Choice Of Thrombolytic Agent Research Articles

Influence of Socioeconomic Status on Patients' Choice of Thrombolytic Agent and its Outcome in Acute Ischemic Stroke.

Alteplase, a recombinant tissue-type plasminogen activator (rtPA) is the only FDA-approved thrombolytic drug in acute ischemic stroke (AIS). Tenecteplase is a modified rtPA, which is cheaper. We aimed to study influence of socioeconomic status (SES) in patients' preference of thrombolytic agent and its outcome. This prospective observational study conducted in PGIMER, a tertiary care center in India, recruited AIS patients thrombolyzed between July 2017 and September 2018. We studied variables including SES, thrombolytic agent chosen, and outcomes like National Institutes of Health Stroke Scale (NIHSS) scores at 24-h and at discharge; and modified Rankin Scale (mRS) after 3 months. Thirty-nine patients received tenecteplase and 39 patients received alteplase. Seven patients belonged to upper class, all of whom (100%) chose alteplase. Thirty patients belonged to upper middle class, of whom 25 (83.3%) and five (16.7%) patients chose alteplase and tenecteplase, respectively. Twenty-five patients belonged to lower middle class in which seven (28%) and 15 (72%) chose alteplase and Tenecteplase, respectively. Twenty patients were in upper lower class, of whom 4 (20%) and 16 (80%) chose alteplase and Tenecteplase, respectively. The difference in distribution of SES in tenecteplase and alteplase groups was significant (P = 0.000). Median 3 month-mRS scores were 3 and 3.5 in alteplase and tenecteplase groups, respectively (P = 0.608). There were no significant differences in NIHSS score improvement at 24 h postthrombolysis (P = 0.537) or at discharge (P = 0.429) among different SES categories. No correlation between SES and 3 month-mRS score was found (Spearman's ρ = 0.101, P = 0.398). Majority of patients in upper and lower SES chose alteplase and Tenecteplase, respectively. However, there were no significant differences in outcomes among various SES categories.

Influence of Socio-Economic Status on Patients’ Choice of Thrombolytic Agent and It's Outcome in Acute Ischemic Stroke

Background and Purpose: Alteplase, a recombinant tissue-type plasminogen activator(rtPA) is the only FDA-approved thrombolytic drug in acute ischemic stroke(AIS). Tenecteplase is a modified rtPA which is cheaper. We aimed to study role of Socio-economic status(SES) in patients’ preference of thrombolytic agent and its outcome. Methods: This prospective observational study conducted in PGIMER, a tertiary care center in India, recruited AIS patients thrombolysed between July 2017 and September 2018. We studied variables including SES, thrombolytic agent chosen and outcomes like NIHSS scores at 24 hours and at discharge; and modified Rankin Scale(mRS) after 3months. Results: 39 patients received tenecteplase and 39 patients received alteplase. 7 patients belonged to upper class, all of whom(100%) chose alteplase. 30 patients belonged to upper middle class, of whom 25(83.3%) and 5(16.7%) patients chose alteplase and tenecteplase respectively. 25 patients belonged to lower middle class in which 7(28%) and 15(72%) chose alteplase and tenecteplase respectively. 20 patients were in upper lower class, of whom 4(20%) and 16(80%) chose alteplase and tenecteplase respectively. The difference in distribution of SES in tenecteplase and alteplase groups was significant(p=0.000). Median 3month-mRS scores were 3 and 3.5 in alteplase and tenecteplase groups respectively(p=0.608). There were no significant differences in NIHSS score improvement at 24 hours post-thrombolysis(p=0.537) or at discharge(p=0.429) among different SES categories. No correlation between SES and 3month-mRS score was found(Spearman’s rho=0.101, p=0.398). Conclusions: Majority of patients in upper and lower SES chose alteplase and tenecteplase respectively. However, there were no significant differences in outcomes among various SES categories. Funding: None to declare. Declaration of Interest: None to declare. Ethical Approval: Ethical clearance was obtained from institution’s Ethics committee.

Primary angioplasty and pharmaco-invasive strategies in the treatment of ST-elevated myocardial infarction

The lecture is devoted to the choice of tactics and the rules of reperfusion therapy for ST-elevated myocardial infarction. Since the time of reperfusion is crucial for the survival of these patients and the preservation of a viable myocardium, proper organization of care and strict adherence to the guidelines for drug-induced and non-drug interventions is necessary. The lecture substantiates the tactics of pharmaco-invasive intervention, the choice of thrombolytic agent, provides data on indications and contraindications for thrombolytic therapy, dosing regimen of thrombolytic drugs, other antiplatelet and anticoagulant drugs required for reperfusion. Knowledge of current guidelines should help reduce ischemia time and cases of unjustified refusal to effective interventions.

