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Placebo-controlled randomized trials of platelet glycoprotein (GP) IIb/IIIa blockade during percutaneous coronary intervention have demonstrated efficacy of these agents for reducing the risk of periprocedural ischemic events. However, cost-effectiveness of this adjunctive pharmacotherapy has been scrutinized. Extrapolation of cost-efficacy observations from clinical trials to "real world" interventional practice is problematic.Consecutive percutaneous coronary interventions (n = 1472) performed by Ohio Heart Health Center operators at The Christ Hospital, Cincinnati, Ohio, in 1997 were analyzed for procedural and long-term (6-month) outcomes and charges. Observations on cost and efficacy (survival) were adjusted for nonrandomized abciximab allocation by means of "propensity scoring" methods.Abciximab therapy was associated with a survival advantage to 6 months after percutaneous coronary intervention. The average reduction in mortality rate at 6 months was 3.4% (unadjusted) and 4.9% when adjusted for nonrandomization. The average charge increment to 6 months was $1512 (unadjusted) and $950 when adjusted for nonrandomization. Patients deriving the greatest reduction in mortality rates also had a reduction in total cardiovascular charges to 6 months. Distinguishing demographics of this population included multivessel coronary intervention, coronary stent deployment, intervention within 1 week of myocardial infarction, and lower left ventricular ejection fraction. The average cost per life-year gained in this study was $2875 for all patients (unadjusted) and $1243 when adjusted for nonrandomization.Abciximab provides a cost-effective survival advantage in high-volume interventional practice that compares favorably with currently accepted standards. Clinical and procedural demographics associated with increased cost-effectiveness included multivessel coronary intervention, stent deployment, recent (1 week) myocardial infarction, and impaired left ventricular function.

We evaluated the differential effect of platelet count in platelet-rich plasma (PRP) on the level of ex vivo inhibition of platelet aggregation provided by abciximab, eptifibatide, and tirofiban as part of a randomized, comparative trial of these agents on platelet function in patients with unstable angina pectoris undergoing percutaneous coronary intervention. Platelet count

Anciximab provides potent, but variable degrees of platelet inhibition both during the duration of intravenous administration and at 12 hours following therapy. Platelet function was assessed using the PC-RPFA system in 78 patients scheduled for percutaneous coronary revascularization who were administered the standard abciximab weight-adjusted bolus and 12-hour infusion. The PC-RPFA system is a cartridge-based, semiautomated point-of-care whole-blood assay that incorporates fibrinogen-coated polystyrene beads, buffers, and a modified thrombin receptor activating peptide (Isotrap) in lyophilized form. The instrument detects the agglutination rate between the stimulated platelets and the fibrinogen-coated beads, and provides a quantitative digital display in less than 2 minutes. No differences in the level of platelet inhibition were observed in these abciximab-treated patients by diabetic status, gender, smoking, diagnosis (unstable angina, chronic stable angina, recent myocardial infarction), or abciximab treatment status (first time vs. retreatment). Nocorrelation of the PC-RPFA rate of platelet aggregation with clinical demographic factors was observed, with the exception of baseline hematocrit (r2 = 0.4556). The relationship between the PC-RPFA rate of aggregation and hematocrit reflects light absorbance by erythrocytes and is specific to the PC-RPFA system. The absolute rate of platelet aggregation (slope) reported by the PC-RPFA is correlated with percent aggregation, thus making it potentially possible to predict the level of aggregation without reference to a baseline (pretreatment) measure of platelet function. This correlation was closest for patients having

