Aggressive lipid-lowering therapy compared with angioplasty in stable coronary artery disease. Atorvastatin versus Revascularization Treatment Investigators.

BACKGROUND: Percutaneous coronary revascularization is widely used in improving symptoms and exercise performance in patients with ischemic heart disease and stable angina pectoris. In this study, we compared percutaneous coronary revascularization with lipid-lowering treatment for reducing the incidence of ischemic events. METHODS: We studied 341 patients with stable coronary artery disease, relatively normal left ventricular function, asymptomatic or mild-to-moderate angina, and a serum level of low-density lipoprotein (LDL) cholesterol of at least 115 mg per deciliter (3.0 mmol per liter) who were referred for percutaneous revascularization. We randomly assigned the patients either to receive medical treatment with atorvastatin, at 80 mg per day (164 patients), or to undergo the recommended percutaneous revascularization procedure (angioplasty) followed by usual care, which could include lipid-lowering treatment (177 patients). The follow-up period was 18 months. RESULTS: Twenty-two (13 percent) of the patients who received aggressive lipid-lowering treatment with atorvastatin (resulting in a 46 percent reduction in the mean serum LDL cholesterol level, to 77 mg per deciliter [2.0 mmol per liter]) had ischemic events, as compared with 37 (21 percent) of the patients who underwent angioplasty (who had an 18 percent reduction in the mean serum LDL cholesterol level, to 119 mg per deciliter [3.0 mmol per liter]). The incidence of ischemic events was thus 36 percent lower in the atorvastatin group over an 18-month period (P=0.048, which was not statistically significant after adjustment for interim analyses). This reduction in events was due to a smaller number of angioplasty procedures, coronary-artery bypass operations, and hospitalizations for worsening angina. As compared with the patients who were treated with angioplasty and usual care, the patients who received atorvastatin had a significantly longer time to the first ischemic event (P=0.03). CONCLUSIONS: In low-risk patients with stable coronary artery disease, aggressive lipid-lowering therapy is at least as effective as angioplasty and usual care in reducing the incidence of ischemic events.     

Long-term follow-up after percutaneous transluminal coronary angioplasty. The early Zurich experience

The first 169 patients in whom percutaneous transluminal coronary angioplasty was performed have now been followed for five to eight years. The procedure was technically successful in 133 patients (79 percent). In the follow-up period, nine of the 133 patients died (five of cardiac disease), and actuarial cardiac survival was 96 percent at six years. All patients were symptomatic before angioplasty, but 67 percent of the 133 who had technically successful procedures were asymptomatic at the last follow-up evaluation. Exercise stress testing, positive in 97 percent before angioplasty, was positive at the last follow-up study in only 10 percent of the patients who had technically successful procedures. Stenosis recurred during the first six months in 30 percent of the patients, and six more recurrences were observed among the 41 patients who had follow-up angiograms at two to seven years. A second angioplasty was required in 27 patients, and coronary bypass surgery was subsequently needed in 19. Actuarial event-free survival (freedom from death, myocardial infarction, and coronary bypass surgery) was 79 percent at six years. Follow-up of patients with multivessel disease showed a higher mortality from cardiac causes and a lower rate of long-term success than occurred among patients with single-vessel disease. These long-term results indicate that most episodes of restenosis occurred within six months of angioplasty, but some late recurrences were seen. Patients with single-vessel disease had a better long-term outcome after angioplasty than those with multivessel disease.     

Transmyocardial revascularization with a carbon dioxide laser in patients with end-stage coronary artery disease.

