R.T. van Domburg

The benefits of statins in people without established cardiovascular disease but with cardiovascular risk factors: meta-analysis of randomised controlled trials

Objectives To investigate whether statins reduce all cause mortality and major coronary and cerebrovascular events in people without established cardiovascular disease but with cardiovascular risk factors, and whether these effects are similar in men and women, in young and older (>65 years) people, and in people with diabetes mellitus. Design Meta-analysis of randomised trials. Data sources Cochrane controlled trials register, Embase, and Medline. Data abstraction Two independent investigators identified studies on the clinical effects of statins compared with a placebo or control group and with follow-up of at least one year, at least 80% or more participants without established cardiovascular disease, and outcome data on mortality and major cardiovascular disease events. Heterogeneity was assessed using the Q and I2 statistics. Publication bias was assessed by visual examination of funnel plots and the Egger regression test. Results 10 trials enrolled a total of 70 388 people, of whom 23 681 (34%) were women and 16 078 (23%) had diabetes mellitus. Mean follow-up was 4.1 years. Treatment with statins significantly reduced the risk of all cause mortality (odds ratio 0.88, 95% confidence interval 0.81 to 0.96), major coronary events (0.70, 0.61 to0.81), and major cerebrovascular events (0.81, 0.71 to 0.93). No evidence of an increased risk of cancer was observed. There was no significant heterogeneity of the treatment effect in clinical subgroups. Conclusion In patients without established cardiovascular disease but with cardiovascular risk factors, statin use was associated with significantly improved survival and large reductions in the risk of major cardiovascular events.

Individual risk assessment for intracranial haemorrhage during thrombolytic therapy

Thrombolytic therapy improves outcome in patients with myocardial infarction but is associated with an increased risk of intracranial haemorrhage. For some patients, this risk may outweigh the potential benefits of thrombolytic treatment. Using data from other studies, we developed a model for the assessment of an individuals risk of intracranial haemorrhage during thrombolysis. Data were available from 150 patients with documented intracranial haemorrhage and 294 matched controls. 49 patients with intracranial haemorrhage and 122 controls had been treated with streptokinase, whereas 88 cases and 148 controls had received alteplase. By multivariate analysis, four factors were identified as independent predictors of intracranial haemorrhage; age over 65 years (odds ratio 2.2 [95% Cl 1.4-3.5]), body weight below 70 kg (2.1 [1.3-3.2]), hypertension on hospital admission (2.0 [1.2-3.2]), and administration of alteplase (1.6 [1.0-2.5]). If the overall incidence of intracranial haemorrhage is assumed to be 0.75%, patients without risk factors who receive streptokinase have a 0.26% probability of intracranial haemorrhage. The risk is 0.96%, 1.32%, and 2.17% in patients with one, two, or three risk factors, respectively. We present a model for individual risk assessment that can be used easily in clinical practice.

Excellent survival and low incidence of arrhythmias, stroke and heart failure long-term after surgical ASD closure at young age. A prospective follow-up study of 21-33 years

AIMS Although studies have suggested good long-term results, arrhythmias, pulmonary hypertension and left ventricular dysfunction are mentioned as sequelae long-term after surgical atrial septal defect closure at young age. Most studies were performed only by questionnaire and in a retrospective manner. The long-term outcome is very important with regard to future employment and acceptance on insurance schemes. METHODS AND RESULTS One hundred and thirty-five consecutive ASD-patients, operated on in childhood, were studied longitudinally with ECG, echocardiography, exercise testing and Holter-recording 15 (10-22) and 26 (21-33) years after surgery. During follow-up no cardiovascular mortality, stroke, heart failure and no pulmonary hypertension occurred. Symptomatic supraventricular tachyarrhythmias were present in 6% after 15 years, and an additional 2% occurred in the last decade; 5% needed pacemaker implantation. No relation was found between arrhythmias and type of ASD, baseline data, right ventricular dimensions, or age at operation. Left and right ventricular function and dimension remained unchanged. Slightly more patients had right atrial dilatation at last follow-up. Exercise capacity was comparable with the normal Dutch population. CONCLUSIONS The long-term outcome after ASD closure at young age shows excellent survival and low morbidity. The incidence of supraventricular arrhythmias is lower than in natural history studies of ASD patients and also lower than after surgical correction at adult age.

