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Background Current treatment standards for patients undergoing primary percutaneous coronary intervention support early infusion of abciximab, followed by bare-metal stent (BMS) implantation. Whether the use of sirolimus-eluting stent (SES) would result in a further improvement of clinical outcomes remains to be proven. Similarly, whether tirofiban administered at high-bolus dose (HBD) followed by standard infusion is a valuable alternative to abciximab in the setting of ST-segment elevation myocardial infarction remains uncertain. Study Design Multicentre evaluation of single high-bolus dose tirofiban versus abciximab and sirolimus-eluting versus bare metal stent in acute myocardial infarction (MULTI-STRATEGY) is a phase III, open-label, multinational investigator-driven clinical trial evaluating, with a 2-by-2 factorial design, the safety/efficacy profile of 4 interventional strategies of reperfusion: tirofiban given at HBD (bolus of 25 μg/kg over 3 minutes), followed by an infusion of 0.15 μg/kg per minute for 18 to 24 hours versus abciximab and SES, as compared to BMS implantation in primary percutaneous coronary intervention. The coprimary objectives are (i) the evaluation of the effect of SES versus BMS on the incidence of major adverse cardiac events within 8 months of the index procedure and (ii) the degree of ST-segment resolution obtained after the mechanical intervention for the comparison of HBD tirofiban versus abciximab. The protocol mandates clinical follow-up for 5 years. Conclusions MULTI-STRATEGY will evaluate the role of SES and HBD tirofiban versus BMS and abciximab in the acute management of patients presenting with ST-segment elevation myocardial infarction.

The impact of abciximab therapy on mortality in unselected patients with acute myocardial infarction (AMI) undergoing routine primary infarct-related artery (IRA) stent implantation is not yet defined, and previous randomized studies have produced conflicting results.A strategy of IRA stenting alone as opposed to IRA stenting plus abciximab was compared in a series of 561 consecutive unselected patients with AMI. Abciximab treatment was strongly encouraged for all patients. The contraindication for abciximab therapy was a high risk of major bleeding as assessed by the operator before mechanical intervention.Of 561 patients, 348 patients underwent abciximab therapy and 213 underwent primary IRA stenting alone. The 1-month overall mortality rate was 2.9% in the abciximab group and 10.8% in the stent alone group (P.001). The relative reduction in mortality rate was 73% for patients overall, 77% in the subset of patients agedor =70 years (mortality rate, 1.2% vs 5.2%, P =.020), 57% in patients aged70 years (7.7% vs 18%, P =.043), 63% in patients with cardiogenic shock (17% vs 46%, P =.022), and 77% in patients without cardiogenic shock (1.3% vs 5.6%, P =.002). Multivariate analyses on the basis of all patients, and on the subset of patients agedor =70 years, showed that abciximab therapy was independently related to the risk of death at 1 month. No differences were seen between groups in the procedural success rate (99.1% vs 98.1%) or in the incidence rates of nonfatal reinfarction (0.3% vs 1.9%) or repeat target vessel revascularization (1.7% vs 1.9%).The results of this study strongly support the use of abciximab therapy in nonselected patients with AMI undergoing routine IRA stent implantation. The mechanism of the clinical benefit of abciximab was not related to the patency of the IRA.

Background In patients with acute myocardial infarction (AMI), the rate of microvascular embolization and no-reflow promoted by coronary stenting with the use of conventional techniques (CS) appears to be greater than the one that occurs with balloon angioplasty. The minor invasiveness of direct stenting (DS) of the infarct artery without predilation could be expected to reduce embolization in the coronary microvasculature and no-reflow in patients with AMI. Methods In a cohort of 423 consecutive patients with AMI who underwent infarct-artery stenting, we compared CS and DS in terms of angiographic no-reflow rate and 1-month clinical outcome. Results At baseline patients who underwent DS (n = 110) had a better risk profile compared with the use of CS (n = 313). The incidence of angiographic no-reflow was 12% in the CS group and 5.5% in the DS group ( P =.040). The 1-month mortality rate was 8% in the CS group and 1% in the DS group ( P =.008). The mortality rate was 11% in patients with no-reflow and 5.6% in patients with a normal flow. Multivariate analysis showed that age, preprocedure patent infarct artery, and lesion length were related to the risk of no-reflow. In the subset of patients with a target lesion length ≤15 mm, the variables independently related to the risk of no-reflow were age, DS, and final balloon inflation pressure. Conclusions DS in patients with AMI may reduce the incidence of angiographic no-reflow, thereby increasing ultimate effective myocardial reperfusion. (Am Heart J 2001;142:684-90.)