OBJECTIVE: To review the methods and summarize the findings of clinical trials evaluating the use of intravenous magnesium (Mg2+) in acute myocardial infarction (AMI); to discuss serum Mg2+ in AMI and the potential mechanisms by which intravenous Mg2+ may be effective. Tables are used extensively to provide detailed information about the various trials. DATA SOURCES: A MEDLINE search was used to identify pertinent literature. Additional references were obtained from the articles retrieved from that search. STUDY SELECTION: Studies randomized and/or placebo-controlled were selected for review. Additional relevant citations were used in the introductory material and discussion. DATA EXTRACTION: There were surprisingly few large, placebo-controlled trials. All clinical trials available at the time of publication were reviewed. Only eight trials enrolled sufficient numbers of patients and/or were of adequate design to make meaningful interpretations. The description of the methods and results of these articles are the basis of this review. Although additional controlled studies with more subjects are needed, the results to date form a foundation from which to make inferences regarding the utility of this therapeutic modality. DATA SYNTHESIS: Intravenous Mg2+ has been demonstrated, albeit inconclusively, to reduce immediate and long-term morbidity and mortality when given in the immediate postinfarction period. Six of the eight controlled trials discussed report a decrease in the overall incidence of arrhythmia or in the frequency of arrhythmia requiring treatment. Four of the eight reported statistical significance. Five of the six trials evaluating mortality reported a decrease in the mortality rate from intravenous Mg2+ administered post-MI. Four of the five reported statistical significance. The favorable effect of intravenous Mg2+ on the mortality rate appears to occur in the first 30 days post-MI and is maintained through at least one year. The effects appear to be independent of concurrent therapy and do not appeart to relate to baseline serum Mg2+ concentrations. Intravenous Mg2+ appears to be safe and well tolerated. Flushing, hypotension, and atrioventricular (AV) node conduction abnormalities occur on occasion and seem related to the rate of administration. The exact dosage in this setting remains to be determined. CONCLUSIONS: Additional, well-designed, multicenter, controlled trials evaluating intravenous Mg2+ in AMI are needed. The pending Fourth International Study of Infarct Survival, with an anticipated 400 000 subjects, should clarify a number of unresolved issues regarding this therapy. Based on the information available to date, however, intravenous Mg2+ as a significant therapeutic modality for AMI shows promise. Pending further investigation, however, it should be avoided in patients with significant sinoatrial or AV conduction disturbances.

OBJECTIVE: To survey the causes of clinical hypomagnesemia and Mg deficiency. The relationship of hypomagnesemia to digitalis toxicity, congestive heart failure, arrhythmias, and acute myocardial infarction is discussed, as is the clinical interrelationship of Mg and K concentrations, the principal intracellular cations. DATA SOURCES: A MEDLINE search and retrieval was used to identify relevant references. STUDY SELECTION: Clinical reports, as well as studies, were selected for this review. DATA EXTRACTION: There were very few placebo-controlled clinical studies. Clinical observations were related primarily to compilation of series in which Mg was administered and clinical results reported. In addition, conclusions derived from review articles on the subject of clinical Mg depletion were used. DATA SYNTHESIS: Clinical diagnosis of Mg deficiency is ascertained most expeditiously by estimating serum Mg concentrations. Although available on order by physicians, the lack of routine serum Mg analysis as part of the “electrolyte panel” impedes the diagnosis of clinical Mg deficiency. Renal loss of Mg resulting from the widespread use of loop diuretics is responsible for significant numbers of patients with Mg deficiency and hypomagnesemia. Life threatening cardiac arrhythmias and seizures represent the most serious manifestations of clinical hypomagnesemia and Mg depletion. In the most critically ill patients, treatment with intravenous Mg is recommended. Oral repletion of Mg is reserved for the less critically ill hospitalized patients and ambulatory patients. Close attention must be paid to optimizing K replenishment in hypokalemic patients by concurrent treatment of any accompanying hypomagnesemia to avoid the problem of refractory K repletion. CONCLUSIONS: Hypomagnesemia is one of the most frequent serum electrolyte abnormalities in current clinical practice. Routine inclusion of serum Mg analysis in the electrolyte panel will enhance the clinical recognition and treatment of hypomagnesemic Mg-depleted patients. Failure to respond to treatment of recurrent ventricular tachycardia/fibrillation to usual antiarrhythmic therapy in patients with acute myocardial infarction, idiopathic dilated cardiomyopathy, and congestive heart failure should alert the clinician to consider administering intravenous Mg. Repair of coexisting hypomagnesemia in hypokalemic patients is essentialto avoid the problem of refractory K repletion caused by coexisting Mg depletion. More controlled clinical studies of Mg deficiency are necessary to ascertain the cost-effectiveness of Mg replacement therapy.

