B-type natriuretic peptide(BNP) and the N-terminus of pro-BNP(NT-pro-BNP) have prognostic value in patients with heart failure and patients with acute coronary syndromes. Little is known about the prognostic value of ...B-type natriuretic peptide(BNP) and the N-terminus of pro-BNP(NT-pro-BNP) have prognostic value in patients with heart failure and patients with acute coronary syndromes. Little is known about the prognostic value of baseline NT-pro-BNP alone or in combination with C-reactive protein(CRP) for clinical outcome after percutaneous coronary intervention(PCI). Within a single center registry of contemporaneous PCI, we investigated the prognostic value of baseline plasma NT-pro-BNP and CRP concentrations for the prediction of death or nonfatal myocardial infarction(MI) during 12 to 14 months of follow-up. Among 1,172 consecutive patients, the occurrence of death or MI increased significantly with baseline NT-pro-BNP before PCI(first quartile 0 of 294, second quartile 6 of 291[2.1%], third quartile 4 of 294[1.4%], fourth quartile 22 of 293[7.5%)]; p< 0.0001). NT-pro-BNP in the top quartile significantly predicted death(odds ratio[OR] 13.37, 95%confidence interval[CI] 4.50 to 40.38, p< 0.0001) and was associated with nonfatal MI(OR 2.53, 95%CI 0.77 to 8.34, p=0.22)An abnormal CRP was significantly associated with death(OR 3.47, 95%CI 1.26 to 9.54, p=0.019). Stepwise multivariate logistic regression analysis identified age >65 years and NT-pro-BNP as independent significant predictors of death/MI(age OR 3.18, 95%CI 1.32 to 7.67, p=0.01; NT-pro-BNP OR 4.57, 95%CI 2.07 to 10.10, p=0.0001). Baseline NT-pro-BNP before PCI provides important, independent prognostic information for the occurrence of death or nonfatal MI during long-term follow-up.展开更多
Background: Studies have postulated that cyclooxygenase-2(COX-2) selective inhibitors affect cardiovascular risk through various mechanisms. Some of these mechanisms could increase risk(for example, inhibition of pros...Background: Studies have postulated that cyclooxygenase-2(COX-2) selective inhibitors affect cardiovascular risk through various mechanisms. Some of these mechanisms could increase risk(for example, inhibition of prostacyclin production), and some could decrease risk(for example, inhibition of inflammation). Objective: To determine the effect of COX-2 inhibitors on risk for nonfatal myocardial infarction(MI). Design: Case-control study. Setting: 36 hospitals in a 5-county area. Participants: 1718 case-pa-tients with a first, nonfatal MI admitted to these hospitals and 6800 controls randomly selected from the same counties. Measurements: Self-reported medication use assessed through telephone interviews. Results: The adjusted odds ratio for MI among celecoxib users, relative to persons who did not use nonaspirin nonsteroidal anti-inflammatory drugs(NSAIDs), was 0.43(95%CI, 0.23 to 0.79) compared with 1.16(CI, 0.70 to 1.93) among rofecoxib users. The use of rofecoxib was associated with a statistically significant higher odds of MI compared with the use of celecoxib(adjusted odds ratio for rofecoxib vs. celecoxib, 2.72[CI, 1.24 to 5.95]; P=0.01). Nonselective NSAIDs were associated with a reduced odds of nonfatal MI relative to nonusers. Comparisons of COX-2 inhibitors with nonselective NSAIDs were the following: rofecoxib versus naproxen(odds ratio,3.39[CI, 1.37 to 8.40]) and celecoxib versus ibuprofen or diclofenac(odds ratio, 0.77[CI, 0.40 to 1.48]). Limitations: The possibility of recall bias and uncontrolled confounding in this observational study limit the ability to make definitive conclusions. The association of celecoxib with a lower odds of MI could have occurred by chance. Only about 50%of eligible participants completed telephone interviews. Conclusion: Celecoxib and rofecoxib were associated with different odds of MI. Cardiovascular effects among the COX-2 inhibitors seem different, but further studies, preferably randomized trials, are needed to fully understand the spectrum of effects of COX-2 inhibitors and potential differences among them.展开更多
Background: Determinants of survival and of risk of vascular events after tra nsient ischaemic attack (TIA) or minor ischaemic stroke are not well defined in the long term. We aimed to restudy these risks in a prospec...Background: Determinants of survival and of risk of vascular events after tra nsient ischaemic attack (TIA) or minor ischaemic stroke are not well defined in the long term. We aimed to restudy these risks in a prospective cohort of patien ts after TIA or minor ischaemic stroke (Rankin grade≤ 3), after 10 years or mor e. Methods: We assessed the survival status and occurrence of vascular events in 2473 participants of the Dutch TIA Trial (recruitment in 1986- 89; arterial ca use of cerebral ischaemia). We included 24 hospitals in the Netherlands that rec ruited at least 50 patients. Primary outcomes were all- cause mortality and the composite event of death from all vascular causes, non- fatal stroke, and non - fatal myocardial infarction. We assessed cumulative risks by Kaplan- Meier a nalysis and prognostic factors with Cox univariate and multivariate analysis. Fi ndings: Follow- up was complete in 2447 (99% ) patients. After a mean follow- up of 10.1 years, 1489 (60% ) patients had died and 1336 (54% ) had had at le ast one vascular event. 10- year risk of death was 42.7% (95% CI 40.8- 44. 7). Age and sex- adjusted hazard ratios were 3.33 (2.97- 3.73) for age over 65 years, 2.10 (1.79- 2.48) for diabetes, 1.77 (1.45- 2.15) for claudication, 1. 94 (1.42- 2.65) for previous peripheral vascular surgery, and 1.50 (1.31- 1.71 ) for pathological Q waves on baseline electrocardiogram. 10- year risk of a vascular event was 44.1% (42.0- 46.1). After falling in the first 3 years, yearly risk of a vascular ev ent increased over time. Predictive factors for risk of vascular events were sim ilar to those for risk of death. Interpretation: Long- term secondary preventio n in patients with cerebral ischaemia still has room for further improvement.展开更多
