scholarly journals The efficacy and safety of dual-pathway inhibition therapy among patients with peripheral arterial disease – a meta-analysis

2021 ◽  
Vol 42 (Supplement_1) ◽  
Author(s):  
J Mapili ◽  
A S Davin ◽  
L M Villanueva

Abstract Background and objectives Peripheral artery disease (PAD) affects more than 200 million people worldwide and it is associated with an increased risk for cardiovascular morbidity and mortality. Current recommendations regarding the management of PAD have been controversial. Our meta-analysis investigated the efficacy of direct Xa inhibitor plus antiplatelet, also known as dual-pathway inhibition (DPI), on the individual components of major adverse cardiovascular events (stroke, myocardial infarction, and cardiovascular death) and major adverse limb events (amputation, restenosis, revascularization, and acute limb ischemia), the composite of MACE and MALE and its safety, in terms of bleeding, compared to antiplatelet therapy among patients with PAD. Methodology We performed a random-effects meta-analysis among patients with PAD comparing DPI to antiplatelet therapy. PubMed, EMBASE, CENTRAL, and ClinicalTrials.gov were searched from their dates of inception to August 2020 for Randomized Controlled Trials. Three studies met the inclusion criteria for final analysis. The selected studies were assessed for risk of bias using the Cochrane RoB2 tool and the overall quality of evidence was assessed using the GRADE approach. Results Among patients with PAD, DPI significantly reduces the risk of adverse limb events excluding amputation (RR 0.69, 95% CI 0.57–0.83) and composite MACE and MALE (RR 0.80, 95% CI 0.69–0.93) but significantly increases risk of major bleeding (RR 1.43, 95% CI 1.06–1.93) compared to antiplatelet therapy alone. Overall, DPI did not reduce myocardial infarction, stroke, cardiovascular death, or amputation, or increase the risk of fatal bleeding. Conclusions Among patients with PAD, DPI is more effective than antiplatelet therapy alone in preventing adverse limb events excluding amputation with an increased risk of major bleeding. We recommend the use of DPI among patients with PAD who are at a low risk of bleeding. FUNDunding Acknowledgement Type of funding sources: None.

2020 ◽  
Vol 26 (44) ◽  
pp. 5739-5745
Author(s):  
Jieqiong Guan ◽  
Wenjing Song ◽  
Pan He ◽  
Siyu Fan ◽  
Hong Zhi ◽  
...  

Objective: The aim was to evaluate the efficacy and safety of duration of dual antiplatelet therapy (DAPT) for patients who received percutaneous coronary intervention (PCI) with a drug-eluting stent. Background: The optimal duration of DAPT to balance the risk of ischemia and bleeding in CAD patients undergoing drug-eluting stent (DES) implantation remains controversial. Methods: PubMed, Cochrane Library, Web of Science, Clinicaltrials.gov, CNKI and Wanfang Databases were searched for randomized controlled trials of comparing different durations of DAPT after DES implantation. Primary outcomes were major adverse cardiac and cerebrovascular events (MACCE), and major bleeding, and were pooled by Bayes network meta-analysis. Net adverse clinical and cerebral events were used to estimate the surface under the cumulative ranking (SUCRA) curves. The subgroup analysis based on clinical status, follow-up and area was conducted using traditional pairwise meta-analysis. Results: A total of nineteen trials (n=51,035) were included, involving six duration strategies. The network metaanalysis showed that T2 (<6-month DAPT followed by aspirin, HR:1.51, 95%CI:1.02-2.22), T3 (standard 6-month DAPT, HR:1.47, 95%CI:1.14-1.91), T4 (standard 12-month DAPT, HR:1.41, 95%CI:1.15-1.75) and T5 (18-24 months DAPT, HR:1.47, 95%CI:1.09-1.97) was associated with significantly increased risk of MACCE compared to T6 (>24-month DAPT). However, no significant difference was found in MACCE risk between T1 (<6-month DAPT followed by P2Y12 monotherapy) and T6. Moreover, T5 was associated with significantly increased risk of bleeding compared to T1(RR:3.94, 95%CI:1.66-10.60), T2(RR:3.65, 95%CI:1.32-9.97), T3(RR:1.93, 95%CI:1.21-3.50) and T4(RR:1.89, 95%CI:1.15-3.30). The cumulative probabilities showed that T6(85.0%), T1(78.3%) and T4(44.5%) were the most efficacious treatment compared to the other durations. In the ACS (<50%) subgroup, T1 was observed to significantly reduce the risk of major bleeding compared to T4, but not in the ACS (≥50%) subgroup. Conclusions: Compared with other durations, short DAPT followed by P2Y12 inhibitor monotherapy showed non-inferiority, with a lower risk of bleeding and not associated with an increased MACCE. In addition, the risk of major bleeding increased significantly, starting with DAPT for 18-month. Compared with the short-term treatment, patients with ACS with the standard 12-month treatment have a better prognosis, including lower bleeding rate and the decreased risk of MACCE. Due to study's limitations, the results should be verified in different risk populations.


