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Temporal trends and geographical variations in cardiovascular disease attributable to high systolic blood pressure in China are not yet fully understood. The aim of this study was to quantify the cardiovascular disease burden attributable to high systolic blood pressure at national and provincial levels in China.In this population-based study, we evaluated systolic blood pressure and estimated the number of deaths, age-standardised mortality rates, and years of life lost (YLLs) due to cardiovascular disease and its subcategories (including ischaemic heart disease, ischaemic stroke, haemorrhagic stroke, and other cardiovascular diseases) attributable to high systolic blood pressure, at the national level and by 31 provincial levels, in China, from 2005 to 2018. We pooled blood pressure data of 1·30 million adults aged 25 years and older from the China Chronic Disease and Risk Factor Surveillance project, the China National Nutrition Survey, and the China Hypertension Survey. We applied a temporal-spatial Bayesian hierarchical model to estimate age-specific, sex-specific, province-specific, and year-specific average systolic blood pressure, and a comparative risk assessment method to compute the cardiovascular disease burden attributable to high systolic blood pressure by age, sex, year, and province.Nationally, age-standardised mean systolic blood pressure was 132·5 mm Hg (95% uncertainty interval [UI] 124·6-140·3) in men and 129·4 mm Hg (121·7 to 137·2) in women. 2·67 million (95% UI 2·61 to 2·72) cardiovascular disease deaths in China were attributable to high systolic blood pressure, including 1·12 million deaths (1·07 to 1·16) due to ischaemic heart disease, 0·63 million deaths (0·60 to 0·65) due to ischaemic stroke, 0·58 million deaths (0·57 to 0·60) due to haemorrhagic stroke, and 0·34 million deaths (0·32 to 0·36) due to other cardiovascular disease. The age-standardised cardiovascular disease mortality rates associated with high systolic blood pressure were 268·99 per 100 000 people (95% UI 264·11 to 273·51) in 2005 and 220·84 per 100 000 people (216·30 to 224·76) in 2018, a percentage change of -17·90%; the rate changed by an average of -1·50% (95% UI -1·55% to -1·45%) per year from 2005 to 2018 nationally. YLL rates for total cardiovascular disease caused by high systolic blood pressure varied substantially across provinces, ranging from 3078·33 (95% UI 2807·40 to 3303·57) per 100 000 people in Beijing to 7189·98 (95% UI 6817·18 to 7507·99) per 100 000 people in Heilongjiang in 2018. Age-standardised YLL rates for ischaemic heart disease and ischaemic stroke attributable to high systolic blood pressure were particularly high in northeastern provinces, including Heilongjiang, Liaoning, and Jilin.The deaths and YLLs for cardiovascular disease attributable to high systolic blood pressure in China increased between 2005 and 2018, and age-standardised cardiovascular disease mortality rates decreased in the same timeframe. Our findings could help policy makers in promoting blood pressure control measures and implementing effective and locally adapted preventive interventions to reduce the prevalence of high systolic blood pressure and reduce the burden of systolic blood pressure-related cardiovascular disease in China.China National Key Research and Development Program, China National ScienceTechnology Pillar Program, and National Health Commission of the People's Republic of China.For the Chinese translation of the abstract see Supplementary Materials section.

Every year, results from many important randomised, controlled trials are published. Knowing the elements of trial design and having the skills to critically read and incorporate results are important to medical practitioners. The goal of this article is to help physicians determine the validity of trial conclusions to improve patient care through more informed medical decision making. This article includes a review of 162 randomised, controlled non-inferiority (n = 116) and equivalence (n = 46) hypothesis studies as well as the larger Stroke Prevention using Oral Thrombin Inhibitor in atrial Fibrillation V study and the Ongoing Telmisartan Alone and in Combination with Ramipril Global Endpoint Trial. Evaluation of data from small and large trials uncovers significant flaws in design and models employed and uncertainty about calculations of statistical measures. As one example of questionable study design, discussion includes a large (n = 3922), double-blind, randomised, multicentre trial comparing the efficacy of ximelagatran with warfarin for prevention of stroke and systemic embolism in patients with non-valvular atrial fibrillation and additional stroke risk factors. Investigators concluded that ximelagatran was effective compared with well-controlled warfarin for prevention of thromboembolism. However, deficiencies in design, as well as concerns about liver toxicity, resulted in the rejection of the drug by the US Food and Drug Administration. Many trials fail to follow good design principles, resulting in conclusions of questionable validity. Well-designed non-inferiority trials can provide valuable data and demonstrate efficacy for beneficial new therapies. Objectives and primary end-points must be clearly stated and rigorous standards met for sample size, establishing the margin, patient characteristics and adherence to protocol.

Cardiac troponins I (cTnI) and T (cTnT) are useful for assessing prognosis in patients with unstable angina and non-ST-segment elevation myocardial infarction (UA/NSTEMI). However, the use of cardiac troponins for predicting benefit of an invasive vs conservative strategy in this patient population is not clear.To prospectively test whether an early invasive strategy provides greater benefit than a conservative strategy in acute coronary syndrome patients with elevated baseline troponin levels.Prospective, randomized trial conducted from December 1997 to June 2000.One hundred sixty-nine community and tertiary care hospitals in 9 countries.A total of 2220 patients with acute coronary syndrome were enrolled. Baseline troponin level data were available for analysis in 1821, and 1780 completed the 6-month follow-up.Patients were randomly assigned to receive (1) an early invasive strategy of coronary angiography between 4 and 48 hours after randomization and revascularization when feasible based on coronary anatomy (n = 1114) or (2) a conservative strategy of medical treatment and, if stable, predischarge exercise tolerance testing (n = 1106). Conservative strategy patients underwent coronary angiography and revascularization only if they manifested recurrent ischemia at rest or on provocative testing.Composite end point of death, MI, or rehospitalization for acute coronary syndrome at 6 months.Patients with a cTnI level of 0.1 ng/mL or more (n = 1087) experienced a significant reduction in the primary end point with the invasive vs conservative strategy (15.3% vs 25.0%; odds ratio [OR], 0.54; 95% confidence interval [CI], 0.40-0.73). Patients with cTnI levels of less than 0.1 ng/mL had no detectable benefit from early invasive management (16.0% vs 12.4%; OR, 1.4; 95% CI, 0.89-2.05; P.001 for interaction). The benefit of invasive vs conservative management through 30 days was evident even among patients with low-level (0.1-0.4 ng/mL) cTnI elevation (4.4% vs 16.5%; OR, 0.24; 95% CI, 0.08-0.69). Directionally similar results were observed with cTnT.In patients with clinically documented acute coronary syndrome who are treated with glycoprotein IIb/IIIa inhibitors, even small elevations in cTnI and cTnT identify high-risk patients who derive a large clinical benefit from an early invasive strategy.

