Sandra Forman

Asymptomatic Cardiac Ischemia Pilot (ACIP) Study Improvement of Cardiac Ischemia at 1 Year After PTCA and CABG

BACKGROUND Cardiac ischemia on the ambulatory ECG (AECG) and/or on the exercise treadmill test (ETT) is associated with an increased risk of adverse outcome. Myocardial revascularization more often suppresses cardiac ischemia than does medical management alone. However, few studies have compared the effects of percutaneous transluminal coronary angioplasty (PTCA) with those of coronary artery bypass grafting (CABG) on cardiac ischemia and clinical outcome. METHODS AND RESULTS A total of 558 patients were randomly assigned to one of three treatment strategies in the Asymptomatic Cardiac Ischemia Pilot (ACIP) study: angina-guided medical strategy (n = 184), ischemia-guided medical strategy (n = 182), or revascularization (n = 192). In patients assigned to revascularization, the choice of the procedure, PTCA or CABG, was made by the clinical unit staff and patient based on a coronary angiogram usually performed within 2 months of enrollment. CABG was selected in 78 patients and PTCA in 92 patients. At 12 weeks, ischemia on the AECG was suppressed in 70% of CABG patients versus 46% of PTCA patients (P = .002). Ischemia on the ETT was no longer present in 46% versus 23% of the patients, respectively (P = .005). Angina, within 4 weeks of the follow-up visit, was absent in 90% versus 68%, respectively (P = .001). These clinical variables remained improved in both groups at 1 year. Clinical events (myocardial infarction or repeat revascularization) occurred in 1 CABG patient versus 7 PTCA patients at 12 weeks, and in 1 versus 16 patients, respectively, at 12 months (P < .001). CONCLUSIONS Ischemia on the AECG and ETT and angina were relieved in many patients after both procedures; however, CABG was superior to PTCA, and it was associated with a lower incidence of clinical events at 1 year. These results suggest that more complete revascularization relates to better clinical outcome. However, a large trial is needed to confirm these results.

Asymptomatic Cardiac Ischemia Pilot (ACIP) Study Two-Year Follow-up Outcomes of Patients Randomized to Initial Strategies of Medical Therapy Versus Revascularization

BACKGROUND Patients with ischemia during stress testing and ambulatory ECG monitoring have an increased risk of cardiac events, but it is not known whether their prognosis is improved by more aggressive treatment with anti-ischemic drugs or revascularization. METHODS AND RESULTS The Asymptomatic Cardiac Ischemia Pilot study randomized 558 such patients who had coronary anatomy suitable for revascularization to three treatment strategies: angina-guided drug therapy (n=183), angina plus ischemia-guided drug therapy (n=183), or revascularization by angioplasty or bypass surgery (n=192). Two years after randomization, the total mortality was 6.6% in the angina-guided strategy, 4.4% in the ischemia-guided strategy, and 1.1% in the revascularization strategy (P<.02). The rate of death or myocardial infarction was 12.1% in the angina-guided strategy, 8.8% in the ischemia-guided strategy, and 4.7% in the revascularization strategy (P<.04). The rate of death, myocardial infarction, or recurrent cardiac hospitalization was 41.8% in the angina-guided strategy, 38.5% in the ischemia-guided strategy, and 23.1% in the revascularization strategy (P<.001). Pairwise testing revealed significant differences between the revascularization and angina-guided strategies for each comparison. CONCLUSIONS A strategy of initial revascularization appears to improve the prognosis of this population compared with angina-guided medical therapy. A larger long-term study is needed to confirm this benefit and to adequately test the potential of more aggressive drug therapy.

Immediate versus deferred beta-blockade following thrombolytic therapy in patients with acute myocardial infarction. Results of the Thrombolysis in Myocardial Infarction (TIMI) II-B Study.

