to compare data on pre- and in hospital treatment of non ST-elevation (NSTE) acute coronary syndromes (ACS) in Russian ACS registers RECORD (recruitment from 11.2007 to 02.2008) and RECORD-2 (from 04/2009 to 04.2011).
Four of 7 hospitals participating in RECORD-2 were invasive (57.1% vs. 55.6% in RECORD). In RECORD-2 10-30 consecutive patients with NSTEACS were included monthly in each center; recruitment in RECORD was described elsewhere.
Mean age of patients was similar in two registries. Portion of women was significantly higher in RECORD-2 (42.9% vs. 26.0% in RECORD; 140) gave results close to those in all patients except mortality which was statistically similar but numerically higher in RECORD-2 (9.3 vs. 7.9% in RECORD; p=0.68).
Comparison of data of 2 limited NSTEACS registers conducted with interval of about 2 years showed only modest shift towards fulfillment of contemporary recommendations which was not associated with increase in rates of PCI and improvement of outcomes especially in high risk patients.
Patients' responses to oral antiplatelet therapy are subject to variation. Bedside monitoring offers the opportunity to improve outcomes after coronary stenting by individualizing therapy.
We randomly assigned 2440 patients scheduled for coronary stenting at 38 centers to a strategy of platelet-function monitoring, with drug adjustment in patients who had a poor response to antiplatelet therapy, or to a conventional strategy without monitoring and drug adjustment. The primary end point was the composite of death, myocardial infarction, stent thrombosis, stroke, or urgent revascularization 1 year after stent implantation. For patients in the monitoring group, the VerifyNow P2Y12 and aspirin point-of-care assays were used in the catheterization laboratory before stent implantation and in the outpatient clinic 2 to 4 weeks later.
In the monitoring group, high platelet reactivity in patients taking clopidogrel (34.5% of patients) or aspirin (7.6%) led to the administration of an additional bolus of clopidogrel, prasugrel, or aspirin along with glycoprotein IIb/IIIa inhibitors during the procedure. The primary end point occurred in 34.6% of the patients in the monitoring group, as compared with 31.1% of those in the conventional-treatment group (hazard ratio, 1.13; 95% confidence interval [CI], 0.98 to 1.29; P=0.10). The main secondary end point, stent thrombosis or any urgent revascularization, occurred in 4.9% of the patients in the monitoring group and 4.6% of those in the conventional-treatment group (hazard ratio, 1.06; 95% CI, 0.74 to 1.52; P=0.77). The rate of major bleeding events did not differ significantly between groups.
This study showed no significant improvements in clinical outcomes with platelet-function monitoring and treatment adjustment for coronary stenting, as compared with standard antiplatelet therapy without monitoring. (Funded by Allies in Cardiovascular Trials Initiatives and Organized Networks and others; ARCTIC ClinicalTrials.gov number, NCT00827411.).
Comment In: N Engl J Med. 2013 Feb 28;368(9):87123445102
Clinical and economic examinations were made to study whether it is appropriate to use antiplatelet therapy (APT) with ticagrelor in combination with acetylsalicylic acid (ASA) versus a combination of clopidogrel and ASA in patients with acute coronary syndrome (ACS) following coronary artery bypass surgery (CABS).
A budget impact analysis was used. Data on the efficiency and safety of APT were taken from a relevant analysis in the subgroups of the randomized controlled trial PLATO. Direct medical cost due to APT and expenses on therapy for acute myocardial infarction, stroke, and massive bleeding, and those on medical care for patients dying from cardiovascular events and other causes, as well as indirect cost - gross domestic product (GDP) losses due to untimely death, were taken into account. The findings were assessed from the perspectives of society.
The analysis indicated that direct medical costs per patient following CABS, both in case of calculation based on the recorded price for ticagrelor and on the median registered prices for clopidogrel generics, and based on the auction prices for comparison agents proved to be lower when clopidogrel was administered because of the higher cost of ticagrelor-based APT. At the same time GDP losses due to untimely death, as calculated per patient with ACS during post-CABS therapy with clopidogrel + ASA, were more than twice above average losses per patient taking ticagrelor in combination with ACA (107,122 and 221,645 rubles, respectively). From the registered price for ticagrelor and the median registered prices for clopidogrel generics, the total costs per patient with ACS following CABS were lower if Brilinta was used in combination with ASA versus therapy with clopidogrel in combination with ASA (210,092 and 273,257 rubles per year, respectively; the cost savings were 63,165 rubles per patient per year when ticagrelor was administered). On the basis of the auction prices for comparison drugs, the total costs per patient with ACS after CABS proved to be lower if Brilinta was used in combination with ASA versus therapy with brand name clopidogrel in combination with ASA (201,018 and 293,982 rubles per patients year, respectively; the cost savings were 92,963 rubles per patient per year when ticagrelor was used).
The use of ticagrelor in combination with ASA ensures resource savings to treat ACS patients undergoing CABS as compared with a regiment including a combination of clopidogrel and ASA.
The impact of adherence to the recommended duration of dual antiplatelet therapy after first generation drug-eluting stent implantation is difficult to assess in real-world settings and limited data are available.
