Reperfusion Strategies for Acute Myocardial Infarction: Mechanical vs. Thrombolytic Therapy

The California Journal of Emergency Medicine III:1, January 2002 page 3 REVIEW ARTICLE (9.3%, p < 0.001). Furthermore, recent data suggests that while epicar- dial blood flow is paramount, perfusion at the tissue level or microcir- culation of the myocardium may be equally or more important. 10 TIMI myocardial perfusion grading is a new angiographic method for assess- ing the microcirculation. This technique allows additional risk stratifi- cation within the TIMI epicardial grade flow. In data taken from the TIMI 10B trial, myocardial perfusion was an independent predictor of mortality regardless of epicardial TIMI grade flow. 11 However, there is a synergistic effect between epicardial blood flow and microvascular perfusion and their relationship to mortality, the higher the flow / perfusion the lower the mortality. This finding has generated signifi- cant enthusiasm in the arena of combining thrombolytics with glyco- protein IIB/IIIA inhibitors as the latter is postulated to have a benefi- cial effect on the microcirculation. Reperfusion Strategies for Acute Myocardial Infarction: Mechanical vs. Thrombolytic Therapy J. Douglas Kirk, MD Division of Emergency Medicine University of California Davis Medical Center Sacramento, CA Introduction Management of patients with acute myocardial infarction rep- resents a great challenge to emergency physicians, a task more recently complicated by the myriad of potential treatment options available. The goal of reperfusion therapy in patients with ST segment elevation myo- cardial infarction (STEMI) is the safest, earliest and most complete res- toration of normal (TIMI-3) flow in the infarct related artery. Current strategies include thrombolysis, primary angioplasty or a combination of the two. Recent advances in antiplatelet and antithrombotic therapy with glycoprotein IIB / IIIA inhibitors and low molecular weight heparins have introduced another option, multimodal combination pharmacologi- cal therapy. 1,2 Multiple clinical trials which included thousands of patients undergoing thrombolytic therapy for STEMI have demonstrated a sub- stantial improvement in mortality with their use. 3 The principle determi- nants of survival after reperfusion therapy are speed of reperfusion and the magnitude of patency restoration. Retrospective analysis by Tiefenbrunn and Boersma of data from more than 20 clinical trials dem- onstrates a clear time dependant benefit from reperfusion therapy. 4,5 In both models, the benefit / time curve is very steep until approx 2 hours after symptom onset, suggesting the greatest benefit was achieved early, with more modest results occurring between 2 and 12 hours after symp- tom onset. Therapy after 12 hours from symptom onset is generally regarded as not beneficial. 3 Likewise, this time dependent benefit has been shown in trials where primary angioplasty was performed. In the Gusto IIB cohort of 1,138 patients with acute myocardial infarction, 565 patients underwent primary angioplasty. 6 The primary endpoint was thirty-day mortality, which in patients treated within 60 minutes of presentation was 1%. A consistent decline in mortality benefit was seen with increasing door to balloon times. The mortality in patients treated after 90 minutes was 6.4%. In addition, data from more than 27,000 patients enrolled in the National Registry of Myocardial Infarction (NRMI-2), an industry sponsored observational registry of patients with acute myocardial infarction, showed a nearly 50% increase in mortality if more than 2 hours elapsed from arrival to balloon inflation. 7 The impact of complete restoration of patency is equally im- portant to clinical outcome and is part in parcel to the goal of therapy - early and full reperfusion. 8 Gibson’s analysis of angiographic data from nearly 5,500 patients enrolled in fibrinolytic trials shows a clear relation- ship between 90-minute patency and mortality. 9 Short-term mortality (4-6weeks) in patients with TIMI-3 flow (3.7%) was significantly lower than in patients with TIMI-2 flow ( 6.1 %, p < 0.001) and TIMI-0/1 flow Thrombolytics -vs- Primary Angioplasty As one can probably surmise, the principal determinants of survival are not equally inherent to these two treatment strategies. Outlining the advantages and disadvantages of each strategy will help shed some light on the controversy faced by emergency physicians and cardiologist in determining the best treatments for their patients. Thrombolytic therapy has a wealth of supporting clinical trial data which demonstrates a proven mortality benefit. 3,12 It’s ease of use, rapid administration, and universal availability have made it the historical gold standard of reperfusion therapy. It requires no special- ized equipment or personnel and is essentially available in any emer- gency setting. Unfortunately, this universal agent comes with a price, most notably bleeding complications. The most feared is intracranial hemorrhage or stroke which occurs in approximately 1% of treated patients. 3,12 In addition, the risk of intracranial hemorrhage increases with advancing age. There are also numerous contraindications related to bleeding risk which limits its use in certain patients. Although the speed of patency restoration for thrombolytic therapy is excellent, it’s extent is not. Only 50-60% of patients achieve TIMI-3 flow at 90 minutes. 8 Further, many patients have subsequent reocclusion and recurrent infarction, likely as a result of paradoxical activation of the coagulation cascade. This prothrombotic effect has prompted investi- gators to look at alternate pharmacologic strategies such as a combina- tion of thrombolytics with glycoprotein IIB / IIIA inhibitors to poten- tially attenuate this effect. 1,2 Strategies for reperfusion employing primary angioplasty have been gaining momentum in the last decade, encouraged by clinical trials and meta-analysis suggesting its superiority over thrombolytic therapy 13,14,15 as well as interventional cardiologist enthusiasm for performing the procedure. This strategy’s main attributes are superior patency of the infarct related artery (90% TIMI-3 flow at 90 minutes) and low risk of bleeding complication, especially intracranial hemor- rhage. 16 There are few contraindications and it provides the physician with immediate knowledge of the coronary anatomy. This may afford further risk stratification and in some cases of diagnostic uncertainty, may provide the definitive diagnosis. Additionally, primary angioplasty is the preferred strategy in patients with cardiogenic shock, those with acute myocardial infarction and persistent symptoms beyond 12 hours and those who fail to reperfuse with thrombolytic therapy. 17