BACKGROUND: The construction of subendocardial channels to perfuse ischemic areas of the myocardium has been investigated since the 1950s. We assessed the safety and efficacy of transmyocardial revascularization with a carbon dioxide laser in patients with refractory angina and left ventricular free-wall ischemia that was not amenable to direct coronary revascularization. METHODS: In a prospective, controlled, multicenter trial, we randomly assigned 91 patients to undergo transmyocardial revascularization and 101 patients to receive continued medical treatment. The severity of angina (according to the Canadian Cardiovascular Society [CCS] classification), quality of life, and cardiac perfusion (as assessed by thallium-201 scanning) were evaluated at base line and 3, 6, and 12 months after randomization. RESULTS: At 12 months, angina had improved by at least two CCS classes in 72 percent of the patients assigned to transmyocardial revascularization, as compared with 13 percent of the patients assigned to medical treatment who continued medical treatment (P<0.001). Patients in the transmyocardial-revascularization group also had a significantly improved quality of life as compared with the medical-treatment group. Myocardial perfusion improved by 20 percent in the transmyocardial-revascularization group and worsened by 27 percent in the medical-treatment group (P=0.002). In the first year of follow-up, 2 percent of patients assigned to undergo transmyocardial revascularization were hospitalized because of unstable angina, as compared with 69 percent of patients assigned to medical treatment (P<0.001). The perioperative mortality rate associated with transmyocardial revascularization was 3 percent. The rate of survival at 12 months was 85 percent in the transmyocardial-revascularization group and 79 percent in the medical-treatment group (P=0.50). CONCLUSIONS: In patients with angina refractory to medical treatment and coronary artery disease that precluded coronary-artery bypass surgery or percutaneous transluminal coronary angioplasty, transmyocardial revascularization improved cardiac perfusion and clinical status over a 12-month period.     

Abnormal coronary vasoconstriction as a predictor of restenosis after successful coronary angioplasty in patients with unstable angina pectoris

BACKGROUND. High rates of restenosis after coronary angioplasty have been reported in patients with vasospastic angina. This study was designed to determine whether the occurrence of abnormal coronary vasoconstriction, detected by means of hyperventilation testing before angioplasty, influences the risk of restenosis after successful dilation. METHODS. Hyperventilation testing was performed 0 to 4 days before coronary angioplasty in 106 consecutive patients with unstable angina and single-vessel coronary artery disease. Abnormal coronary vasoconstriction was considered present if hyperventilation-induced myocardial ischemia occurred during the recovery phase of the test. All patients had follow-up angiography 8 to 12 months after angioplasty. RESULTS. Abnormal coronary vasoconstriction was observed in 48 patients (group 1), whereas 58 patients (group 2) had either a negative response throughout the test or a positive response only during the overbreathing phase of the hyperventilation test. Angioplasty was successful in 40 patients in group 1 and 51 in group 2. Restenosis was documented in 29 patients (73 percent) in group 1 and 13 (25 percent) in group 2 (relative risk of restenosis, 2.84; 95 percent confidence interval, 1.69 to 4.28; P less than 0.001). In a multivariate analysis, the following three characteristics were independently related to the risk of restenosis (in descending order of importance): ST-segment elevation during spontaneous ischemic attacks (P less than 0.001), hyperventilation-induced abnormal coronary vasoconstriction (P less than 0.001), and the presence of a lesion more than 10 mm long in the left anterior descending coronary artery (P less than 0.05). CONCLUSIONS. In patients with unstable angina and single-vessel coronary artery disease who have been selected for coronary angioplasty, the presence of hyperventilation-induced abnormal coronary vasoconstriction identifies a subgroup at high risk for restenosis.     

Comparison of transmyocardial revascularization with medical therapy in patients with refractory angina.

