Impact of Clopidogrel on-Treatment Platelet Reactivity on Stent Thrombosis After Percutaneous Coronary Intervention: Results From a Collaborative Meta-Analysis of Individual Participant Data

Brar, Somjot; Berg, Jurriën Ten; Marcucci, Rossella; Price, Matthew J.; Valgimigli, Marco; Kim, Hyo–Soo; Patti, Giuseppe; Breet, Nicoline J.; DiSciascio, Germano; Cuisset, Thomas; Dangas, George

doi:10.1016/s0735-1097(11)61632-x

Cited by 125 publications

(182 citation statements)

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“…There is considerable inter-individual variability in response to clopidogrel, current data suggesting that about 10% to 50% of patients treated with conventional doses do not display adequate anti-platelet response [17][18][19][20]. Four independent meta-analyses studiesemphasised the association between high non-clopidogrel platelet reactivity and significant increase in stent thrombosis, non-fatal myocardial infarction and cardiovascular mortality [21][22][23][24].…”

Section: Clopidogrelmentioning

confidence: 99%

Anti-platelet Therapy Resistance – Concept, Mechanisms and Platelet Function Tests in Intensive Care Facilities

Mărginean

Bănescu

Scridon

et al. 2016

The Journal of Critical Care Medicine

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It is well known that critically ill patients require special attention and additional consideration during their treatment and management. The multiple systems and organ dysfunctions, typical of the critical patient, often results in different patterns of enteral absorption in these patients. Anti-platelet drugs are the cornerstone in treating patients with coronary and cerebrovascular disease. Dual anti-platelet therapy with aspirin and clopidogrel is the treatment of choice in patients undergoing elective percutaneous coronary interventions and is still widely used in patients with acute coronary syndromes. However, despite the use of dual anti-platelet therapy, some patients continue to experience cardiovascular ischemic events. Recurrence of ischemic events is partly attributed to the fact that some patients have poor inhibition of platelet reactivity despite treatment. These patients are considered low-or nonresponders to therapy. The underlying mechanisms leading to resistance are not yet fully elucidated and are probably multifactorial, cellular, genetic and clinical factors being implicated. Several methods have been developed to asses platelet function and can be used to identify patients with persistent platelet reactivity, which have an increased risk of thrombosis. In this paper, the concept of anti-platelet therapy resistance, the underlying mechanisms and the methods used to identify patients with low responsiveness to anti-platelet therapy will be highlighted with a focus on aspirin and clopidogrel therapy and addressing especially critically ill patients.

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Section: Clopidogrelmentioning

confidence: 99%

Anti-platelet Therapy Resistance – Concept, Mechanisms and Platelet Function Tests in Intensive Care Facilities

Mărginean

Bănescu

Scridon

et al. 2016

The Journal of Critical Care Medicine

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“…1 The premature discontinuation of these medications 1 is associated with an increased risk of instent thrombosis, cardiovascular events and death. [2][3][4][5][6] Unfortunately, lack of medication adherence is common and is associated with significant health care costs and mortality. 7,8 Vulnerable groups such as racial minorities and the elderly have a higher risk of poor adherence.…”

Section: Introductionmentioning

confidence: 99%

“…7,8 Vulnerable groups such as racial minorities and the elderly have a higher risk of poor adherence. 5,6,9,10 In the case of antiplateletet medications, blacks are more likely to not receive a clopidogrel prescription 11 or to not fill it after PCI. Further, our prior analyses of insurer claims data showed that minority populations were less adherent to antiplatelet medications post drug-eluting stent (DES) placement.…”