Endocardial electromechanical mapping(EEM) has been proposed as a method for myocardial viability assessment. However, the impact of EEM data on clinical outcome has not been studied before. We sought to assess the pr...Endocardial electromechanical mapping(EEM) has been proposed as a method for myocardial viability assessment. However, the impact of EEM data on clinical outcome has not been studied before. We sought to assess the prognostic value of EEM in patients with left ventricular(LV) dysfunction undergoing percutaneous coronary intervention (PCI). Seventyfive patients with coronary artery disease and LV dysfunction(angiographic LV ejection fraction 49±15%) underwent LV EEM for myocardial viability assessment before coronary revascularization. EEM parameters included mean unipolar electrographic amplitude, mean local shortening, LV volumes, LVEF, number of regions with electrographic amplitudes< 7.5 mV, number of electromechanical mismatch, and match regions. Cardiac death, nonfatal myocardial infarction, nonfatal stroke, and acute heart failure requiring hospitalizationwere defined as clinical events. During a follow-up of 3.6±1.8 years, 20 clinical events occurred. Event-free survival after coronary revascularizationwas significantly better in patientswith amean unipolar electrographic amplitude of ≥9.5 mV than in patients with a mean unipolar electrographic amplitude of< 9.5 mV(88%vs 57%; p< 0.005). Cox regression analysis revealed angiographic LVEF, mean electrographic amplitude, number of regions with electrographic amplitudes< 7.5 mV, number of electromechanical match regions, and EEM EF as univariate predictors of clinical events. In a multivariate analysis, angiographic LVEF< 40%(hazard ratio 4.78, p< 0.005) and mean electrographic amplitude< 9.5 mV (hazard ratio 2.92, p< 0.05) were independent predictors of clinical events. Thus, EEM provides prognostic information in patients with LV dysfunction undergoing coronary revascularization.展开更多
Background: N-terminal pro-brain natriuretic peptide (NtproBNP) and N -termi nal pro-atrial natriuretic peptide (Nt-proANP) are strong cardiovascular risk markers in patients with chronic heart failure, as well as in ...Background: N-terminal pro-brain natriuretic peptide (NtproBNP) and N -termi nal pro-atrial natriuretic peptide (Nt-proANP) are strong cardiovascular risk markers in patients with chronic heart failure, as well as in the general popula tion. We investigated whether high Nt-proBNP or NtproANP could also predict the composite endpoint (CEP) of cardiovascular death, non-fatal stroke or non-fat al myocardial infarction in patients with hypertension and left ventricular (LV) hypertrophy. Methods: After 2 weeks of placebo treatment, clinical, laboratory and echocardiographic variables were assessed in 183 hypertensive participants i n the LIFE echo substudy with electrocardiographic LV hypertrophy. Nt-proBNP an d Nt-proANP were measured by immunoassay at baseline. The patients were followe d for 60 ±5 months. Results: Using Cox regression analysis, the 25 CEP were pre dicted by In(Nt-proBNP) (hazard ratio 1.61 per 2.73-fold increase, P < 0.01) a s well as In(Nt-pro-ANP) (hazard ratio 2.93, P < 0.05). Nt-proBNP above the m edian value of 21.8 pmol/ml was associated with higher incidence of CEP (19.6 versus 7.7%, P < 0.05). Nt-proBNP above the median value was associated with higher incidence of CEP in the 123 patients without history of diabetes or cardiovascular diseas e (14.8 versus 4.3%, P < 0.05), but the association was insignificant in the 60 patients with a history of diabetes or cardiovascular disease (26.3 versus 18.2 %, NS). Nt-proANP showed the same tendency. Conclusion: Nt-proBNP, more than Nt-proANP, strongly predicts cardiovascular events in patients with hypertensio n and LV hypertrophy, especially in patients without diabetes or clinically over t cardiovascular disease.展开更多
Background: The aim of this study was to define the utility of the combined measurement of troponin I, myoglobin, C- reactive protein, fibrinogen, and homocysteine to predict risk in non- ST elevation acute coronary s...Background: The aim of this study was to define the utility of the combined measurement of troponin I, myoglobin, C- reactive protein, fibrinogen, and homocysteine to predict risk in non- ST elevation acute coronary syndromes. Methods: Troponin I, myoglobin, high- sensitivity C- reactive protein, fibrinogen, and homocysteine were measured in 557 consecutive patients admitted to our institution for non- ST elevation acute coronary syndrome. The risk for major events(death or nonfatal myocardial infarction) at first month and at first year follow- up was analyzed. Results: In a multivariate model adjusting for baseline characteristics and electrocardiographic changes, the only biomarkers related to major events at first month were C- reactive protein(P=.007) and myoglobin(P=.02), and at first year troponin I(P=.02), C- reactive protein(P=.03), and homocysteine(P=.04). The rate of major events depending on the number(0- 5) of elevated biomarkers were at first month: 4.1% , 3.7% , 5.7% , 6.1% , 6.5% , and 30.8% (P< .0001), and at first year: 8.2% , 11.1% , 12.3% , 16.2% , 23.7% , and 50% (P< . 0001). A simple score including the number of elevated biomarkers showed an adjusted risk of major events of 1.6[1.3- 1.9] at first month and of 1.4[1.2- 1.7] at first year. Conclusions: Markers of myocardial damage, inflammation, and homocysteine analyzed separately provide prognostic information. The number of elevated biomarkers is an independent risk predictor of major events.展开更多
Context: Limited data are available evaluating how the timing and intensity of statin therapy following an acute coronary syndrome (ACS) event affect clinical outcome. Objective: To compare early initiation of an inte...Context: Limited data are available evaluating how the timing and intensity of statin therapy following an acute coronary syndrome (ACS) event affect clinical outcome. Objective: To compare early initiation of an intensive statin regimen with delayed initiation of a less intensive regimen in patients with ACS. Design , Setting, and Participants: International, randomized, double blind trial of p atients with ACS receiving 40 mg/d of simvastatin for 1 month followed by 80 mg/ d thereafter (n=2265) compared with ACS patients receiving placebo for 4 months followed by 20 mg/d of simvastatin (n=2232), who were enrolled in phase Z of the A to Z trial between December 29, 1999, and January 6, 2003. Main Outcome Measu re: The primary end point was a composite of cardiovascular death, nonfatal myoc ardial infarction, readmission for ACS, and stroke. Follow up was for at least 6 months and up to 24 months. Results Among the patients in the placebo plus sim vastatin group, the median low density lipoprotein (LDL) cholesterol level achi eved while taking placebo was 122mg/dL (3.16 mmol/L) at 1 month and was 77mg/dL (1.99 mmol/L) at 8 months while taking 20 mg/d of simvastatin. Among the patient s in the simvastatin only group, the median LDL cholesterol level achieved at 1 month while taking 40 mg/d of simvastatin was 68mg/dL (1.76 mmol/L) and was 63 m g/dL (1.63 mmol/L) at 8 months while taking 80 mg/d of simvastatin. A total of 3 43 patients (16.7%) in the placebo plus simvastatin group experienced the prima ry end point compared with 309 (14.4%) in the simvastatin only group (40 mg/80 mg) (hazard ratio [HR], 0.89; 95%confidence interval [Cl] 0.76-1.04; P=.14 ). C ardiovascular death occurred in 109 (5.4%) and 83 (4.1 %) patients in the 2 gr oups (HR, 0.75; 95%Cl, 0.57-1.00; P=.05) but no differences were observed in other individual components of the primary end po int. No difference was evident during the first 4 months between the groups for the primary end point (HR, 1.01; 95%Cl, 0.83-1.25; P=.89), but from 4 months t hrough the end of the study the primary end point was significantly reduced in t he simvastatin only group (HR, 0.75; 95%Cl, 0.60-0.95; P=.02). Myopathy (creat ine kinase>10 times the upper limit of normal associated with muscle symptoms) o ccurred in 9 patients (0.4%) receiving simvastatin 80 mg/d, in no patients rece iving lower doses of simvastatin, and in 1 patient receiving placebo (P=.02). Co nclusions: The trial did not achieve the prespecified end point. However, among patients with ACS, the early initiation of an aggressive simvastatin regimen res ulted in a favorable trend toward reduction of major cardiovascular events.展开更多