BACKGROUND: Transmyocardial revascularization involves the creation of channels in the myocardium with a laser to relieve angina. We compared the safety and efficacy of transmyocardial revascularization performed with a holmium laser with those of medical therapy in patients with refractory class IV angina (according to the criteria of the Canadian Cardiovascular Society). METHODS: In a prospective study conducted between March 1996 and July 1998 at 18 centers, 275 patients with medically refractory class IV angina and coronary disease that could not be treated with percutaneous or surgical revascularization were randomly assigned to receive transmyocardial revascularization followed by continued medical therapy (132 patients) or medical therapy alone (143 patients). RESULTS: After one year of follow-up, 76 percent of the patients who had undergone transmyocardial revascularization had improvement in angina (a reduction of two or more classes), as compared with 32 percent of the patients who received medical therapy alone (P<0.001). Kaplan-Meier survival estimates at one year (based on an intention-to-treat analysis) were similar for the patients assigned to undergo transmyocardial revascularization and those assigned to receive medical therapy alone (84 percent and 89 percent, respectively; P=0.23). At one year, the patients in the transmyocardial-revascularization group had a significantly higher rate of survival free of cardiac events (54 percent, vs. 31 percent in the medical-therapy group; P<0.001), a significantly higher rate of freedom from treatment failure (73 percent vs. 47 percent, P<0.001), and a significantly higher rate of freedom from cardiac-related rehospitalization (61 percent vs. 33 percent, P<0.001). Exercise tolerance and quality-of-life scores were also significantly higher in the transmyocardial-revascularization group than in the medical-therapy group (exercise tolerance, 5.0 MET [metabolic equivalent] vs. 3.9 MET; P=0.05); quality-of-life score, 21 vs. 12; P=0.003). However, there were no differences in myocardial perfusion between the two groups, as assessed by thallium scanning. CONCLUSIONS: Patients with refractory angina who underwent transmyocardial revascularization and received continued medical therapy, as compared with similar patients who received medical therapy alone, had a significantly better outcome with respect to improvement in angina, survival free of cardiac events, freedom from treatment failure, and freedom from cardiac-related rehospitalization.     

Emergency coronary angioplasty in refractory unstable angina

We performed percutaneous transluminal coronary angioplasty as an emergency procedure in 60 patients with unstable angina pectoris that was refractory to treatment with maximally tolerated doses of beta-blockers, calcium antagonists, and intravenous nitroglycerin. The initial success rate for angioplasty was 93 per cent (56 patients). There were no deaths related to the procedure, although total occlusion occurred in four patients. Despite emergency bypass grafting, all four sustained a myocardial infarction. All the patients were followed for at least six months. Late cardiac death occurred in one patient, whereas eight had recurrent angina pectoris. There was no progression to myocardial infarction. The restenosis rate was 28 per cent (13 of 46) in the patients with initially successful coronary angioplasty who had repeat angiography. Improved cardiac functional status after sustained successful coronary angioplasty was demonstrated by an almost normal capacity on bicycle exercise testing and the absence of ischemia during thallium isotope studies in 80 per cent. We conclude that emergency percutaneous transluminal coronary angioplasty may be useful for the treatment of selected patients with unstable angina pectoris who are unresponsive to intensive pharmacologic treatment.     

Long-term benefit of primary angioplasty as compared with thrombolytic therapy for acute myocardial infarction.

BACKGROUND: As compared with thrombolytic therapy, primary coronary angioplasty results in a higher rate of patency of the infarct-related coronary artery, lower rates of stroke and reinfarction, and higher in-hospital or 30-day survival rates. However, the comparative long-term efficacy of these two approaches has not been carefully studied. METHODS: We randomly assigned a total of 395 patients with acute myocardial infarction to treatment with angioplasty or intravenous streptokinase. Clinical information was collected for a mean (+/-SD) of 5+/-2 years, and medical charges associated with the two treatments were compared. RESULTS: A total of 194 patients were assigned to undergo primary angioplasty, and 201 to receive streptokinase. Mortality was 13 percent in the angioplasty group, as compared with 24 percent in the streptokinase group (relative risk, 0.54; 95 percent confidence interval, 0.36 to 0.87). Nonfatal reinfarction occurred in 6 percent and 22 percent of the two groups, respectively (relative risk, 0.27; 95 percent confidence interval, 0.15 to 0.52). The combined incidence of death and nonfatal reinfarction was also lower among patients assigned to angioplasty than among those assigned to streptokinase, with a relative risk of 0.13 (95 percent confidence interval, 0.05 to 0.37) for early events (within the first 30 days) and a relative risk of 0.62 (95 percent confidence interval, 0.43 to 0.91) for late events (after 30 days). The rates of readmission for heart failure and ischemia were also lower among patients in the angioplasty group than among patients in the streptokinase group. Total medical charges per patient were lower in the angioplasty group (16,090 dollars) than in the streptokinase group (16,813 dollars, P=0.05). CONCLUSIONS: During five years of follow-up, primary coronary angioplasty for acute myocardial infarction was associated with lower rates of early and late death and nonfatal reinfarction, fewer hospital readmissions for ischemia or heart failure, and lower total medical charges than treatment with intravenous streptokinase.     