Background Myocardial reperfusion in patients with acute myocardial infarction may be successfully achieved with primary angioplasty. However, angioplasty, as a primary reperfusion strategy, has limitations such as early recurrent ischemia and late restenosis and reocclusion. To improve the short- and long-term results of primary angioplasty, the use of adjunct strategies has been proposed. Methods We reviewed published studies on the effectiveness of primary angioplasty, stenting, and platelet glycoprotein IIb/IIIa receptor blockade and identified the advantages and disadvantages of these interventions in patients with acute myocardial infarction. Results Recent findings suggest that patients may benefit from stenting of the infarct artery and from the use of more potent antiplatelet agents such as platelet glycoprotein IIb/IIIa receptor inhibitors. In randomized trials that compared primary angioplasty versus primary stenting, stent implantation was associated with a lower rate of death, reinfarction, and especially target vessel revascularization. Platelet glycoprotein IIb/IIIa receptor inhibitors prevented acute ischemic complications after primary angioplasty and primary stenting. In addition to maintaining large vessel patency, these drugs may protect the microvasculature after primary stenting, allowing better functional recovery of the risk area. Conclusions Coronary artery stenting in acute myocardial infarction reduces the rate of restenosis and the incidence of problems related to recurrent ischemia. Platelet glycoprotein IIb/IIIa receptor inhibitors may come to play a key role in association with mechanical reperfusion. However, the cost-effectiveness and long-term clinical outcome of this combined pharmacologic/mechanical intervention require further study before this strategy can be recommended for routine use. (Am Heart J 2001;141:S26-35.)

Background Notwithstanding the negative result of the International Study of Infarct Survival-4 (ISIS-4), the controversy about the role of magnesium in acute myocardial infarction is still open because, according to experimental data, magnesium could decrease myocardial damage and mortality only if infusion is started before reperfusion. This randomized placebo-controlled trial was designed to evaluate the effect of intravenous magnesium, delivered before, during, and after direct coronary angioplasty, in patients with acute myocardial infarction. Methods One-hundred fifty patients were randomized to intravenous magnesium sulfate or placebo. The primary end point was an infarct zone wall motion score index at 30 days, as a measure of infarct size. The secondary end points included creatine kinase peak, ventricular fibrillation/tachycardia within the first 24 hours, death and congestive heart failure within the 30-day follow-up, and 30-day left ventricular ejection fraction. Analysis was by intention to treat. Results There were no significant differences between the magnesium and placebo groups in the 30-day infarct zone wall motion score index (1.93 ± 0.61 vs 1.85 ± 0.51, P =.39), ventricular arrhythmias (24% vs 15%, P =.15), death (0 vs 1%, P =.32), heart failure (8% vs 7%, P =.75), and 30-day left ventricular ejection fraction (49% ± 11% vs 50% ± 9%, P = 0.55). There was a trend toward a higher creatine kinase peak in the magnesium group (3059 ± 2359 vs 2404 ± 1673, P =.052). Conclusions Intravenous magnesium delivered before, during, and after reperfusion did not decrease myocardial damage and did not improve the short-term clinical outcome in patients with acute myocardial infarction treated with direct angioplasty. (Am Heart J 2000;140:891-7.)

