Hence, there were a total number of 10 studies with eligibility [ 12 , 21 — 29 ]. Figure 1 revealed the detailed search process. The abovementioned studies were based on evidence with moderate to high quality.
Table 1 described the major characteristics of the qualified studies in more detail. Pooled analysis of stroke Stroke rate was available for 7 trials. In the analysis of MI in patients who were treated with ticagrelor or clopidogrel, eight studies were included. Pooled data revealed that ticagrelor was not associated with higher trend of rate than clopidogrel, with the pooled OR being 0.
Pooled analysis of dyspnea events The incidences of dyspnea events in patients with ACS were available for four studies Fig. Dual antiplatelet therapy, usually accompanied with a P2Y12 receptor antagonist and aspirin, is generally acknowledged as a vital approach in treating ACS patients, partly because of the increased occurrence of thrombogenesis. Dual antiplatelet therapy has been also regarded as a standard therapy especially after PCI according to several clinical guidelines [ 14 , 30 ].
Clopidogrel, a P2Y12 receptor antagonist, has been generally utilized with aspirin as prescribed antiplatelet agents in an attempt to decrease the MI risk and stent thrombosis in patients with acute coronary syndromes with or without ST elevation [ 22 ]. However, clopidogrel requires 2-step hepatic metabolism as an inactive pro-drug that has a strong link to delayed onset and various responses [ 31 , 32 ].
Ticagrelor is a direct-acting oral antagonist of P2Yreceptor antagonist with reversibility and without catabolite activation, which can have a substantial impact on faster with consistent greater platelet inhibition than clopidogrel [ 10 , 12 ]. However, previous trial supported by some studiers demonstrated no remarkable difference in terms of the bleeding rate with the use of ticagrelor in comparison of clopidogrel.
Additionally, results of ventricular pauses on Holter monitoring as well as the dose-related episodes of dyspnea were found with high occurrence when using ticagrelor [ 12 ]. We conducted the study to evaluate the function of ticagrelor in terms of its superior effect to clopidogrel for ACS patients. The present analysis showed no statistical reduction of bleeding incidence, MI as well as stroke in ticagrelor in comparison of clopidogrel.
Nonetheless, dyspnea was more common in the ticagrelor group. Although susceptibility of higher bleeding risk was affected by platelet inhibition, controversy existed regarding to the link of bleeding risk and platelet inhibition level, of which the risk of major bleeding based on platelet inhibition level has not been estimated [ 33 , 34 ]. As shown in human race, there is variation in the drug response with different populations.
Comparing with non-Asian patients, Asian patients tend to be more susceptive with high bleeding risk in terms of the lower body weight, different genetic background, disease patterns as well as comorbidities [ 35 ].
Higher bleeding risk in Asian population has gained interests with standard doses of new P2Y12 inhibitors, especially in East Asian patients [ 36 ]. Furthermore, on basis of clinical experience and evidence, there may be a dissimilarity between the Chinese and Japanese patients [ 37 , 38 ]. It is always important to take different genetic predisposition into consideration in order to perform proper antiplatelet therapy if clopidogrel is applied as a control.
Compared with clopidogrel, ticagrelor is less likely to be influenced by CYP2C19 polymorphism [ 39 ]. The role of platelet inhibition in ticagrelor may gain popularity among Asian patients who are prone to have higher prevalence of loss of CYP2C19 function polymorphism, which may be associated with the remarkable decrease of ischemic events [ 40 ]. Increased risk of cardiovascular events usually leads to bleeding [ 41 ].
However, the risk factors of subsequent cardiovascular events were associated with major bleeding with differences in degree between Asian and non-Asian patient individuals. Debates exists concerning the reason for the susceptibility of Asian patients to subsequent cardiovascular events.
Asian patients who suffer numerically higher subsequent ischemic events are those who are associated with major bleeding than without bleeding [ 40 ]. In addition, another strong predictor of adverse prognosis after ACS is the age of patients [ 42 , 43 ]; ACS patients with older age tend to be accompanied with drug-related bleeding complications and increased risk of CV death.
Previous clinical prognosis of older age with ACS is often further complicated by more common comorbidity [ 44 , 45 ]. The abovementioned findings need further evaluation to offer strong evidence.
Dyspnea is another pivotal parameter as adverse effect in addition to bleeding. In our study, ticagrelor exerted increased dyspnea incidence in comparison of clopidogrel, which mainly due to its function in increasing the inhibition of P2Y12 on sensory neurons and the endogenous adenosine concentration [ 46 — 48 ].
The main strength of our study is the use of a well-maintained and updated database including studies that were designed as random control trials RCTs and propensity score matching PSM control trials. Nevertheless, potential bias exists by the intrinsic retrospective study and the imbalance in baseline demographics and clinical characteristics, which may impact the comparison of relevant outcomes.