Coronary perforation is an uncommon but potentially life-threatening complication of percutaneous coronary intervention. The use of both atheroablative technologies for coronary intervention and adjunctive platelet glycoprotein blockade pharmacology may increase the incidence of or risk for life-threatening bleeding complications following the occurrence of coronary artery perforation. The interventional database for 6,214 percutaneous coronary interventions performed between January 1995 and June 1999 was analyzed. Hospital charts and cine angiograms for all patients identified in the database as having had coronary perforation were reviewed. Coronary perforation complicated 0.58% of all procedures and was more commonly observed in patients with a history of congestive heart failure and following use of atheroablative interventional technologies (2.8%). There was no association of abciximab therapy with either the incidence of or classification for coronary perforation. Adverse clinical outcomes (death, emergency surgical exploration) were related to the angiographic classification of perforation and were more frequently observed in patients who experienced a class 3 coronary perforation. These data suggest that specific clinical and procedural demographic factors are associated with the occurrence and severity of angiographic coronary perforation. An angiographic perforation class-specific algorithm for treatment of coronary perforation is proposed.

Adjunctive platelet glycoprotein IIb/IIIa blockade during percutaneous coronary intervention (PCI) reduces platelet-mediated adverse ischemic outcomes. Although abciximab, eptifibatide, and tirofiban have received U.S. Food and Drug Administration approval for use, these agents differ in their pharmacodynamic profiles. Each of these agents has been compared in randomized trials with placebo for patients undergoing PCI, but no randomized comparative studies of these agents have been performed. We compared ex vivo platelet function by both standard light transmission aggregometry and rapid platelet function assay during and after administration of abciximab, eptifibatide, or tirofiban in approved dose regimens on a randomized basis at the time of PCI in patients with unstable angina pectoris. A reduced intensity of platelet inhibition by light transmission aggregometry was observed for tirofiban compared with either eptifibatide or abciximab. In addition, the 30-minute bolus strategy used for tirofiban was associated with delayed onset of maximal platelet inhibition relative to the initiation of bolus infusion. Whether the trends in platelet function observed in this study will be translated into differences in clinical outcomes awaits definition by larger scale randomized clinical trials comparing these platelet glycoprotein IIb/IIIa inhibitors.

Electrolyte balance has been regarded as a factor important to cardiovascular stability, particularly in congestive heart failure. Among the common electrolytes, the significance of magnesium has been debated because of difficulty in accurate measurement and other associated factors, including other electrolyte abnormalities. The serum magnesium level represents < 1% of total body stores and does not reflect total-body magnesium concentration, a clinical situation very similar to that of serum potassium. Magnesium is important as a cofactor in several enzymatic reactions contributing to stable cardiovascular hemodynamics and electrophysiologic functioning. Its deficiency is common and can be associated with risk factors and complications of heart failure. Typical therapy for heart failure (digoxin, diuretic agents, and ACE inhibitors) are influenced by or associated with significant alteration in magnesium balance. Magnesium therapy, both for deficiency replacement and in higher pharmacologic doses, has been beneficial in improving hemodynamics and in treating arrhythmias. Magnesium toxicity rarely occurs except in patients with renal dysfunction. In conclusion, the intricate role of magnesium on a biochemical and cellular level in cardiac cells is crucial in maintaining stable cardiovascular hemodynamics and electrophysiologic function. In patients with congestive heart failure, the presence of adequate total-body magnesium stores serve as an important prognostic indicator because of an amelioration of arrhythmias, digitalis toxicity, and hemodynamic abnormalities.

Serious hemorrhage and vascular complications after abciximab therapy are associated with elevated activated clotting time values. Our preliminary experience suggests that low-dose intravenous protamine administration is both safe and effective in reducing elevated in-laboratory activated clotting time values and the potential for serious hemorrhage in abciximab-treated patients.

Experimental and clinical observations support the view that uncorrected magnesium (Mg) deficiency impairs repletion of cellular potassium (K). This is consistent with the observed close association between K and Mg depletion. Concomitant Mg deficiency in K-depleted patients ranges from 38% to 42%. Refractory K repletion due to unrecognized concurrent Mg deficiency can be clinically perplexing. Refractory K repletion as a consequence of Mg deficiency may be operative in patients with congestive failure, digitalis toxicity, cisplatin therapy, and in patients receiving potent loop diuretics. Therefore, we recommend that: (1) serum Mg be routinely assessed in any patients in whom serum electrolytes are necessary for clinical management and (2) until serum Mg is routinely performed consideration should be given to treating hypokalemic patients with both Mg as well as K to avoid the problem of refractory K repletion due to coexisting Mg deficiency. ( Arch Intern Med . 1992;152:40-45)