Context: Increased baseline left ventricular(LV) mass predicts cardiovascular( CV) complications of hypertension, but the relation between lower LV mass and ou tcome during treatment for hypertension is uncertain. Obj...Context: Increased baseline left ventricular(LV) mass predicts cardiovascular( CV) complications of hypertension, but the relation between lower LV mass and ou tcome during treatment for hypertension is uncertain. Objective: To determine wh ether reduction of LV mass during antihypertensive treatment modifies risk of ma jor CV events independent of blood pressure change. Design, Setting, and Partici pants: Prospective cohort substudy of the Losartan Intervention For Endpoint Red uction in Hypertension(LIFE) randomized clinical trial, conducted from 1995 to 2 001. A total of 941 prospectively identified patients aged 55 to 80 years with e ssential hypertension and electrocardiographic LV hypertrophy had LV mass measur ed by echocardiography at enrollment in the LIFE trial and thereafter were follo wed up annually for a mean(SD) of 4.8(1.0) years for CV events. Main Outcome Mea sures: Composite end point of CV death, fatal or nonfatal myocardial infarction, and fatal or nonfatal stroke. Results: The composite end point occurred in 104 patients(11%). The multivariable Cox regression model showed a strong associati on between lower intreatment LV mass index and reduced rate of the composite C V end point(hazard ratio[HR], 0.78 per 1SD(25.3) decrease in LV mass index; 95 %confidence interval[CI], 0.65-0.94; P=.009) over and above that predicted by reduction in blood pressure. There were parallel associations between lower in treatment LV mass index and lower CV mortality (HR, 0.62; 95%CI, 0.47-0.82; P= .001), stroke (HR, 0.76; 95%CI, 0.60-0.96; P=.02), myocardial infarction (HR, 0.85; 95%CI, 0.62-1.17, P=.33), and allcause mortality (HR, 0.72; 95%CI, 0. 59-0.88, P=.002), independent of systolic blood pressure and assigned treatment . Results were confirmed in analyses adjusting for additional CV risk factors, e lectrocardiographic changes, or when only considering events after the first yea r of study treatment. Conclusion: In patients with essential hypertension and ba seline electrocardiographic LV hypertrophy, lower LV mass during antihypertensiv e treatment is associated with lower rates of clinical end points, additional to effects of blood pressure lowering and treatment modality.展开更多
Echocardiographically determined left ventricular(LV) hypertrophy may be a str onger risk factor of cardiovascular disease(CVD) for women than for men, althoug h it is unclear whether reported gender differences are r...Echocardiographically determined left ventricular(LV) hypertrophy may be a str onger risk factor of cardiovascular disease(CVD) for women than for men, althoug h it is unclear whether reported gender differences are real or attributable to confounding. We evaluated echocardiographic LV hypertrophy(defined as LV mass/he ight 2.7< 51 g/m2.7) collected from the African-American population of the Athe rosclerosis Risk in Communities Study. Incident CVD events(57 in men, 62 in wome n) were determined during a median follow-up of 4.9 years (interquartile range 4.3 to 5.6) and included nonfatal myocardial infarction, cardiac death, coronary revascularization, and stroke. We conducted 2 analyses. First, we created match ed samples of 340 men and 812 women who had LV hypertrophy based on propensity s core and estimated the gen-der-specific incidence rate ratios and population- attributable risks. Second, we evaluated the complete cohort(604 men and 1,113 w omen) with Poissons regression after adjusting for age, body mass index, hyper tension, diabetes mellitus, ratio of total cholesterol to high-density lipoprot ein cholesterol, current smoking, and education level. LV hypertrophy was signif icantly predictive of incident CVD, and the association shown by analyses of mat ched propensity scores was similar in men and women(incidence rate ratio 1.88 vs 1.92, p=0.97 for men, population-attributable risk 0.22 vs 0.26, p< 0.07 for w omen). In the multivariate analysis, we found comparable effect estimates for LV hypertrophy (incidence rate ratio 1.66 vs 2.09, p=0.55 for men; population-att ributable risk 0.24 vs 0.32, p< 0.07 for women). Thus, LV hypertrophy is a stron g predictor of CVD in African-Americans, and the effect of LV hypertrophy on CV D is similar in men and women.展开更多
The aim of this study was to investigate the effects of gender on long-term prognosis of patients undergoing dobutamine stress echocardiography(DSE). Gender differences in the predictors of outcome among patients with...The aim of this study was to investigate the effects of gender on long-term prognosis of patients undergoing dobutamine stress echocardiography(DSE). Gender differences in the predictors of outcome among patients with known or suspected coronary artery disease undergoing DSE have not been adequately studied. We studied 2,276 men and 1,105 women with known or suspected coronary artery diseasewho underwent DSE. Followup events were cardiac death and nonfatal myocardial infarction(MI). Dobutamine stress echocardiography was normal in 687 men(30%)and 483 women(44%)(p< 0.0001). Ischemia on DSE was present in 1,194 men(52%)and 416 women(38%)(p< 0.001). During a mean follow-up of 7±3.4 years, there were 894(26%)deaths(442 attributed to cardiac causes)and 145(4%)nonfatal MIs. The annual cardiac event rate was 2.5%in men and 1.2%in women with normal DSE. Independent predictors of cardiac events in patients with normal DSE using a Cox proportional hazards regression analysis were male gender(hazard ratio [HR]: 1.7 [range 1.1 to 2.8]), age(HR: 1.02 [range 1.01 to 1.04]), history of heart failure(HR: 3.4 [range 1.5 to 7.9]), previous MI(HR: 1.7 [range 1.1 to 2.8]), and diabetes(HR: 2.4 [range 1.3 to 4.5]). Independent predictors of cardiac events in patients with an abnormal DSE were age(HR: 1.03 [range 1.02 to 1.04]), history of heart failure(HR: 1.7[range 1.3 to 2.1]), diabetes(HR: 1.4 [range 1.1 to 1.8]), heart rate at rest(HR: 2.8[range 1.4 to 5.8]), wall motion abnormalities at rest(HR: 1.06 [range 1.04 to 1.09]), and ischemia on DSE(HR: 1.04 [range 1.02 to 1.07]). Myocardial ischemia was an independent predictor of cardiac events in both men and women. Dobutamine stress echocardiography provides independent prognostic information in both men and women. In patients with normal DSE, gender is independently associated with cardiac events. The outcome of patients with abnormal DSE is not related to gender, after adjusting for stress echocardiographic abnormalities.展开更多