Background There are conflicting data about the efficacy of aggressive treatment and early intervention among high-risk patients with acute myocardial infarction (AMI), such as elderly patients. This study sought to determine the short- and long-term outcome of octogenarian and older patients after primary percutaneous transluminal coronary angioplasty (PTCA). Methods In our tertiary referral center a program of primary PTCA was begun in 1995, and the systematic care for AMI included primary PTCA in all patients with AMI, with no age restriction. Over a period of 3 years, 55 octogenarian or older patients underwent primary PTCA. Results Between January 1995 and July 1998, 719 patients with AMI underwent primary PTCA. Of these, 55 patients were octogenarians or older (mean age, 84 ± 3 years). Primary PTCA failure occurred in 3 (5%) patients. An optimal acute angiographic result was achieved in 51 (93%) patients. Stenting of the infarct vessel was accomplished in 33 (60%) patients. The 30-day mortality rate was 16%. The mortality rate was 4% in patients without cardiogenic shock on presentation and 70% in patients with cardiogenic shock. The recurrent ischemia rate was 13% and resulted in nonfatal reinfarction in 2 patients and repeat PTCA in 5 patients. As determined by multivariate analysis, an optimal acute angiographic result and cardiogenic shock were significantly related to mortality. The 1-year survival rate was 77%. Conclusions The results of this study suggest that the benefits of primary PTCA apply to the very elderly and support an early aggressive strategy for this high-risk patient subset. (Am Heart J 1999;138:670-4.)

Ventricular remodeling after acute myocardial infarction is characterized by alteration in left ventricular (LV) size, shape, and wall thickness and involves both the infarcted and the noninfarcted regions of the ventricle. These structural changes are the result of several distinct pathologic processes that contribute to progressive LV dilation: rearrangement of wall structure, myocyte hypertrophy, and increasing muscle mass without an increase in wall thickness (eccentric hypertrophy). The pathogenesis of LV remodeling is multifactorial. Multiple factors may in fact contribute at different stages from the time of coronary occlusion until the development of ventricular dilation: These include the magnitude of the loss of contractile elements, the abrupt alteration in systolic and diastolic loading conditions, the activation of circulating neurohormones and local autocrine trophic factors, and the patency of the infarct-related artery. Although remodeling occurring early after infarction may be an appropriate compensatory response to preserve ventricular function, recent observations have suggested that this long process has a deleterious effect on LV function and prognosis. Thus attempts to inhibit these structural changes have been the focus of recent experimental and clinical studies. This review focuses on interactive factors that influence postinfarction LV remodeling, emphasizing the role of some new emerging determinants such as the extent of surviving myocardium within the infarcted and noninfarcted zones. (Am Heart J 1999;138:S79-S83.)

Background Randomized trials have demonstrated that planned coronary stenting may lower restenosis rate in patients with de novo short lesions. In a prospective study we sought to determine the frequency of restenosis, reocclusion, and adverse cardiovascular events after coronary stenting in a series of 258 consecutive nonselected patients, including those with complex lesions not fulfilling past and ongoing randomized trial criteria for stent implantation. Methods Criteria for stenting were as follows: (1) dissection associated with occlusion or threatened closure, (2) a residual percentage stenosis ≤30% or nonocclusive dissection, (3) restenotic lesion or chronic total occlusion. Results In most cases (89%) the target lesion had two or more unfavorable morphologic characteristics, whereas only 11% of target lesions could be classified as type A or B1 lesions. Overall, the 6-month restenosis rate was 23%. By use of subgroup analysis restenosis rate was found to range widely, from 11% to 46%. With multivariate analysis, only four variables were found to be independently related to restenosis: age >63 years (odds ratio [OR] = 2.651, p = 0.011), female sex (OR = 3.807, p = 0.002), lesion length >12 mm (OR 3.185, p = 0.002), and type C lesion (OR 2.527, p = 0.014). Conclusions Results from randomized trials on coronary stenting cannot be extrapolated to current clinical practice because most of the treated lesions do not fulfill the criteria adopted in these studies for stent implantation. The restenosis rate is nearly four times greater for long and complex lesions treated by multiple stent implantation as compared with simple lesions, and additional studies need to be performed to evaluate the efficacy of stenting on these lesions. (Am Heart J 1998;135:510-8.)