Major adverse cardiac events

To control risk factors and prevent major adverse cardiac events, statin therapy should be considered in all patients with ischemic heart disease, particularly in those with elevated low-density lipoprotein cholesterol. In the absence of contraindications, angiotensin-converting enzyme inhibitors should be considered in ischemic heart disease patients who also have diabetes melli-tus, left ventricular dysfunction, history of myocardial infarction, or any combination of these. Angiotensin receptor blockers... 

When drug therapy fails or if extensive coronary atherosclerosis is present, PCI is often performed to restore coronary blood flow, relieve symptoms, and prevent major adverse cardiac events. Patients with one or more critical coronary stenoses (i.e., greater than 70% occlusion of the coronary lumen) detected during coronary angiography may be candidates for PCI. Several catheter-based interventions maybe used during PCI, including ... 

Over the last decade, several studies in tens of thousands of patients have revealed that lowering cholesterol, specifically lowering LDL cholesterol with statins, is effective for both primary and secondary prevention of IHD-related events. Statins shown to decrease morbidity and mortality associated with IHD include lovastatin, simvastatin, pravastatin, and atorvas-tatin.22,23 A recent meta-analysis showed that the risk of major adverse cardiac events is reduced by 21% with the use of statins in patients at high risk for IHD-related events.23... 

Like dyslipidemia, hypertension is a major, modifiable risk factor for the development of IHD and related complications. Unfortunately, awareness, treatment, and control of blood pressure are not nearly enough.30 Aggressive identification and control of hypertension is warranted in patients with IHD to minimize the risk of major adverse cardiac events. Goal blood pressure in patients with IHD is less than 140/90 mm Hg or less than 130/80 mm Hg in patients with diabetes. Because of their cardioprotective benefits, 3-blockers and ACE inhibitors (or ARBs in ACE-inhibitor-intolerant patients), either alone or in combination, are appropriate for most patients with both hypertension and IHD. 

Hey has been shown to reduce binding of tPA to its endothelial cell receptor, annexin II, in cell cultures (50). Animal studies have indicated that elevated plasma tHcy could cause acquired dysfibrinogenemia, leading to the formation of clots that are abnormally resistant to fibrinolysis (51), Elevated plasminogen activator inhibitor and tHcy in patients with acute coronary syndrome have been shown to be associated with increased risk for major adverse cardiac events (MACE) after successful percutaneous coronary intervention (PCI) and stenting (52), whereas factor V Leiden mutation and lipoprotein (a) were not. 

Marcucci R, et al. PAI-1 and homocysteine, but not lipoprotein (a) nor thrombophilic polymorphism, are associated with the occurrence of major adverse cardiac events after successful coronary stenting. Heart 2005 92(3) 377—381. 

Abbreviations CDK, cyclin-dependent kinase CREST, cilostazol for restenosis trial MACE, major adverse cardiac events ORAR, oral rapamycin to prevent restenosis ORBIT, oral rapamune to inhibit restenosis REAR, peroxisome proliferator-activated receptor PRESTO, prevention of restenosis with tranilast and its outcomes SMC. smooth muscle cell ThR, target lesion revascularization tREAT, Tranilast restenosis following angioplasty trials TVR, target vessel failure. ... 

In 1997, Condado et al. was the first to investigate the effectiveness of ICB after PTCA in human coronary arteries. Twenty-one patients who underwent PTCA for unstable angina received ICB (gamma radiation) for prevention of restenosis, Immediate and six-month follow-up revealed improved freedom from major adverse cardiac event (MACE) defined as death, myocardial infarction or target lesion revascularization compared with several previously completed balloon angioplasty trials (20), More importantly, this trial demonstrated that ICB was a feasible technique for the prevention of restenosis without any unexpected acute complications in humans. 

The first study of the TAXUS paclitaxel-eluting stent in humans, TAXUS I, reported major adverse cardiac events at one-year follow-up at 3.2% for the TAXUS DES group versus 10.0% for the BMS control group (p = NS) (68). TAXUS I, now has data through four years and these benefits were maintained for the TAXUS group (Fig. 12). 

PTCA). The primary objective was to evaluate the occurrence of major adverse cardiac events (MACE) [death, recurrent myocardial infarction (Ml), or clinically driven target lesion revascularization] 30 days postprocedure. The secondary objectives were to evaluate the binary restenosis, incidence of (sub)acute stent thrombosis at 30 days follow-up, MACE at 6 and 12 months and the QCA endpoints at 6 months. This study was designed to allow a comparison with the patient population and the results of a larger randomized DISTINCT (BiodivYsio stent in controlled clinical trial) study previously conducted in the U.S. 