2020 ◽  
Vol 120 (10) ◽  
pp. 1352-1356
Author(s):  
Dion Stub ◽  
Himawan Fernando ◽  
James D. McFadyen ◽  
Jathushan Palasubramaniam ◽  
James Shaw ◽  
...  

AbstractThere have been numerous and intriguing advancements in antithrombotic therapy for myocardial infarction since it was described in the earliest issues of Thrombosis and Haemostasis. In this article, we revisit historical breakthroughs and describe the four most challenging contemporary themes relating to antithrombotic therapy in myocardial infarction. In all four, the challenge is to find the best balance of reducing specific levels of ischaemic risks without increasing bleeding risk. The first is the question of the optimal duration of dual antiplatelet therapy (DAPT) after percutaneous coronary intervention (PCI). This includes discussion of monotherapy after a period of DAPT. The second relates to the role of genotype and phenotype-guided individualisation of antiplatelet therapy. There is emerging evidence for a role of pheno/genotyping in identifying individuals at high risk for recurrent ischaemic events or in guiding the timing of cardiac surgery for patients on DAPT. The third addresses the increasing evidence for dual pathway inhibition, for example, with rivaroxaban in addition to aspirin in patients where high ischaemic and low bleeding risk is demonstrated. Finally the fourth highlights the challenge of the most appropriate combination of antiplatelet and anticoagulation therapy for patients with known atrial fibrillation after PCI. In most individuals, oral P2Y12 inhibitor therapy combined with a direct acting oral anticoagulant appears to be the best strategy based on the available evidence. Overall, the progress in antithrombotic therapy achieved over the last seven decades is remarkable, however, there are important issues to address and progress still to be made.


Author(s):  
Anne-Marie Schjerning Olsen ◽  
Emil L Fosbøl ◽  
Jesper Lindhardsen ◽  
Charlotte Andersson ◽  
Fredrik Folke ◽  
...  

Background: Non steroidal anti-inflammatory drugs(NSAIDs) utilization has been associated with worsened outcomes among patients with established cardiovascular disease.We analyzed the cause-specific cardiovascular risk associated with use of NSAIDs in a nationwide cohort of patients with prior myocardial infarction (MI). Methods: By individual-level linkage of nationwide registries of hospitalizations and drug dispenses from pharmacies in Denmark, patients aged >30 years admitted with first-time MI during 1997-2009 and their subsequent NSAID use were identified. The risk of cardiovascular death, a composite of coronary death or nonfatal MI, and fatal or nonfatal stroke with NSAID use was analyzed by adjusted Cox proportional hazard models. Results: Of 97,698 patients included (mean age 69 years (SD 13.0), 63.0% men),44.0% received NSAIDs during follow-up. Relative to no NSAID use, overall NSAID was associated with an increased risk of cardiovascular death (hazard ratio [HR] 1.52 95% confidence interval [CI] 1.34-1.73). In particular, use of the nonselective NSAID diclofenac and the selective cyclooxygenase-2 (COX-2) inhibitor rofecoxib was associated with increased risk of cardiovascular death (HR 2.05 95% confidence interval CI 1.88-2.23) and HR 1.74(CI.1.53-1.98), respectively) with a dose dependent increase in risk. Use of ibuprofen was associated with increased risk of fatal/nonfatal stroke (HR 1.27(CI. 1.14-1.41)).Naproxen was associated with the lowest risk of all outcomes, although higher than no NSAID use. Conclusion: The cause specific cardiovascular risks associated with the use of individual NSAIDs found to differ and in particular rofecoxib and diclofenac were associated with increased cardiovascular morbidity and mortality. These results further support caution in use of NSAIDs in patients with prior MI.


