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De-Escalation of Dual Antiplatelet Therapy in Patients With Acute Coronary Syndromes.
Shoji, S, Kuno, T, Fujisaki, T, Takagi, H, Briasoulis, A, Deharo, P, Cuisset, T, Latib, A, Kohsaka, S
Journal of the American College of Cardiology. 2021;(8):763-777
Abstract
BACKGROUND Balancing the effects of dual antiplatelet therapy (DAPT) in the era of potent P2Y12 inhibitors has become a cornerstone of acute coronary syndrome (ACS) management. Recent randomized controlled trials (RCTs) have investigated DAPT de-escalation to decrease the risk of bleeding outcomes. OBJECTIVES The aim of this study was to compare the efficacy and safety outcomes of various DAPT strategies in patients with ACS, including de-escalation from a potent P2Y12 inhibitor to clopidogrel or low-dose prasugrel. METHODS MEDLINE and EMBASE were searched through January 2021 for RCTs investigating the efficacy and safety of DAPT in patients with ACS, and a network meta-analysis was conducted. The primary efficacy outcome was a composite of cardiovascular death, myocardial infarction, and stroke. The primary bleeding outcome was trial-defined major or minor bleeding. RESULTS Our search identified 15 eligible RCTs, including 55,798 patients with ACS. De-escalation therapy was associated with reduced risk of primary bleeding outcomes (HR: 0.48 [95% CI: 0.30-0.77] vs clopidogrel; HR: 0.32 [95% CI: 0.20-0.52] vs ticagrelor; HR: 0.36 [95% CI: 0.24-0.55] vs standard-dose prasugrel; and HR: 0.40 [95% CI: 0.22-0.75] vs low-dose prasugrel) without negatively affecting primary efficacy outcomes. There were no significant differences in ischemic or bleeding outcomes between de-escalation to clopidogrel or low-dose prasugrel. CONCLUSIONS Compared with other established uses of DAPT, de-escalation was the most effective strategy for ACS treatment, resulting in fewer bleeding events without increasing ischemic events.
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Double or triple antithrombotic therapy after coronary stenting and atrial fibrillation: A systematic review and meta-analysis of randomized clinical trials.
Andò, G, Costa, F
International journal of cardiology. 2020;:95-102
Abstract
AIMS: Double or triple antithrombotic therapy (DAT/TAT) including or excluding aspirin in association with oral anticoagulant and P2Y12 inhibitor are currently two available options in patients with atrial fibrillation (AF) undergoing percutaneous coronary intervention (PCI). We evaluated efficacy and safety outcomes for DAT vs. TAT. METHODS AND RESULTS Four non-vitamin K oral anticoagulants (NOAC)-based randomized controlled trials comparing DAT vs. TAT with a total of 10,938 patients were pooled. Bleeding events occurred more frequently than ischemic events. DAT as compared to TAT was associated to an increased risk of stent thrombosis (RR 1.54, 95% CI 1.10-2.14; p = 0.03), myocardial infarction (RR 1.23, 95% CI 1.04-1.46; p = 0.03) and cardiovascular mortality (RR 1.09, 95% CI 1.01-1.19; p = 0.04) and to a reduced risk of ISTH major or clinically relevant non-major bleeding (RR 0.59, 95% CI 0.62-0.93; p = 0.03). A consistent effect was observed in all safety endpoints. Intracranial haemorrhage was numerically reduced by DAT. No difference for all-cause death was observed. CONCLUSION Antithrombotic treatment in patients with AF undergoing PCI represents a trade-off between ischemia and bleeding. A careful patient selection based on baseline ischemic and bleeding risk may optimize the net clinical balance in this population.
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Pharmacological treatment for Buerger's disease.