Context: Individual contributions of obesity and physical fitness (physical ac tivity and functional capacity) to risk of coronary heart disease in women remai n unclear. Objective: To investigate the relationships of...Context: Individual contributions of obesity and physical fitness (physical ac tivity and functional capacity) to risk of coronary heart disease in women remai n unclear. Objective: To investigate the relationships of measures of obesity (b ody mass index [BMI], waist circumference, waist hip ratio, and waist height r atio) and physical fitness (self reported Duke Activity Status Index [DASI] a nd Postmenopausal Estrogen Progestin Intervention questionnaire [PEPI Q] score s) with coronary artery disease (CAD) risk factors, angiographic CAD, and adverse cardiovascular (CV) events in women evaluated for suspected myocardial ischemia. Design, Setting, and Participants: The National Heart, Lung, and Blood Institut e sponsored Womens Ischemia Syndrome Evaluation (WISE) is a multicenter prosp ective cohort study. From 1996-2000,936 women were enrolled at 4 US academic me dical centers at the time of clinically indicated coronary angiography and then assessed (mean follow up, 3.9 [SD,1.8] years) for adverse outcomes. Main Outc om e Measures: Prevalence of obstructive CAD (any angiographic stenosis ≥50%) and incidence of adverse CV events (all cause death or hospitalization for nonfata l myocardial infarction, stroke, congestive heart failure, unstable angina, or o ther vascular events) during follow up. Results: Of 906 women (mean age, 58 [S D , 12] years) with complete data, 19%were of nonwhite race, 76%were overweight (BMI ≥25), 70%had low functional capacity (DASI scores <25, equivalent to ≤7 metabolic equivalents [METs]), and 39%had obstructive CAD. During follow up, 3 37 (38%)-women had a first adverse event, 118(13%) had a major adverse event, and 68 (8%) died. Overweight women were more likely than normal weight women t o have CAD risk factors, but neither BMI nor abdominal obesity measures were sig nificantly associated with obstructive CAD or adverse CV events after adjusting for other risk factors (P=.05 to .88). Conversely, women with lower DASI scores were significantly more likely to have CAD risk factors and obstructive CAD (44 %vs 26%, P<.001) at baseline, and each 1-MET increase in DASI score was indep endently associated with an 8%(hazard ratio, 0.92; 95%confidence interval, 0.8 5-0.99; P=.02) decrease in risk of major adverse CV events during follow up. C onclusions: Among women undergoing coronary angiography for suspected ischemia, higher self reported physical fitness scores were independently associated with fewer CAD risk factors, less angiographic CAD, and lower risk for adverse CV ev ents. Measures of obesity were not independently associated with these outcomes.展开更多
Objective: To assess clinical outcomes in the Study on Cognition and Prognosis in the Elderly(SCOPE) in patients who did not receive add-on antihypertensive therapy after randomization, i.e. in patients that best refl...Objective: To assess clinical outcomes in the Study on Cognition and Prognosis in the Elderly(SCOPE) in patients who did not receive add-on antihypertensive therapy after randomization, i.e. in patients that best reflect the original intention of a placebo-controlled trial. Design: Post-hoc analysis of a prospective, randomized, controlled trial. Settings and participants: Five hundred and twenty-seven centres in 15 countries participated in SCOPE. Patients aged 70-89 years, with systolic blood pressure 160-179 mmHg and/or diastolic blood pressure 90-99 mmHg, and preserved cognitive function were eligible. Out of 4937 patients in SCOPE, 2098 did not receive add-on therapy. Intervention: The number of patients who received candesartan 8-16 mg once daily was 1253, and 845 received placebo. Mean follow-up was 3.7 and 3.5 years, respectively. Main outcome measures: Primary: major cardiovascular events(cardiovascular mortality, non-fatal stroke or non-fatal myocardial infarction). Secondary: total mortality, cardiovascular mortality, fatal and non-fatal myocardial infarction, fatal and non-fatal stroke, cognitive function, and dementia. Results: The treatment groupswere generally well balanced for baseline characteristics. Blood pressure fell by 21.8/11.0 mmHg in the candesartan group and by 17.2/ 8.4mmHgin the placebo group. There were significant relative risk reductions with candesartan in major cardiovascular events(32%,P=0.013), cardiovascular mortality(29%,P=0.049), and total mortality(27%, P =0.018). There were no significant differences between the treatment groups in cognitive outcomes. Both treatments were generally well tolerated. Conclusions: Treatment of elderly patients with mild hypertension is beneficial and supports current recommendations. Candesartan appears an appropriate therapy in such patients, in view of its favourable tolerability profile and ability to reduce major cardiovascular events.展开更多