More large-scale studies with greater statistical significance are warranted for the confirmation of the safety as well as efficacy profile of ticagrelor and clopidogrel. In summary, we present a meta-analysis with evidence-based data comparing ticagrelor and clopidogrel in treating ACS patients. Aggregated results showed no increase in major bleeding rate, MI and stroke with the use of ticagrelor except for dyspnea rate. However, considering ticagrelor is less likely to be influenced by metabolic activation and various drug action between individuals, it has potential to be a valid, alternative antiplatelet drug in comparison of clopidogrel.
Hence, ticagrelor may be a valid and even more potent antiplatelet drug than clopidogrel, especially as an alternative strategy in treating patients with clopidogrel intolerance or resistance. Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations. National Center for Biotechnology Information , U.
BMC Cardiovasc Disord. Published online Nov Tell your doctor about all the medicines you take, including prescription and over-the-counter medicines, vitamins, and herbal supplements. Tell your doctor if you are breastfeeding or plan to breastfeed. Patients were studied for up to 1 year. Patients were matched using a large-scale propensity score algorithm, and the date of final follow-up was March Main Outcomes and Measures The primary end point was net adverse clinical events NACE at 12 months, composed of ischemic events recurrent myocardial infarction, revascularization, or ischemic stroke and hemorrhagic events hemorrhagic stroke or gastrointestinal bleeding.
Secondary outcomes included NACE or mortality, all-cause mortality, ischemic events, hemorrhagic events, individual components of the primary outcome, and dyspnea at 12 months. The database-level hazard ratios HRs were pooled to calculate summary HRs by random-effects meta-analysis. The 1-year risk of NACE was not significantly different between ticagrelor and clopidogrel There was also no significant difference in the risk of all-cause mortality 2.
The risks of hemorrhagic events 2. Because the possibility of unmeasured confounders cannot be excluded, further research is needed to determine whether ticagrelor is more effective than clopidogrel in this setting. Quiz Ref ID Ticagrelor is an oral, reversible, direct-acting P2Y12 inhibitor that exhibits more profound platelet inhibition with more rapid onset on the basis of platelet function testing, compared with clopidogrel.
Questions remain, however, about the greater efficacy of ticagrelor compared with clopidogrel. Written informed consent was waived due to the deidentified nature of the databases. Analyses of deidentified data were performed in accordance with local laws and regulation with approvals from respective scientific and ethics committees. All 3 databases were standardized to the Observational Medical Outcomes Partnership common data model, version 5 eMethod 1 in Supplement 1.
We performed distributed network analyses. According to this protocol, the study package for the entire process was built on the OHDSI Methods Library in R and released with a Docker image providing a computational reproducible environment.
Next, the predesignated statistical results without patient-level information were shared for interpretation and database-level meta-analysis. The index date was defined as the date of PCI. To avoid left censoring, we excluded patients who had been enrolled in the database for less than 1 year before the index date.
The other exclusion criteria were a history of ischemic stroke, hemorrhagic stroke, or gastrointestinal bleeding any time before the index date; and a prescription of prasugrel, clopidogrel for the ticagrelor group , or ticagrelor for the clopidogrel group during the 30 days preceding the index date.
Further details of the cohort definition are presented in eMethod 2 in Supplement 1. Ticagrelor or clopidogrel use was ascertained from prescription records within the 7 days before the index date. Quiz Ref ID The primary outcome was net adverse clinical events NACE , which included ischemic events recurrent acute myocardial infarction [AMI], revascularization, or ischemic stroke and hemorrhagic events hemorrhagic stroke or gastrointestinal bleeding from day 1 to days after PCI.
The secondary outcomes consisted of an extended definition of NACE that included mortality NACE or mortality , all-cause mortality, composite ischemic events recurrent AMI, revascularization, or ischemic stroke , composite hemorrhagic events hemorrhagic stroke or gastrointestinal bleeding , and individual components of the primary outcome within 1 year.
The 1-year risk of dyspnea, a well-known adverse event of ticagrelor, was also evaluated. Cardiovascular-related mortality was identified by a death record with at least 1 cardiovascular-related diagnosis AMI, stroke, sudden cardiac death, or hospitalization for heart failure in the 30 days before death as described previously.
For the Optum EHR, we also included race and baseline laboratory values in the logistic regression model because they were available and can be associated with the selection of the drug and clinical outcomes.