Cacione, DG, Macedo, CR, do Carmo Novaes, F, Baptista-Silva, JC
The Cochrane database of systematic reviews. 2020;(5):CD011033
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Abstract
BACKGROUND Buerger's disease (thromboangiitis obliterans) is a non-atherosclerotic, segmental inflammatory pathology that most commonly affects the small and medium sized arteries, veins, and nerves in the upper and lower extremities. The aetiology is unknown, but involves hereditary susceptibility, tobacco exposure, immune and coagulation responses. In many cases, there is no possibility of revascularisation to improve the condition. Pharmacological treatment is an option for patients with severe complications, such as ischaemic ulcers or rest pain.This is an update of the review first published in 2016. OBJECTIVES To assess the effectiveness of any pharmacological agent (intravenous or oral) compared with placebo or any other pharmacological agent in patients with Buerger's disease. SEARCH METHODS The Cochrane Vascular Information Specialist searched the Cochrane Vascular Specialised Register, Cochrane Central Register of Controlled Trials, MEDLINE, Embase, CINAHL, AMED, the World Health Organization International Clinical Trials Registry Platform and ClinicalTrials.gov trials register to 15 October 2019. The review authors searched LILACS, ISRCTN, Australian New Zealand Clinical Trials Registry, EU Clinical Trials Register, clincialtrials.gov and the OpenGrey Database to 5 January 2020. SELECTION CRITERIA We included randomised controlled trials (RCTs) involving pharmacological agents used in the treatment of Buerger's disease. DATA COLLECTION AND ANALYSIS Two review authors, independently assessed the studies, extracted data and performed data analysis. MAIN RESULTS No new studies were identified for this update. Five randomised controlled trials (total 602 participants) compared prostacyclin analogue with placebo, aspirin, or a prostaglandin analogue, and folic acid with placebo. No studies assessed other pharmacological agents such as cilostazol, clopidogrel and pentoxifylline or compared oral versus intravenous prostanoid. Compared with aspirin, intravenous prostacyclin analogue iloprost improved ulcer healing (risk ratio (RR) 2.65; 95% confidence interval (CI) 1.15 to 6.11; 98 participants; 1 study; moderate-certainty evidence), and helped to eradicate rest pain after 28 days (RR 2.28; 95% CI 1.48 to 3.52; 133 participants; 1 study; moderate-certainty evidence), although amputation rates were similar six months after treatment (RR 0.32; 95% CI 0.09 to 1.15; 95 participants; 1 study; moderate-certainty evidence). When comparing prostacyclin (iloprost and clinprost) with prostaglandin (alprostadil) analogues, ulcer healing was similar (RR 1.13; 95% CI 0.76 to 1.69; 89 participants; 2 studies; I² = 0%; very low-certainty evidence), as was the eradication of rest pain after 28 days (RR 1.57; 95% CI 0.72 to 3.44; 38 participants; 1 study; low-certainty evidence), while amputation rates were not measured. Compared with placebo, the effects of oral prostacyclin analogue iloprost were similar for: healing ischaemic ulcers (iloprost 200 mcg: RR 1.11; 95% CI 0.54 to 2.29; 133 participants; 1 study; moderate-certainty evidence, and iloprost 400 mcg: RR 0.90; 95% CI 0.42 to 1.93; 135 participants; 1 study; moderate-certainty evidence), eradication of rest pain after eight weeks (iloprost 200 mcg: RR 1.14; 95% CI 0.79 to 1.63; 207 participants; 1 study; moderate-certainty evidence, and iloprost 400 mcg: RR 1.11; 95% CI 0.77 to 1.59; 201 participants; 1 study; moderate-certainty evidence), and amputation rates after six months (iloprost 200 mcg: RR 0.54; 95% CI 0.19 to 1.56; 209 participants; 1 study, and iloprost 400 mcg: RR 0.42; 95% CI 0.13 to 1.31; 213 participants; 1 study). When comparing folic acid with placebo in patients with Buerger's disease and hyperhomocysteinaemia, pain scores were similar, there were no new cases of amputation in either group, and ulcer healing was not assessed (very low-certainty evidence). Treatment side effects such as headaches, flushing or nausea were not associated with treatment interruptions or more serious consequences. Outcomes such as amputation-free survival, walking distance or pain-free walking distance, and ankle brachial index were not assessed by any study. Overall, the certainty of the evidence was very low to moderate, with few studies, small numbers of participants, variation in severity of disease of participants between studies and missing information (for example regarding baseline tobacco exposure). AUTHORS' CONCLUSIONS Moderate-certainty evidence suggests that intravenous iloprost (prostacyclin analogue) is more effective than aspirin for eradicating rest pain and healing ischaemic ulcers in Buerger's disease, but oral iloprost is not more effective than placebo. Very low and low-certainty evidence suggests there is no clear difference between prostacyclin (iloprost and clinprost) and the prostaglandin analogue alprostadil for healing ulcers and relieving pain respectively in severe Buerger's disease. Very low-certainty evidence suggests there is no clear difference in pain scores and amputation rates between folic acid and placebo, in people with Buerger's disease and hyperhomocysteinaemia. Further well designed RCTs assessing the effectiveness of pharmacological agents (intravenous or oral) in people with Buerger's disease are needed.