Coronary angioplasty with or without stent implantation for acute myocardial infarction. Stent Primary Angioplasty in Myocardial Infarction Study Group

BACKGROUND: Coronary-stent implantation is frequently performed for treatment of acute myocardial infarction. However, few studies have compared stent implantation with primary angioplasty alone. METHODS: We designed a multicenter study to compare primary angioplasty with angioplasty accompanied by implantation of a heparin-coated Palmaz-Schatz stent. Patients with acute myocardial infarction underwent emergency catheterization and angioplasty. Those with vessels suitable for stenting were randomly assigned to undergo angioplasty with stenting (452 patients) or angioplasty alone (448 patients). RESULTS: The mean (+/-SD) minimal luminal diameter was larger after stenting than after angioplasty alone (2.56+/-0.44 mm vs. 2.12+/-0.45 mm, P<0.001), although fewer patients assigned to stenting had grade 3 blood flow (according to the classification of the Thrombolysis in Myocardial Infarction trial) (89.4 percent, vs. 92.7 percent in the angioplasty group; P=0.10). After six months, fewer patients in the stent group than in the angioplasty group had angina (11.3 percent vs. 16.9 percent, P=0.02) or needed target-vessel revascularization because of ischemia (7.7 percent vs. 17.0 percent, P<0.001). In addition, the combined primary end point of death, reinfarction, disabling stroke, or target-vessel revascularization because of ischemia occurred in fewer patients in the stent group than in the angioplasty group (12.6 percent vs. 20.1 percent, P<0.01). The decrease in the combined end point was due entirely to the decreased need for target-vessel revascularization. The six-month mortality rates were 4.2 percent in the stent group and 2.7 percent in the angioplasty group (P=0.27). Angiographic follow-up at 6.5 months demonstrated a lower incidence of restenosis in the stent group than in the angioplasty group (20.3 percent vs. 33.5 percent, P<0.001). CONCLUSIONS: In patients with acute myocardial infarction, routine implantation of a stent has clinical benefits beyond those of primary coronary angioplasty alone.     

Psychologic predictors of psychosocial and medical outcomes in patients undergoing coronary angioplasty

The relationship between psychologic variables (the match between repressive style and level of cardiac information, and anxiety level) and medical complications, re-stenosis (renarrowing), and psychosocial adjustment was studied in 97 patients undergoing percutaneous transluminal coronary angioplasty (PTCA) for treatment of narrowed coronary arteries. Three major findings emerged for outcomes measured 6 months after PTCA: repressors with a high level of cardiac information (coping style-information level mismatch) and no history of heart attack were at higher risk for late medical complications (p less than 0.001); sensitizers with a low level of cardiac information (coping style-information level mismatch) and whose PTCA was only moderately successful were at higher risk for re-stenosis of the artery previously widened during PTCA (p less than 0.01); and patients who were more anxious during hospitalization had poorer social functioning and more mood disturbance 6 months after PTCA (p less than 0.05). Thus, psychologic, information, and medical factors are important in predicting 6-month outcomes in patients undergoing PTCA.     

Functional characteristics of coronary vasomotor function following intramyocardial gene therapy with naked DNA encoding for vascular endothelial growth factor165.