Structure of BRILLIANT EU. Abbreviations IVUS, intravascular ultrasound MACE, major adverse cardiac events MLA, minimal luminal area MLD, minimal luminal diameter QCA, qualitative coronary angiography SAT, subacute stent thrombosis TLR, target lesion revascularization TVF, target vessel failure TVR, target vessel revascularization. 

Table 5 Ranked major adverse cardiac events by descending severity and number of events during six-month follow-up...

Abbreviations BRILLIANT-EU, Batimastat (BB94) anti-restenosis trial utilizing the BiodivYsio local drug delivery PC-stent CABG, coronary artery bypass graft MACE, major adverse cardiac events Ml. myocardial infarction TLR, target lesion revascularization. 

Specific safety issues have been reported for myoblasts (electrical instability), for mesenchymal stem cells (restenosis and microinfarction), and for granulocyte-colony stimulating factor (G-CSF)-mobilized BM progenitors [restenosis and major adverse cardiac events (MACE)]. 

Bertrand ME, Esplugas E, Piessens J, Rasch W [Visipaque in Percutaneous Transluminal Coronary Angioplasty VIP.] Trial Investigators. Influence of a nonionic, iso-osmolar contrast medium (iodixanol) versus an ionic, low-osmolar contrast medium (ioxaglate) on major adverse cardiac events in patients undergoing percutaneous transluminal coronary angioplasty a multicenter, randomized, doubleblind study. Circulation 2000 101(2) 131-6. 

Reminiscent of the above experimental studies, inflammatory responses are also seen in those clinical scenarios where coronary microembolization is likely to occur, i.e. nuclear factor - v.B is activated in patients with unstable angina79 and serum C-reactive protein is increased in patients who died from an acute coronary syndrome80. Interleukin-6 was higher up to 48 h in patients with unstable angina who experienced a major adverse cardiac event.81 These markers of inflammation were assumed to originate from... 

Elevated serum cholesterol levels and in particular LDL-cholesterol levels are strongly associated with cardiovascular mortality across the spectrum of epidemiologic studies and pharmacologic intervention studies in primary and secondary prevention trials (Ligure 4.4). In the Cholesterol Treatment Trialists Collaborators meta-analysis of >90,000 patients studied in 14 randomized trials of statin therapy, a reduction in LDL cholesterol of 1 mmol/L (39 mg/dL) was associated with a 12% proportional reduction in all-cause mortality, predominantly driven by a 19% proportional reduction in cardiovascular mortality (45). Among patients with pre-existing heart disease there were 14 fewer deaths per 1000 participants per mmol LDL cholesterol reduction, as well as an approximately 25% reduction in major adverse cardiac events. 

Figure 4.3 Inddence of major adverse cardiac events (death, myocardial infarction, disabling stroke, or ischania-driven target vessel revascularization) at 6 months in the CADILLAC trial (34).

In the only comparable U.S. trial of such a strategy, the Air Primary Angioplasty in Myocardial Infarction (AIR PAMI) study, door-to-balloon times were 155 minutes, including 35 minutes from presentation to randomization. Unfortunately, this promising study was terminated early secondary to slow patient accrual. Point estimates favoring transfer for primary PCI over on-site fibrinolysis were seen among the 138 patients who were randomized, with major adverse cardiac events (death, reinfarction, or stroke) occurring in 8.4% of patients treated with PCI versus 13.6% of patients treated with fibrinolysis... 

MiStent was tested in the DESSOLVE I trial which demonstrated minimal progression of late lumen loss (LLL) up to 18 months monitoring. Median in-stent LLL was 0.08 mm (-0.30 to 0.46 mm), with no target lesion major adverse cardiac events (MACE). The stent also proved to have complete strut coverage and no stent thrombosis events within 18 months [18]. The subsequent DESSOLVE II randomized trial compared MiStent versus the Endeavor zotarolimus-eluting stent [19]. Two-year MACE rates were comparably low in both cohorts. MiStent demonstrated superiority to the Endeavor stent for the primary endpoint of in-stent late lumen loss at nine months (0.27 0.46 mm versus 0.58 0.41 mm, respectively). 

Incorporation of tacrolimus on cardiac drug-eluting stent platforms has not performed as favorably to other drugs. Tacrolimus suppresses smooth muscle and endothelial cell proliferation but is less potent than sirolimus. Unlike sirolimus though, taaolimus does not affect tissue factor and endothelial nitric oxide synthase expression. The Mahoroba DBS applies tacrolimus to a cobalt chromium platform with a PLGA biodegradable polymer. The first-in-man results unfortunately demonstrated failure to prevent neointimal hyperplasia, with a cumulative major adverse cardiac events rate of 23.4% at 6 months [7,8]. 

Arbel, Y., Shenhar-Tsarfaty S., Waiskopf, N., et al, 2014. Decline in serum cholinesterase activities predicts 2 year major adverse cardiac events. Mol. Med. 20,38-45. 

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