In the Thrombolysis in Myocardial Infarction (TIMI) Phase II trial, patients received intravenous recombinant tissue-type plasminogen activator (rt-PA) and were randomized to either a conservative or an invasive strategy. Within this study, the effects of immediate versus deferred beta-blocker therapy were also assessed in patients eligible for beta-blocker therapy, a group of 1,434 patients of which 720 were randomized to the immediate intravenous group and 714 to the deferred group. In the immediate intravenous group, within 2 hours of initiating rt-PA metoprolol was given (5 mg intravenously at 2-minute intervals over 6 minutes, for a total intravenous dose of 15 mg, followed by 50 mg orally every 12 hours in the first 24 hours and 100 mg orally every 12 hours thereafter). The patients assigned to the deferred group received metoprolol, 50 mg orally twice on day 6, followed by 100 mg orally twice a day thereafter. The therapy was tolerated well in both groups and the primary end point, resting global ejection fraction at hospital discharge, averaged 50.5% and was virtually identical in the two groups. The regional ventricular function was also similar in the two groups. Overall, there was no difference in mortality between the immediate intravenous and deferred groups, but in the subgroup defined as low risk there were no deaths at 6 weeks among those receiving immediate beta-blocker therapy in contrast to seven deaths among those in whom beta-blocker therapy was deferred. These findings for a secondary end point in a subgroup were not considered sufficient to warrant a recommendation regarding clinical use. There was a lower incidence of reinfarction (2.7% versus 5.1%, p = 0.02) and recurrent chest pain (18.8% versus 24.1%, p less than 0.02) at 6 days in the immediate intravenous group. Thus, in appropriate postinfarction patients, beta-blockers are safe when given early after thrombolytic therapy and are associated with decreased myocardial ischemia and reinfarction in the first week but offer no benefit over late administration in improving ventricular function or reducing mortality.

A randomized trial of the efficacy of multidisciplinary care in heart failure outpatients at high risk of hospital readmission

OBJECTIVES We sought to determine whether a multidisciplinary outpatient management program decreases chronic heart failure (CHF) hospital readmissions and mortality over a six-month period. BACKGROUND Hospital admission for CHF is an important problem amenable to improved outpatient management. METHODS Two hundred patients hospitalized with CHF at increased risk of hospital readmission were randomized to a multidisciplinary program or usual care. A study cardiologist and a CHF nurse evaluated each patient and made recommendations to the patients primary physician before randomization. The intervention team consisted of a cardiologist, a CHF nurse, a telephone nurse coordinator and the patients primary physician. Contact with the patient was on a prespecified schedule. The CHF nurse followed an algorithm to adjust medications. Patients in the nonintervention group were followed as usual. The primary outcome was the composite of the number of CHF hospital admissions and deaths over six months, compared by using a log transformation t test by intention-to-treat analysis. RESULTS The median age of the study patients was 63.5 years, and 39.5% were women. There were 43 CHF hospital admissions and 7 deaths in the intervention group, as compared with 59 CHF hospital admissions and 13 deaths in the nonintervention group (p = 0.09). The quality-of-life score, percentage of patients on target vasodilator therapy and percentage of patients compliant with diet recommendations were significantly better in the intervention group. Cost per patient, in 1998 U.S. dollars, was similar in both groups. CONCLUSIONS This study demonstrates that a six-month, multidisciplinary approach to CHF management can improve important clinical outcomes at a similar cost in recently hospitalized high-risk patients with CHF.

Long-Term Effects on Clinical Outcomes of Aggressive Lowering of Low-Density Lipoprotein Cholesterol Levels and Low-Dose Anticoagulation in the Post Coronary Artery Bypass Graft Trial

Background —The Post Coronary Artery Bypass Graft Trial, designed to compare the effects of 2 lipid-lowering regimens and low-dose anticoagulation versus placebo on progression of atherosclerosis in saphenous vein grafts of patients who had had CABG surgery, demonstrated that aggressive lowering of LDL cholesterol (LDL-C) levels to <100 mg/dL compared with a moderate reduction to 132 to 136 mg/dL decreased the progression of atherosclerosis in grafts. Low-dose anticoagulation did not significantly affect progression. Methods and Results —Approximately 3 years after the last trial visit, Clinical Center Coordinators contacted each patient by telephone to ascertain the occurrence of cardiovascular events and procedures. The National Death Index was used to ascertain vital status for patients who could not be contacted. Vital status was established for all but 3 of 1351 patients. Information on nonfatal events was available for 95% of surviving patients. A 30% reduction in revascularization procedures and 24% reduction in a composite clinical end point were observed in patients assigned to aggressive strategy compared with patients assigned to moderate strategy during 7.5 years of follow-up, P =0. 0006 and 0.001, respectively. Reductions of 35% in deaths and 31% in deaths or myocardial infarctions with low-dose anticoagulation compared with placebo were also observed, P =0.008 and 0.003, respectively. Conclusions —The long-term clinical benefit observed during extended follow-up in patients assigned to the aggressive strategy is consistent with the angiographic findings of delayed atherosclerosis progression in grafts observed during the trial. The apparent long-term benefit of low-dose warfarin remains unexplained.