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Meta-analysis of Antithrombotic Therapy in Patients With Atrial Fibrillation Undergoing Percutaneous Coronary Intervention.
Kuno, T, Ueyama, H, Takagi, H, Ando, T, Numasawa, Y, Briasoulis, A, Fox, J, Bangalore, S
The American journal of cardiology. 2020;(4):521-527
Abstract
For patients with atrial fibrillation (AF) who undergo percutaneous coronary intervention (PCI), antithrombotic therapy including oral anticoagulants and antiplatelets are indicated. The optimal combination is not known. We investigated the efficacy and safety of different antithrombotic strategies in patients with AF undergoing PCI. PUBMED and EMBASE were searched through September 2019 for randomized trials investigating the efficacy and safety of different antithrombotic strategies in patients with AF who underwent PCI and/or acute coronary syndrome. Nine antithrombotic strategies were compared including combinations of vitamin K antagonist (VKA) with dual antiplatelet therapy (DAPT) or P2Y12 inhibitor, combinations of direct oral anticoagulants (DOAC) (apixaban, dabigatran, rivaroxaban, and edoxaban) with DAPT or P2Y12 inhibitor (clopidogrel, prasugrel, and ticagrelor). The primary safety outcome was trial defined primary bleeding outcome. The primary efficacy outcome was trial defined major adverse cardiovascular events. Our search identified 5 eligible trials that enrolled a total of 11,532 patients and compared 9 treatment strategies. VKA + DAPT significantly increased bleeding when compared with most combinations (for example, vs VKA + P2Y12 inhibitor: odds ratio 2.11; 95% confidence interval [1.76 to 2.52], p <0.001). Of all the combinations, apixaban + P2Y12 inhibitor showed the lowest bleeding risk (for example, vs VKA + P2Y12 inhibitor: odds ratio 0.63; 95% confidence interval [0.51 to 0.78], p <0.001) and was ranked the best treatment. There were no significant differences in ischemic outcome of major adverse cardiovascular events between various antithrombotic regimens. In conclusion, in patients with AF undergoing PCI, apixaban + P2Y12 inhibitors were associated with lowest bleeding compared with other regimens including other DOACs + P2Y12 inhibitors with no increase in ischemic outcomes.
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Antithrombotic regimen for patients with cardiac indication for dual antiplatelet therapy and anticoagulation: a meta-analysis of randomized trials.
