Koon-Hou Mak

Influence of Diabetes Mellitus on Clinical Outcome in the Thrombolytic Era of Acute Myocardial Infarction

Abstract Objectives. This study was undertaken to define and better understand the characteristics and outcomes of patients with diabetes treated for acute myocardial infarction with contemporary thrombolysis. Background. Although thrombolysis has substantially improved survival of patients with myocardial infarction, diabetes mellitus remains an independent predictor for a poor prognosis. Methods. We characterized the contemporary relation between diabetes and outcome after myocardial infarction treated with thrombolytic agents from a large international cohort. Of 41,021 patients randomized to receive accelerated tissue-type plasminogen activator (t-PA), streptokinase or a combination of both agents in the Global Utilization of Streptokinase and Tissue Plasminogen Activator for Occluded Coronary Arteries study, there were 5,944 patients with diabetes and 34,888 patients without diabetes. Results. Patients with diabetes were older and more likely to be female, to present with anterior wall infarction, to receive thrombolysis later and to have triple-vessel coronary artery disease. Mortality at 30 days was highest among diabetic patients treated with insulin (12.5%) compared with non–insulin-treated diabetic (9.7%) and nondiabetic (6.2%) patients (p Conclusions. Diabetes, alone and in association with its comorbidities, portends a substantially worse 30-day and 1-year prognosis for patients with myocardial infarction. (J Am Coll Cardiol 1997;30:171–9)

Ethnic differences in acute myocardial infarction in Singapore

AIMS We compare the myocardial infarction (MI) event and mortality rates among Chinese, Malay and Indian residents of Singapore. METHODS Residents, aged 20 to 64 years, with an MI event were identified from hospital discharge listings, postmortem reports, and the Registry of Births and Deaths. All pathology laboratories flagged patients with elevated creatine phosphokinase (CPK) levels. Modified MONICA (multinational monitoring of trends and determinants in cardiovascular disease) criteria were used for determining MI events. RESULTS From 1991 to 1999, 12 481 MI events were identified. Chinese patients were older and less likely to have typical symptoms or previous MI. Malays had the highest peak CPK level. Among all three ethnic groups, MI event and age-adjusted case-fatality rates declined. Compared with Chinese, MI event rates were >2-fold and >3-fold higher, and age-standardized coronary mortality rates were 2.4 and 3.0 higher times for Malays and Indians, respectively. Malays have the highest 3.1-year case-fatality, with an adjusted hazard ratio of 1.26 (95% confidence interval, 1.14 to 1.38) compared with Chinese. CONCLUSION We found strong ethnic differences in MI event, case-fatality and coronary mortality rates among the three ethnic groups in Singapore. While Indians have the greatest MI event rates, Malays have the highest case-fatality.

Effect of platelet glycoprotein IIb/IIIa receptor inhibition on distal embolization during percutaneous revascularization of aortocoronary saphenous vein grafts

Percutaneous treatment of narrowed aortocoronary saphenous vein graft disease represents a viable option for patients with recurrent angina following coronary artery bypass grafting. Present strategies are limited by high rates of distal embolization, non-Q-wave acute myocardial infarction (AMI), and restenosis. Because these complications may be mediated by platelets, inhibition of platelet glycoprotein IIb/IIIa receptor, the final common pathway for aggregation, may improve clinical outcomes. In the Evaluation of IIb/IIIa platelet receptor antagonist 7E3 in Preventing Ischemic Complications (EPIC) trial, 2,099 patients undergoing high-risk percutaneous coronary revascularization were randomized to receive abciximab bolus and infusion, abciximab bolus followed by placebo infusion or placebo. A total of 101 patients were treated for narrowing of saphenous vein grafts, 38 in the bolus and infusion group, 34 in the bolus group and 29 in the placebo group. Clinical end points included all-cause mortality, nonfatal AMI and need for repeat revascularization at 30 days. Compared with placebo, bolus and infusion therapy resulted in a significant reduction in distal embolization (2% vs 18%, p = 0.017) and a trend towards reduction in early large non-Q-wave AMI (2% vs 12%, p = 0.165). The occurrence of a 30-day composite end point was similar among the 3 treatment groups. At 6 months, there was also no difference in the composite end point. These results suggest that adjunctive therapy with abciximab during percutaneous treatment of narrowed saphenous vein grafts reduces the occurrence of distal embolization, and possibly non-Q-wave AMI.