Vascular endothelial growth factor (VEGF) is a potent angiogenic factor. VEGF gene therapy improves perfusion of ischemic myocardium in experimental models and possibly in patients with end-stage coronary artery disease. In addition to its proliferative and migratory effect on endothelial cells, it also activates and up-regulates endothelial nitric oxide synthase (eNOS). Therefore, the authors investigated coronary endothelium-dependent vasodilatation in patients before and after VEGF gene therapy. The effect of intracoronary acetylcholine infusion on coronary diameter was assessed at baseline and after 3 months follow-up in patients with end-stage coronary artery disease treated with VEGF gene and in controls scheduled for elective percutaneous transluminal coronary angioplasty (PTCA) (acetylcholine test at diagnostic angiography and before a subsequently scheduled PTCA). Five out of six VEGF patients experienced a reduction in anginal complaints. Angiographic evidence for improved collateral filling was evident in two out of six patients. The vasoconstrictive response to acetylcholine was partly converted into dilatation. In contrast, the acetylcholine response in control patients remained vasoconstrictive. In conclusion, VEGF gene therapy has an important beneficial effect on the functional characteristics of the myocardial vascular network. Therefore, this therapy can potentially play an important role in all stages of the atherosclerotic process.     

T lymphocyte activation and restenosis after percutaneous transluminal coronary angioplasty.

We investigated the relation between the activation of T lymphocytes and the occurrence of restenosis after percutaneous transluminal coronary angioplasty (PTCA) in 10 stable angina patients. Recent studies have suggested that PTCA causes an inflammatory response, which may affect restenosis after angioplasty. Soluble interleukin-2 receptor (sIL-2R) is a useful marker to evaluate the activation of T lymphocytes. sIL-2R was measured before and 2 h after successful PTCA, and 3-month follow-up coronary angiography was done to observe restenosis. Four of 10 patients showed restenosis. The restenosis group of 4 patients had a higher level of sIL-2R after PTCA than the no-restenosis group of 6 patients (495 vs. 274 U/ml, p < 0.01). This study suggests that sIL-2R may offer prognostic information after elective PTCA and identify a subgroup of patients at high risk for clinical restenosis in a few months.     

Underuse of coronary revascularization procedures in patients considered appropriate candidates for revascularization

BACKGROUND: Ratings by an expert panel of the appropriateness of treatments may offer better guidance for clinical practice than the variable decisions of individual clinicians, yet there have been no prospective studies of clinical outcomes. We compared the clinical outcomes of patients treated medically after angiography with those of patients who underwent revascularization, within groups defined by ratings of the degree of appropriateness of revascularization in varying clinical circumstances. METHODS: This was a prospective study of consecutive patients undergoing coronary angiography at three London hospitals. Before patients were recruited, a nine-member expert panel rated the appropriateness of percutaneous transluminal coronary angioplasty (PTCA) and coronary-artery bypass grafting (CABG) on a nine-point scale (with 1 denoting highly inappropriate and 9 denoting highly appropriate) for specific clinical indications. These ratings were then applied to a population of patients with coronary artery disease. However, the patients were treated without regard to the ratings. A total of 2552 patients were followed for a median of 30 months after angiography. RESULTS: Of 908 patients with indications for which PTCA was rated appropriate (score, 7 to 9), 34 percent were treated medically; these patients were more likely to have angina at follow-up than those who underwent PTCA (odds ratio, 1.97; 95 percent confidence interval, 1.29 to 3.00). Of 1353 patients with indications for which CABG was considered appropriate, 26 percent were treated medically; they were more likely than those who underwent CABG to die or have a nonfatal myocardial infarction--the composite primary outcome (hazard ratio, 4.08; 95 percent confidence interval, 2.82 to 5.93)--and to have angina (odds ratio, 3.03; 95 percent confidence interval, 2.08 to 4.42). Furthermore, there was a graded relation between rating and outcome over the entire scale of appropriateness (P for linear trend=0.002). CONCLUSIONS: On the basis of the ratings of the expert panel, we identified substantial underuse of coronary revascularization among patients who were considered appropriate candidates for these procedures. Underuse was associated with adverse clinical outcomes.     