We sought to define the risks facing octogenarians undergoing contemporary percutaneous coronary interventions (PCIs).The procedural risks of PCI for octogenarians have not been well established.We compared the clinical characteristics and in-hospital outcomes of 7,472 octogenarians (mean age 83 years) with those of 102,236 younger patients (mean age 62 years) who underwent PCI at 22 National Cardiovascular Network (NCN) hospitals from 1994 through 1997.Octogenarians had more comorbidities, more extensive coronary disease and a two- to fourfold increased risk of complications, including death (3.8% vs. 1.1%), Qwave myocardial infarction (1.9% vs. 1.3%), stroke (0.58% vs. 0.23%), renal failure (3.2% vs. 1.0%) and vascular complications (6.7% vs. 3.3%) (p0.001 for all comparisons). Independent predictors of procedural mortality in octogenarians included shock (odds ratio [OR] 5.4, 95% confidence interval [CI] 3.3 to 8.8), acute myocardial infarction (OR 3.2, 95% CI 2.3 to 4.4), left ventricular ejection fraction (LVEF)35% (OR 2.9, 95% CI 2.1 to 3.9), renal insufficiency (OR 2.8, 95% CI 2.0 to 3.8), first PCI (OR 2.3, 95% CI 1.7 to 3.3), age85 years (OR 2.1, 95% CI 1.5 to 2.7) and diabetes mellitus (OR 1.5, 95% CI 1.1 to 2.0). For elective procedures, octogenarian mortality varied nearly 10-fold, and was strongly influenced by comorbidities (0.79% mortality with no risk factors vs. 7.2% with renal insufficiency or LVEF35%). Despite similar case-mix, PCI outcomes in octogenarians improved significantly over the four years of observation (OR of 0.61 for death/myocardial infarction/stroke in 1997 vs. 1994; 95% CI 0.45 to 0.85).Risks to octogenarians undergoing PCI are two- to fourfold higher than those of younger patients, strongly influenced by comorbidities, and have decreased in the stent era.

To identify factors responsible for the variation in real hospital costs and length of stay for patients with diabetes undergoing coronary angioplasty or coronary bypass surgery.Retrospective study of patients with diabetes and coronary artery disease treated at a single hospital.The study population included 1809 patients with diabetes and multivessel (2-vessel or 3-vessel) coronary artery disease who underwent an initial coronary angioplasty or coronary bypass surgery between 1988 and 1996. After accounting for the extent and severity of the patient's coronary artery disease, a sequential model was used to assess if diabetic characteristics were independently associated with higher hospital resource utilization during revascularization.Multivariate regression results indicated that for patients with diabetes who underwent coronary angioplasty, a baseline creatinine level ofor = 2.0 mg/dL was associated with significantly higher hospital costs and longer length of stay. For patients with diabetes who underwent a coronary bypass surgery only, a baseline creatinine level ofor = 2.5 mg/dL was associated with higher hospital costs and longer hospital length of stay.After controlling for coronary risk factors, selected diabetes-specific characteristics are associated with higher hospital resource utilization. Risk adjustments in hospital reimbursement may be needed to assure that patients with diabetes who have cardiovascular disease have access to revascularization procedures.

There are limited data on the use of percutaneous revascularization techniques for transplant coronary artery disease (CAD).Medical records and angiographic results for cardiac transplant patients undergoing percutaneous revascularization at Emory University Hospital were reviewed. Procedural results, results of angiography 4Eth 6 months after intervention, and clinical follow-up were recorded.Nineteen patients underwent 51 interventions. Thirty-eight lesions (75%) were de novo and 13 (25%) were restenotic. All patients had hypertension, 37% had diabetes, 79% had elevated lipid levels, and 53% had at least one episode of moderate to severe allograft rejection (grade 3A or greater). The primary procedural success rate was 100% with no major complications. Six-month restenosis rate (defined as50%) was 49%. At 23+/-17 months follow-up, 6 patients were dead or retransplanted (31%). Thirteen patients were alive without retransplantation (9 New York Heart Association class I, 3 class II, 1 class III).Percutaneous revascularization is safe and has a high initial procedural success rate in patients with transplant CAD. However, the restenosis rate in this population remains higher than reported for atherosclerotic coronary disease and the long-term prognosis remains poor.

The fiftieth anniversary of the ACC and the end of the twentieth century are arbitrary points in time, yet they seem to coincide with a true watershed. The last 50 years have brought a rush of new techniques and understandings that have, for the first time, given cardiovascular specialists real tools to prevent and fight cardiovascular disease. Only now, for the first time, has science begun to understand exactly what happens when plaque forms in an artery, when heart muscle fibers cross-link and weaken, when an atrial chamber fibrillates, and when heart muscle cells die en masse after a heart attack. We are beginning to track down the actual chemical, mechanical, and electrical pathways by which the heart is damaged or dies. When we can interfere with those pathways and stop the chain of events, we will have defeated heart disease. Imagination is rapid, but progress is often both uncertain and slow because of the many constraints of cost, regulation, and time needed to test and evaluate new developments. Yet we can now foresee a future in which medical science might actually defeat cardiovascular disease the way it has defeated polio, smallpox, and other serious scourges of the past.