Background and Purpose - Results from randomized controlled trials of dipyridamole, given with or without aspirin, for secondary prevention after ischemic stroke or transient ischemic attack (TIA) have given conflicti...Background and Purpose - Results from randomized controlled trials of dipyridamole, given with or without aspirin, for secondary prevention after ischemic stroke or transient ischemic attack (TIA) have given conflicting results. We performed a meta- analysis using individual patient data from relevant randomized controlled trials. Methods - Randomized controlled trials involving dipyridamole in patients with previous ischemic stroke or TIA were sought from searches of the Cochrane Library, other electronic databases, references lists, earlier reviews, and contact with the manufacturer of dipyridamole. Individual patient data were merged from 5 of 7 relevant trials involving 11 459 patients. Results were adjusted for age, gender, qualifying event, and history of previous hypertension. Results- Recurrent stroke was reduced by dipyridamole as compared with control (OR, 0.82; 95% CI, 0.68 to 1.00), and by combined aspirin and dipyridamole versus aspirin alone (OR, 0.78; 95% CI, 0.65 to 0.93), dipyridamole alone (OR, 0.74; 95% CI, 0.60 to 0.90), or control (OR, 0.61; 95% CI, 0.51 to 0.71). The point estimates obtained for the comparisons of aspirin and dipyridamole versus control (OR, 0.63; significant) or versus aspirin (OR, 0.88; nonsignificant) were similar if the data from the largest trial, ESPS II (which provided 57% of data), were excluded. Similar findings were observed for nonfatal stroke. The combination of aspirin and dipyridamole also significantly reduced the composite outcome of nonfatal stroke, nonfatal myocardial infarction, and vascular death as compared with aspirin alone (OR, 0.84; 95% CI, 0.72 to 0.97), dipyridamole alone (OR, 0.76; 95% CI, 0.64 to 0.90), or control (OR, 0.66; 95% CI, 0.57 to 0.75). Vascular death was not altered in any group. Conclusions - Dipyridamole, given alone or with aspirin, reduces stroke recurrence in patients with previous ischemic cerebrovascular disease. The combination of aspirin and dipyridamole also reduces the composite of nonfatal stroke, nonfatal myocardial infarction, and vascular death as compared with aspirin alone.展开更多
文摘B-type natriuretic peptide(BNP) and the N-terminus of pro-BNP(NT-pro-BNP) have prognostic value in patients with heart failure and patients with acute coronary syndromes. Little is known about the prognostic value of baseline NT-pro-BNP alone or in combination with C-reactive protein(CRP) for clinical outcome after percutaneous coronary intervention(PCI). Within a single center registry of contemporaneous PCI, we investigated the prognostic value of baseline plasma NT-pro-BNP and CRP concentrations for the prediction of death or nonfatal myocardial infarction(MI) during 12 to 14 months of follow-up. Among 1,172 consecutive patients, the occurrence of death or MI increased significantly with baseline NT-pro-BNP before PCI(first quartile 0 of 294, second quartile 6 of 291[2.1%], third quartile 4 of 294[1.4%], fourth quartile 22 of 293[7.5%)]; p< 0.0001). NT-pro-BNP in the top quartile significantly predicted death(odds ratio[OR] 13.37, 95%confidence interval[CI] 4.50 to 40.38, p< 0.0001) and was associated with nonfatal MI(OR 2.53, 95%CI 0.77 to 8.34, p=0.22)An abnormal CRP was significantly associated with death(OR 3.47, 95%CI 1.26 to 9.54, p=0.019). Stepwise multivariate logistic regression analysis identified age >65 years and NT-pro-BNP as independent significant predictors of death/MI(age OR 3.18, 95%CI 1.32 to 7.67, p=0.01; NT-pro-BNP OR 4.57, 95%CI 2.07 to 10.10, p=0.0001). Baseline NT-pro-BNP before PCI provides important, independent prognostic information for the occurrence of death or nonfatal MI during long-term follow-up.
文摘Background: Studies have postulated that cyclooxygenase-2(COX-2) selective inhibitors affect cardiovascular risk through various mechanisms. Some of these mechanisms could increase risk(for example, inhibition of prostacyclin production), and some could decrease risk(for example, inhibition of inflammation). Objective: To determine the effect of COX-2 inhibitors on risk for nonfatal myocardial infarction(MI). Design: Case-control study. Setting: 36 hospitals in a 5-county area. Participants: 1718 case-pa-tients with a first, nonfatal MI admitted to these hospitals and 6800 controls randomly selected from the same counties. Measurements: Self-reported medication use assessed through telephone interviews. Results: The adjusted odds ratio for MI among celecoxib users, relative to persons who did not use nonaspirin nonsteroidal anti-inflammatory drugs(NSAIDs), was 0.43(95%CI, 0.23 to 0.79) compared with 1.16(CI, 0.70 to 1.93) among rofecoxib users. The use of rofecoxib was associated with a statistically significant higher odds of MI compared with the use of celecoxib(adjusted odds ratio for rofecoxib vs. celecoxib, 2.72[CI, 1.24 to 5.95]; P=0.01). Nonselective NSAIDs were associated with a reduced odds of nonfatal MI relative to nonusers. Comparisons of COX-2 inhibitors with nonselective NSAIDs were the following: rofecoxib versus naproxen(odds ratio,3.39[CI, 1.37 to 8.40]) and celecoxib versus ibuprofen or diclofenac(odds ratio, 0.77[CI, 0.40 to 1.48]). Limitations: The possibility of recall bias and uncontrolled confounding in this observational study limit the ability to make definitive conclusions. The association of celecoxib with a lower odds of MI could have occurred by chance. Only about 50%of eligible participants completed telephone interviews. Conclusion: Celecoxib and rofecoxib were associated with different odds of MI. Cardiovascular effects among the COX-2 inhibitors seem different, but further studies, preferably randomized trials, are needed to fully understand the spectrum of effects of COX-2 inhibitors and potential differences among them.
文摘Background: Determinants of survival and of risk of vascular events after tra nsient ischaemic attack (TIA) or minor ischaemic stroke are not well defined in the long term. We aimed to restudy these risks in a prospective cohort of patien ts after TIA or minor ischaemic stroke (Rankin grade≤ 3), after 10 years or mor e. Methods: We assessed the survival status and occurrence of vascular events in 2473 participants of the Dutch TIA Trial (recruitment in 1986- 89; arterial ca use of cerebral ischaemia). We included 24 hospitals in the Netherlands that rec ruited at least 50 patients. Primary outcomes were all- cause mortality and the composite event of death from all vascular causes, non- fatal stroke, and non - fatal myocardial infarction. We assessed cumulative risks by Kaplan- Meier a nalysis and prognostic factors with Cox univariate and multivariate analysis. Fi ndings: Follow- up was complete in 2447 (99% ) patients. After a mean follow- up of 10.1 years, 1489 (60% ) patients had died and 1336 (54% ) had had at le ast one vascular event. 10- year risk of death was 42.7% (95% CI 40.8- 44. 7). Age and sex- adjusted hazard ratios were 3.33 (2.97- 3.73) for age over 65 years, 2.10 (1.79- 2.48) for diabetes, 1.77 (1.45- 2.15) for claudication, 1. 94 (1.42- 2.65) for previous peripheral vascular surgery, and 1.50 (1.31- 1.71 ) for pathological Q waves on baseline electrocardiogram. 10- year risk of a vascular event was 44.1% (42.0- 46.1). After falling in the first 3 years, yearly risk of a vascular ev ent increased over time. Predictive factors for risk of vascular events were sim ilar to those for risk of death. Interpretation: Long- term secondary preventio n in patients with cerebral ischaemia still has room for further improvement.