The effect of previous coronary-artery bypass surgery on the prognosis of patients with diabetes who have acute myocardial infarction. Bypass Angioplasty Revascularization Investigation Investigators

BACKGROUND: Acute myocardial infarction in patients with diabetes is associated with high mortality. We studied whether previous revascularization by coronary-artery bypass grafting (CABG), as compared with percutaneous transluminal coronary angioplasty (PTCA), influences the prognosis in such patients. METHODS: We classified all patients eligible for the Bypass Angioplasty Revascularization Investigation who underwent coronary revascularization within three months after entry into the study according to whether they had diabetes and whether they had undergone CABG, either initially or after PTCA. The protective effect of CABG with regard to mortality in the presence and in the absence of subsequent spontaneous Q-wave myocardial infarction was estimated with the use of Cox regression models. RESULTS: Among the 641 patients with diabetes and the 2962 without diabetes, the cumulative five-year rates of death were 20 percent and 8 percent, respectively (P<0.001), and the five-year rates of spontaneous Q-wave myocardial infarction were 8 percent and 4 percent (P<0.001). CABG greatly reduced the risk of death after spontaneous Q-wave myocardial infarction in the patients with diabetes (relative risk, 0.09; 95 percent confidence interval, 0.03 to 0.29). Among patients with diabetes who had undergone CABG but did not have spontaneous Q-wave myocardial infarctions, the corresponding relative risk of death was 0.65 (95 percent confidence interval, 0.45 to 0.94). Among the patients without diabetes, no protective effect of CABG was evident. CONCLUSIONS: Among patients with diabetes, previous coronary bypass surgery, as compared with coronary angioplasty, has a highly favorable influence on prognosis after acute myocardial infarction and a smaller beneficial effect among patients who do not have infarction. These findings should influence the type of coronary revascularization procedure selected for patients with diabetes who have multivessel coronary artery disease.     

Coronary bypass for stable angina: a prospective randomized study.

To evaluate the effects of coronary-artery bypass, 100 patients with stable, disabling angina were randomized to medical (49) or surgical (51) therapy. There was no statistical difference in major cardiac events after three years (death in five medical vs. four surgical, infarction in eight vs. 10, and unstable angina requiring operation or reoperation in eight vs. three cases). Surgical patients with three-vessel disease had fewer major events (P less than 0.05) than the comparable medical group and less unstable angina requiring operation (P less than 0.02). All unstable angina was less frequent in the surgical group (15 vs. six, P less than 0.01). Functional classification improved more in surgical patients at six months (P less than 0.01) and at late followup examination (P less than 0.05). After six months, surgical patients achieved significantly higher exercise work loads (P less than 0.01), exercise heart rates (P less than 0.05), maximum paced heart rates (P less than 0.01) and myocardial lactate extraction (P less than 0.01). On the basis of this interim report of a relatively small group of patients, we conclude that bypass results in greater functional improvement and less unstable angina than medical therapy. The likelihood of death and myocardial infarction is unchanged by operation.     

Technical achievement: transthoracic Doppler echocardiography can be used to detect LAD restenosis after coronary angioplasty.

We investigated the capability of transthoracic Doppler echocardiography (TTE) to detect and quantify the severity of restenosis in the left anterior descending coronary artery (LAD) after percutaneous transluminal coronary angioplasty (PTCA). We studied 10 consecutive patients assigned for quantitative coronary angiography (qCA) due to a recurrent angina pectoris after PTCA of the LAD. The LAD was visualized by TTE, and the presence of local turbulence and an increase in the blood flow velocity was regarded to indicate coronary stenosis. To assess the severity of the stenosis, the increase of blood flow velocity was measured. Angiography showed stenoses of various degrees (27-100%) in all patients. All stenoses were detectable using TTE. Moreover, the ratio of maximal blood flow velocity at the site of stenosis to the pre-stenotic blood flow velocity (M/P-ratio) correlated significantly with the reduction of the luminal diameter of LAD (r = 0.85, P < 0.003). A M/P-ratio higher than 3.0 predicted a diameter reduction of 50% or higher with sensitivity and specificity of 100% in patients with a subtotal stenosis (n = 9). Our results indicate that stenoses in the LAD could be found and the severity of the stenoses could be quantified reliably with TTE. This approach is totally non-invasive and less expensive than coronary angiography and can be used clinically in clarifying restenosis after coronary angioplasty.     