Coronary catheterization laboratories (CCLs) are the cornerstones of the delivery system for many cardiovascular procedures performed in the United States. However, few comprehensive data exist benchmarking physician activities in CCLs. This study benchmarks cost and time data on 82,548 consecutive patient encounters in 53 CCLs for the 18-month period of January 1997 through June 1998. The data are compiled from the OEP program, a relational database developed by Boston Scientific/Scimed (Maple Grove, Minnesota) for use in CCLs. CCL productivity (total time and procedure time) and cost (variable costs and device costs) benchmarks are created for: 1) left heart catheterization; 2) right and left heart catheterization; 3) percutaneous transluminal coronary balloon angioplasty (PTCA); 4) atherectomy; and 5) coronary stents. Results show the variable costs (those costs that vary in direct proportion to changes in CCL activities) for the five procedures are: $308, left heart catheterization; $395, right and left heart catheterization; $841, PTCA; $2,768, atherectomy; and $3,186, coronary stent. These variable costs are lower than the typical average costs reported for these procedures because they do not include hospital, laboratory, and physician costs, only the procedure-specific activity-related costs most directly controlled and/or influenced by CCL physicians or administrators. The total time for the left heart catheterization averaged 64 minutes and 84 minutes for the right and left heart catheterization, respectively, and procedural times averaged 25 and 32 minutes, respectively. For the major interventional procedures N PTCA, atherectomy, and coronary stents, total times averages were 102, 135, and 117 minutes, respectively. Procedural times for these procedures averaged between 60 and 65 percent of the total time. The major implications of these findings are discussed and limitations noted.

This paper, the second in a series of 2, reviews major developments and trends in the current healthcare arena that will affect cardiovascular disease (CVD) treatment over the next 10 years. The paper also discusses the implications and future outlook for cardiovascular services in a managed care environment.

The dramatic transformations taking place in the healthcare environment have created a new paradigm for healthcare and pose far-reaching changes for cardiovascular care. This 2-part paper reviews these changes and discusses the major implications for cardiovascular specialists, based on literature reviews and summaries of legislative initiatives. The new healthcare paradigm focuses on a continuum of care, wellness maintenance and promotion, accountability for the healthcare of defined populations, and provider differentiation based on ability to add 'value' to the patient's healthcare outcome. This paradigm will become 'standard operating procedure' in the cardiovascular market. As a result, major areas of change in the cardiovascular environment include: continuing growth of managed care arrangements, expanding physician and other payment reforms, growing influence of state and private payer initiatives, expanding role of 'centers of excellence,' continuing surplus of physicians, growth in pharmaceuticals and new technologies, and extension of evidence-based guidelines. Practice guidelines, in particular, will become an integral part of medical practice and will represent the standards against which medical practice will be measured. Given the prominent position of cardiovascular disease in healthcare, cardiovascular specialists will remain in the forefront of these developments.

This study was conducted to assess the impact of GPIIb/IIIa blockade with tirofiban on costs during the initial hospitalization and at 30 days among patients undergoing high-risk coronary angioplasty.GPIIb/IIIa blockers are a new class of compounds that have been shown in clinical studies to prevent complications after high-risk angioplasty.The RESTORE trial was a multinational, blinded placebo-controlled study of 2,197 patients randomized to tirofiban or placebo following coronary angioplasty. This economic assessment was a prospective substudy of the RESTORE trial, and included 1,920 patients enrolled in the U.S. Costs were estimated for the U.S. cohort based on their utilization of healthcare resources and on costs measured directly in 820 U.S. patients at 30 sites.There was a 36% difference in the rate of the composite event of death, myocardial infarction (MI) and revascularization at two days between tirofiban and placebo (8% vs. 12%, p = 0.002). This difference was attributed to a reduction in nonfatal MI, repeat angioplasty, coronary surgery and stent placement. These clinical benefits followed a similar trend at 30 days, with a 16% reduction in the composite event (p = 0.10). In-hospital cost, including professional and study drug costs, was $12,145 +/- 5,882 with placebo versus $12,230 +/- 5,527 with tirofiban (p = 0.75). The 30-day cost was $12,402 +/- 6,147 with placebo versus $12,446 +/- 5,814 with tirofiban (p = 0.87).Tirofiban has been shown to decrease in-hospital and possibly 30-day events after high-risk angioplasty. The beneficial clinical effects of tirofiban in high-risk patients can be achieved at no increased cost.

In the management of unstable angina and non-Q-wave acute myocardial infarction (AMI), there is considerable debate regarding the use of invasive strategy versus conservative strategy. The Thrombolysis In Myocardial Infarction (TIMI) III B trial found similar clinical outcomes for the 2 strategies, but the Veterans Administration Non-Q-Wave Infarction Strategies in-Hospital trial found a higher mortality with the invasive strategy. Both these trials were conducted before platelet glycoprotein IIb/IIIa inhibition and coronary stenting, both of which improve clinical outcome. Thus, there is a need to reexamine the question of which management strategy is optimal in the current era of platelet glycoprotein IIb/IIIa inhibition and new coronary interventions. The Treat Angina with Aggrastat and determine Cost of Therapy with an Invasive or Conservative Strategy (TACTICS-TIMI 18) trial is an international, multicenter, randomized trial that is evaluating the clinical efficacy of early invasive and early conservative treatment strategies in patients with unstable angina or non-Q-wave AMI treated with tirofiban, heparin, and aspirin. Patients are randomized to an invasive strategy, involving cardiac catheterization within 4 to 48 hours and revascularization with angioplasty or bypass surgery if feasible, versus a conservative strategy, where patients are referred for catheterization only for recurrent pain at rest or provokable ischemia. The primary end point is death, MI, or rehospitalization for acute coronary syndromes through a 6-month follow-up. The trial is also testing the "troponin hypothesis," that baseline troponins T and I will be useful in selecting an optimal management strategy.

An econometric model is presented to compare the cost-effectiveness of two alternative procedures, percutaneous transluminal coronary angioplasty (PTCA) and coronary artery bypass surgery (CABG), for the treatment of multivessel coronary artery disease. This study utilizes the MIMIC (multiple indicator multiple cause) health model in a simultaneous equation system to analyse Emory Angioplasty Surgery Trial (EAST) data. This method eliminates the possibility of endogeneity bias, which may have affected the results of previous cost-effectiveness analyses on this topic. The empirical results indicate that neither procedure proves more cost-effective at 3 year follow-up.