文摘Endocardial electromechanical mapping(EEM) has been proposed as a method for myocardial viability assessment. However, the impact of EEM data on clinical outcome has not been studied before. We sought to assess the prognostic value of EEM in patients with left ventricular(LV) dysfunction undergoing percutaneous coronary intervention (PCI). Seventyfive patients with coronary artery disease and LV dysfunction(angiographic LV ejection fraction 49±15%) underwent LV EEM for myocardial viability assessment before coronary revascularization. EEM parameters included mean unipolar electrographic amplitude, mean local shortening, LV volumes, LVEF, number of regions with electrographic amplitudes< 7.5 mV, number of electromechanical mismatch, and match regions. Cardiac death, nonfatal myocardial infarction, nonfatal stroke, and acute heart failure requiring hospitalizationwere defined as clinical events. During a follow-up of 3.6±1.8 years, 20 clinical events occurred. Event-free survival after coronary revascularizationwas significantly better in patientswith amean unipolar electrographic amplitude of ≥9.5 mV than in patients with a mean unipolar electrographic amplitude of< 9.5 mV(88%vs 57%; p< 0.005). Cox regression analysis revealed angiographic LVEF, mean electrographic amplitude, number of regions with electrographic amplitudes< 7.5 mV, number of electromechanical match regions, and EEM EF as univariate predictors of clinical events. In a multivariate analysis, angiographic LVEF< 40%(hazard ratio 4.78, p< 0.005) and mean electrographic amplitude< 9.5 mV (hazard ratio 2.92, p< 0.05) were independent predictors of clinical events. Thus, EEM provides prognostic information in patients with LV dysfunction undergoing coronary revascularization.
文摘Background: N-terminal pro-brain natriuretic peptide (NtproBNP) and N -termi nal pro-atrial natriuretic peptide (Nt-proANP) are strong cardiovascular risk markers in patients with chronic heart failure, as well as in the general popula tion. We investigated whether high Nt-proBNP or NtproANP could also predict the composite endpoint (CEP) of cardiovascular death, non-fatal stroke or non-fat al myocardial infarction in patients with hypertension and left ventricular (LV) hypertrophy. Methods: After 2 weeks of placebo treatment, clinical, laboratory and echocardiographic variables were assessed in 183 hypertensive participants i n the LIFE echo substudy with electrocardiographic LV hypertrophy. Nt-proBNP an d Nt-proANP were measured by immunoassay at baseline. The patients were followe d for 60 ±5 months. Results: Using Cox regression analysis, the 25 CEP were pre dicted by In(Nt-proBNP) (hazard ratio 1.61 per 2.73-fold increase, P < 0.01) a s well as In(Nt-pro-ANP) (hazard ratio 2.93, P < 0.05). Nt-proBNP above the m edian value of 21.8 pmol/ml was associated with higher incidence of CEP (19.6 versus 7.7%, P < 0.05). Nt-proBNP above the median value was associated with higher incidence of CEP in the 123 patients without history of diabetes or cardiovascular diseas e (14.8 versus 4.3%, P < 0.05), but the association was insignificant in the 60 patients with a history of diabetes or cardiovascular disease (26.3 versus 18.2 %, NS). Nt-proANP showed the same tendency. Conclusion: Nt-proBNP, more than Nt-proANP, strongly predicts cardiovascular events in patients with hypertensio n and LV hypertrophy, especially in patients without diabetes or clinically over t cardiovascular disease.
文摘Background: The aim of this study was to define the utility of the combined measurement of troponin I, myoglobin, C- reactive protein, fibrinogen, and homocysteine to predict risk in non- ST elevation acute coronary syndromes. Methods: Troponin I, myoglobin, high- sensitivity C- reactive protein, fibrinogen, and homocysteine were measured in 557 consecutive patients admitted to our institution for non- ST elevation acute coronary syndrome. The risk for major events(death or nonfatal myocardial infarction) at first month and at first year follow- up was analyzed. Results: In a multivariate model adjusting for baseline characteristics and electrocardiographic changes, the only biomarkers related to major events at first month were C- reactive protein(P=.007) and myoglobin(P=.02), and at first year troponin I(P=.02), C- reactive protein(P=.03), and homocysteine(P=.04). The rate of major events depending on the number(0- 5) of elevated biomarkers were at first month: 4.1% , 3.7% , 5.7% , 6.1% , 6.5% , and 30.8% (P< .0001), and at first year: 8.2% , 11.1% , 12.3% , 16.2% , 23.7% , and 50% (P< . 0001). A simple score including the number of elevated biomarkers showed an adjusted risk of major events of 1.6[1.3- 1.9] at first month and of 1.4[1.2- 1.7] at first year. Conclusions: Markers of myocardial damage, inflammation, and homocysteine analyzed separately provide prognostic information. The number of elevated biomarkers is an independent risk predictor of major events.
文摘Context: Limited data are available evaluating how the timing and intensity of statin therapy following an acute coronary syndrome (ACS) event affect clinical outcome. Objective: To compare early initiation of an intensive statin regimen with delayed initiation of a less intensive regimen in patients with ACS. Design , Setting, and Participants: International, randomized, double blind trial of p atients with ACS receiving 40 mg/d of simvastatin for 1 month followed by 80 mg/ d thereafter (n=2265) compared with ACS patients receiving placebo for 4 months followed by 20 mg/d of simvastatin (n=2232), who were enrolled in phase Z of the A to Z trial between December 29, 1999, and January 6, 2003. Main Outcome Measu re: The primary end point was a composite of cardiovascular death, nonfatal myoc ardial infarction, readmission for ACS, and stroke. Follow up was for at least 6 months and up to 24 months. Results Among the patients in the placebo plus sim vastatin group, the median low density lipoprotein (LDL) cholesterol level achi eved while taking placebo was 122mg/dL (3.16 mmol/L) at 1 month and was 77mg/dL (1.99 mmol/L) at 8 months while taking 20 mg/d of simvastatin. Among the patient s in the simvastatin only group, the median LDL cholesterol level achieved at 1 month while taking 40 mg/d of simvastatin was 68mg/dL (1.76 mmol/L) and was 63 m g/dL (1.63 mmol/L) at 8 months while taking 80 mg/d of simvastatin. A total of 3 43 patients (16.7%) in the placebo plus simvastatin group experienced the prima ry end point compared with 309 (14.4%) in the simvastatin only group (40 mg/80 mg) (hazard ratio [HR], 0.89; 95%confidence interval [Cl] 0.76-1.04; P=.14 ). C ardiovascular death occurred in 109 (5.4%) and 83 (4.1 %) patients in the 2 gr oups (HR, 0.75; 95%Cl, 0.57-1.00; P=.05) but no differences were observed in other individual components of the primary end po int. No difference was evident during the first 4 months between the groups for the primary end point (HR, 1.01; 95%Cl, 0.83-1.25; P=.89), but from 4 months t hrough the end of the study the primary end point was significantly reduced in t he simvastatin only group (HR, 0.75; 95%Cl, 0.60-0.95; P=.02). Myopathy (creat ine kinase>10 times the upper limit of normal associated with muscle symptoms) o ccurred in 9 patients (0.4%) receiving simvastatin 80 mg/d, in no patients rece iving lower doses of simvastatin, and in 1 patient receiving placebo (P=.02). Co nclusions: The trial did not achieve the prespecified end point. However, among patients with ACS, the early initiation of an aggressive simvastatin regimen res ulted in a favorable trend toward reduction of major cardiovascular events.
