Cyclooxygenase-2--specific inhibitors and cardiorenal function: a randomized, controlled trial of celecoxib and rofecoxib in older hypertensive osteoarthritis patients.

BACKGROUND: Arthritis and hypertension are common comorbid conditions affecting elderly adults. Use of nonsteroidal anti-inflammatory drugs in patients treated with antihypertensive medication can lead to destabilization of blood pressure control and other cardiorenal events. The potential for similar interactions with cyclooxygenase-2-specific inhibitors has not been fully explored. The authors evaluated the cardiorenal safety of two new cyclooxygenase-2-specific inhibitors, celecoxib and rofecoxib. METHODS: This study was a 6-week, randomized, parallel-group, double-blind trial in patients with osteoarthritis who were > or =65 years of age and were taking antihypertensive agents. Patients received once-daily celecoxib 200 mg or rofecoxib 25 mg. The primary endpoints were the development of edema, changes in systolic blood pressure, and changes in diastolic blood pressure as measured at any time point in the study. Measurements occurred at baseline and after 1, 2, and 6 weeks of treatment. FINDINGS: Eight hundred ten patients received study medication (celecoxib, n = 411; rofecoxib, n = 399). Nearly twice as many rofecoxib- compared with celecoxib-treated patients experienced edema (9.5% vs. 4.9%, P = 0.014). Systolic blood pressure increased significantly in 17% of rofecoxib- compared with 11% of celecoxib-treated patients (P = 0.032) at any study time point. Diastolic blood pressure increased in 2.3% of rofecoxib- compared with 1.5% of celecoxib-treated patients (P = 0.44). At week 6, the change from baseline in mean systolic blood pressure was +2.6 mmHg for rofecoxib compared with -0.5 mmHg for celecoxib (P = 0.007). CONCLUSIONS: Patients taking antihypertensive therapy and receiving cyclooxygenase-2-specific inhibitors should be monitored for the development of cardiorenal events. Patients receiving celecoxib experienced less edema and less destabilization of blood pressure control compared with those receiving rofecoxib.

Comparison of medicine alone, coronary angioplasty, and left internal mammary artery-coronary artery bypass for one-vessel proximal left anterior descending coronary artery disease.

Despite the deleterious and sometimes catastrophic consequences of proximal left anterior descending (LAD) artery occlusion, there is a paucity of data to guide the treatment of patients with such disease. Our aim was to describe outcomes with medical therapy, angioplasty, or left internal mammary artery (LIMA) bypass grafting in patients with 1-vessel, proximal LAD disease. We retrospectively analyzed prospectively collected data from 1,188 patients first presenting only with proximal LAD disease at 1 center over 9 years. We assessed the rates of death, acute myocardial infarction, and repeat intervention by initial treatment over a median 5.7 years of follow-up. Patients undergoing angioplasty or LIMA bypass were more often men and had progressive or unstable angina; those receiving medical therapy had a lower median ejection fraction. Both revascularization procedures offered slightly better adjusted survival versus medicine (hazard ratio for angioplasty, 0.82; 95% confidence interval, 0.60 to 1.11; hazard ratio for bypass, 0.74; 95% confidence interval, 0.44 to 1.23). Bypass, but not angioplasty, was associated with significantly fewer composite end point events (death, infarction, or reintervention, p <0.0001), and angioplasty was associated with a higher composite event rate than bypass or medical therapy (p <0.0001 and p = 0.0003, respectively). The initial advantages of bypass and medicine over angioplasty diminished over time; angioplasty became more advantageous than medicine after 1 year (p = 0.05) and not significantly different from bypass. Treatment of 1-vessel, proximal LAD disease with medicine, angioplasty, or UMA bypass resulted in comparable adjusted survival. However, LIMA bypass alone reduced the long-term incidence of infarctions and repeat procedures.

Thrombolytic, antithrombin, and antiplatelet treatment of acute coronary syndromes.

