of TRK-100STP over placebo was not observed. A prior phase II study on which the Phase IIb/III study design was based included only Japanese patients. We therefore evaluated TRK-100STP efficacy and safety in a subgroup of Japanese patients using the CASSIOPEIR dataset. As the timing of treatment initiation is important in CKD, we conducted additional subgroup analyses based on the baseline serum creatinine (SCr) and eGFR. ITT analysis was performed in a Japanese subgroup (n = 339) in which the primary endpoint was the first occurrence of renal composite endpoint. Significant differences were observed for TRK-100STP 240 μg vs. placebo (P = 0.0493; HR 0.69 [95% CI: 0.47, 1.00]), but no significant difference was observed between TRK-100 120 μg and placebo (P = 0.3523; HR 0.85). More prominent improvement was observed with TRK-100STP 240 μg vs. placebo for baseline SCr < 3.0 mg/dL (P = 0.0031; HR 0.43); SCr < 3.5 mg/dL (P = 0.0237, HR 0.59); and eGFR ≥ 10 mL/min/1.73 m2 (P = 0.0339, HR0.67), respectively. No significant changes in urinary albumin/creatinine ratio and blood pressure were observed. TRK-100STP was generally well tolerated and most adverse drug reactions were mild or moderate in severity. In conclusion, in the Japanese subgroup of CASSIOPEIR, TRK-100STP 240 μg/day significantly improved the renal composite endpoint compared with placebo, with greater efficacy in subjects with SCr < 3.5 or eGFR ≥ 10 mL/min/1.73 m2 .
-
10.
Aspirin versus anticoagulation in cervical artery dissection (TREAT-CAD): an open-label, randomised, non-inferiority trial.
Engelter, ST, Traenka, C, Gensicke, H, Schaedelin, SA, Luft, AR, Simonetti, BG, Fischer, U, Michel, P, Sirimarco, G, Kägi, G, et al
The Lancet. Neurology. 2021;(5):341-350
-
-
Free full text
-
Abstract
BACKGROUND Cervical artery dissection is a major cause of stroke in young people (aged <50 years). Historically, clinicians have preferred using oral anticoagulation with vitamin K antagonists for patients with cervical artery dissection, although some current guidelines-based on available evidence from mostly observational studies-suggest using aspirin. If proven to be non-inferior to vitamin K antagonists, aspirin might be preferable, due to its ease of use and lower cost. We aimed to test the non-inferiority of aspirin to vitamin K antagonists in patients with cervical artery dissection. METHODS We did a multicentre, randomised, open-label, non-inferiority trial in ten stroke centres across Switzerland, Germany, and Denmark. We randomly assigned (1:1) patients aged older than 18 years who had symptomatic, MRI-verified, cervical artery dissection within 2 weeks before enrolment, to receive either aspirin 300 mg once daily or a vitamin K antagonist (phenprocoumon, acenocoumarol, or warfarin; target international normalised ratio [INR] 2·0-3·0) for 90 days. Randomisation was computer-generated using an interactive web response system, with stratification according to participating site. Independent imaging core laboratory adjudicators were masked to treatment allocation, but investigators, patients, and clinical event adjudicators were aware of treatment allocation. The primary endpoint was a composite of clinical outcomes (stroke, major haemorrhage, or death) and MRI outcomes (new ischaemic or haemorrhagic brain lesions) in the per-protocol population, assessed at 14 days (clinical and MRI outcomes) and 90 days (clinical outcomes only) after commencing treatment. Non-inferiority of aspirin would be shown if the upper limit of the two-sided 95% CI of the absolute risk difference between groups was less than 12% (non-inferiority margin). This trial is registered with ClinicalTrials.gov, NCT02046460. FINDINGS Between Sept 11, 2013, and Dec 21, 2018, we enrolled 194 patients; 100 (52%) were assigned to the aspirin group and 94 (48%) were assigned to the vitamin K antagonist group. The per-protocol population included 173 patients; 91 (53%) in the aspirin group and 82 (47%) in the vitamin K antagonist group. The primary endpoint occurred in 21 (23%) of 91 patients in the aspirin group and in 12 (15%) of 82 patients in the vitamin K antagonist group (absolute difference 8% [95% CI -4 to 21], non-inferiority p=0·55). Thus, non-inferiority of aspirin was not shown. Seven patients (8%) in the aspirin group and none in the vitamin K antagonist group had ischaemic strokes. One patient (1%) in the vitamin K antagonist group and none in the aspirin group had major extracranial haemorrhage. There were no deaths. Subclinical MRI outcomes were recorded in 14 patients (15%) in the aspirin group and in 11 patients (13%) in the vitamin K antagonist group. There were 19 adverse events in the aspirin group, and 26 in the vitamin K antagonist group. INTERPRETATION Our findings did not show that aspirin was non-inferior to vitamin K antagonists in the treatment of cervical artery dissection. FUNDING Swiss National Science Foundation, Swiss Heart Foundation, Stroke Funds Basel, University Hospital Basel, University of Basel, Academic Society Basel.