Clinical Outcomes of Patients With Diabetic Nephropathy Randomized to Clopidogrel Plus Aspirin Versus Aspirin Alone (A post hoc Analysis of the Clopidogrel for High Atherothrombotic Risk and Ischemic Stabilization, Management, and Avoidance [CHARISMA] Trial)

No prospective randomized trial has specifically examined the long-term outcomes of clopidogrel use in patients with chronic kidney disease. This study aimed to determine the risks and benefits of long-term clopidogrel administration in patients with diabetic nephropathy, the most common form of chronic kidney disease. We performed a post hoc analysis of the CHARISMA trial, which randomly assigned patients without active acute coronary syndrome, but with established atherosclerotic disease (symptomatic) or multiple risk factors for atherosclerotic disease (asymptomatic), to clopidogrel plus aspirin versus placebo plus aspirin. All CHARISMA patients (n = 15,603) were separated into the 3 groups: nondiabetic patients, diabetic patients without nephropathy, and diabetic patients with nephropathy. Within each group, outcomes of patients randomly assigned to clopidogrel were compared with those of patients randomly assigned to placebo. Outcomes in the prespecified CHARISMA subgroups of asymptomatic and symptomatic patients were also compared with respect to study drug assignment and nephropathy status. Patients with nephropathy who received clopidogrel had no difference in bleeding, but experienced significantly increased cardiovascular (CV) and overall mortality compared with those randomly assigned to placebo. There were no differences in bleeding, overall mortality, or CV mortality for nondiabetic or diabetic patients without nephropathy who received clopidogrel versus placebo. In the asymptomatic cohort, patients with nephropathy randomly assigned to clopidogrel had significantly increased overall and CV mortality compared with placebo, whereas asymptomatic patients without nephropathy randomly assigned to clopidogrel had no significant mortality difference compared with placebo. In conclusion, this post hoc analysis suggested that clopidogrel may be harmful in patients with diabetic nephropathy. Additional studies are needed to investigate this possible interaction.

Emerging Concepts in the Management of Acute Myocardial Infarction in Patients With Diabetes Mellitus

Although fibrinolysis has improved survival of patients after myocardial infarction (MI), such therapy is less likely to be administered to patients with diabetes. Furthermore, these patients present later (15 min) than nondiabetics. Moreover, even with the use of early potent fibrinolytic agents, patients with diabetes continued to suffer excessive morbidity and mortality. This finding is not related to the ability of fibrinolytic agents to restore complete reperfusion or increased risk of reocclusion of the infarct-related artery. Instead, the impaired ventricular performance at the noninfarct areas and metabolic derangements during the acute phase of MI may account for the adverse outcome. The efficacy of percutaneous coronary revascularization procedures for treatment of acute MI requires further evaluation. Therapeutic approaches should consider correcting these abnormalities to afford greater survival benefit for this subset of high-risk patients.

Ethnic variation in adverse cardiovascular outcomes and bleeding complications in the Clopidogrel for High Atherothrombotic Risk and Ischemic Stabilization, Management, and Avoidance (CHARISMA) study

BACKGROUND Atherothrombosis is a common condition affecting individuals worldwide. Its impact on different ethnic groups receiving evidence-based therapy is unclear. We aimed to determine if ethnicity is an independent predictor for cardiovascular events and bleeding complications in a contemporary clinical trial on antiplatelet therapy. METHODS This was a prospective observational study of 15,603 patients enrolled in the CHARISMA trial followed up every 6 months for a median of 28 months. The primary efficacy end point was the first occurrence of cardiovascular death, myocardial infarction, or stroke. The primary safety end point was bleeding. RESULTS The cohort comprised 12,502 (80.1%) white, 486 (3.1%) black, 775 (5.0%) Asian, and 1,613 (10.3%) Hispanic patients. There was no difference in the occurrence of the primary composite end point among the 4 ethnic groups. Compared with Asians, cardiovascular and all-cause mortality occurred more frequently among black (adjusted hazard 2.19 and 2.04) and Hispanic (adjusted hazard, 1.83 and 1.69) patients. Although the occurrence of severe bleeding was similarly low among the 4 ethnic groups, Asian (adjusted hazard, 2.21) and black (adjusted hazard, 3.06) patients were more likely to have moderate bleeding complications than Hispanic patients. CONCLUSION In this trial of individuals at risk of vascular events, ethnicity was not a significant, independent predictor of the primary composite cardiovascular event. However, ethnicity was a significant, independent predictor of the secondary outcomes, cardiovascular and all-cause mortality (blacks and Hispanics), and moderate bleeding complications (blacks and Asians).

Clinical Trials to Prevent Restenosis after Percutaneous Coronary Revascularization

Percutaneous transluminal coronary revascularization (PTCR) is effective in relieving symptoms in patients with angina pectoris. In selected patients, PTCR provides similar protection from cardiac death or myocardial infarction as surgical revascularization.’V2 However, restenosis following PTCR remains the procedure’s major limitation. Besides compromising clinical benefit in terms of recurrence of angina and need for repeat procedures, restenosis markedly increases health care cost by at least

Diabetes abolishes the gender gap in coronary heart disease.