Acute coronary syndromes are a major public health problem and the leading cause of death in the western world. Acute coronary syndromes consist of unstable angina pectoris, non-ST-segment-elevation myocardial infarction, and ST-segment-elevation myocardial infarction. These diseases represent a continuum of increasing severity and are pathophysiologically linked to intracoronary thrombus formation that is nonocclusive, transiently occlusive, or completely occlusive, respectively. Antiplatelet treatment with aspirin is the cornerstone of treatment for all acute coronary syndromes. Newer intravenous antiplatelet agents reduce 30-day mortality and myocardial infarction in unstable angina and non-ST-segment-elevation myocardial infarction. Adenosine diphosphate antagonist antiplatelet agents have an ill-defined role in the treatment of acute coronary syndromes. Fibrinolytic therapy has been shown to reduce mortality in ST-segment-elevation myocardial infarction but may pose a hazard in other acute coronary syndromes.

Adenosine as an adjunct to thrombolytic therapy for acute myocardial infarction: results of a multicenter, randomized, placebo-controlled trial: the Acute Myocardial Infarction STudy of ADenosine (AMISTAD) trial.

OBJECTIVES: The Acute Myocardial Infarction STudy of ADenosine (AMISTAD) trial was designed to test the hypothesis that adenosine as an adjunct to thrombolysis would reduce myocardial infarct size. BACKGROUND: Reperfusion therapy for acute myocardial infarction (MI) has been shown to reduce mortality, but reperfusion itself also may have deleterious effects. METHODS: The AMISTAD trial was a prospective, open-label trial of thrombolysis with randomization to adenosine or placebo in 236 patients within 6 h of infarction onset. The primary end point was infarct size as determined by Tc-99 m sestamibi single-photon emission computed tomography (SPECT) imaging 6+/-1 days after enrollment based on multivariable regression modeling to adjust for covariates. Secondary end points were myocardial salvage index and a composite of in-hospital clinical outcomes (death, reinfarction, shock, congestive heart failure or stroke). RESULTS: In all, 236 patients were enrolled. Final infarct size was assessed in 197 (83%) patients. There was a 33% relative reduction in infarct size (p = 0.03) with adenosine. There was a 67% relative reduction in infarct size in patients with anterior infarction (15% in the adenosine group vs. 45.5% in the placebo group) but no reduction in patients with infarcts located elsewhere (11.5% for both groups). Patients randomized to adenosine tended to reach the composite clinical end point more often than those assigned to placebo (22% vs. 16%; odds ratio, 1.43; 95% confidence interval, 0.71 to 2.89). CONCLUSIONS: Many agents thought to attenuate reperfusion injury have been unsuccessful in clinical investigation. In this study, adenosine resulted in a significant reduction in infarct size. These data support the need for a large clinical outcome trial.

Support for the open-artery hypothesis in survivors of acute myocardial infarction: analysis of 11,228 patients treated with thrombolytic therapy.

We examined the possible benefits of achieving and maintaining infarct-related artery potency beyond the time when preservation of left ventricular function would be expected. The open-artery hypothesis suggests that a patent infarct-related artery confers a survival benefit greater than that expected from myocardial salvage alone, which extends beyond the time when preservation of left ventricular function is expected. We examined the survival experience of patients undergoing thrombolysis in the Global Utilization of Streptokinase and TPA for Occluded Arteries (GUSTO-I) trial for whom data on the potency of the infarct artery were available. Univariable analysis was used to determine the unadjusted relations of angiographic variables and revascularization procedures to both 30-day and 1-year mortality in 30-day survivors. Multivariable analysis was used to test for interactions between patency and each characteristic and to adjust both for all other variables and for baseline characteristics known to predict mortality. In both univariable and multivariable analysis, patients with an open rather than a closed infarct-related artery had significantly lower 30-day mortality (p <0.001). This benefit cannot be accounted for by myocardial salvage alone, because it remained after adjustment for left ventricular ejection fraction. Patency was also associated with lower 1-year mortality in 30-day survivors, but not after adjustment for other variables affecting late mortality. Having an open infarct-related artery at the time of first catheterization confers a survival advantage that extends beyond the benefit of myocardial salvage from thrombolytic therapy, and is independent of ejection fraction.

Progression of renal artery stenosis in patients undergoing cardiac catheterization.