The Emory Angioplasty versus Surgery Trial (EAST) showed that multivessel patients eligible for both percutaneous transluminal coronary angioplasty (PTCA) and coronary bypass surgery (CABG) had equivalent 3-year outcomes regarding survival, myocardial infarction, and major myocardial ischemia. Patients eligible for the trial who were not randomized because of physician or patient refusal were followed in a registry. This study compares the outcomes of the randomized and registry patients. Of the 842 eligible patients, 450 did not enter the trial. Their baseline features closely resembled those of the randomized patients and follow up was performed using the same methods. In the registry there was a bias toward selecting CABG in patients with 3-vessel disease (84%) and PTCA in patients with 2-vessel disease (54%). Three-year survival for the registry patients was 96.4%, which was better than the randomized patients, 93.4% (p = 0.044). Angina relief in the registry was equal for CABG and PTCA patients and was better for the PTCA registry (12.4%) than PTCA randomized patients (19.6%) (p = 0.079). Thus, the registry confirms that EAST is representative of all eligible patients and does not represent a low-risk subgroup. Since baseline differences were small, improved survival in the registry may be due to treatment selection. Physician judgment, even in patients judged appropriate for clinical trials, remains a potentially important predictor of outcomes.

An effective therapy for a costly illness has economic consequences. There may also be differences between provider costs and payer costs and initial versus long-term costs; costs may also vary with the reimbursement scheme. Consider the case of an effective therapy to prevent restenosis after coronary angioplasty. Assume that the initial provider cost of angioplasty is $12,000 and that restenosis within 6 months results in repeat angioplasty in 20% of cases, with a follow-up cost of $2,400, or $14,400 total. Assume that a therapy costs $1,000 per angioplasty and decreases restenosis by 50%, resulting in repeat angioplasty in 10% of cases. This will result in an initial cost of $13,000 and a follow-up cost of $1,300, or $14,300 total. The total societal costs will be -$100, a slight savings. Thus, the $1,100 cost of therapy is offset by reduced costs associated with restenosis, and the societal costs are almost neutral. Assume that under fee for service providers charge costs plus 10% and that without the new therapy either a package price or a capitated system is revenue neutral. Changes in costs resulting from therapy to prevent restenosis are as follows (plus sign indicates cost or loss; minus sign indicates savings or profit): [table: see text] Under fee for service, the payer takes the risks, and the economic consequences to providers are minimal. The situation is reversed under capitation. For whoever takes the risk, there is an initial loss to pay for the therapy, but a long-term gain due to less restenosis. Under package pricing, the providers lose because of the cost of therapy and fewer procedures, while the payers gain. A new therapy, even if it is revenue neutral to society overall, may have considerable economic consequences, which vary with time and with the different perspectives of providers and payers.

Increasingly, patients are returning for a second, third, and even fourth coronary artery bypass graft (CABG) procedure.This report reviews the in-hospital and long-term outcomes for 102 patients undergoing a third or fourth CABG at Emory University from December 1977 to April 1994.The mean interval from the first to second CABG was 5.2 +/- 3.5 years and from the second to the third CABG 6.8 +/- 4.1 years. The mean age was 6 +/- 9 years, 91% were male, 33% had hypertension, 16% diabetes, 86% class III or IV angina (Canadian Cardiovascular Society), 4.4% congestive failure (New York Heart Association), and 73% three-vessel disease. The in hospital mortality rate was 9.8%, with a perioperative myocardial infarction rate of 8.8% and a stroke rate of 1.9%.These perioperative mortality and myocardial infarction rates are several times higher than those reported for initial revascularizations or first-time redo CABG operations. However, the 5- and 10-year survival rates of 79% and 59%, respectively, and a myocardial infarction-free survival of 62% at 5 years, the benefits of a third-time CABG procedure are apparent for this high-risk group of patients.

Completeness of revascularization after coronary artery bypass operation has been shown to improve short- and medium-term outcome. The purpose of this study was to assess the independent contribution of completeness of revascularization to long-term outcome. A total of 2057 patients with multivessel disease with complete revascularization and 803 with incomplete revascularization, mean age 57 +/- 9 years, was studied. The patient groups were similar except for more prior myocardial infarctions, worse left ventricular function, and more three-vessel disease in the incomplete revascularization group. Complications of perioperative infarction and stroke were not different between those having complete versus incomplete revascularization. The hospital death rate for patients having complete revascularization during the period of study was 0.7% versus 1.5% for those having incomplete revascularization (p = 0.06). Length of hospital stay for the two groups of patients also was not different. At late follow-up (mean 11.7 years for complete and 10.8 years for incomplete) patients who had incomplete revascularization had a significantly higher prevalence of recurrent angina. Multivariate analysis demonstrated the strongest predictors of incomplete revascularization to be number of vessels diseased and left ventricular function (ejection fraction). The multivariate correlates of survival were older age, left ventricular dysfunction, and completeness of revascularization. Completeness of revascularization correlated with improved overall patient survival, as well as survival in patients with normal left ventricular function. Furthermore, the curves continued to separate over time, such that the difference was greater at 8 years than at 4 years, although by 12 years the curves started to converge.

The relation between post-percutaneous transluminal balloon angioplasty (post-PTCA) and angiography indexes were investigated in the Lovastatin Restenosis Trial. Post-PTCA percent diameter measured by the operator was found to be a weak predictor of angiographic and clinical follow-up restenosis.

Intracoronary stents are being used to treat acute and threatened closure after percutaneous transluminal coronary angioplasty and to prevent restenosis.The outcomes of 68 patients having coronary artery bypass grafting after stent placement were reviewed. The mean age was 60.5 +/- 9.7 years, and 71% were male. Thirty-seven percent had hypertension, 13% had diabetes, 62% had class III or IV angina, 60% had multivessel disease, and 40% had sustained a prior myocardial infarction. Fifty-three patients underwent emergency operation, 22 with hemodynamic collapse immediately after percutaneous transluminal coronary angioplasty, and 7 others required urgent revascularization within 24 hours of angioplasty. Seventeen underwent coronary artery bypass grafting for acute closure of the stented vessel several days after the angioplasty procedure.There was no correlation between urgency of the procedure, previous infarction, or previous coronary artery bypass grafting with successful procedure. The in-hospital mortality was 4.4%, 21% had a Q-wave myocardial infarction, and 1.5% sustained a stroke. Ejection fraction was the only correlate of long-term mortality.Coronary artery injury for which stents are placed for acute or threatened occlusion or to prevent restenosis but then fail, thus necessitating coronary artery bypass grafting, can be treated successfully. Although the rate of Q-wave myocardial infarction is substantial and related to the initial ischemic insult, the long-term survival and event rates are excellent with prompt surgical revascularization.