Liao, YWB, Wang, TKM
Coronary artery disease. 2020;(3):260-265
Abstract
OBJECTIVES The optimal antithrombotic strategy for patients with a long-term indication for anticoagulation and acute coronary syndrome (ACS) or percutaneous coronary intervention (PCI) remains controversial. This meta-analysis aims to compare randomised trials' outcomes of these patients, focussing on dual versus triple antithrombotic and non vitamin K oral anticoagulants (NOACs) versus vitamin K oral anticoagulants regimens. METHODS Medline, Embase and Cochrane databases were searched from January 1980 to March 2019 yielding 309 articles, and after careful screening, five randomized trials totalling 10 643 patients were included for analysis. RESULTS Dual antithrombotic regimens were associated with significantly less thrombolysis in myocardial infarction (TIMI) major and minor bleeding [odds ratio (OR) 0.53, 95% confidence interval (CI) 0.40-0.71], with no significant difference in major adverse cardiovascular events (OR 0.93, 95% CI 0.72-1.22) or all-cause mortality (OR 0.89, 95% CI 0.61-1.19). NOAC regimens had significantly lower TIMI major and minor bleeding (OR 0.58, 95% CI 0.43-0.78) and intracranial bleeding (OR 0.33, 95% CI 0.16-0.66), with similar rates of major adverse cardiovascular events (OR 1.00, 95% CI 0.86-1.16) and all-cause mortality (OR 1.01, 95% CI 0.81-1.26). CONCLUSION Dual antithrombotic and NOAC regimens have reduced bleeding without compromising the risk of cardiovascular events or mortality, and should be preferred for patients with ACS or PCI also needing long-term anticoagulation.
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Effects of six types of aspirin combination medications for treatment of acute cerebral infarction in China: A network meta-analysis.
Jin, L, Zhou, J, Shi, W, Xu, L, Sheng, J, Fan, J, Yuan, Y, Yuan, H
Journal of clinical pharmacy and therapeutics. 2019;(1):91-101
Abstract
WHAT IS KNOWN AND OBJECTIVE Previous studies have shown that various aspirin combinations might be beneficial for the treatment of acute cerebral infarction (ACI). The aim of this study was to evaluate the efficacy of six aspirin combinations in the treatment of ACI using network meta-analysis (NMA). The performance of these combinations is then ranked according to results of this analysis. METHODS Multiple databases were consulted to find randomized controlled trials (RCT) of six different aspirin combinations for the treatment of ACI. NMA was conducted on the data using stata (13.0) software. The odds ratio (OR) was calculated. The studies included in this paper were divided into a control group (aspirin alone) and an observation group (one of six aspirin combinations). RESULTS A total of 103 eligible RCTs were identified. A total of 13 317 cases were included in the study, and the results showed that the six types of aspirin combinations (aspirin with atorvastatin, ozagrel sodium, low molecular weight heparin [LMWH], clopidogrel, cilostazol and ginkgo damo) were all significantly superior (P < 0.05) to aspirin alone. The combination of aspirin with LMWH had the highest probability of being the most clinically efficacious intervention, with a surface under the cumulative ranking (SUCRA) curve of 79.1. The combination of aspirin with ozagrel sodium was the worst, with a SUCRA value of 29.7. WHAT IS NEW AND CONCLUSION A combination of aspirin with LMWH is the best option among the six aspirin combinations considered for the treatment of ACI. The combination of aspirin with ozagrel sodium was ranked the last.
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Comparative effects of lipid lowering, hypoglycemic, antihypertensive and antiplatelet medications on carotid artery intima-media thickness progression: a network meta-analysis.