2021 ◽  
Vol 27 ◽  
pp. 107602962199681
Author(s):  
Tao Tang ◽  
Ming Zhang ◽  
Wendong Li ◽  
Nan Hu ◽  
Xiaolong Du ◽  
...  

Peripheral artery disease (PAD) is a common disease affecting over 200 million people worldwide. PAD is associated with significant limb and cardiovascular morbidity and mortality which is reduced by antiplatelet and antithrombotic therapy. However, the optimal type, dose, and time of antithrombotic therapy is still uncertain.We searched 4 electronic databases from January 1, 1990, to June 1, 2020, for randomized controlled trials of patients who received oral anticoagulant and antiplatelet therapy for PAD. The primary outcome was a composite of acute limb ischemia, major amputation, myocardial infarction, ischemic stroke, death from cardiovascular events, or death from any cause. Secondary outcomes included major bleeding, fatal bleeding, and intracranial hemorrhage events.We identified 3 studies that satisfied inclusion and exclusion criteria. Compared with antiplatelet alone, oral anticoagulant plus antiplatelet therapy improved acute limb ischemia (p < 0.00001), stroke (p = 0.005), and major amputation events (p = 0.11). However, oral anticoagulant plus antiplatelet therapy was not effective for prevention of myocardial infarction (p = 0.23), death from cardiovascular events (p = 0.65), or death from any cause (p = 0.66). Additionally, a significant increase in major bleeding events was demonstrated (p < 0.00001). There was no significant difference in fatal bleeding (p = 0.16) or intracranial hemorrhage events (p = 0.43). This meta-analysis showed that oral anticoagulant plus antiplatelet therapy for PAD may improve acute limb ischemia and major amputation or stroke risk compared with antiplatelet therapy alone, but could increase the risk of major bleeding events. On the other hand, measuring myocardial infarction, death, fatal bleeding, or intracranial hemorrhage risk remains controversial.


BMC Neurology ◽  
2020 ◽  
Vol 20 (1) ◽  
Author(s):  
Christessa Emille Que Albay ◽  
Frederick Gavril D. Leyson ◽  
Federick C. Cheng

Abstract Background New evidence on the efficacy and safety of dual antiplatelet therapy for secondary stroke prevention have been realized in the recent years. An updated meta analysis was done to determine the effect of the various dual antiplatelets vs aspirin alone on recurrence rate of ischemic stroke, cardiovascular morbidity and mortality, and its safety profile as reported through major bleeding. Methods PubMed, Cochrane and Science Direct data bases were utilized, RCTs evaluating dual antiplatelet vs mono antiplatelet therapy for acute ischemic stroke or transient ischemic attack within < 72 h from ictus were searched up to July 2019. Risk ratio at 95% confidence intervals were calculated to evaluate stroke recurrence, cardiac events and mortality, and major bleeding. Results Sixteen randomized controlled trials with a population of 28, 032 patients were pooled into a meta-analysis. Dual antiplatelet therapy was significantly superior over mono antiplatelet therapy in the reduction of stroke (RR 0.75, 95% CI:0.68–0.83, p value< 0.00001) and composite events namely cardiovascular morbidity and mortality (0.73 95% CI: 0.65–0.82, p value < 0.00001), while bleeding events were noted to be not significant (1.22 95% CI: 0.87–1.70, p value = 0.25). Conclusion In acute non-cardioembolic ischemic strokes or those who have suffered a transient ischemic attack, dual antiplatelet therapy was associated with efficacy in stroke recurrence and composite cardiac events, with a non-significant risk of major bleeding.