In patients with multivessel coronary artery disease who require revascularization there is uncertainty as to the selection of the appropriate patients for percutaneous transluminal coronary angioplasty (PTCA) as opposed to coronary artery bypass grafting (CABG). To define the relative roles of PTCA and CABG for multivessel disease, 392 patients were randomly assigned to revascularization by PTCA or CABG and followed for 3 years. This is a single-center randomized study in which individual group assignment was known but grouped data remained blinded until a full 3 years of follow-up was complete on all patients. The patients were randomized in 4 strata: (1) 2-vessel disease with 1 lesion per vessel; (2) 2-vessel disease with multiple lesions in at least 1 vessel; (3) 3-vessel disease with 1 lesion per vessel; and (4) 3-vessel disease with multiple lesions in at least 1 vessel. All data were collected on study-specific forms and sent to an independent biostatistical coordinating center for entry into a computerized database. All data will be analyzed by intention-to-treat. The primary endpoint of the trial is the composite of death of any cause, Q-wave myocardial infarction within 3 years, or a large reversible thallium defect at 3 years. Multiple secondary endpoints will include each of the components of the primary endpoint, the need for additional procedures, angiographic status at 1 and 3 years measured by an independent quantitative coronary arteriography laboratory, and measures of quality of life. A total of 5,118 patients were screened, of whom 3,371 were excluded for angiographic reasons, 191 because the angioplasty operators or surgeons believed that the patients were anatomically unsuitable, and 714 for clinical exclusions, leaving 842 eligible patients, of whom 392 were randomized. Of these, 40% had triple-vessel disease and 60% had double-vessel disease. There was no baseline difference between the 2 treatment arms for any clinical or major angiographic variable. This randomized trial will permit an in-depth comparison of coronary angioplasty and coronary surgery in comparable patients suitable for either procedure. Clinical, angiographic, and quality-of-life comparisons will be made and should be helpful in medical decision making between the 2 procedures.

Experimental and clinical observations suggest that lowering serum lipid levels may reduce the risk of restenosis after coronary angioplasty. We report the results of a prospective, randomized, double-blind trial evaluating whether lowering lipid levels with lovastatin can prevent or delay restenosis after angioplasty.Seven to 10 days before angioplasty, we randomly assigned eligible patients to receive lovastatin (40 mg orally twice daily) or placebo. Patients who underwent successful, complication-free, first-time angioplasty of a native vessel (the index lesion) continued to receive therapy for six months, when a second coronary angiogram was obtained. The primary end point was the extent of restenosis of the index lesion, as assessed by quantitative coronary arteriography. Of 404 patients randomly assigned to study groups, 384 underwent angioplasty; 354 of the procedures were successful, and 321 patients underwent angiographic restudy at six months.At base line, the patients in the lovastatin group (n = 203) and the placebo group (n = 201) were similar with respect to demographic clinical, angiographic, and laboratory characteristics. At base line the mean (+/- SD) degree of stenosis, expressed as a percentage of the diameter of the vessel, was 64 +/- 11 percent in the lovastatin group, as compared with 63 +/- 11 percent in the placebo group (P = 0.22). Despite a 42 percent reduction in the serum level of low-density lipoprotein cholesterol in the lovastatin group, after six months of treatment the amount of stenosis seen in the second angiogram was 46 +/- 20 percent in the placebo group, as compared with 44 +/- 21 percent in the lovastatin group (P = 0.50). Similarly, there were no significant differences in minimal luminal diameter or other measures of restenosis. A trend was noted toward more myocardial infarctions in the lovastatin group, as a result of acute vessel closure or restenosis at the site of angioplasty, but there were no other important differences between the two groups in the frequency of fatal or nonfatal events at six months.Treatment with high-dose lovastatin initiated before coronary angioplasty does not prevent or delay the process of restenosis in the first six months after the procedure.

The clinical benefit of percutaneous transluminal coronary angioplasty (PTCA) as compared with coronary-artery bypass grafting (CABG) for patients with multivessel coronary artery disease has not been established. To determine the outcomes of these treatments in patients referred for the first time for coronary revascularization, we conducted a three-year prospective, randomized trial comparing the two procedures.Revascularization was performed by accepted methods. Follow-up clinical information was collected every six months, and coronary arteriography and thallium stress scanning were performed at one and three years. The primary end point was a composite of death, Q-wave myocardial infarction, and a large ischemic defect identified on thallium scanning at three years. Secondary end points included clinical and angiographic status and the need for additional revascularization procedures. Data were analyzed according to the intention-to-treat principle.Of the 5118 patients screened for the trial, 842 (16.5 percent) were eligible for enrollment, and 392 (7.7 percent) agreed to participate. A total of 194 patients were randomly assigned to the CABG group, and 198 to the PTCA group. The primary end point occurred in 27.3 percent of the CABG group and 28.8 percent of the PTCA group (P = 0.81). Death occurred in 6.2 percent of the CABG group and 7.1 percent of the PTCA group (P = 0.73 by log-rank test). At three years, the proportions of patients in the CABG group who required repeated bypass surgery (1 percent) or angioplasty (13 percent) were significantly lower than the proportions in the PTCA group (22 and 41 percent, respectively; P0.001). Angiographic studies at three years showed a greater degree of revascularization in the CABG group. Angina was more frequent in the PTCA group (20 percent) than in the CABG group (12 percent).We found that CABG and PTCA did not differ significantly with respect to the occurrence of the composite primary end point. Consequently, the selection of one procedure over the other should be guided by patients' preferences regarding the quality of life and the possible need for subsequent procedures.