Six- and twelve-month follow-up of the Phase I Thrombolysis in Myocardial Infarction (TIMI) trial

The Thrombolysis in Myocardial Infarction (TIMI) trial Phase I was designed to compare the efficacy and side effects of intravenous recombinant tissue-type plasminogen activator (rt-PA) and intravenous streptokinase (SK) in patients with acute myocardial infarction (AMI). As previously reported, rt-PA led to a reperfusion rate of 62% of totally occluded coronary arteries compared with 31% for SK (p less than 0.001). This study was not designed to determine if intravenous thrombolytic therapy decreases the mortality of AMI; however, the findings in these patients after 1 year of follow-up do permit certain insights into the impact of early reperfusion and reocclusion on the clinical course of patients with AMI. The mortality rate at 6 and 12 months was not significantly different in patients treated with rt-PA compared with SK (7.7% and 10.5% rt-PA vs 9.5% and 11.6% for SK). The frequency of recurrent AMI, coronary artery bypass grafting (CABG) and percutaneous transluminal coronary angioplasty (PTCA) was similar in the 2 treatment groups. There was no significant difference in 6- and 12-month mortality or in the rate of recurrent AMI in patients who received thrombolytic therapy before compared with after 4 hours of the onset of AMI symptoms. When the results were analyzed on the basis of the patency of the infarct-related artery, irrespective of thrombolytic agent used, for those patients with patent arteries 90 minutes after the initiation of therapy, there was a trend toward a lower 6-month (5.6% vs 12.5%) and 12-month mortality (8.1% vs 14.8%) (p = 0.07).(ABSTRACT TRUNCATED AT 250 WORDS)

Asymptomatic Cardiac Ischemia Pilot (ACIP) study : outcome at 1 year for patients with asymptomatic cardiac ischemia randomized to medical therapy or revascularization

OBJECTIVES This report discusses the outcome at 1 year in patients in the Asymptomatic Cardiac Ischemia Pilot (ACIP) study. BACKGROUND Comparative efficacy of medical therapy versus revascularization in treatment of asymptomatic ischemia is unknown. The ACIP study assessed the ability of three treatment strategies to suppress ambulatory electrocardiographic (ECG) ischemia to determine whether a large-scale trial studying the impact of these strategies on clinical outcomes was feasible. METHODS Five hundred fifty-eight patients with coronary anatomy amenable to revascularization, at least one episode of asymptomatic ischemia on the 48-h ambulatory ECG and ischemia on treadmill exercise testing were randomized to one of three treatment strategies: 1) medication to suppress angina (angina-guided strategy, n = 183); 2) medication to suppress both angina and ambulatory ECG ischemia (ischemia-guided strategy, n = 183); or 3) revascularization strategy (angioplasty or bypass surgery, n = 192). Medication was titrated atenolol-nifedipine or diltiazem-isosorbide dinitrate. RESULTS The revascularization group received less medication and had less ischemia on serial ambulatory ECG recordings and exercise testing than those assigned to the medical strategies. The ischemia-guided group received more medication but had suppression of ischemia similar to the angina-guided group. At 1 year, the mortality rate was 4.4% in the angina-guided group (8 of 183), 1.6% in the ischemia-guided group (3 of 183) and 0% in the revascularization group (overall, p = 0.004; angina-guided vs. revascularization, p = 0.003; other pairwise comparisons, p = NS). Frequency of myocardial infarction, unstable angina, stroke and congestive heart failure was not significantly different among the three strategies. The revascularization group had significantly fewer hospital admissions and nonprotocol revascularizations at 1 year. The incidence of death, myocardial infarction, nonprotocol revascularization or hospital admissions at 1 year was 32% with the angina-guided medical strategy, 31% with the ischemia-guided medical strategy and 18% with the revascularization strategy (p = 0.003). CONCLUSIONS After 1 year, revascularization was superior to both angina-guided and ischemia-guided medical strategies in suppressing asymptomatic ischemia and was associated with better outcome. These findings require confirmation by a larger scale trial.

Randomized Trial of Percutaneous Coronary Intervention for Subacute Infarct-Related Coronary Artery Occlusion to Achieve Long-Term Patency and Improve Ventricular Function. The Total Occlusion Study of Canada (TOSCA)-2 Trial