ST-Segment Elevation Myocardial Infarction

Patients with acute coronary syndrome fall into two groups: those with unstable angina or non—ST segment elevation (formerly non—Q wave) myocardial infarction (NSTEMI) and those with acute ST segment elevation (formerly Q wave) myocardial infarction (STEMI). STEMI is the focus of this chapter. The epidemiology, pathophysiology, diagnosis, differential diagnosis, and complications of STEMI are elaborated. Reperfusion therapy (including time to reperfusion; diagnostic coronary angiography; primary, facilitated, rescue, and late percutaneous coronary intervention [PCI]; thrombolytic therapy and choice of thrombolytic agent; early invasive strategy; coronary artery bypass grafting; and therapeutic hypothermia), medical therapy (including aspirin, P2Y12 inhibitors, glycoprotein IIb/IIIa inhibitors, anticoagulants, nitrates, beta blockers, inhibition of the renin-angiotensin-aldosterone system, oxygen, analgesia, lipid-lowering therapy, prophylactic antiarrhythmics, and magnesium), risk stratification, secondary prevention, and post-STEMI care are also covered. Tables delineate classifications of MI as defined by proximal cause of myocardial ischemia, Killip classification of acute MI and mortality rates, differential diagnosis of ST segment elevation, contraindications for administering thrombolytic agents, and major recommendations for antithrombotic therapy in patients with STEMI treated with primary PCI and thrombolysis. Algorithms indicate a diagnostic approach to acute coronary syndromes and corresponding pathology and reperfusion strategies. Electrocardiogram changes in STEMI and corresponding territory of myocardium are depicted. A variety of graphs are included. This review contains 11 highly rendered figures, 6 tables, and 151 references.

Primary angioplasty and thrombolysis are both reasonable options in acute myocardial infarction.

Primary angioplasty is increasingly being advocated as the preferred approach for treating acute ST-segment elevation myocardial infarction regardless of whether interinstitutional transfer is required. This review critically analyzes the evidence comparing primary angioplasty with thrombolytic therapy and concludes that reasonable health care professionals may still find considerable uncertainty about the superiority of primary angioplasty for all situations. The magnitude of benefit for primary angioplasty over thrombolysis is probably less than 1 to 2 lives saved/100 patients treated and largely depends on the choice of thrombolytic agent, time to treatment, place of treatment, and adjunctive therapy. There is little evidence that systematically transferring patients for primary angioplasty in routine practice will provide any health benefits over thrombolysis. Consequently, it may be most useful to view these treatments as complementary rather than competitive. Thrombolysis remains a clinically and economically attractive option for the treatment of acute myocardial infarction that does not require the radical restructuring of our health care systems.

Complications Associated with the Use of Urokinase and Recombinant Tissue Plasminogen Activator for Catheter-directed Peripheral Arterial and Venous Thrombolysis

Catheter-directed thrombolytic dissolution of peripheral arterial and venous thrombus is in widespread use, yet the frequency and nature of associated complications remain ill defined. In an effort to better characterize the complications associated with urokinase (UK) and recombinant tissue plasminogen activator (rt-PA), the clinical course of patients treated for lower extremity vascular occlusions at a single institution was reviewed. Over a 9-year period, 653 consecutive patients were treated for lower extremity arterial (527 patients) or venous (126 patients) occlusions with catheter-directed UK (483 patients), rt-PA (144 patients), or both (26 patients). Decisions regarding the choice of thrombolytic agent were made by the clinician. In-hospital complications were subcategorized into hemorrhagic and nonhemorrhagic events and the rate of intracranial hemorrhage was specifically tabulated. There were no significant differences in the demographics or clinical presentation of patients treated with either UK or rt-PA. Bleeding complications occurred less often in the patients treated with UK (insertion site hematoma 21.9% vs. 43.8%, P<.0001, any bleeding necessitating transfusion 12.4% vs. 22.2%, P = .004, and intracranial hemorrhage 0.6% vs. 2.8%, P = .031). Cardiopulmonary complications necessitating transfer to the intensive care unit occurred more frequently in the patients treated with rt-PA (4.9% vs. 1.5%, P = .015). The risk of mortality was not statistically different between the UK and rt-PA treated patients (2.7% vs. 6.2%, P = .221). Thrombolysis appears safer with UK than with rt-PA, with a lower incidence of hemorrhagic complications. It is possible that this finding is related to differential dosing regimens or intrinsic pharmacologic differences between the agents. The observations of this retrospective analysis require confirmation with a prospective, randomized evaluation.

