Double-dose versus standard-dose clopidogrel and high-dose versus low-dose aspirin in individuals undergoing percutaneous coronary intervention for acute coronary syndromes (CURRENT-OASIS 7): a randomised factorial trial

Mehta, Shamir R.; Tanguay, Jean‐François; Eikelboom, John W.; Jolly, Sanjit S.; Joyner, Campbell; Granger, Christopher B.; Faxon, David P.; Rupprecht, Hans‐Jürgen; Budaj, Andrzej; Avezum, Álvaro; Widimský, Petr; Steg, Philippe Gabriel; Bassand, Jean‐Pierre; Montalescot, Gilles; Macaya, Carlos; Pasquale, Giuseppe Di; Niemelä, Kari; Ajani, A.; White, Harvey D.; Chrolavicius, Susan; Gao, Peggy; Fox, Keith A.A.; Yusuf, Salim

doi:10.1016/s0140-6736(10)61088-4

Cited by 732 publications

(443 citation statements)

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“…Recommendations on a loading dose of aspirin in ACS were originally from the period when only aspirin could be applied for oral antiplatelet therapy, and few studies evaluated the effect of loading dose, compared with nonloading dose in the acute phase 17, 18. The majority of studies on P2Y 12 receptor inhibitors evaluated the effectiveness of dual antiplatelet therapy (clopidogrel plus aspirin) versus aspirin alone or compared the effect of different kinds of P2Y 12 receptor inhibitors19, 20, 21 or the effect of a high loading dose of P2Y 12 receptor inhibitors with a low loading dose of P2Y 12 receptor inhibitors 16, 22, 23, 24. Only 1 registry study compared the effect of a loading dose of clopidogrel with a standard dose in patients older than 75 years 25.…”

Section: Discussionmentioning

confidence: 99%

In‐Hospital Outcomes of Dual Loading Antiplatelet Therapy in Patients 75 Years and Older With Acute Coronary Syndrome Undergoing Percutaneous Coronary Intervention: Findings From the CCC‐ACS (Improving Care for Cardiovascular Disease in China‐Acute Coronary Syndrome) Project

Zhao

Zhou

et al. 2018

JAHA

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BackgroundElderly patients with acute coronary syndrome (ACS) are at high risk for ischemic and bleeding events. This study aimed to evaluate the clinical effectiveness and safety of dual loading antiplatelet therapy for patients 75 years and older undergoing percutaneous coronary intervention for ACS.Methods and ResultsThe Improving Care for Cardiovascular Disease in China‐ACS project was a collaborative study of the American Heart Association and Chinese Society of Cardiology. A total of 5887 patients 75 years and older with ACS who had percutaneous coronary intervention and received dual antiplatelet therapy with aspirin and P2Y12 inhibitors (clopidogrel or ticagrelor) between November 2014 and June 2017 were enrolled. The primary effectiveness and safety outcomes were in‐hospital major adverse cardiovascular events and major bleeding. Hazard ratios (HRs) of in‐hospital outcomes with different loading statuses of antiplatelet therapy were estimated using Cox proportional hazard models with multivariate adjustment. A propensity score–matched analysis was also conducted. Compared with patients receiving a dual nonloading dose, patients taking a dual loading dose had increased risks of both major adverse cardiovascular events (HR, 1.66, 95% confidence interval, 1.13–2.44; [P=0.010]) and major bleeding (HR, 2.34, 95% confidence interval, 1.75–3.13; [P<0.001]). Among 3284 propensity score–matched patients, a dual loading dose was associated with a 1.36‐fold risk of major adverse cardiovascular events (HR, 1.36; 95% confidence interval, 0.88–2.11 [P=0.168]) and a 2.08‐fold risk of major bleeding (HR, 2.08; 95% confidence interval, 1.47–2.93 [P<0.001]).ConclusionsA dual loading dose of antiplatelet therapy was associated with increased major bleeding risk but not with decreased major adverse cardiovascular events risk among patients 75 years and older undergoing percutaneous coronary intervention for ACS in China.Clinical Trial Registration URL: http://www.ClinicalTrials.gov. Unique identifier: NCT02306616.

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Section: Discussionmentioning

confidence: 99%

In‐Hospital Outcomes of Dual Loading Antiplatelet Therapy in Patients 75 Years and Older With Acute Coronary Syndrome Undergoing Percutaneous Coronary Intervention: Findings From the CCC‐ACS (Improving Care for Cardiovascular Disease in China‐Acute Coronary Syndrome) Project

Zhao

Zhou

et al. 2018

JAHA

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“…1 Of the study group enrolled, 17 263 patients actually underwent the percutaneous coronary intervention, and the authors performed a subgroup analysis of these patients. 2 The report of this subgroup analysis is the focus of our letter. In our view, the abstract and conclusion of the study report 2 do not adequately represent the results of the study, instead leading the reader to believe that the results are more profound than they truly are.…”