2021 ◽  
Vol 10 (1) ◽  
Author(s):  
Stacey E. Alexeeff ◽  
Noelle S. Liao ◽  
Xi Liu ◽  
Stephen K. Van Den Eeden ◽  
Stephen Sidney

Background Fine particulate matter <2.5 µm in diameter (PM 2.5 ) has known effects on cardiovascular morbidity and mortality. However, no study has quantified and compared the risks of incident myocardial infarction, incident stroke, ischemic heart disease (IHD) mortality, and cerebrovascular mortality in relation to long‐term PM 2.5 exposure. Methods and Results We sought to quantitatively summarize studies of long‐term PM 2.5 exposure and risk of IHD and stroke events by conducting a review and meta‐analysis of studies published by December 31, 2019. The main outcomes were myocardial infarction, stroke, IHD mortality, and cerebrovascular mortality. Random effects meta‐analyses were used to estimate the combined risk of each outcome among studies. We reviewed 69 studies and included 42 studies in the meta‐analyses. In meta‐analyses, we found that a 10‐µg/m 3 increase in long‐term PM 2.5 exposure was associated with an increased risk of 23% for IHD mortality (95% CI, 15%–31%), 24% for cerebrovascular mortality (95% CI, 13%–36%), 13% for incident stroke (95% CI, 11%–15%), and 8% for incident myocardial infarction (95% CI, −1% to 18%). There were an insufficient number of studies of recurrent stroke and recurrent myocardial infarction to conduct meta‐analyses. Conclusions Long‐term PM 2.5 exposure is associated with increased risks of IHD mortality, cerebrovascular mortality, and incident stroke. The relationship with incident myocardial infarction is suggestive of increased risk but not conclusive. More research is needed to understand the relationship with recurrent events.


Blood ◽  
2013 ◽  
Vol 122 (21) ◽  
pp. 3633-3633
Author(s):  
Jonathan Douxfils ◽  
Fanny Buckinx ◽  
François Mullier ◽  
Valentine Minet ◽  
Véronique Rabenda ◽  
...  

Abstract Introduction Dabigatran etexilate (DE) is an oral direct thrombin inhibitor approved for prevention of stroke and systemic embolism in adult patients with non-valvular atrial fibrillation (NVAF). In the RE-LY trial, myocardial infarction (MI) rates were increased with DE 110mg bid and 150mg bid when compared to warfarin. The risk of MI associated with the use of DE was assessed in a previous meta-analysis of 7 non-inferiority randomized controlled trials (RCTs) showing a significant 33% increase in MI. We performed an updated meta-analysis of RCTs comparing DE with active comparators or placebo to assess the effect of this agent on MI risk as a primary objective. The outcome of major bleeding (MB) and all-cause mortality was also assessed to provide global safety and efficacy measure. Stratifications by comparators (enoxaparin, warfarin or placebo) and by studies using the 150mg bid and the 110mg bid dose regimen were performed. Materials and Methods We conducted searches of the published literature and a clinical-trials registry maintained by the drug manufacturer till 22th of March, 2013. Criteria for inclusion in our meta-analysis included all RCTs and the availability of outcome data for MI, MB and all-cause mortality. Among the 423 unique references identified, 13 RCTs fulfilled the inclusion criteria. All methodologies were performed according to the PRISMA Statement. Results Myocardial infarction occurs in 287 of 23,839 patients (1.20%) treated with DE and in 106 of 13,536 patients treated with controls (0.78%). Major bleeding occur in 948 of 27,063 patients (3.50%) treated with DE and in 551/15,341 patients (3.59%) treated with controls. Death occurs in 989 of 24,162 patients (4.09%) treated with DE and in 570 of 14,498 patients (3.93%) treated with controls. Overall OR for MI, MB and all-cause mortality were 1.32 (95% CI; 1.07-1.63; P=0.010), 0.85 (95% CI: 0.79-0.98; P=0.010) and 0.90 (95% CI; 0.81-1.00; P=0.046) (Figure 1). When compared to warfarin, OR for MI, MB and all-cause mortality were 1.38 (95% CI: 1.08-1.77; P=0.010), 0.85 (95% CI: 0.75-0.95; P=0.006) and 0.90 (95% CI: 0.81-1.01; P=0.069), respectively (Figure 1). In RCTs using the 150mg bid dose regimen, OR for MI, MB and all-cause mortality were 1.44 (95% CI: 1.09-1.90; P=0.010), 0.92 (95% CI: 0.81 to 1.05; P=0.228) and 0.88 (95% CI: 0.78-1.00; P=0.045), respectively (Figure 2). Results of the 110mg bid dose were mainly driven by the RE-LY trial. Discussion DE significantly reduced MB and all-cause mortality compared to controls. However, while the reduction of MB is statistically significant versus warfarin, the reduction in all-cause mortality is not (Figure 1B & 1C). The increased risk of MI with the 150mg bid dose is significant but the reduction in MB and mortality is non-statistically significant (Figure 2). Taken together, these remarks suggest that in frail patients presenting comorbidities, the choice of the 150mg bid dose should be carefully discussed and the 110mg bid dose might be considered. Based on our results, one cannot conclude that the 110mg bid dose is associated with a higher risk of MI. However, in terms of absolute risk, such an increased risk of MI should be tempered when compared to the outcomes of stroke or systemic embolism, MB and all-cause mortality. The results from the RE-LY trial showed that the benefits of DE over warfarin outweigh this increase risk of MI. The risk difference was greatly in favor of DE regarding the composite of stroke/systemic embolism, MI, MB and all-cause mortality. Conclusion This meta-analysis of RCTs provides robust evidence that DE is associated with an overall significant 32% increase in the risk of MI. The risk was principally identified when warfarin is used as comparator (38% increase). In RCTs using the 150mg bid DE dose, a significant 44% overall increased risk of MI was identified. No definitive conclusion about the absence of the risk of MI with the 110mg bid DE dose can be drawn at this time. However, this increase risk has to be tempered with the overall benefit of DE especially in the patients with NVAF. In conclusion, we suggest that health care professionals and regulators should consider additional risk minimization strategy to prevent the risk of MI in vulnerable population. Disclosures: No relevant conflicts of interest to declare.


