14 Oct 10

Guidelines for the use of antiplatelet therapy in patients with coronary stents undergoing non-cardiac surgery

Posted in Antiplatelet therapy, Coronary artery disease, Pre-operatie evaluation at 10:00 by Laci

By The Cardiac Society of Australia and New Zealand

Coronary stent thrombosis is an uncommon but clinically devastating complication of coronary artery stenting that usually results in significant myocardial infarction or death. The pathophysiology of stent thrombosis is related to non-endothelialisation of the stent struts, often due to inadequate deployment or delayed healing in the case of drug eluting stents.

Approximately 40% of reported cases have occurred in the context of non-cardiac surgery (NCS) performed in patients with coronary artery stents, in whom dual antiplatelet therapy or clopidogrel alone has been ceased.

In patients with coronary disease cessation of aspirin or clopidogrel is associated with an approximate 2-3 fold increase in subsequent death or myocardial infarction. This risk is further elevated in patients with intracoronary stent and is of added concern because the dramatic consequences of stent occlusion. There is uncertainty regarding the risks of stent thrombosis in individual patients, and in particular how to balance this risk against that of surgical complications if antiplatelet therapy is continued throughout the perioperative period.

This guideline provides consensus advice regarding the use of antiplatelet therapy in patients with intracoronary stents for whom non-cardiac invasive procedures are planned. It is designed for cardiologists, anaesthetists, surgeons and dentists preparing patients for these procedures.

Urgent surgery in patients with a recently implanted coronary drug-eluting stent: a phase II study of ‘bridging’ antiplatelet therapy with tirofiban during temporary withdrawal of clopidogrel

Posted in Antiplatelet therapy, Coronary artery disease, Pre-operatie evaluation at 9:55 by Laci

By S Savonitto, M D’Urbano, M Caracciolo, F Barlocco, G Mariani, M Nichelatti,

BJA 2010;104:285-291

Patients with a recently implanted coronary drug-eluting stent (DES) who need urgent surgery are at increased risk of surgical bleeding unless clopidogrel is discontinued beforehand, but clopidogrel discontinuation has been associated with a high rate of adverse events due to stent thrombosis. This pilot study tested the hypothesis that the i.v. perioperative administration of the short-acting antiplatelet agent tirofiban allows the safe withdrawal of clopidogrel without increasing the rate of surgical bleeding.

Methods
Phase II study with a Simon two-stage design.

Results
Thirty patients with a recently implanted DES [median (range) 4 (1–12) months] and high-risk characteristics for stent thrombosis underwent urgent major surgery or eye surgery. Clopidogrel was to be withdrawn 5 days before surgery, and tirofiban started 24 h later, continued until 4 h before surgery, and resumed 2 h after surgery until oral clopidogrel was resumed. The use of aspirin was decided by the surgeon. There were no cases of death, myocardial infarction, stent thrombosis, or surgical re-exploration due to bleeding during the index admission, with a risk estimate of 0–11.6% (one-tail 97.5% CI). There was one case of thrombolysis in myocardial infarction (TIMI) major and one of TIMI minor bleeding in the postoperative phase; another four patients were transfused without meeting the TIMI criteria for major or minor bleeding.

Conclusions
In patients with a recently implanted DES and high-risk characteristics for stent thrombosis needing urgent surgery, a ‘bridging strategy’ using i.v. tirofiban may allow temporary withdrawal of oral clopidogrel without increasing the risk of bleeding.

25 Sep 10

Antithrombotics in acute coronary syndromes

Posted in Coronary artery disease at 1:12 by Laci

By M Bonaca, P Steg, L Feldman, J Canales, J Ferguson, L Wallentin

JACC 2009;54:969-984

Antithrombotic agents are an integral component of the medical regimens and interventional strategies currently recommended to reduce thrombotic complications in patients with acute coronary syndromes (ACS). Despite great advances with these therapies, associated high risks for thrombosis and hemorrhage remain as the result of complex interactions involving patient comorbidities, drug combinations, multifaceted dosing adjustments, and the intricacies of the care environment. As such, the optimal combinations of antithrombotic therapies, their timing, and appropriate targeted subgroups remain the focus of intense research. During the last several years a number of new antithrombotic treatments have been introduced, and new data regarding established therapies have come to light. Although treatment guidelines include the most current available data, subsequent findings can be challenging to integrate. This challenge is compounded by the complexity associated with different efficacy and safety measures and the variability in study populations, presenting syndromes, physician, and patient preferences. In this work we review recent data regarding clinically available antiplatelet and anticoagulation agents used in the treatment of patients with ACS. We address issues including relative efficacy, safety, and timing of therapies with respect to conservative and invasive treatment strategies. In specific cases we will highlight remaining questions and controversies and ongoing trials, which will hopefully shed light in these areas. In addition to reviewing existing agents, we take a look forward at the most promising new antithrombotics currently in late-stage clinical development and their potential role in the context of ACS management.

29 Jul 10

Statins and all-cause mortality in high-risk primary prevention

Posted in Coronary artery disease at 1:37 by Laci

By K Ray, S Seshasai, S Erqou, P Sever, J Jukema, I Ford, N Sattar

Arch Intern Med 2010;170:1024-1031

Statins have been shown to reduce the risk of all-cause mortality among individuals with clinical history of coronary heart disease. However, it remains uncertain whether statins have similar mortality benefit in a high-risk primary prevention setting. Notably, all systematic reviews to date included trials that in part incorporated participants with prior cardiovascular disease (CVD) at baseline. Our objective was to reliably determine if statin therapy reduces all-cause mortality among intermediate to high-risk individuals without a history of CVD.

Data sources
Trials were identified through computerized literature searches of MEDLINE and Cochrane databases (January 1970-May 2009) using terms related to statins, clinical trials, and cardiovascular end points and through bibliographies of retrieved studies.

Study selection
Prospective, randomized controlled trials of statin therapy performed in individuals free from CVD at baseline and that reported details, or could supply data, on all-cause mortality.

Data extraction
Relevant data including the number of patients randomized, mean duration of follow-up, and the number of incident deaths were obtained from the principal publication or by correspondence with the investigators.

Data synthesis
Data were combined from 11 studies and effect estimates were pooled using a random-effects model meta-analysis, with heterogeneity assessed with the I2 statistic. Data were available on 65 229 participants followed for approximately 244 000 person-years, during which 2793 deaths occurred. The use of statins in this high-risk primary prevention setting was not associated with a statistically significant reduction (risk ratio, 0.91; 95% confidence interval, 0.83-1.01) in the risk of all-cause mortality. There was no statistical evidence of heterogeneity among studies (I2 = 23%; 95% confidence interval, 0%-61% [P = .23]).

Conclusion
This literature-based meta-analysis did not find evidence for the benefit of statin therapy on all-cause mortality in a high-risk primary prevention set-up.

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