Huang, R, Mills, K, Romero, J, Li, Y, Hu, Z, Cao, Y, Huang, H, Xu, Y, Jiang, L
Cardiovascular diabetology. 2019;(1):14
Abstract
BACKGROUND Carotid artery intima-media thickness (cIMT) progression is a surrogate marker of atherosclerosis with a high predictive value for future CVD risk. This study evaluates the comparative efficacies of lipid lowering, hypoglycemic, antihypertensive and antiplatelet medications on cIMT progression. METHODS We conducted a network meta-analysis (NMA) to evaluate the relative efficacies of several drug classes in modifying cIMT progression. After a literature search in several electronic databases, studies were selected by following predetermined eligibility criteria. An inverse variance-heterogeneity model was used for NMA. Sensitivity analyses were performed to check the reliability of the overall NMA, and transitivity analyses were performed to examine the effects of modifiers on the NMA outcomes. RESULTS Data were taken from 47 studies (15,721 patients; age: 60.2 years [95% confidence interval (CI) 58.8, 61.6]; BMI: 27.2 kg/m2 [95% CI 26.4, 28.0]; and gender: 58.3% males [95% CI 48.3, 68.3]). Treatment duration was 25.8 months [95% CI 22.9, 28.7]. Of the 13 drug classes in the network, treatment with phosphodiesterase III inhibitors was the most effective in retarding annual mean cIMT against network placebo (weighted mean difference (WMD) - 0.059 mm [95% CI - 0.099, - 0.020) followed by the calcium channel blockers (WMD - 0.055 mm [95% CI - 0.099, 0.001]) and platelet adenosine diphosphate inhibitors (WMD - 0.033 mm [95% CI - 0.058, 0.008]). These 3 drug classes also attained the same positions when the NMA was conducted by using first-year changes in mean cIMT. In transitivity analyses, longer treatment duration, higher body mass index (BMI), and a higher baseline cIMT were found to be independently associated with a lesser reduction in annual mean cIMT. However, in a multivariate analysis with these 3 modifiers, none of these factors was significantly associated with annual change in mean cIMT. In the placebo group, age was inversely associated with annual change in mean cIMT independently. CONCLUSION Phosphodiesterase III inhibitors and calcium channel blockers are found more effective than other drug classes in retarding cIMT progression. Age, BMI, and baseline cIMT may have some impact on these outcomes.
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Oral Anticoagulants With Dual Antiplatelet Therapy Versus Clopidogrel in Patients After Percutaneous Coronary Intervention: A Meta-Analysis.
Palla, M, Briasoulis, A, Kondur, A
American journal of therapeutics. 2019;(1):e143-e150
Abstract
BACKGROUND In patients on oral anticoagulation (OAC), dual antiplatelet therapy (DAPT) is often indicated after percutaneous coronary intervention (PCI). AREAS OF UNCERTAINTY We sought to investigate the effects of triple antithrombotic therapy (TT) versus dual therapy (DT) with OAC and clopidogrel on all-cause mortality, cardiovascular death, major bleeding, myocardial infarction (MI), stroke, and stent thrombosis. DATA SOURCES We systematically searched on MEDLINE, EMBASE, and CENTRAL for randomized controlled or cohort studies, which investigated the comparative effects of TT versus DT. We performed a meta-analysis of 6 studies (1 randomized control study and 5 cohort studies). RESULTS The included studies enrolled 7259 patients; 4630 (63.8%) were on TT and 2629 (36.2%) were on DT. The average follow-up time was 1.4 years. No significant differences were found between TT and DT in all-cause mortality (P = 0.70; I = 64%), stent thrombosis (P = 0.41), myocardial infarction (P = 0.43; I = 0%), stroke (P = 0.36; I = 0%), and major bleeding (P = 0.43; I = 0%). CONCLUSIONS In patients who are on OAC with vitamin K antagonist and underwent percutaneous coronary intervention, no significant differences were found in mortality, ischemic, and hemorrhagic complications between the patients treated with TT and DT. Thus, tailored treatment based on individual thromboembolic and bleeding risk might be the most reasonable approach in these patients.
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Reaching cardiovascular prevention guideline targets with a polypill-based approach: a meta-analysis of randomised clinical trials.