Circulation ◽  
2015 ◽  
Vol 132 (suppl_3) ◽  
Author(s):  
Alexandros Briasoulis ◽  
Shikha Sharma ◽  
Sagar Mallikethi-Reddy ◽  
Nikolaos Papageorgiou ◽  
Mohan Palla ◽  
...  

Background: Combined use of dual antiplatelet therapy with oral anticoagulation (OAC) is required in some patients with after coronary artery stenting or acute coronary syndrome (ACS). Methods: We performed a meta-analysis of the comparative effects of triple antithrombotic therapy (TT) vs OAC with single antiplatelet therapy (DT) on all-cause mortality, stroke, cardiovascular death, myocardial infarction, target vessel revascularization and major bleeding. We conducted an EMBASE and MEDLINE search for prospective controlled trials and cohort studies of patients requiring anticoagulation after coronary stenting. Results: We identified 3 prospective controlled studies and 5 cohort studies, which compared TT vs dual therapy (DT). We identified 4 prospective controlled and 6 cohort studies with 4564 patients on TT and 1848 on DT with an average follow up duration of 10.1 months. TT is associated with similar rates of all-cause mortality, stroke and major bleeding but significantly lower rates of myocardial infarction compared to DT (mainly OAC plus clopidogrel). Conclusion: Triple antithrombotic therapy is associated with similar mortality and bleeding rates but less myocardial infarctions compared with OAC and single antiplatelet therapy.


2021 ◽  
Vol 11 (6) ◽  
pp. 508
Author(s):  
Milan Hromadka ◽  
Zuzana Motovska ◽  
Ota Hlinomaz ◽  
Petr Kala ◽  
Frantisek Tousek ◽  
...  