Psychosocial functioning of the adult with congenital heart disease: a 20–33 years follow-up

AIMS Since knowledge about the psychosocial function of adult patients with congenital heart disease is limited, we compared biographical characteristics, and emotional and social functioning of these patients with that of the reference groups. METHODS AND RESULTS Patients with congenital heart disease (N=362, aged 20-46 years), belonging to five diagnostic groups, were subjected to extensive medical and psychological examination, 20-33 years after their first open heart surgery. All the patients were seen by the same psychologist, who examined their psychosocial functioning using a structured interview and questionnaires. The majority (78%)was living independently and showed favourable outcome regarding the marital status. Among married/cohabitant patients, 25-39-year-olds showed normal offspring rates. None of the 20-24-year-old patients had any children. The offspring rate dropped after the age of 40. The proportion of adult patients with a history of special education was high (27%). Accordingly, patients showed lower educational and occupational levels compared to reference groups. As regard to the emotional and social functioning (leisure-time activities), the sample showed favourable results. CONCLUSIONS Overall, this sample of patients with congenital heart disease seemed capable of leading normal lives and seemed motivated to make good use of their abilities.

Which patients benefit most from early thrombolytic therapy with intracoronary streptokinase

The effect of thrombolysis in acute myocardial infarction on enzymatic infarct size, left ventricular function, and early mortality was studied in subsets of patients in a randomized trial. Early thrombolytic therapy with intracoronary streptokinase (152 patients) or with intracoronary streptokinase preceded by intravenous streptokinase (117 patients) was compared with conventional treatment (264 patients). All 533 patients were admitted to the coronary care unit within 4 hr after onset of symptoms indicative of acute myocardial infarction. Four hundred eighty-eight patients were eligible for this detailed analysis, and 245 of these were allocated to thrombolytic therapy and 243 to conventional treatment. Early angiographic examinations were performed in 212 patients allocated to thrombolytic therapy. Patency of the infarct-related artery was achieved in 181 patients (85%). Enzymatic infarct size, as measured from cumulative alpha-hydroxybutyrate dehydrogenase release, was smaller in patients allocated to thrombolytic therapy (median 760 vs 1170 U/liter in control patients, p = .0001). Left ventricular ejection fraction measured by radionuclide angiography before discharge from the hospital was higher after thrombolytic therapy (median 50% vs 43% in control patients, p = .0001). Three month mortality was lower in patients allocated to thrombolytic therapy (6% vs 14% in the control group, p = .006). With the use of multivariate regression analysis, infarct size limitation, improvement in left ventricular ejection fraction, and three month mortality were predicted by sum of the ST segment elevation, time from onset of symptoms to admission, and Killip class at admission. Thrombolysis was most effective in patients admitted within 2 hr after onset of symptoms and in patients with a sum of ST segment elevation of 1.2 mV or more. On the other hand, no beneficial effects of streptokinase on enzymatic infarct size, left ventricular function, or mortality were observed in the subset of patients with a sum of ST segment elevation of less than 1.2 mV who were admitted between 2 and 4 hr after onset of symptoms.

Routine sirolimus eluting stent implantation for unselected in-stent restenosis: insights from the rapamycin eluting stent evaluated at Rotterdam cardiology hospital (RESEARCH) registry

Objective: To assess the effectiveness of routine sirolimus eluting stent (SES) implantation for unselected patients with in-stent restenosis and to provide preliminary information about the angiographic outcome for lesion subgroups and for different in-stent restenosis patterns. Design: Prospective, single centre registry. Setting: Tertiary referral centre. Patients: 44 consecutive patients (53 lesions) without previous brachytherapy who were treated with SES for in-stent restenosis were evaluated. Routine angiographic follow up was obtained at six months and the incidence of major adverse cardiovascular events was evaluated. Results: At baseline, 42% of the lesions were focal, 21% diffuse, 26% proliferative, and 11% total occlusions. Small vessel size (reference diameter ⩽ 2.5 mm) was present in 49%, long lesions (> 20 mm) in 30%, treatment of bypass grafts in 13%, and bifurcation stenting in 18%. At follow up, post-SES restenosis was observed in 14.6%. No restenosis was observed in focal lesions. For more complex lesions, restenosis rates ranged from 20–25%. At the one year follow up, the incidence of death was 0, myocardial infarction 4.7% (n  =  2), and target lesion revascularisation 16.3% (n  =  7). The target lesion was revascularised because of restenosis in 11.6% (n  =  5). Conclusions: Routine SES implantation is highly effective for focal in-stent restenosis and appears to be a promising strategy for more complex patterns of restenosis.

Reduced positive affect (anhedonia) predicts major clinical events following implantation of coronary-artery stents.

Objective.  Emotional distress has been related to clinical events in patients with coronary artery disease, but the influence of positive affect (i.e. mood states such as activity, joy and cheerfulness) has received little attention. Therefore, we wanted to investigate the role of positive affect on clinical outcome after percutaneous coronary intervention (PCI) with stent implantation in these patients.