There is uncertainty as to the relative efficacy of coronary artery bypass graft surgery (CABG) in men and women. Differences between sexes may be of greater importance than heretofore because of increased frequency of risk factors for adverse outcome. It is the purpose of this study to examine the changing clinical characteristics of patients undergoing CABG and to determine the influence of these changes on the results of CABG in men and in women.The source of data was the clinical database at Emory University Hospitals. The population comprised 13,368 patients (2648 women, 10,720 men) who had cardiac catheterization followed by CABG between 1974 and 1991. The patients were divided into the time periods 1974 through 1979 (532 women, 2792 men), 1980 through 1983 (727 women, 3151 men), 1984 through 1987 (695 women, 2619 men), and 1988 through 1991 (694 women, 2158 men). Data were collected prospectively and entered into a computerized database. The women were older (63 +/- 10 versus 58 +/- 10 years, P.0001) and more frequently had diabetes (26.0% versus 15.4%, P.0001). The in-hospital mortality was 3.8% in women and 1.6% in men. The multivariate correlates of death were older age, emergent surgery, reduced ejection fraction, female sex, diabetes, and more severe distribution of coronary arterial narrowings. Each of these risk factors for death became more prevalent, such that the mortality in men increased from 1.0% in 1974 through 1979 to 2.7% in 1988 through 1991, whereas the mortality in women increased from 1.3% in 1974 through 1979 to 5.4% in 1988 through 1991.The population undergoing CABG has aged, with correlates of in-hospital death becoming more common. The higher mortality in women could only partially be explained by other clinical variables. In addition, the risk of death after CABG has increased in women more than in men because women have consistently been older, have more emergent surgery and diabetes, and in recent years more women undergoing CABG have three-vessel or left main disease.

The purpose of this study was to retrospectively evaluate the effectiveness of screening for coronary artery disease before elective repair of abdominal aortic aneurysms (AAA) was performed.Results of a screening algorithm for coronary artery disease in 263 patients admitted to a single hospital for elective repair of AAA between January 1986 and December 1989 were analyzed. Patients with no coronary artery disease indicators proceeded to surgery without further workup. Patients with cardiac disease indicators underwent dipyridamole-thallium scintigraphy, and patients with angina were screened by use of cardiac catheterization; those with a recent coronary revascularization underwent no additional screening unless symptoms or electrocardiographic changes suggested an intervening event. Twenty-eight patients underwent no screen other than medical history and electrocardiogram.Among 164 patients screened with dipyridamole-thallium scintigraphy, 44 patients had redistribution defects that required catheterization, and 11 of these underwent coronary revascularization. Cardiac catheterization was performed directly in 42 patients, which led to 11 revascularizations before AAA repair. Previous coronary artery bypass or percutaneous transluminal angioplasty obviated additional screening in 29 patients. Of the 263 scheduled AAA repairs, 15 were cancelled because of unacceptable operative risks, 13 for cardiac reasons. One patient died of a ruptured AAA after an uneventful coronary artery bypass. Among the 247 AAA repairs performed, there were three perioperative deaths (1.2%), all of which resulted from sudden cardiac events; three additional patients had nonfatal myocardial infarctions (1.2%), for a total cardiac complication rate of 2.4%.The low rate of cardiac complications in this experience affirms the effectiveness of preoperative screening and selective coronary revascularization before AAA repair.

The observation of the primary endpoints of a clinical trial is only one part of what goes into determining the flow of benefits an individual receives from the treatments under consideration. An optimal comparison of CABG and PTCA requires a consideration of the varying time paths of patient "utility" associated with each procedure because these procedures differ in that CABG will have a higher initial morbidity and mortality while PTCA involves more frequent recurrent angina pectoris resulting in more repeat procedures or crossovers. This paper introduces a survey which can be used to estimate the patient's utility associated with two alternative forms of therapy, CABG and PTCA, for the treatment of multivessel coronary artery disease. Once these estimates of utility are determined, they can be combined with expected years of survival to create Quality Adjusted Life Years (QALYs).

The metabolic effect of excessive oxygenation and frequency of administration of antegrade crystalloid cardioplegic solution was assessed in 33 patients undergoing routine coronary artery bypass graft operations. Four patient groups were designed in which the initial aortic root injection was 1000 ml and then 100 ml administered through the vein grafts after completion of each distal anastomosis. The groups were divided as follows: group 1, single dose, normally oxygenated cardioplegic solution infused via the aortic root; group 2, single dose, high oxygen content cardioplegic solution infused via the aortic root; group 3, normally oxygenated cardioplegic solution with additional 250 ml doses via the aortic root every 20 minutes; group 4, high oxygen content cardioplegic solution with additional 250 ml doses via the aortic root every 20 minutes. In all groups myocardial mean septal temperature showed an immediate fall to approximately 11 degrees C with the initial aortic root doses and then a gradual rewarming to approximately 20 degrees C during the crossclamp period (mean 58.6 minutes). Metabolic parameters measured or calculated from the coronary sinus effluent were myocardial oxygen extraction, lactate production, base deficit, inorganic phosphate, glucose, potassium, creatine kinase (total and myocardial band fraction), and catecholamine production. There was no statistically significant difference in any of these determinations between each patient group. Furthermore, myocardial recovery, myocardial performance, and postoperative recovery characteristics were not different. We conclude that single or multidose aortic root crystalloid cardioplegic solution (either oxygen enriched or normally oxygenated) is equally effective in routine coronary artery bypass graft operations when septal temperatures are maintained between 15 degrees and 21 degrees C for a total arrest time of 60 minutes or less. In this study, increasing the volume cardioplegic solution given in multiple doses appeared to offer no significant metabolic or functional advantage in patients without complications who had satisfactory left ventricular function.

Restenosis remains a critical limitation of percutaneous transluminal coronary angioplasty (PTCA). Recent experimental and clinical data have suggested that lovastatin, an hydroxymethylglutaryl coenzyme A reductase inhibitor, may reduce the rate of restenosis through reduction of low density-lipoprotein (LDL) cholesterol or possibly by direct effects. Lovastatin may therefore produce favorable alterations in endothelial healing, resulting in a decreased smooth muscle cell proliferative response to injury after angioplasty. Emory University, in conjunction with Merck Research Laboratories, has initiated a 10-center double-blinded, placebo-controlled, randomized trial to assess the effect of both pretreatment and aggressive lipid lowering with lovastatin in reducing the rate of restenosis. Lovastatin achieves approximately 75% of its effect on LDL cholesterol by 1 week. Thus, patients scheduled for PTCA are randomly assigned pretreatment with lovastatin, 40 mg twice daily, or placebo 7 to 10 days before PTCA. Therapy is continued for 6 months, at which time repeat coronary arteriography is performed. A detailed safety algorithm was designed, with patients receiving lovastatin and matching placebo back-titrated on a 1:1 basis for LDL cholesterol less than 50 mg/dl. The power is a 90%, alpha = 0.05, 2-tailed test to reduce restenosis from 30 to 15%. The sample size is 360 patients in the 2 arms; allowing for a 10% dropout rate, approximately 400 patients will be randomized. Patients with successful PTCA, less than 50% residual diameter stenosis and greater than or equal to 20% diameter stenosis reduction are analyzed for restenosis at 4 to 6 months by quantitative coronary arteriography.(ABSTRACT TRUNCATED AT 250 WORDS)