Aim. This study was designed to evaluate the relationship between microRNAs (miRNAs), miR-126-3p and miR-223-3p, as new biomarkers of platelet activation, and predicting recurrent thrombotic events after acute myocardial infarction (AMI). Methods and Results. The analysis included 598 patients randomized in the PRAGUE-18 study (ticagrelor vs. prasugrel in AMI). The measurements of miRNAs were performed by using a novel miRNA immunoassay method. The association of miRNAs with the occurrence of the ischemic endpoint (EP) (cardiovascular death, nonfatal MI, or stroke) and bleeding were analyzed. The miR-223-3p level was significantly related to an increased risk of occurrence of the ischemic EP within 30 days (odds ratio (OR) = 15.74, 95% confidence interval (CI): 2.07–119.93, p = 0.008) and one year (OR = 3.18, 95% CI: 1.40–7.19, p = 0.006), respectively. The miR-126-3p to miR-223-3p ratio was related to a decreased risk of occurrence of EP within 30 days (OR = 0.14, 95% CI: 0.03–0.61, p = 0.009) and one year (OR = 0.37, 95% CI: 0.17–0.82, p = 0.014), respectively. MiRNAs were identified as independent predictors of EP even after adjustment for confounding clinical predictors. Adding miR-223-3p and miR-126-3p to miR-223-3p ratios as predictors into the model calculating the ischemic risk significantly increased the predictive accuracy for combined ischemic EP within one year more than using only clinical ischemic risk parameters. No associations between miRNAs and bleeding complications were identified. Conclusion. The miR-223-3p and the miR-126-3p are promising independent predictors of thrombotic events and can be used for ischemic risk stratification after AMI.


2020 ◽  
Vol 41 (Supplement_2) ◽  
Author(s):  
M.E Gimbel ◽  
D.R.P.P Chan Pin Yin ◽  
R.S Hermanides ◽  
F Kauer ◽  
A.H Tavenier ◽  
...  

Abstract Background Elderly patients form a large and growing part of the patients presenting with non-ST-elevation myocardial infarction (NSTEMI). Choosing the optimal antithrombotic treatment in these elderly patients is more complicated because they frequently have characteristics indicating both a high ischaemic and high bleeding risk. Purpose We describe the treatment of elderly patients (&gt;75 years) admitted with NSTEMI, present the outcomes (major adverse cardiovascular events (MACE) and bleeding) and aim to find predictors for adverse events. Methods The POPular AGE registry is an investigator initiated, prospective, observational, multicentre study of patients aged 75 years or older presenting with NSTEMI. Patients were recruited between August 1st, 2016 and May 7th, 2018 at 21 sites in the Netherlands. The primary composite endpoint of MACE included cardiovascular death, non-fatal myocardial infarction and non-fatal stroke at one-year follow-up. Results A total of 757 patients were enrolled. During hospital stay 76% underwent coronary angiography, 34% percutaneous coronary intervention and 12% coronary artery bypass grafting (CABG). At discharge 78.6% received aspirin (non-users mostly because of the combination of oral anticoagulant and clopidogrel), 49.7% were treated with clopidogrel, 34.2% with ticagrelor and 29.6% were prescribed oral anticoagulation. Eighty-three percent of patients received dual antiplatelet therapy (DAPT) or dual therapy consisting of oral anticoagulation and at least one antiplatelet agent for a duration of 12 months. At one year, the primary outcome of cardiovascular death, myocardial infarction or stroke occurred in 12.3% of patients and major bleeding (BARC 3 or 5) occurred in 4.8% of the patients. The risk of MACE and major bleeding was highest during the first month and stayed high over time for MACE while the risk for major bleeding levelled off. Independent predictors for MACE were age, renal function, medical history of CABG, stroke and diabetes. The only independent predictor for major bleeding was haemoglobin level on admission. Conclusion In this all-comers registry, most elderly patients (≥75 years) with NSTEMI are treated with DAPT and undergoing coronary angiography the same way as younger NSTEMI patients from the SWEDEHEART registry. Aspirin use was lower as was the use of the more potent P2Y12 inhibitors compared to the SWEDEHEART which is very likely due to the concomitant use of oral anticoagulation in 30% of patients. The fact that ischemic risk stays constant over 1 year of follow-up, while the bleeding risk levels off after one month may suggest the need of dual antiplatelet therapy until at least one year after NSTEMI. Funding Acknowledgement Type of funding source: Private grant(s) and/or Sponsorship. Main funding source(s): AstraZeneca


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