Medical decision making in the choice of a thrombolytic agent for acute myocardial infarction. Quebec Acute Coronary Care Working Group.

Little is known about how physicians make decisions when the evidence is incomplete or controversial. While thrombolysis improves survival following acute myocardial infarction (AMI), conflicting evidence exists as to any specific agent's superiority, particularly if cost-effectiveness is considered. Using a Bayesian hierarchical model, the authors examined the patient, physician, and hospital characteristics that are related to the decision-making process concerning the choice of thrombolytic agent in a prospective registry of 1,165 AMI patients receiving thrombolysis. Tissue plasminogen activator (t-PA) was administered to 432 patients (31.8%) and streptokinase (SK) to the remainder. The presence of an anterior infarction, a previous myocardial infarction, low blood pressure, a cardiologist decision maker, younger age, and receiving treatment within six hours after the start of symptoms were independent predictors of receiving t-PA. The levels of importance that physicians accorded to these patient characteristics differed according to their practicing institutions. Generally, they followed evidence-based medicine and reasonably targeted high-risk patients to receive the more expensive t-PA. However, they also preferentially treated younger patients, where only a small absolute advantage appears to exist.

Impact of a Simple Inexpensive Quality Assurance Effort on Physician's Choice of Thrombolytic Agents and Door-to-Needle Time: Implication for Costs of Management.

The objective of this study were to assess the impact of a quality assurance effort on the door-to-needle time and the choice of thrombolytic agent for the management of acute myocardial infarction in the emergency department. The study design involved a prospective collection of data on a series of consecutive patients who received a thrombolytic agent for a presumed acute myocardial infarction. The study was carried out in the emergency department of a major university urban tertiary care center. A total of 349 patients were studied from September 1989 to March 1994. The quality assurance program began in 1989 and included chart review of all patients receiving thrombolytic therapy, with special attention to all patients with door-to-needle times >60 minutes to identify causes for delay. Feedback was directed to pharmacy, nursing, and physician staff. Biannual reports were distributed throughout the hospital and the emergency department. Nursing-specific feedback led to the development of protocols for all aspects of the delivery of thrombolytic agents. The choice of thrombolytic agent was not dictated by the protocol, but the physician staff was continuously updated on the results of the latest clinical trials comparing one thrombolytic agent with another. The mean age was 58 years for men and 67 years for women in this cohort consisting of 78% men and 22% women. Thirty-seven percent of the myocardial infarctions were in an anterior location and 56% were in an inferior location. The median duration of chest pain before presentation to the emergency department was 120 minutes. Hospital mortality was 3%. Median door-to-needle time fell from 46 (1989-1991) to 36 (1992-1994) minutes, P& < 0.01. The percentage of patients with a door-to-needle time >60 minutes decreased from 35% (1989-1991) to 16% (1992-1994) minutes, P < 0.0001. Corresponding with the ISIS-3 report, there was a significant increase in the proportion of patients receiving streptokinase over the first 3 years of the study (P < 0.0001), which changed to a trend toward increased utilization of tissue plasminogen activator with the GUSTO report in the final 6 months of the study. In conclusion, a quality assurance program led to a significant reduction in the door-to-needle time, and recent megatrials were found to influence the choice of thrombolytic agent used.

Clinical outcomes according to time to treatment.

Twenty years ago, pathophysiologic studies showed that myocardial salvage in acute myocardial infarction depends on early intervention. A meta-analysis of the largest thrombolytic trials showed 1.6 lives saved/1000 treated for each hour closer to symptom onset, and that patients treated in the first hour have a much higher survival rate. The MITI trial found a seven-fold decrease in mortality in patients treated within 70 min of symptom onset. The GUSTO study showed similar results, except that during the first hour mortality was actually higher than in the second hour. In contrast, studies have found that while little survival benefit accrues from treatment after a 12 h delay, significant benefit is achieved by treatment between 6 and 12 h from symptom onset. Thus, mechanisms other than myocardial salvage are at work. A GUSTO substudy demonstrated considerable in-hospital delays in attaining electrocardiographic readings, in deciding on the course of therapy, and most of all in the time to infuse the drug. Other delays in both presentation and treatment are related to patient characteristics such as age, gender, diabetes, and Killip class. The medical community cannot control delays in presentation, but it has been able to reduce in-hospital delays, with resultant benefits in morbidity as well as mortality. At the end of the day, reducing delay outweighs the choice of thrombolytic agent.