Coronary surgery is being used increasingly in older and more seriously ill patients. To evaluate the importance of age in predicting complications and mortality after coronary surgery, the results in 13,625 patients undergoing coronary surgery were evaluated. There were 321 patients under the age of 40, 1,758 were 40-49, 4,167 were 50-59, 5,049 were 60-69, 2,184 were 70-79, and 146 were over 80. As patients aged the proportion of women increased, the prevalence of severe angina and congestive heart failure increased, and the severity of the distributions of the coronary stenoses increased. The incidence of the complications of neurological events, wound infections, and death rose in every decade after the age of 40 years. The incidence of death was 0.6% for patients aged 40-49, 1.5% for those aged 50-59, 1.9% for those aged 60-69, 5.0% for those aged 70-79, and 8.3% for those aged 80-89. Advanced age was the most significant independent correlate of neurological events, wound infections, and death. The other multivariate correlates of neurological events were diabetes, hypertension, and, surprisingly, angina class. Again surprisingly, the only other multivariate correlate of wound infections was angina class. The other multivariate correlates of death were emergent surgery, female gender, ejection fraction, severity of coronary disease, diabetes, and a history of congestive heart failure. Of interest, periprocedural Q wave myocardial infarction was independent of age. The most predictive and significant correlate of periprocedural myocardial infarction was emergent surgery; hypertension, absence of a previous myocardial infarction, and a normal ejection fraction were weaker correlates. The ability to predict any complication was relatively weak compared with the ability to predict death. The relative infrequency of coronary surgery over the age of 80 years suggests that there is already strong selection against surgery in octogenarians. In addition, the risk of death, and to some extent other complications, may be predicted in advance based on extensive patient experience.

Patients undergoing coronary bypass grafting have undergone an evolution in recent years. To document this change, we analyzed two groups of patients in 1981 (n = 1586) and 1987 (n = 1513) to document preoperative and postoperative variables important in determining immediate morbidity and mortality after isolated coronary bypass. Between 1981 and 1987, patients were found to be older (greater than or equal to 70 years, 8.7% versus 21.8%, p less than 0.0001), more often diabetic (15% versus 24%, p less than 0.0001), have a greater prevalence of triple vessel disease (14.5% versus 46.1%, p less than 0.0001), and have more left ventricular dysfunction (ejection fraction 0.60 +/- 14 versus 0.54 +/- 13, p less than 0.0001). To facilitate analysis and because of overlap between subgroups, we subdivided patients into three subgroups for statistical comparison of the years 1981 and 1987: subgroup I, no prior procedure (n = 1546 in 1981 and 1396 in 1987); subgroup II, optimal group (n = 503 in 1981 and 292 in 1987, and defined as no prior procedure, ejection fraction greater than or equal to 0.50 and age less than 65 years); subgroup III, patients having reoperations (n = 40 in 1981 and 117 in 1987). Internal mammary artery grafting was infrequently used in 1981 but was used in 72.1% in 1987. Major postoperative morbidity between the 2 years for the total population increased significantly: need for intraaortic balloon pumping, 1.4% versus 4.7%, p less than 0.0001; myocardial infarction 3.5% versus 5.5%, p less than 0.008; stroke, 1.4% versus 2.8%, p less than 0.008; and wound infection, 1.0% versus 3.0%, p less than 0.001. Wound infection (all types) in 1987 was increased sevenfold in patients having a perioperative myocardial infarction (0.7% versus 5%, p less than 0.0001). For young patients with good left ventricular function (subgroup II), there was no increase in these morbid events between 1981 and 1987. Hospital mortality in the total population increased significantly between 1981 and 1987 from 1.2% to 3.1% (p less than 0.0002), respectively. It was lowest for the patients in optimal condition (subgroup II) in both years, 0.8% versus 1.1%, and highest for reoperative patients, 5.3% versus 4.3%. In 1981, 58% of patients (503/870) were in the optimal group compared with 35% (292/828) in 1987 (p less than 0.0001). The last six years have seen a progressive trend in surgically treating older, sicker patients who have more complex disease, with a significant reduction in the best candidate group.(ABSTRACT TRUNCATED AT 400 WORDS)

The epidemiologic evidence linking cigarette smoking to coronary artery disease has been supported by multiple studies over a period of 30 years. Community based cohort studies such as the Framingham study have shown that cigarette smokers are at a markedly elevated risk of developing cardiovascular events. These studies have also shown that former cigarette smokers have a decline in the excess incidence over a period of several years to approach that of non-smoking populations. Uncertainty then appears to exist as to whether cigarette smokers are at increased risk of cardiovascular events solely because of acute effects of smoking or whether cigarette smoking is also a risk factor for atherosclerosis. Evidence that cigarette smoking is a risk factor for atherosclerosis comes from autopsy and cardiac catheterization laboratory. While not all of these studies show a relationship, the data do, for the most part, show a definite relationship between cigarette smoking and atherosclerosis. Catheterization and autopsy studies suffer from biases that prevent application of prediction models to the general population. However, the combined view of the community based, catheterization and autopsy studies supports a unifying hypothesis of acute effects that may lead to cardiovascular events in the setting of established vascular disease as well as vascular damage that may promote the development of atherosclerosis. Cessation of smoking will rapidly remove the acute effects, and may lead to inactivation of acute lesions. The underlying substrate of atherosclerosis and coronary obstructive lesions appears to be correlated with long term cigarette smoking.

Recent studies have suggested that patients with three-vessel coronary disease and abnormal left ventricular function have better survival rates with bypass surgery than with medical therapy alone. Case-control studies may give accurate survival estimates, but to be valid, selection biases must be taken into account. A matched case-control method was used to compare survival patterns in patients treated medically or surgically during the 1980s. Fifty medical patients with potentially operable coronary disease and 46 surgical patients were matched for significant three-vessel disease and abnormal ventricular function. These two groups had no significant differences with regard to 24 variables, including age (64 +/- 8 versus 63 +/- 10 years), chest pain class, congestive heart failure signs, ejection fraction (36 +/- 8 versus 37 +/- 9 percent), segmental wall score, or a coronary score evaluating lesion site and severity. There were slight differences between the two groups with regard to congestive heart failure symptoms (p = 0.04). Patients undergoing bypass surgery had improved four-year survival rates compared with the medical group (89 versus 55 percent; p = 0.01). Thus, this study used an effective case-control method to suggest that, in the 1980s, coronary surgery improves prognosis substantially in surgically approachable patients with severe coronary disease and ventricular dysfunction.