Background— In the present study, we sought to determine whether opening a persistently occluded infarct-related artery (IRA) by percutaneous coronary intervention (PCI) in patients beyond the acute phase of myocardial infarction (MI) improves patency and indices of left ventricular (LV) size and function. Methods and Results— Between May 2000 and July 2005, 381 patients with an occluded native IRA 3 to 28 days after MI (median 10 days) were randomized to PCI with stenting (PCI) or optimal medical therapy alone. Repeat coronary and LV angiography was performed 1 year after randomization (n=332, 87%). Coprimary end points were IRA patency and change in LV ejection fraction. Secondary end points included change in LV end-systolic and end-diastolic volume indices and wall motion. PCI was successful in 92%. At 1 year, 83% of PCI versus 25% of medical therapy–only patients had a patent IRA (P<0.001). LV ejection fraction increased significantly (P<0.001) in both groups, with no between-group difference: PCI 4.2±8.9 (n=150) versus medical therapy 3.5±8.2 (n=136; P=0.47). Median change (interquartile range) in LV end-systolic volume index was −0.5 (−9.3 to 5.0) versus 1.0 (−5.7 to 7.3) mL/m2 (P=0.10), whereas median change (interquartile range) in LV end-diastolic volume index was 3.2 (−8.2 to 13.3) versus 5.3 (−4.6 to 23.2) mL/m2 (P=0.07) in the PCI (n=86) and medical therapy–only (n=76) groups, respectively. Conclusions— PCI with stenting of a persistently occluded IRA in the subacute phase after MI effectively maintains long-term patency but has no effect on LV ejection fraction. On the basis of these findings and the lack of clinical benefit in the main Occluded Artery Trial, routine PCI is not recommended for stable patients with a persistently occluded IRA after MI.

Risk stratification before thrombolytic therapy in patients with acute myocardial infarction

Several studies in the prethrombolytic era on the treatment of acute myocardial infarction identified selected variables from the patients history, physical examination, chest roentgenogram and electrocardiogram that could be used to estimate mortality in patients with evolving infarction. To extend such assessment to patients receiving thrombolytic therapy, this study evaluated the prognostic utility of several risk factors in the 3,339 patients (2,742 men, 597 women, aged 24 to 78 years) enrolled in Phase II of the Thrombolysis in Myocardial Infarction (TIMI) trial. Before intravenous tissue plasminogen activator was given, the presence of each of eight risk factors was noted: age greater than or equal to 70 years, female gender, a history of diabetes mellitus or previous myocardial infarction, electrocardiographic evidence of evolving anterior infarction or atrial fibrillation, evidence on physical examination of mild pulmonary congestion or hypotension (systolic pressure less than 100 mm Hg) and sinus tachycardia (heart rate greater than 100 beats/min). Of the 3,339 patients, the 78 with pulmonary edema or cardiogenic shock were excluded because their risk was known to be high. Of the remaining 3,261, 864 (26%) had no risk factor (low risk); their mortality rate at 6 weeks was only 1.5%. In contrast, 2,397 (74%) had one or more risk factors (not low risk); of these, 5.3% died in 6 weeks (p less than 0.001). Among those with one or more risk factors, mortality at 6 weeks was related to the number of risk factors on admission; those with four or more had a mortality rate at 6 weeks of 17.2%. Thus, these eight risk factors can be easily remembered and assessed in patients with myocardial infarction who are candidates for thrombolytic therapy and can be used to estimate short-term mortality.

Left Ventricular, Peripheral Vascular, and Neurohumoral Responses to Mental Stress in Normal Middle-Aged Men and Women Reference Group for the Psychophysiological Investigations of Myocardial Ischemia (PIMI) Study

BACKGROUND The normal cardiovascular response to mental stress in middle-aged and older people has not been well characterized. METHODS AND RESULTS We studied 29 individuals 45 to 73 years old (15 women, 14 men) who had no coronary risk factors, no history of coronary artery disease, and a negative exercise test. Left ventricular (LV) volumes and global and regional function were assessed by radionuclide ventriculography at rest and during two 5-minute standardized mental stress tasks (simulated public speaking and the Stroop Color-Word Test), administered in random order. A substantial sympathetic response occurred with both mental stress tests, characterized by increases in blood pressure, heart rate, rate-pressure product, cardiac index, and stroke work index and rises in plasma levels of epinephrine and norepinephrine but not beta-endorphin or cortisol. Despite this sympathetic response, LV volume increased and ejection fraction (EF) decreased secondary to an increase in afterload. The change in EF during mental stress-varied among individuals but was associated positively with changes in LV contractility and negatively with baseline EF and changes in afterload. EF decreased > 5% during mental stress in 12 individuals and > 8% in 5; 3 developed regional wall motion abnormalities. CONCLUSIONS Mental stress in the laboratory results in a substantial sympathetic response in normal middle-aged and older men and women, but EF commonly falls because of a concomitant rise in afterload. These results provide essential age- and sex-matched reference data for studies of mental stress-induced ischemia in patients with coronary artery disease.