Survey of practicing cardiologists in maryland on their choice of thrombolytic therapy for acute myocardial infarction

In November 1990, we surveyed 160 practicing community cardiologists in the state of Maryland and 20 academic cardiologists at the University of Maryland Medical Center to determine each individual's preference for aggressive versus nonaggressive therapy for various presentations of acute myocardial infarction. The survey was repeated in April 1991 following a report of the results of the Third International Study of Infarct Survival. All 100 responding cardiologists chose aggressive therapy to manage an early (< 2 hours) acute anterior myocardial infarction in a 50-yearold patient. However, less aggressive therapy was chosen by many community cardiologists for management of early inferior acute myocardial infarction or for elderly patients. Most community cardiologists chose tissue plasminogen activator as their thrombolytic drug of choice, whereas university cardiologists favored streptokinase. Although there were substantial shifts in choice of thrombolytic agent on the repeat survey, most community physicians still chose tissue plasminogen activator over the less expensive streptokinase.

The Impact of Economic Considerations on Clinical Decisionmaking: The Case of Thrombolytic Therapy

This study examines the intravenous use of two thrombolytic agents [streptokinase (SK) and tissue plasminogen activator (tPA)] in the acute phase of myocardial infarction (MI). These two agents have very different costs and offer an excellent opportunity to study both the impact of economic factors on clinical decisionmaking and the potential for cost savings by limiting the use of expensive new therapeutic agents. A nationwide survey of the 5,792 acute care general hospitals listed in the American Hospital Association's 1988 data file was responded to by 2,651 hospitals (46%) and revealed that 2,384 of these responding hospitals (90%) were using thrombolytic therapy. For 2,200 of these 2,384 hospitals (92%), the respondent was a physician who primarily used one of the two drugs. Eight hundred eighty-six of these 2,200 physicians (40%) primarily used SK while 1,314 (60%) primarily used tPA. SK users were more concentrated in federal public hospitals (69% used SK) than in nonfederal public hospitals (47% used SK), and were least concentrated in private hospitals (36% used SK). There was no difference between the rate of SK vs tPA use in investor-owned and not-for-profit private hospitals. SK users most often (62%) cited various economic factors as the reason for their choice. The users of tPA primarily (73%) cited clinical preferability as the reason for their choice even though trials are still ongoing to see which drug is preferable. Several multivariate analyses shed light upon the association between choice of thrombolytic agent and various additional physician and hospital characteristics. These data clearly indicate that while new therapies are rapidly implemented by the medical community, considerations of cost have a substantial impact upon the pattern of implementation and reflect a desire to implement cost savings in the use of new drugs.

Management of acute myocardial infarction 1990: A perspective

Rising costs have reached a point at which physicians must assume a major role in dealing with the cost of medicine. Little information is available regarding actual practice at the community hospital level. In order to develop some insight on this issue, a survey of cardiovascular specialists was conducted regarding management of acute myocardial infarction in 1990. The results indicate a major lack of correlation between efficacy, cost, and practice patterns in terms of current knowledge. Perhaps legal concerns have contributed to these current practice patterns. Clearly, aside from choice of thrombolytic agent and/or PTCA, early treatment of acute myocardial infarction has emerged as a most important factor in reducing mortality.

Thrombolytic Agents: Balancing Cost, Efficacy, and Side Effects

Balancing the benefits, risks, and cost of thrombolytic treatment is a complex issue which depends considerably upon the variable threat of the thrombus to organ physiology and patient survival. For example, after deep vein thrombosis (DVT), the major risk is long-term disability due to the postphlebitic syndrome, while in pulmonary embolism (PE) patients, the risks concern short-term mortality and impaired pulmonary physiology. Thus, for treating DVT or PE, the question is whether thrombolytic therapy would be valuable in addition to other antithrombotic approaches. Clearly, the best indication for thrombolytic therapy is in acute myocardial infarction (MI) patients, because this therapy has the potential for reducing coronary artery thrombus mortality. In acute MI the major issues concern the choice of thrombolytic agent and the relative merits of nonpharmacologic interventions such as angioplasty and bypass surgery. An optimal window of treatment opportunity exists for all of the indications. The window is shortest for MI, intermediate for PE, and longest for DVT patients.