We followed 4,154 patients treated with coronary drug-eluting stents in Western Denmark for 1 year and obtained data on redeemed clopidogrel prescriptions and major adverse cardiovascular events (MACE, i.e., cardiac death, myocardial infarction, or stent thrombosis) from medical databases.
Discontinuation of clopidogrel within the first 3 months after stent implantation was associated with a significantly increased rate of MACE at 1-year follow-up (hazard ratio (HR) 2.06; 95% confidence interval (CI): 1.08-3.93). Discontinuation 3-6 months (HR 1.29; 95% CI: 0.70-2.41) and 6-12 months (HR 1.29; 95% CI: 0.54-3.07) after stent implantation were associated with smaller, not statistically significant, increases in MACE rates. Among patients who discontinued clopidogrel, MACE rates were highest within the first 2 months after discontinuation.
Discontinuation of clopidogrel was associated with an increased rate of MACE among patients treated with drug-eluting stents. The increase was statistically significant within the first 3 months after drug-eluting stent implantation but not after 3 to 12 months.
Cites: Am J Cardiol. 2009 Dec 15;104(12):1668-7319962472
Cites: N Engl J Med. 2010 Apr 15;362(15):1374-8220231231
The CREDO trial demonstrated the clinical efficacy of 12-month antiplatelet therapy with clopidogrel compared to standard 28-day treatment with a 27% relative reduction in the combined risk of death, myocardial infarction, or stroke in patients undergoing percutaneous coronary intervention (PCI) and being treated with aspirin. This study evaluated the long-term cost-effectiveness of 12-month vs. 28-day therapy with clopidogrel in Sweden. A Markov model was developed which assumed a hypothetical cohort of patients in a post-PCI state to have certain risks of suffering one of the endpoints of the CREDO trial: stroke, myocardial infarction, or death. The model predicted a mean survival of 12.098 years in the 12-month arm vs. 12.026 in the 28-day arm, an incremental gain of 0.072 life-years. The gain in survival came at a predicted incremental cost of Euro 217, resulting in an incremental cost-effectiveness ratio of Euro 3,022. Thus the predicted cost-effectiveness ratio of long-term treatment with clopidogrel in patients undergoing PCI is well below the threshold values currently considered cost-effective.
OBJECTIVE: To analyse the cost-effectiveness of Taxus compared to a bare-metal stent in patients with coronary artery disease in the Swedish healthcare setting. DESIGN: A decision-analytic model combining clinical data on revascularization rates with Swedish unit costs for medical resources and utility data from the literature. RESULTS: For patients of moderate risk, the average cost per patient at 12 months is 72,200 SEK for Taxus and 66,900 SEK for a bare-metal stent, while the average cost for high risk patients is nearly equivalent (73,000 vs. 71,700 SEK). The cost per revascularization avoided is generally favourable, while the incremental cost per QALY gained varies depending on the assumptions made; from 2,351,000 SEK for patients of moderate risk at 12-months to cost saving at 24 months for high risk patients. Budget impact scenarios at 12 months are cost-neutral. CONCLUSION: The Taxus stent is cost-effective in high risk patients, particularly at 24 months. Although it may be less cost-effective for the general population, there is still a substantial offset of initial procedure costs through lower rate of repeat revascularizations.
Duration of clopidogrel treatment and risk of mortality and recurrent myocardial infarction among 11 680 patients with myocardial infarction treated with percutaneous coronary intervention: a cohort study.
The optimal duration of clopidogrel treatment after percutaneous coronary intervention (PCI) is unclear. We studied the risk of death or recurrent myocardial infarction (MI) in relation to 6- and 12-months clopidogrel treatment among MI patients treated with PCI.
Using nationwide registers of hospitalizations and drug dispensing from pharmacies we identified 11 680 patients admitted with MI, treated with PCI and clopidogrel. Clopidogrel treatment was categorized in a 6-months and a 12-months regimen. Rates of death, recurrent MI or a combination of both were analyzed by the Kaplan Meier method and Cox proportional hazards models. Bleedings were compared between treatment regimens.
The Kaplan Meier analysis indicated no benefit of the 12-months regimen compared with the 6-months in all endpoints. The Cox proportional hazards analysis confirmed these findings with hazard ratios for the 12-months regimen (the 6-months regimen used as reference) for the composite endpoint of 1.01 (confidence intervals 0.81-1.26) and 1.24 (confidence intervals 0.95-1.62) for Day 0-179 and Day 180-540 after discharge. Bleedings occurred in 3.5% and 4.1% of the patients in the 6-months and 12-months regimen (p = 0.06).
We found comparable rates of death and recurrent MI in patients treated with 6- and 12-months' clopidogrel. The potential benefit of prolonged clopidogrel treatment in a real-life setting remains uncertain.
The article shows results obtained from 146 patients with acute coronary syndrome without ST-segment elevation and with concurrent heart failure stage IIA. All patients had profound changes of the hemostasis system. The use in a complex therapy klopidogrel medication, inhibitor of ADP-induced platelets aggregation considerably benefits state of blood coagulation properties: increases prothrombin time, INR-International normalized relation and APTT (activated partial thromboplastin time), decreases prothrombin index and fibrinogen quantity. Selective inhibitor of heart sinus node, ivabradin (koraksan) does not influence on hemogram indices and has positive influence on the course of the disease by lowering heart contraction frequency.