2 billion per year in the United States.3 Despite extensive research on restenosis, the pathophysiologic mechanisms remain unclear. The process appears to be the result of a complex reparative process from vascular injury (FIG. l).4 The denudation to the endothelium exposes collagen, tissue, and other factors that in turn activate platelets and initiate the coagulation cascade, resulting in thrombus formation and reparatory response. Growth factors, such as platelet-derived growth factor (PDGF) and basic fibroblast growth factor (bFGF), released from platelets and smooth muscle cells, induce the proliferation process via proto-oncogenes, such as c-fos and c-myc. In addition, the thrombus may act as a “bioabsorbable matrix”5 for cell migration and proliferation at the sites of treatment, with thrombin amplifying the response.6 Smooth muscle cells and fibroblasts also secrete large amounts of extracellular matrix, forming another important component in restenotic lesions. Contracting mechanical forces occurring in minutes to hours (vessel recoil) and days (remodeling) following vascular injury may lead to vessel contracture or “shrinkage” contributing to restenosis.’ In one recent stuTdy: immunochemical labeling for proliferating cell nuclear antigen (PCNA) was absent in 74% of restenotic coronary atherosclerotic specimens, suggesting the increasing importance of the remodeling process in restenosisY Based on this paradigm of thrombus formation, cellular proliferation, and vessel contracture, several pharmacological and mechanical approaches have been evaluated in clinical trials in limiting restenosis.

Combined fibrinolysis using reduced-dose alteplase plus abciximab with immediate rescue angioplasty versus primary angioplasty with adjunct use of abciximab for the treatment of acute myocardial infarction: Asia-Pacific Acute Myocardial Infarction Trial (APAMIT) pilot study.

See doi:10.1016/S1095-668X(03)00197-0for the article to which this editorial refers. Prior to menopause, the incidence of coronary heart disease (CHD) is considerably lower among women than men. One reason to account for this disparity is that males are more likely to be associated with an adverse risk profile. Interestingly, the relative risks conferred by several of the various coronary risk factors, including cholesterol level, diastolic blood pressure, smoking and social class, were approximately similar for both sexes. However, the adverse relationship of other coronary risk factors, such as diabetes, low high-density lipoprotein cholesterol and high triglycerides, was greater in women. Indeed, patients with diabetes, especially women, were twice as likely to suffer from coronary events.1Subsequent data from the Finnish Study suggested that patients with diabetes, regardless of sex, were considered as coronary equivalents.2 In this issue of the European Heart Journal , Becker et al.3evaluated the 10-year risk of cardiovascular events in a cohort of 2461 Caucasians with and without diabetes. Although diabetes was associated with a greater risk for adverse cardiovascular events, the effect was modified by gender. Comparing individuals without diabetes but with prior cardiovascular disease to those with diabetes but without prior cardiovascular disease, the risk for unfavourable cardiovascular events was lower for men ( adjusted hazard, 0.5; 95% confidence interval [CI], 0.3–0.9) but similar for women ( adjusted hazard, 1.0; 95% CI, 0.6–1.7). The authors concluded that only women but not men with diabetes should be considered as coronary …

Reuse of coronary angioplasty equipment: Technical and clinical issues

We conducted a randomized feasibility pilot study comparing combined fibrinolysis with immediate rescue angioplasty vs. primary angioplasty with adjunctive abciximab in patients with acute myocardial infarction (AMI). Seventy patients with ST segment elevation AMI of ≤ 6 hr were randomized to either 50 mg of alteplase and abciximab (n = 34) or primary angioplasty with adjunctive abciximab (n = 36). Coronary angiography was performed at 60 min in the combined lytic group and TIMI 3 flow was present in 65% of patients as compared to 25% (P = 0.001) in the primary angioplasty group prior to intervention. Treatment success, defined as TIMI 3 flow, was achieved in 83% of patients in the primary angioplasty group (P = 0.075 compared to 65% in combined lytic group before rescue angioplasty). There was no difference in overall treatment success between primary angioplasty and combined lytic group with rescue angioplasty (83% vs. 94%; P = NS). Major adverse cardiac events at 1 month were not significant (15% vs. 11%; P = NS), but there was a trend toward more events in the combined lytic group at 6 months (32% vs. 14%; P = 0.066), particularly in target vessel revascularization. In this feasibility pilot study, high rate of TIMI 3 flow was attained in patients with AMI with both combined fibrinolysis and primary angioplasty with adjunctive abciximab. A larger randomized trial is currently ongoing to compare these two strategies. Cathet Cardiovasc Intervent 2004;62:445–452.