CC Cardiol Croat Cardiologia Croatica Cardiol. Croat. 1848-543X 1848-5448 Croatian Cardiac Society CC_2013_8_9_280 10.15836/ccar.2013.280 Extended Abstract Impact of repeated clopidogrel reloading doses and increased maintenance dose in patients with acute coronary syndrome and persistent low response to clopidogrel in 30-day follow-up KrpanMiroslav1SamardzicJure1BrestovacMarija2SkoricBosko1JurinHrvoje1VelagicVedran1MilicicDavor1 University of Zagreb School of Medicine, University Hospital Centre Zagreb, Zagreb, Croatia Dr. Andrija Stampar Institute of Public Health, Zagreb, Croatia Correspondence to Miroslav Krpan, Klinicki bolnicki centar Zagreb, Kispaticeva 12, HR-10000 Zagreb, Croatia; Phone: +385-1-2367-506; E-mail: miroslav.krpan@gmail.com 092013 092013 8 9 280 280 Croatian Cardiac Society 2013 Croatian Cardiac Society KEYWORDS: acute coronary syndromeclopidogrelresidual platelet reactivity

Objectives: Platelet response to clopidogrel is not uniform.1 It is known that inadequate effect of clopidogrel on platelets increases the risk for new ischeamic events2-3. We aimed to investigate whether repeated clopidogrel reloading regimen and increased maintenance dose in persistent low responders is an effective and a safe strategy.

Patients and Methods: Patients with acute coronary syndrome who underwent coronary stenting were tested with impendance aggregometer — Multiplate® function analyzer. This is a point of care instrument which measures residual platelet reactivity (RPR) in small quantities of the whole blood. Low clopidogrel responders received another loading dose and underwent aggregometry testing the following day. The remaining low responders on repeated aggregometry received the third loading dose followed by a maintenance dose of 150 mg/day. On day 7, we repeated aggregometry testing and patients who remained low responders were assigned to a clopidogrel maintenance dose of 300 mg/day. After one month follow-up we conducted control interview and Multiplate® testing.

Results: Persistent low response to clopidogrel was found in 12 patients out of 43 initially low responders (27.9%). After one month of follow-up no patient had a major bleeding event. Furthermore, three patients sustained a new ischaemic event: non fatal myocardial infarction, ischaemic (fatal) stroke and in-stent thrombosis. After 30 days, seven patients (63.6%) still had high RPR.

Conclusion: Our study showed that repeated clopidogrel reloading doses and very high maintenance doses can be safe in persistent low responders in terms of bleeding complications. However, certain number of patients are still inadequately treated and sustain new ischaemic events. Changing clopidogrel by a new thienopyridine like ticagrelor or prasugrel should be considered for those patients, if available. (1-3) (Table 1)

Demographic data.
Patient Gender Age ACS HLP AH DM2 Smoking Aspirin resistance CYP2C19*2 MACCE HTPR after 30 days
1 F 64 STEMI yes yes no no yes yes no no yes
2 F 81 STEMI yes no yes no no no no no yes
3 F 45 STEMI yes yes yes no no no yes no yes
4 F 57 STEMI yes yes yes no yes yes no no yes
5 M 63 STEMI yes yes yes yes yes no no isch. CVI, death N/A
6 M 57 NSTEMI no no no no no yes yes no yes
7 M 54 STEMI yes yes yes yes no yes yes non fatal MI no
8 M 60 NSTEMI yes yes no no no yes no no no
9 M 60 NSTEMI yes yes yes no no yes no no no
10 F 68 STEMI yes yes no yes no yes no no yes
11 M 52 STEMI yes yes no yes yes no yes IST yes
12 F 70 STEMI yes yes yes no no yes no no no

HLP = hyperlipidemia, HA = arterial hypertension, DM2 = diabetes mellitus type 2, MACCE = major adverse cardiac and cerebrovascular event, CVI = stroke, MI = myocardial infarction, HRPR = high residual platelet reactivity.

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