Topic
Loading dose
About: Loading dose is a research topic. Over the lifetime, 3293 publications have been published within this topic receiving 110170 citations.
Papers published on a yearly basis
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Papers
TL;DR: Following PCI, long-term clopidogrel therapy significantly reduced the risk of adverse ischemic events and subgroup analyses suggest that longer intervals between the loading dose and PCI may reduce events.
Abstract: ContextFollowing percutaneous coronary intervention (PCI), short-term clopidogrel
therapy in addition to aspirin leads to greater protection from thrombotic
complications than aspirin alone. However, the optimal duration of combination
oral antiplatelet therapy is unknown. Also, although current clinical data
suggest a benefit for beginning therapy with a clopidogrel loading dose prior
to PCI, the practical application of this therapy has not been prospectively
studied.ObjectivesTo evaluate the benefit of long-term (12-month) treatment with clopidogrel
after PCI and to determine the benefit of initiating clopidogrel with a preprocedure
loading dose, both in addition to aspirin therapy.Design, Setting, and ParticipantsThe Clopidogrel for the Reduction of Events During Observation (CREDO)
trial, a randomized, double-blind, placebo-controlled trial conducted among
2116 patients who were to undergo elective PCI or were deemed at high likelihood
of undergoing PCI, enrolled at 99 centers in North America from June 1999
through April 2001.InterventionsPatients were randomly assigned to receive a 300-mg clopidogrel loading
dose (n = 1053) or placebo (n = 1063) 3 to 24 hours before PCI. Thereafter,
all patients received clopidogrel, 75 mg/d, through day 28. From day 29 through
12 months, patients in the loading-dose group received clopidogrel, 75 mg/d,
and those in the control group received placebo. Both groups received aspirin
throughout the study.Main Outcome MeasuresOne-year incidence of the composite of death, myocardial infarction
(MI), or stroke in the intent-to-treat population; 28-day incidence of the
composite of death, MI, or urgent target vessel revascularization in the per-protocol
population.ResultsAt 1 year, long-term clopidogrel therapy was associated with a 26.9%
relative reduction in the combined risk of death, MI, or stroke (95% confidence
interval [CI], 3.9%-44.4%; P = .02; absolute reduction,
3%). Clopidogrel pretreatment did not significantly reduce the combined risk
of death, MI, or urgent target vessel revascularization at 28 days (reduction,
18.5%; 95% CI, −14.2% to 41.8%; P = .23). However,
in a prespecified subgroup analysis, patients who received clopidogrel at
least 6 hours before PCI experienced a relative risk reduction of 38.6% (95%
CI, −1.6% to 62.9%; P = .051) for this end
point compared with no reduction with treatment less than 6 hours before PCI.
Risk of major bleeding at 1 year increased, but not significantly (8.8% with
clopidogrel vs 6.7% with placebo; P = .07).ConclusionsFollowing PCI, long-term (1-year) clopidogrel therapy significantly
reduced the risk of adverse ischemic events. A loading dose of clopidogrel
given at least 3 hours before the procedure did not reduce events at 28 days,
but subgroup analyses suggest that longer intervals between the loading dose
and PCI may reduce events.
3,158 citations
TL;DR: The use of a pharmacogenetic algorithm for estimating the appropriate initial dose of warfarin produces recommendations that are significantly closer to the required stable therapeutic dose than those derived from a clinical algorithm or a fixed-dose approach.