Section: Current-oasis: a Potential Mirage Of Numbersmentioning

confidence: 93%

“…2 We think that this statement is misleading. The term "cardiovascular events" implies a much broader meaning than the results actually show.…”

Section: Current-oasis: a Potential Mirage Of Numbersmentioning

confidence: 99%

CURRENT-OASIS: A Potential Mirage of Numbers

Magnusson

Tejani

2011

CJHP

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“…The CURRENT OASIS-7 trial [6,7], undertaken in 597 centres in 39 countries, randomly assigned, in a 2×2 factorial design, 25086 patients with an acute coronary syndrome who were referred for an invasive strategy to either double-dose clopidogrel (a 600 mg loading dose on day 1, followed by 150 mg daily for 6 days and 75 mg daily thereafter) or standard-dose clopidogrel (a 300 mg loading dose and 75 mg daily thereafter) and either higher-dose aspirin (300 to 325 mg daily) or lower-dose aspirin (75 to 100 mg daily). Aspirin dose had no effect on outcome.…”

Section: When Is Intense P2y 12 Adp Receptor Blockade Needed?mentioning

confidence: 99%

Measuring Platelet Reactivity after Clopidogrel-Has it Reached the End of the Road?

Wong¹

2013

Cardiol Pharmacol

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Clopidogrel is traditionally prescribed at 75 mg daily after a 300 mg loading dose. It is a pro-drug, with a two-step activation process involving a series of cytochrome P-450 (CYP) isoenzymes. Its antiplatelet effect is variable and susceptible to genetic polymorphisms. In particular, patients with either 1 or 2 loss-of-function CYP2C19 alleles have an attenuated pharmacologic response and worse clinical outcomes with standard dose clopidogrel [1]. Among clopidogrel-treated subjects in TRITON-TIMI 38, carriers had higher risk of cardiovascular death, myocardial infarction, or stroke as compared with non-carriers (12.1% vs. 8.0%; P=0.01) and higher risk of stent thrombosis (2.6% vs. 0.8%; p=0.02) [1]. Also, the common polymorphisms in the CYP2C19 gene, seen in approximately 30% of whites, may be more common in other ethnic groups -40% of blacks and >55% of East Asians [2].To achieve higher platelet inhibition, Prasugrel and Ticagrelor are newer P2Y 12 ADP receptor blockers that surpass clopidogrel in platelet inhibition [3,4]. Alternatively increasing clopidogrel dose may sometimes suffice. Among patients with stable cardiovascular disease, tripling the maintenance dose of clopidogrel to 225 mg daily in CYP2C19*2 heterozygotes, achieved levels of platelet reactivity similar to that seen with the standard 75 mg dose in non-carriers; for CYP2C19*2 homozygotes, doses as high as 300 mg daily did not result in comparable degrees of platelet inhibition [5]. When is Intense P2Y 12 ADP Receptor Blockade Needed?The CURRENT OASIS-7 trial [6,7], undertaken in 597 centres in 39 countries, randomly assigned, in a 2×2 factorial design, 25086 patients with an acute coronary syndrome who were referred for an invasive strategy to either double-dose clopidogrel (a 600 mg loading dose on day 1, followed by 150 mg daily for 6 days and 75 mg daily thereafter) or standard-dose clopidogrel (a 300 mg loading dose and 75 mg daily thereafter) and either higher-dose aspirin (300 to 325 mg daily) or lower-dose aspirin (75 to 100 mg daily). Aspirin dose had no effect on outcome.These findings illustrate that clopidogrel dosage and consequently the degree of platelet inhibition only matters in patients undergoing stenting but not in those managed medically. This conclusion echoes well with the recent findings from the TRILOGY ACS study [8] and its platelet function sub study [9] showing that both the use of prasugrel and the consequent stronger platelet inhibition as measured by the point-of care Verify Now P2Y 12 testing (Accumetrics, San Diego, California) have no independent relationship to outcome compared to the use of standard dose clopidogrel, in a cohort of medically managed patients.

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Double-dose versus standard-dose clopidogrel and high-dose versus low-dose aspirin in individuals undergoing percutaneous coronary intervention for acute coronary syndromes (CURRENT-OASIS 7): a randomised factorial trial

Cited by 732 publications

References 38 publications

In‐Hospital Outcomes of Dual Loading Antiplatelet Therapy in Patients 75 Years and Older With Acute Coronary Syndrome Undergoing Percutaneous Coronary Intervention: Findings From the CCC‐ACS (Improving Care for Cardiovascular Disease in China‐Acute Coronary Syndrome) Project

In‐Hospital Outcomes of Dual Loading Antiplatelet Therapy in Patients 75 Years and Older With Acute Coronary Syndrome Undergoing Percutaneous Coronary Intervention: Findings From the CCC‐ACS (Improving Care for Cardiovascular Disease in China‐Acute Coronary Syndrome) Project

CURRENT-OASIS: A Potential Mirage of Numbers

Measuring Platelet Reactivity after Clopidogrel-Has it Reached the End of the Road?

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