Long term outcome after coronary stent implantation: a 10 year single centre experience of 1000 patients

OBJECTIVE To describe the long term clinical outcome (up to 11 years) after coronary stenting. DESIGN A single centre observational study encompassing 1000 consecutive patients with a first stent implantation (1560 stents) between 1986 and 1996, who were followed for at least one year with a median follow up of 29 months (range 12–132 months). RESULTS Up to July 1997 the cumulative incidence of the major adverse cardiac events (MACE) of death, non-fatal acute myocardial infarction, coronary artery bypass grafting, and repeat percutaneous transluminal coronary angioplasty was 8.2%, 12.8%, 13.1%, and 22.4%, respectively. Survival at one, three, and five years was 95%, 91%, and 86%, respectively. Comparison of MACE incidence during the “anticoagulant era” and the “ticlopidine era” revealed significantly improved event free survival with ticlopidine (27% v13%; p < 0.005). Multivariable analyses showed that ejection fraction < 50% (relative risk (RR) 4.1), multivessel disease (RR 3.0), diabetes (RR 2.9), implantation in saphenous vein graft (RR 2.1), indication for unstable angina (RR 1.9), and female sex (RR 1.7) were independent predictors of increased mortality after stenting. Independent predictors of any MACE were multivessel stenting (RR 2.0), implantation in saphenous bypass graft (RR 1.6), diabetes (RR 1.5), anticoagulant treatment (versus ticlopidine and aspirin) (RR 1.5), bailout stenting (RR 1.5), multivessel disease (RR 1.4), and multiple stent implantation (RR 1.5). CONCLUSIONS Long term survival and infarct free survival was good, particularly in non-diabetic men with single vessel disease and good ventricular function, who had a single stent implanted in a native coronary artery. A dramatic improvement was observed in event free survival, both early and late, with the replacement of anticoagulation by ticlopidine. This, of course, cannot be separated from improved stent implantation techniques between 1986 and 1995. Ultimately, almost 40% of the patients experienced an adverse cardiac event (mainly repeat intervention) in the long term. New advances in restenosis treatments and in secondary prevention must be directed at this aspect of patient management after stenting.

One year clinical follow up of paclitaxel eluting stents for acute myocardial infarction compared with sirolimus eluting stents

Objective: To compare clinical outcome of paclitaxel eluting stents (PES) versus sirolimus eluting stents (SES) for the treatment of acute ST elevation myocardial infarction. Design and patients: The first 136 consecutive patients treated exclusively with PES in the setting of primary percutaneous coronary intervention for acute myocardial infarction in this single centre registry were prospectively clinically assessed at 30 days and one year. They were compared with 186 consecutive patients treated exclusively with SES in the preceding period. Setting: Academic tertiary referral centre. Results: At 30 days, the rate of all cause mortality and reinfarction was similar between groups (6.5% v 6.6% for SES and PES, respectively, p  =  1.0). A significant difference in target vessel revascularisation (TVR) was seen in favour of SES (1.1% v 5.1% for PES, p  =  0.04). This was driven by stent thrombosis (n  =  4), especially in the bifurcation stenting (n  =  2). At one year, no significant differences were seen between groups, with no late thrombosis and 1.5% in-stent restenosis (needing TVR) in PES versus no reinterventions in SES (p  =  0.2). One year survival free of major adverse cardiac events (MACE) was 90.2% for SES and 85% for PES (p  =  0.16). Conclusions: No significant differences were seen in MACE-free survival at one year between SES and PES for the treatment of acute myocardial infarction with very low rates of reintervention for restenosis. Bifurcation stenting in acute myocardial infarction should, if possible, be avoided because of the increased risk of stent thrombosis.

COPD and cancer mortality: the influence of statins

Background: Chronic obstructive pulmonary disease (COPD) is associated with an increased risk of lung cancer, independently of smoking. However, the relationship between COPD and total cancer mortality is less certain. A study was undertaken to investigate the association between COPD and total cancer mortality and to determine whether the use of statins, which have been associated with cancer risk in other settings, modified this relationship. Methods: The study included 3371 patients with peripheral arterial disease who underwent vascular surgery between 1990 and 2006; 1310 (39%) had COPD and the rest did not. The primary end point was cancer mortality (lung and extrapulmonary) over a median follow-up of 5 years. Results: COPD was associated with an increased risk of both lung cancer mortality (hazard ratio (HR) 2.06; 95% CI 1.32 to 3.20) and extrapulmonary cancer mortality (HR 1.43; 95% CI 1.06 to 1.94). The excess risk was mostly driven by patients with moderate and severe COPD. There was a trend towards a lower risk of cancer mortality among patients with COPD who used statins compared with patients with COPD who did not use statins (HR 0.57; 95% CI 0.32 to 1.01). Interestingly, the risk of extrapulmonary cancer mortality was lower among statin users with COPD (HR 0.49; 95% CI 0.24 to 0.99). Conclusions: COPD was associated with increased lung and extrapulmonary cancer mortality in this large cohort of patients with peripheral arterial disease undergoing vascular surgery. The risk of lung cancer mortality increased with progression of COPD. Statins were associated with a reduced risk of extrapulmonary cancer mortality in patients with COPD.