BACKGROUND: Renal artery stenosis is potentially correctable by either revascularization surgery or percutaneous methods. However, appropriate use of these techniques has been hampered by a lack of data on the natural history of this disease. This study assesses the prevalence, risk factors for progression, and effect on renal function of angiographically demonstrated renal artery disease in patients undergoing cardiac catheterization. METHODS: The severity of renal artery stenosis was quantified in all patients who underwent abdominal aortography as part of a diagnostic cardiac catheterization study at Duke University Medical Center between January 1989 and February 1996. RESULTS: There were 14,152 patients in the study (mean age 61+/-12 years, 62% male). Normal renal arteries were identified in 12,543 (88.7%) patients, insignificant disease (<50% stenosis) in 1 or more vessels in 726 patients (5.1 %), and significant stenosis in 883 patients (6.3%). Significant bilateral renal artery stenosis was present in 178 patients (1.3%). By multivariate logistic regression, elevated serum creatinine level, coronary artery disease, peripheral vascular disease, hypertension, cerebrovascular disease, older age, female sex, and family history of coronary artery disease were identified as independent predictors of significant renal arterial disease. Disease progression was assessed in 1189 patients. Mean time between cardiac catheterizations was 2.6+/-1.6 years. Significant disease progression occurred in 133 patients (11.1 %). Independent predictors of disease progression were female sex, age, coronary artery disease at baseline, and time between baseline and follow-up. At follow-up, serum creatinine level was significantly higher in patients who demonstrated > or =75% stenosis in 1 or more vessels (mean creatinine level 141+114 micromol/L compared with those with insignificant disease (mean creatinine level 97+/-44 micromol/L (P= .01). CONCLUSIONS: Renal artery disease is frequently progressive in patients who undergo cardiac catheterization for investigation of coronary artery disease. Significant stenotic disease may develop over a short period despite evidence of normal renal arteries at prior catheterization.

The natural history of single-vessel chronic coronary occlusion: a 25-year experience.

To determine the natural history of patients with a total occlusion of a single coronary artery, we searched the Duke Databank for Cardiovascular Disease to find all patients who underwent a first coronary angiogram >2 days after a symptomatic myocardial infarction between 1969 and 1994. Patients who underwent angiography >30 days after the acute event had a low risk of death in the first year (3%), and a proximal left anterior descending coronary occlusion did not confer substantially higher risk of death (4%). Patients undergoing angiography <30 days after the acute event had a higher mortality (5%), especially those with proximal left anterior descending occlusion (10%). The time from the acute event to angiography was a predictor of death (p = 0.04). Despite low 1-year mortality rates, patients with total occlusion of an isolated coronary vessel treated medically had substantial mortality, myocardial infarction, and revascularization rates over a long-term follow-up period.

Percutaneous revascularization of chronic coronary occlusions: an overview.

Patients with a chronic coronary occlusion often undergo coronary angiography after weeks to months of occlusion. The published reports underestimate the extent of this problem because such patients are often arbitrarily assigned to receive medical therapy or undergo bypass surgery as a result of poor success with percutaneous revascularization and substantial restenosis. Thus, there is controversy about the role of angioplasty in this patient cohort. The goal of this overview was to evaluate the available information about angioplasty in chronic coronary occlusions. The primary indication for attempted recanalization of a chronic coronary occlusion has been symptomatic angina pectoris. Anginal status often improves after successful procedures (70% vs. 31% with a failed procedure); left ventricular function may improve; and subsequent referral for coronary artery bypass graft surgery is uncommon (3% vs. 28% in unsuccessful cases). Successful recanalization is achieved in approximately 65% of attempted procedures. Inability to cross the stenosis with a guide wire is the most common cause of procedural failure. Statistically significant predictors of procedural success include older occlusions (75% < 3 months old vs. 37% > or = 3 months old), absence of any anterograde flow through the occlusion (76% with vs. 58% without), angiographically abrupt-appearing occlusions (50% vs. 77% with tapered occlusions), presence of bridging collateral vessels (23% with vs. 71% without) and lesions > 15 mm. Procedural complications occur at a slightly lower incidence than in angioplasty of high grade subtotal stenoses. Long-term success is limited, and restenosis can be expected in > 50% of the patients. The experience with chronic total occlusions of saphenous vein bypass grafts is small, but there appear to be limited procedural success and significant procedural complications, particularly associated with distal emboli. The role of new pharmacologic agents has yet to be defined and that of new devices has been disappointing so far, but further technologic advances are on the horizon.