The introduction of aortic balloon valvuloplasty has prompted review of established techniques to treat aortic valve disease. To this end, the surgical results were reviewed for 1,148 patients undergoing aortic valve replacement, with and without associated coronary artery bypass grafting, for aortic stenosis between January 1, 1975 and September 1, 1987. The overall death rate was 4.6%. The neurological event rate (stroke or reversible ischemic event) was 4.2%, the myocardial infarction rate was 3.5%, and 30.7% had a hospital stay in excess of 10 days. Mortality for isolated elective aortic valve replacement rose from 2.5% for patients under age 70 to 7.3% for those over age 70. Mortality for elective aortic valve replacement plus coronary bypass was 3.8% for patients under age 70 and 11.6% for patients over age 70. The neurological event rate rose from 3.0% to 8.4% and the prolonged length of stay from 28% to 42%. By stepwise logistic regression analysis, the predictors of in-hospital mortality were age and emergent surgery. Age was the only multivariate predictor of neurological events. The year of surgery and emergent status were the multivariate predictors of prolonged length of hospital stay. Aortic valve replacement for aortic stenosis is a well-established technique with low neurological event rates and mortality, which may be predicted in advance. Newer techniques must be considered in light of data such as these.

Patients with neutral protamine Hagedorn and protamine-zinc insulin-dependent diabetes, a history of fish allergy, or prior vasectomy have been reported to be at an increased risk for protamine reactions after cardiopulmonary bypass because of prior sensitization. We prospectively evaluated cardiac surgical patients with prior vasectomies and fish allergies and retrospectively evaluated a cohort of 3245 consecutive cardiac surgical patients requiring cardiopulmonary bypass over a 2-year period for protamine-containing insulin use and clinical evidence of adverse reactions after protamine administration for heparin reversal after cardiopulmonary bypass. Clinical reactions to protamine did not occur in six patients with fish allergies or 16 patients with prior vasectomies. There was one reaction (0.6%) in 160 patients with neutral protamine Hagedorn insulin-dependent diabetes. The incidence of clinical reactions in the other patients was 2/3085 (0.06%). The incidence of clinical reactions in the patients with neutral protamine Hagedorn insulin-dependent diabetes is not significantly different from that in other patients. We conclude that prior neutral protamine Hagedorn insulin use, a history of fish allergy, or prior vasectomy does not represent a contraindication to protamine administration after cardiopulmonary bypass.

This study was performed to determine the procedural characteristics and in-hospital complications associated with failed percutaneous transluminal coronary angioplasty that necessitates coronary artery bypass graft surgery. The study population consisted of 316 patients from 1980 to 1986; 202 patients (64%) had emergency coronary artery bypass graft surgery and the remainder elective surgery during the same hospitalization. Mean age of the population was 56 +/- 9 years, 69% were male, and 69% had single-vessel disease. The failed percutaneous transluminal coronary angioplasty occurred most commonly on the first vessel attempted and was usually secondary to coronary artery dissection. Analysis of surgical technique revealed increased use of intra-aortic balloon pump in the emergency group (24% vs. 2% in the elective group, p less than 0.05). Overall, 2.0 +/- 1.0 (mean +/- SD) bypass grafts were placed, with increased use of the internal thoracic artery in the elective (32%) versus the emergency group (20%, p less than 0.05). A new, nonfatal, postprocedural Q-wave myocardial infarction occurred in 18% and developed more frequently in the emergency (27%) than in the elective (4%) cohorts. There were six in-hospital deaths (1.9%), an incidence which did not differ between groups. This analysis revealed a significant difference in operative technique between the emergency and the elective coronary artery bypass graft patients. Preoperative ischemia was significantly related to the development of the Q-wave myocardial infarction, yet not to in-hospital mortality.(ABSTRACT TRUNCATED AT 250 WORDS)

Inappropriate use of the internal mammary artery for complex coronary artery bypass operations may have disastrous yet avoidable consequences. In 712 consecutive coronary artery bypass operations performed between January 1985 and September 1986, five patients had an intraoperative course suggesting internal mammary artery hypoperfusion. In three, coronary artery bypass was performed as a reoperative procedure. The following similarities were noted in all five patients: a technically satisfactory internal mammary artery anastomosis, a left anterior descending coronary artery having critical proximal stenosis (greater than or equal to 90%), a distal artery at least 2.0 mm diameter free of disease, satisfactory left ventricular function, a catastrophic clinical outcome (death in three, cardiac transplantation in one, 3-month hospitalization in one), and all patients could be weaned from cardiopulmonary bypass only after insertion of a saphenous vein graft distal to the internal mammary artery graft. Bilateral internal mammary grafts were used in four of five patients. In both patients without prior coronary artery bypass, there was a discrepancy in internal mammary artery flow and myocardial demand: cardiac hypertrophy, large (2.5 mm) distal left anterior descending supplied by a small (less than 2.0 mm) internal mammary artery, and sequentially grafted arteries. All three patients having reoperative coronary artery bypass had normal anterior wall motion, and in two of the three patients, the left anterior descending-saphenous vein graft was arteriographically normal and the sole source of blood to the anterior, septum, and inferior myocardium. In two patients the normal left anterior descending-saphenous vein graft supply a large left anterior descending (greater than 2.0 mm) was replaced with a small left internal mammary artery. Internal mammary artery hypoperfusion typically occurred 30 to 40 minutes after discontinuation of cardiopulmonary bypass but was also seen in the intensive care unit. The condition may be confused with internal mammary artery or coronary artery spasm. It may be avoided by careful prebypass planning of the operation, intraoperative assessment of internal mammary artery flow and size with prudent use of sequential internal mammary artery grafting, avoiding use of the terminal left anterior descending (unless large), retaining nonobstructed saphenous vein grafts when the internal mammary artery has marginal flow or size, and placement of a saphenous vein graft distal to the left internal mammary artery when size or flow in the latter is small.