The missingness in laboratory values were matched between the ticagrelor and clopidogrel groups and missing values were not imputed. Next, the study populations were matched using one-to-one greedy matching of the propensity score. The Cox proportionality assumption was tested based on the Schoenfeld residuals, and no relevant violations were found for the primary outcome. Patients were censored when they were no longer observed in the database, while they remained in the primary analysis if they discontinued the allocated drug or switched the drug within the first year.
We then performed random-effects meta-analysis to calculate summary hazard ratio HR pooling effect estimates across the databases. To assess the robustness of the findings, a large set of sensitivity analyses were conducted using differing definitions of the at-risk time window, the statistical approaches, the study population, and the outcomes.
First, in addition to one-to-one propensity score matching, 2 additional propensity score adjustments were performed: 1 variable-ratio propensity score matching with a maximum ratio of 10; and 2 propensity score stratification using deciles of the propensity score distribution.
Second, 2 more time-at-risk windows were applied—a 5-year period and an on-treatment period. Fourth, since a diagnosis code—based outcome definition may include false-positive cases, we applied a restricted definition of outcome that only considered primary diagnoses. Fifth, we conducted an additional analysis to apply an identical study period to all databases, namely March and December , because ticagrelor was covered by national insurance in South Korea from March Sixth, as a post hoc analysis and since the individual events in NACE are not equivalent, we calculated the weighted incidence of NACE, weighted by the HR of individual events, for 1-year mortality after an event relative to death after ischemic stroke eMethod 4 in Supplement 1.
In addition, we employed a total of 96 falsification end points using a data-rich algorithm to quantify systematic error eMethod 5 in Supplement 1. We performed empirical calibration of the CIs by fitting an empirical null distribution to point estimates of these falsification end points.
To assess the association of ticagrelor vs clopidogrel with clinical outcomes in the United States, we also performed a post hoc meta-analysis that was restricted to the 2 US databases. Because of the potential for type 1 error due to multiple comparisons, findings for analyses of secondary outcomes should be interpreted as exploratory.
All analyses were performed using R programming language version 3. The proportion of patients in the ticagrelor group in the entire study population consistently increased in all 3 databases over time, such that it reached The baseline characteristics of the overall study population before and after propensity score matching are reported in the Table. The baseline characteristics before and after propensity score matching in each database are presented online eTables in Supplement 1.
The aggregated patient cohort size, follow-up duration, incidences of NACE, and minimum detectable relative risk before and after propensity score matching in the 3 databases are shown in eTable 4 in Supplement 1. Among matched patients, At 1 year after the index date, mean medication possession ratios were 0. Overall, 1-year incidence of NACE was This may not be a complete list of all possible drug interactions.
Consult a doctor with all the medications you may be taking. Both Brilinta and Plavix have a higher risk of bleeding associated with their use. Especially when combined with other blood-thinning drugs, Brilinta or Plavix can increase the risk of internal bleeding, such as intracranial hemorrhage or gastrointestinal bleeding. The use of antiplatelet agents like Brilinta and Plavix is cautioned if you have a known history of bleeding or ulcers.
Brilinta should not be started in patients undergoing a coronary artery bypass graft surgery CABG. However, if bleeding can be managed during this procedure, it may be recommended to continue Brilinta treatment. Brilinta should not be taken with aspirin doses greater than mg. Higher doses of aspirin may decrease how well Brilinta works. People who have a genetic dysfunction with CYP2C19 liver enzymes can experience reduced effectiveness with Plavix.
If you are suspected to be a CYP2C19 poor metabolizer, you can take a test to find out. Brilinta is a prescription antiplatelet medication that is used to treat people with acute coronary syndrome ACS. Also known by its generic name ticagrelor, Brilinta is taken twice daily to prevent the formation of blood clots.
Brilinta is manufactured by AstraZeneca. Plavix is an antiplatelet medication that is taken as a once-daily tablet for people with ACS. Plavix is available as a brand-name and generic version. Like Brilinta and other P2Y12 inhibitors, Plavix is taken with a daily aspirin. Brilinta and Plavix are not the same. They are administered in different ways and have some differences in side effects and drug interactions. Brilinta has been marketed and studied as a more effective drug than Plavix.
It has been shown to be a better drug for reducing rates of cardiovascular death and preventing heart attack or stroke. However, it may be more likely to produce adverse effects such as bleeding and shortness of breath. There is not enough data to show that Brilinta and Plavix are completely safe during pregnancy. These drugs are not generally recommended unless their benefits outweigh the risks.
Talk to your doctor about your available treatment options while pregnant. It is best to avoid drinking alcohol while taking blood thinners like Brilinta or Plavix.
This is because alcohol also has blood-thinning properties. Drinking alcohol can compound the effects of these drugs and increase the risk of serious bleeding. Brilinta is taken for at least 12 months after a stent placement, also known as a percutaneous coronary intervention.
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