文摘Context: Increased baseline left ventricular(LV) mass predicts cardiovascular( CV) complications of hypertension, but the relation between lower LV mass and ou tcome during treatment for hypertension is uncertain. Objective: To determine wh ether reduction of LV mass during antihypertensive treatment modifies risk of ma jor CV events independent of blood pressure change. Design, Setting, and Partici pants: Prospective cohort substudy of the Losartan Intervention For Endpoint Red uction in Hypertension(LIFE) randomized clinical trial, conducted from 1995 to 2 001. A total of 941 prospectively identified patients aged 55 to 80 years with e ssential hypertension and electrocardiographic LV hypertrophy had LV mass measur ed by echocardiography at enrollment in the LIFE trial and thereafter were follo wed up annually for a mean(SD) of 4.8(1.0) years for CV events. Main Outcome Mea sures: Composite end point of CV death, fatal or nonfatal myocardial infarction, and fatal or nonfatal stroke. Results: The composite end point occurred in 104 patients(11%). The multivariable Cox regression model showed a strong associati on between lower intreatment LV mass index and reduced rate of the composite C V end point(hazard ratio[HR], 0.78 per 1SD(25.3) decrease in LV mass index; 95 %confidence interval[CI], 0.65-0.94; P=.009) over and above that predicted by reduction in blood pressure. There were parallel associations between lower in treatment LV mass index and lower CV mortality (HR, 0.62; 95%CI, 0.47-0.82; P= .001), stroke (HR, 0.76; 95%CI, 0.60-0.96; P=.02), myocardial infarction (HR, 0.85; 95%CI, 0.62-1.17, P=.33), and allcause mortality (HR, 0.72; 95%CI, 0. 59-0.88, P=.002), independent of systolic blood pressure and assigned treatment . Results were confirmed in analyses adjusting for additional CV risk factors, e lectrocardiographic changes, or when only considering events after the first yea r of study treatment. Conclusion: In patients with essential hypertension and ba seline electrocardiographic LV hypertrophy, lower LV mass during antihypertensiv e treatment is associated with lower rates of clinical end points, additional to effects of blood pressure lowering and treatment modality.
文摘Echocardiographically determined left ventricular(LV) hypertrophy may be a str onger risk factor of cardiovascular disease(CVD) for women than for men, althoug h it is unclear whether reported gender differences are real or attributable to confounding. We evaluated echocardiographic LV hypertrophy(defined as LV mass/he ight 2.7< 51 g/m2.7) collected from the African-American population of the Athe rosclerosis Risk in Communities Study. Incident CVD events(57 in men, 62 in wome n) were determined during a median follow-up of 4.9 years (interquartile range 4.3 to 5.6) and included nonfatal myocardial infarction, cardiac death, coronary revascularization, and stroke. We conducted 2 analyses. First, we created match ed samples of 340 men and 812 women who had LV hypertrophy based on propensity s core and estimated the gen-der-specific incidence rate ratios and population- attributable risks. Second, we evaluated the complete cohort(604 men and 1,113 w omen) with Poissons regression after adjusting for age, body mass index, hyper tension, diabetes mellitus, ratio of total cholesterol to high-density lipoprot ein cholesterol, current smoking, and education level. LV hypertrophy was signif icantly predictive of incident CVD, and the association shown by analyses of mat ched propensity scores was similar in men and women(incidence rate ratio 1.88 vs 1.92, p=0.97 for men, population-attributable risk 0.22 vs 0.26, p< 0.07 for w omen). In the multivariate analysis, we found comparable effect estimates for LV hypertrophy (incidence rate ratio 1.66 vs 2.09, p=0.55 for men; population-att ributable risk 0.24 vs 0.32, p< 0.07 for women). Thus, LV hypertrophy is a stron g predictor of CVD in African-Americans, and the effect of LV hypertrophy on CV D is similar in men and women.
文摘The aim of this study was to investigate the effects of gender on long-term prognosis of patients undergoing dobutamine stress echocardiography(DSE). Gender differences in the predictors of outcome among patients with known or suspected coronary artery disease undergoing DSE have not been adequately studied. We studied 2,276 men and 1,105 women with known or suspected coronary artery diseasewho underwent DSE. Followup events were cardiac death and nonfatal myocardial infarction(MI). Dobutamine stress echocardiography was normal in 687 men(30%)and 483 women(44%)(p< 0.0001). Ischemia on DSE was present in 1,194 men(52%)and 416 women(38%)(p< 0.001). During a mean follow-up of 7±3.4 years, there were 894(26%)deaths(442 attributed to cardiac causes)and 145(4%)nonfatal MIs. The annual cardiac event rate was 2.5%in men and 1.2%in women with normal DSE. Independent predictors of cardiac events in patients with normal DSE using a Cox proportional hazards regression analysis were male gender(hazard ratio [HR]: 1.7 [range 1.1 to 2.8]), age(HR: 1.02 [range 1.01 to 1.04]), history of heart failure(HR: 3.4 [range 1.5 to 7.9]), previous MI(HR: 1.7 [range 1.1 to 2.8]), and diabetes(HR: 2.4 [range 1.3 to 4.5]). Independent predictors of cardiac events in patients with an abnormal DSE were age(HR: 1.03 [range 1.02 to 1.04]), history of heart failure(HR: 1.7[range 1.3 to 2.1]), diabetes(HR: 1.4 [range 1.1 to 1.8]), heart rate at rest(HR: 2.8[range 1.4 to 5.8]), wall motion abnormalities at rest(HR: 1.06 [range 1.04 to 1.09]), and ischemia on DSE(HR: 1.04 [range 1.02 to 1.07]). Myocardial ischemia was an independent predictor of cardiac events in both men and women. Dobutamine stress echocardiography provides independent prognostic information in both men and women. In patients with normal DSE, gender is independently associated with cardiac events. The outcome of patients with abnormal DSE is not related to gender, after adjusting for stress echocardiographic abnormalities.