Selak, V, Webster, R, Stepien, S, Bullen, C, Patel, A, Thom, S, Arroll, B, Bots, ML, Brown, A, Crengle, S, et al
Heart (British Cardiac Society). 2019;(1):42-48
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Abstract
OBJECTIVE The aim of this study was to determine the effect of polypill-based care on the achievement of 2016 European Society of Cardiology (ESC) guideline targets for blood pressure (BP), low-density lipoprotein (LDL) cholesterol and antiplatelet therapy. METHODS We conducted an individual participant data meta-analysis of three randomised clinical trials that compared a strategy using a polypill containing aspirin, statin and antihypertensive therapy with usual care in patients with a prior cardiovascular disease (CVD) event or who were at high risk of their first event. Overall, the trials included 3140 patients from Australia, England, India, Ireland, the Netherlands and New Zealand (75% male, mean age 62 years and 76% with a prior CVD event). The primary outcome for this study was the proportion of people achieving ESC guideline targets for BP, LDL and antiplatelet therapy. RESULTS Those randomised to polypill-based care were more likely than those receiving usual care to achieve recommended targets for BP (62% vs 58%, risk ratio (RR) 1.08, 95% CI 1.02 to 1.15), LDL (39% vs 34%, RR 1.13, 95% CI 1.02 to 1.25) and all three targets for BP, LDL and adherence to antiplatelet therapy (the latter only applicable to those with a prior CVD event) simultaneously (24% vs 19%, RR 1.27, 95% CI 1.10 to 1.47) at 12 months. There was no difference between groups in antiplatelet adherence (96% vs 96%, RR 1.00, 95% CI 0.98 to 1.01). There was heterogeneity by baseline treatment intensity such that treatment effects increased with the fewer the number of treatments being taken at baseline: for patients taking 3, 2 and 0-1 treatment modalities the RRs for reaching all three guideline goals simultaneously were 1.10 (95% CI 0.94 to 1.30, 22% vs 20%), 1.62 (95% CI 1.09 to 2.42, 27% vs 17%) and 3.07 (95% CI 1.77 to 5.33, 35% vs 11%), respectively. CONCLUSIONS Polypill-based therapy significantly improved the achievement of all three ESC targets for BP, LDL and antiplatelet therapy compared with usual care, particularly among those undertreated at baseline.
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Economic evaluation of the use of non-vitamin K oral anticoagulants in patients with atrial fibrillation on antiplatelet therapy: a modelling analysis using the healthcare system in the Netherlands.
Bennaghmouch, N, de Veer, AJWM, Mahmoodi, BK, Jofre-Bonet, M, Lip, GYH, Bode, K, Ten Berg, JM
European heart journal. Quality of care & clinical outcomes. 2019;(2):127-135
Abstract
AIMS: Non-vitamin K oral anticoagulants (NOACs) have consistently demonstrated superior efficacy in terms of stroke prevention and safety in terms of bleeding over vitamin K antagonist (VKA) in patients with non-valvular atrial fibrillation (AF). The potential use of NOACs in AF patients requiring antiplatelet therapy (APT) has only been assessed in small meta-analyses reporting consistent benefits of NOACs over VKAs. However, the prescription costs of NOACs are higher than those of VKAs. The aim of his study was to estimate the cost-effectiveness (CE) of NOACs compared to VKAs in patients with non-valvular AF also requiring APT with the Dutch healthcare system used as a surrogate of many European healthcare systems. METHODS AND RESULTS A decision tree was constructed to analyse the CE of NOACs compared to VKAs in patients with non-valvular AF with an indication for APT over a horizon of 1 year. Beside the base-case analysis, univariate probabilistic sensitivity and two sensitivity analyses were performed: first, we assessed the impact of VKA home monitoring; second, we varied the NOACs price assuming patent expiration. Use of NOACs instead of VKA is associated with a health gain of 0.0171 quality-adjusted life years (QALYs) and with an incremental cost of €357, resulting in an incremental cost-effectiveness ratio of €20 919, which is almost equal to the generally accepted CE threshold of €20 000 used in the Netherlands. The probability that NOACs are cost-effective at a conservative willingness-to-pay threshold of €20 000 per QALY was 50%. Introducing home monitoring increased VKAs costs so much that NOACs became the dominant option (less costly and more effective). Price drops associated to patent expiration of NOACs increased its CE. CONCLUSION This analysis suggests that the use of NOACs is a cost-effective alternative of VKAs in patients with AF needing APT. Our findings in the Netherlands healthcare system are probably consistent with other European populations.