Aspirin and dipyridamole in the prevention of restenosis after percutaneous transluminal coronary angioplasty

To examine the role of antiplatelet therapy in the prevention of arterial restenosis after percutaneous transluminal coronary angioplasty (PTCA), we conducted a randomized, double-blind, placebo-controlled study in 376 patients. The active treatment consisted of an oral aspirin-dipyridamole combination (330 mg-75 mg) given three times daily, beginning 24 hours before PTCA. Eight hours before PTCA, the oral dipyridamole was replaced with intravenous dipyridamole at a dosage of 10 mg per hour for 24 hours, and oral aspirin was continued. Sixteen hours after PTCA, the initial combination was reinstituted. Treatment was continued in patients with a successfully dilated vessel until follow-up angiography four to seven months after PTCA--or earlier, if symptoms dictated. Of 249 patients who underwent follow-up angiography, 37.7 percent of patients receiving the active drug had restenosis in at least one segment, as compared with 38.6 percent of patients taking placebo (P not significant). The number of stenotic segments was virtually the same in the two groups. Among the 376 randomized patients, there were 16 periprocedural Q-wave myocardial infarctions--13 in the placebo group and 3 in the active-drug group (6.9 percent vs. 1.6 percent, P = 0.0113). Although the use of this antiplatelet regimen before and after PTCA did not reduce the six-month rate of restenosis after successful coronary angioplasty, it markedly reduced the incidence of transmural myocardial infarction during or soon after PTCA. Thus, the short-term use of antiplatelet agents in relation to PTCA can be recommended.     

Acute hemodynamic effects of carvedilol in comparison with propranolol in patients with coronary heart disease

In a randomized, double-blind study oral doses of 50 mg carvedilol (Dilatrend) were compared with 40 mg propranolol in 16 male patients with coronary heart disease, CHD [12 without significant stenoses following percutaneous transluminal coronary angioplasty (PTCA), 4 with multivessel disease]. Bicycle ergometry in the supine position was performed before and 80 min after drug application; measurements were done at rest, during and after exercise. Clinically, the total exercise time and the onset of angina and exhaustion were noted, while the investigated hemodynamic parameters were heart rate, systemic and pulmonary pressures and resistances, cardiac index, and lower limb blood flow. Clinically, carvedilol improved the exercise tolerance more than propranolol as regards angina and exhaustion. Hemodynamically, carvedilol did not lead, as the classic betablocker propranolol does, to an increase in systemic or pulmonary resistance, to a decrease in cardiac output, or to an increase of the pulmonary capillary wedge pressure during exercise, but instead caused opposite changes. In contrast to propranolol, the post exercise lower limb blood flow had increased significantly. The differences in action between the two betablockers can be explained by the vasodilating properties of carvedilol. Due to these acute effects, carvedilol may be preferred to propranolol in the treatment of CHD patients with hypertension, peripheral occlusive artery disease, and/or coronary vasospasm.     

Twelve-year follow-up of survival in the randomized European Coronary Surgery Study

We studied survival rates among 767 men with good left ventricular function who participated in the European Coronary Surgery Study, 10 to 12 years after they were randomly assigned to either early coronary bypass surgery or medical therapy. At the projected five-year follow-up interval, we observed a significantly higher survival rate (+/- 95 percent confidence interval) in the group that was assigned to surgical treatment than in the group assigned to medical treatment (92.4 +/- 2.7 vs. 83.1 +/- 3.9 percent; P = 0.0001). During the subsequent seven years, the percentage of patients who survived decreased more rapidly in the surgically treated than in the medically treated group (70.6 +/- 5.8 vs. 66.7 +/- 5.3 percent at 12 years). Thus, the improvement in the survival rate among patients with stable angina who were treated surgically appears to have been attenuated after five years. However, the gradually diminishing difference between the two survival curves still favored surgical treatment after 12 years (P = 0.04), despite the fact that 136 patients in the medically treated group had coronary bypass surgery and 23 in the "surgically treated" group did not. The benefit of surgical treatment tended to be greater, but not significantly so, as assessed by interaction analysis in the subgroups of patients who were older or who had signs of ischemia or previous infarction on the resting electrocardiogram, a markedly ischemic response to exercise testing, peripheral arterial disease, an absence of hypertension, and proximal obstruction in the left anterior descending artery. The reasons for the loss of a beneficial effect of surgery after five years are unknown and merit further study.     