文摘Context: Individual contributions of obesity and physical fitness (physical ac tivity and functional capacity) to risk of coronary heart disease in women remai n unclear. Objective: To investigate the relationships of measures of obesity (b ody mass index [BMI], waist circumference, waist hip ratio, and waist height r atio) and physical fitness (self reported Duke Activity Status Index [DASI] a nd Postmenopausal Estrogen Progestin Intervention questionnaire [PEPI Q] score s) with coronary artery disease (CAD) risk factors, angiographic CAD, and adverse cardiovascular (CV) events in women evaluated for suspected myocardial ischemia. Design, Setting, and Participants: The National Heart, Lung, and Blood Institut e sponsored Womens Ischemia Syndrome Evaluation (WISE) is a multicenter prosp ective cohort study. From 1996-2000,936 women were enrolled at 4 US academic me dical centers at the time of clinically indicated coronary angiography and then assessed (mean follow up, 3.9 [SD,1.8] years) for adverse outcomes. Main Outc om e Measures: Prevalence of obstructive CAD (any angiographic stenosis ≥50%) and incidence of adverse CV events (all cause death or hospitalization for nonfata l myocardial infarction, stroke, congestive heart failure, unstable angina, or o ther vascular events) during follow up. Results: Of 906 women (mean age, 58 [S D , 12] years) with complete data, 19%were of nonwhite race, 76%were overweight (BMI ≥25), 70%had low functional capacity (DASI scores <25, equivalent to ≤7 metabolic equivalents [METs]), and 39%had obstructive CAD. During follow up, 3 37 (38%)-women had a first adverse event, 118(13%) had a major adverse event, and 68 (8%) died. Overweight women were more likely than normal weight women t o have CAD risk factors, but neither BMI nor abdominal obesity measures were sig nificantly associated with obstructive CAD or adverse CV events after adjusting for other risk factors (P=.05 to .88). Conversely, women with lower DASI scores were significantly more likely to have CAD risk factors and obstructive CAD (44 %vs 26%, P<.001) at baseline, and each 1-MET increase in DASI score was indep endently associated with an 8%(hazard ratio, 0.92; 95%confidence interval, 0.8 5-0.99; P=.02) decrease in risk of major adverse CV events during follow up. C onclusions: Among women undergoing coronary angiography for suspected ischemia, higher self reported physical fitness scores were independently associated with fewer CAD risk factors, less angiographic CAD, and lower risk for adverse CV ev ents. Measures of obesity were not independently associated with these outcomes.
文摘Objective: To assess clinical outcomes in the Study on Cognition and Prognosis in the Elderly(SCOPE) in patients who did not receive add-on antihypertensive therapy after randomization, i.e. in patients that best reflect the original intention of a placebo-controlled trial. Design: Post-hoc analysis of a prospective, randomized, controlled trial. Settings and participants: Five hundred and twenty-seven centres in 15 countries participated in SCOPE. Patients aged 70-89 years, with systolic blood pressure 160-179 mmHg and/or diastolic blood pressure 90-99 mmHg, and preserved cognitive function were eligible. Out of 4937 patients in SCOPE, 2098 did not receive add-on therapy. Intervention: The number of patients who received candesartan 8-16 mg once daily was 1253, and 845 received placebo. Mean follow-up was 3.7 and 3.5 years, respectively. Main outcome measures: Primary: major cardiovascular events(cardiovascular mortality, non-fatal stroke or non-fatal myocardial infarction). Secondary: total mortality, cardiovascular mortality, fatal and non-fatal myocardial infarction, fatal and non-fatal stroke, cognitive function, and dementia. Results: The treatment groupswere generally well balanced for baseline characteristics. Blood pressure fell by 21.8/11.0 mmHg in the candesartan group and by 17.2/ 8.4mmHgin the placebo group. There were significant relative risk reductions with candesartan in major cardiovascular events(32%,P=0.013), cardiovascular mortality(29%,P=0.049), and total mortality(27%, P =0.018). There were no significant differences between the treatment groups in cognitive outcomes. Both treatments were generally well tolerated. Conclusions: Treatment of elderly patients with mild hypertension is beneficial and supports current recommendations. Candesartan appears an appropriate therapy in such patients, in view of its favourable tolerability profile and ability to reduce major cardiovascular events.
文摘Background and Purpose - Results from randomized controlled trials of dipyridamole, given with or without aspirin, for secondary prevention after ischemic stroke or transient ischemic attack (TIA) have given conflicting results. We performed a meta- analysis using individual patient data from relevant randomized controlled trials. Methods - Randomized controlled trials involving dipyridamole in patients with previous ischemic stroke or TIA were sought from searches of the Cochrane Library, other electronic databases, references lists, earlier reviews, and contact with the manufacturer of dipyridamole. Individual patient data were merged from 5 of 7 relevant trials involving 11 459 patients. Results were adjusted for age, gender, qualifying event, and history of previous hypertension. Results- Recurrent stroke was reduced by dipyridamole as compared with control (OR, 0.82; 95% CI, 0.68 to 1.00), and by combined aspirin and dipyridamole versus aspirin alone (OR, 0.78; 95% CI, 0.65 to 0.93), dipyridamole alone (OR, 0.74; 95% CI, 0.60 to 0.90), or control (OR, 0.61; 95% CI, 0.51 to 0.71). The point estimates obtained for the comparisons of aspirin and dipyridamole versus control (OR, 0.63; significant) or versus aspirin (OR, 0.88; nonsignificant) were similar if the data from the largest trial, ESPS II (which provided 57% of data), were excluded. Similar findings were observed for nonfatal stroke. The combination of aspirin and dipyridamole also significantly reduced the composite outcome of nonfatal stroke, nonfatal myocardial infarction, and vascular death as compared with aspirin alone (OR, 0.84; 95% CI, 0.72 to 0.97), dipyridamole alone (OR, 0.76; 95% CI, 0.64 to 0.90), or control (OR, 0.66; 95% CI, 0.57 to 0.75). Vascular death was not altered in any group. Conclusions - Dipyridamole, given alone or with aspirin, reduces stroke recurrence in patients with previous ischemic cerebrovascular disease. The combination of aspirin and dipyridamole also reduces the composite of nonfatal stroke, nonfatal myocardial infarction, and vascular death as compared with aspirin alone.