Section: Introductionmentioning

confidence: 99%

Can Phone-Based Motivational Interviewing Improve Medication Adherence to Antiplatelet Medications After a Coronary Stent Among Racial Minorities? A Randomized Trial

et al. 2014

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BACKGROUND:Minorities have lower adherence to cardiovascular medications and have worst cardiovascular outcomes post coronary stent placement OBJECTIVE: The aim of this study is to compare the efficacy of phone-delivered Motivational Interviewing (MINT) to an educational video at improving adherence to antiplatelet medications among insured minorities. DESIGN: This was a randomized study. PARTICIPANTS: We identified minorities with a recently placed coronary stent from an administrative data set by using a previously validated algorithm. INTERVENTIONS: MINT subjects received quarterly phone calls and the DVD group received a one-time mailed video. MAIN MEASURES: Outcome variables were collected at baseline and at 12-month post-stent, using surveys and administrative data. The primary outcome was antiplatelet (clopidogrel and prasugrel) adherence measured by Medication Possession Ratio (MPR) and self-reported adherence (Morisky score). We also measured appropriate adherence defined as an MPR ≥ 0.80. KEY RESULTS: We recruited 452 minority subjects with a new coronary stent (44 % Hispanics and 56 % Black). The patients had a mean age of 69.5±8.8, 58 % were males, 78 % had an income lower than $30,000 per year and only 22 % had achieved high school education or higher. The MPR for antiplatelet medications was 0.77 for the MINT group compared to 0.70 for the DVD group (p<0.05). The percentage of subjects with adequate adherence to their antiplatelet medication was 64 % in the MINT group and 50 % in the DVD group (p<0.01). Self-reported adherence at 12 months was higher in the MINT group compared to the DVD group (p<0.01). Results were similar among drug-eluting stent (DES) recipients. CONCLUSIONS: Among racial minorities, a phone-based motivational interview is effective at improving adherence to antiplatelet medications post coronary stent placement. Phone-based MINT seems to be a promising and cost-effective strategy to modify risk behaviors among minority populations at high cardiovascular risk. BACKGROUNDThe safe use of coronary stents requires the daily use of thienopyridines for 3 to 12 months after percutaneous coronary intervention (PCI). 1 The premature discontinuation of these medications 1 is associated with an increased risk of instent thrombosis, cardiovascular events and death. 2-6 Unfortunately, lack of medication adherence is common and is associated with significant health care costs and mortality. 7,8 Vulnerable groups such as racial minorities and the elderly have a higher risk of poor adherence. 5,6,9,10 In the case of antiplateletet medications, blacks are more likely to not receive a clopidogrel prescription 11 or to not fill it after PCI. Further, our prior analyses of insurer claims data showed that minority populations were less adherent to antiplatelet medications post drug-eluting stent (DES) placement. 12 The lack of appropriate use of evidence-based therapies after PCI may partially contribute to the excess morbidity and mortality reported among minorities. 13,14,6 The improvement of med...

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“…A collaborative meta-analysis [10] used patient-level data for the Verify Now P2Y 12 assay to assess clopidogrel responsiveness in 3,059 patients after PCI. The primary endpoint of composite death, myocardial infarction, or stent thrombosis occurred more frequently in higher quartiles of P2Y 12 Mechanistically, stent thrombosis is a particularly relevant outcome as imaging studies months to year's post-stenting have clearly documented areas of stent malapposition, ectasia, neoatherosclerosis with thin cap atheroma and even thrombus formation [11].…”

Section: Can Measuring Adp Mediated Platelet Reactivity After Clopidomentioning

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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Impact of Clopidogrel on-Treatment Platelet Reactivity on Stent Thrombosis After Percutaneous Coronary Intervention: Results From a Collaborative Meta-Analysis of Individual Participant Data

Cited by 125 publications

References 0 publications

Anti-platelet Therapy Resistance – Concept, Mechanisms and Platelet Function Tests in Intensive Care Facilities

Anti-platelet Therapy Resistance – Concept, Mechanisms and Platelet Function Tests in Intensive Care Facilities

Can Phone-Based Motivational Interviewing Improve Medication Adherence to Antiplatelet Medications After a Coronary Stent Among Racial Minorities? A Randomized Trial

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

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