Comparison of early invasive and conservative strategies in patients with unstable coronary syndromes treated with the glycoprotein IIb/IIIa inhibitor tirofiban.

BACKGROUND: There is continued debate as to whether a routine, early invasive strategy is superior to a conservative strategy for the management of unstable angina and myocardial infarction without ST-segment elevation. METHODS: We enrolled 2220 patients with unstable angina and myocardial infarction without ST-segment elevation who had electrocardiographic evidence of changes in the ST segment or T wave, elevated levels of cardiac markers, a history of coronary artery disease, or all three findings. All patients were treated with aspirin, heparin, and the glycoprotein IIb/IIIa inhibitor tirofiban. They were randomly assigned to an early invasive strategy, which included routine catheterization within 4 to 48 hours and revascularization as appropriate, or to a more conservative (selectively invasive) strategy, in which catheterization was performed only if the patient had objective evidence of recurrent ischemia or an abnormal stress test. The primary end point was a composite of death, nonfatal myocardial infarction, and rehospitalization for an acute coronary syndrome at six months. RESULTS: At six months, the rate of the primary end point was 15.9 percent with use of the early invasive strategy and 19.4 percent with use of the conservative strategy (odds ratio, 0.78; 95 percent confidence interval, 0.62 to 0.97; P=0.025). The rate of death or nonfatal myocardial infarction at six months was similarly reduced (7.3 percent vs. 9.5 percent; odds ratio, 0.74; 95 percent confidence interval, 0.54 to 1.00; P<0.05). CONCLUSIONS: In patients with unstable angina and myocardial infarction without ST-segment elevation who were treated with the glycoprotein IIb/IIIa inhibitor tirofiban, the use of an early invasive strategy significantly reduced the incidence of major cardiac events. These data support a policy involving broader use of the early inhibition of glycoprotein IIb/IIIa in combination with an early invasive strategy in such patients.     

Percutaneous transluminal coronary angioplasty of focal coronary lesions after cardiac transplantation

Summary Transplant coronary artery disease is the greatest impediment to long-term survival beyond the first year after cardiac transplantation. Transplant coronary artery disease shows a heterogeneous angiographic appearance, but focal stenoses can occur alone or at least predominate. Based on an angiographic indication 35 critical focal lesions causing narrowing by 75% or more were treated by PTCA during 23 procedures in seven patients 18–84 months after cardiac transplantation. Three patients each underwent only one procedure and four underwent repeated procedures [2, 3, 4 and 11, respectively]. Primary success was achieved without any complication in 35 of 35 lesions (100%). The mean degree of stenosis was reduced from 86±9% to 28±17% (P<0.001). The rate of restenosis was 18/29 (62%) at a mean of 4 months after angioplasty. Four patients are alive and free of adverse effects (symptoms, myocardial infarction, repeated percutaneous transluminal coronary angioplasty, retransplantation) 16±10 months after their last angioplasty. One patient underwent a successful second heart transplantation 26 months after the first angioplasty. Two patients died, 1 and 31 months after the last angioplasty. In conclusion, percutaneous transluminal coronary angioplasty can be performed safely with an excellent primary success rate in critical focal transplant coronary artery disease. The rate of restenosis is higher than in native coronary artery disease. Long-term follow-up depends on the individually variable accelerated nature of graft atherosclerosis.Abbreviations PTCA percutaneous transluminal coronary angioplasty - TxCAD transplant coronary artery disease - HTX heart transplantation - LAD left anterior decending artery - CFX circumflex artery - RCA right coronary artery