Abstract: Warfarin is one of the most widely used anticoagulants in the world. Treatment is complicated by a large inter-individual variation in the dose needed to reach adequate levels of anticoagulation i.e. INR 2.0 – 3.0. The objective of this thesis was to evaluate which factors, mainly genetic but also non-genetic, that affect the response to warfarin in terms of required maintenance dose, efficacy and safety with special focus on warfarin dose prediction.Through candidate gene and genome-wide studies, we have shown that the genes CYP2C9 and VKORC1 are the major determinants of warfarin maintenance dose. By combining the SNPs CYP2C9 *2, CYP2C9 *3 and VKORC1 rs9923231 with the clinical factors age, height, weight, ethnicity, amiodarone and use of inducers (carbamazepine, phenytoin or rifampicin) into a prediction model (the IWPC model) we can explain 43 % to 51 % of the variation in warfarin maintenance dose. Patients requiring doses < 29 mg/week and doses ≥ 49 mg/week benefitted the most from pharmacogenetic dosing. Further, we have shown that the difference across ethnicities in percent variance explained by VKORC1 was largely accounted for by the allele frequency of rs9923231. Other novel genes affecting maintenance dose (NEDD4 and DDHD1), as well as the replicated CYP4F2 gene, have small effects on dose predictions and are not likely to be cost-effective, unless inexpensive genotyping is available.Three types of prediction models for warfarin dosing exist: maintenance dose models, loading dose models and dose revision models. The combination of these three models is currently being used in the warfarin treatment arm of the European Pharmacogenetics of Anticoagulant Therapy (EU-PACT) study. Other clinical trials aiming to prove the clinical validity and utility of pharmacogenetic dosing are also underway.The future of pharmacogenetic warfarin dosing relies on results from these ongoing studies, the availability of inexpensive genotyping and the cost-effectiveness of pharmacogenetic driven warfarin dosing compared with new oral anticoagulant drugs.
1,640 citations
TL;DR: In patients with severe, low-output heart failure, levosimendan improved haemodynamic performance more effectively than dobutamine and was accompanied by lower mortality in the levosIMendan group than in theDobutamine group for up to 180 days.
1,221 citations
TL;DR: Ticagrelor achieved more rapid and greater platelet inhibition than high-loading-dose clopidogrel; this was sustained during the maintenance phase and was faster in offset after drug discontinuation.
Abstract: Background— Ticagrelor is the first reversibly binding oral P2Y 12 receptor antagonist. This is the first study to compare the onset and offset of platelet inhibition (IPA) with ticagrelor using the PLATO (PLATelet inhibition and patient Outcomes) trial loading dose (180 mg) with a high loading dose (600 mg) of clopidogrel. Methods and Results— In a multicenter, randomized, double-blind study, 123 patients with stable coronary artery disease who were taking aspirin therapy (75 to 100 mg/d) received ticagrelor (180-mg load, 90-mg BID maintenance dose [n=57]), clopidogrel (600-mg load, 75-mg/d maintenance dose [n=54]), or placebo (n=12) for 6 weeks. Greater IPA (20 μmol/L ADP, final extent) occurred with ticagrelor than with clopidogrel at 0.5, 1, 2, 4, 8, and 24 hours after loading and at 6 weeks ( P 50% IPA (98% versus 31%, P 70% IPA (90% versus 16%, P P P =NS). IPA for ticagrelor on day 3 after the last dose was comparable to clopidogrel at day 5; IPA on day 5 for ticagrelor was similar to clopidogrel on day 7 and did not differ from placebo ( P =NS). Conclusions— Ticagrelor achieved more rapid and greater platelet inhibition than high-loading-dose clopidogrel; this was sustained during the maintenance phase and was faster in offset after drug discontinuation. Clinical Trial Registration Information— URL: http://www.clinicaltrials.gov. Unique identifier: NCT00528411.
1,137 citations
TL;DR: In patients with minor isChemic stroke or high‐risk TIA, those who received a combination of clopidogrel and aspirin had a lower risk of major ischemic events but a higher risk ofMajor hemorrhage at 90 days than those who receive aspirin alone.
Abstract: Background Combination antiplatelet therapy with clopidogrel and aspirin may reduce the rate of recurrent stroke during the first 3 months after a minor ischemic stroke or transient ischemic attack (TIA). A trial of combination antiplatelet therapy in a Chinese population has shown a reduction in the risk of recurrent stroke. We tested this combination in an international population. Methods In a randomized trial, we assigned patients with minor ischemic stroke or high-risk TIA to receive either clopidogrel at a loading dose of 600 mg on day 1, followed by 75 mg per day, plus aspirin (at a dose of 50 to 325 mg per day) or the same range of doses of aspirin alone. The dose of aspirin in each group was selected by the site investigator. The primary efficacy outcome in a time-to-event analysis was the risk of a composite of major ischemic events, which was defined as ischemic stroke, myocardial infarction, or death from an ischemic vascular event, at 90 days. Results A total of 4881 patients were en...
1,137 citations
Related Topics (5)
Performance Metrics
| Year | Papers |
|---|---|
| 2025 | 5 |
| 2024 | 15 |
| 2023 | 26 |
| 2022 | 54 |
| 2021 | 147 |
| 2020 | 142 |