Jan Mannsverk

Randomized Study on Simple Versus Complex Stenting of Coronary Artery Bifurcation Lesions: The Nordic Bifurcation Study

Background— The optimal stenting strategy in coronary artery bifurcation lesions is unknown. In the present study, a strategy of stenting both the main vessel and the side branch (MV+SB) was compared with a strategy of stenting the main vessel only, with optional stenting of the side branch (MV), with sirolimus-eluting stents. Methods and Results— A total of 413 patients with a bifurcation lesion were randomized. The primary end point was a major adverse cardiac event: cardiac death, myocardial infarction, target-vessel revascularization, or stent thrombosis after 6 months. At 6 months, there were no significant differences in rates of major adverse cardiac events between the groups (MV+SB 3.4%, MV 2.9%; P=NS). In the MV+SB group, there were significantly longer procedure and fluoroscopy times, higher contrast volumes, and higher rates of procedure-related increases in biomarkers of myocardial injury. A total of 307 patients had a quantitative coronary assessment at the index procedure and after 8 months. The combined angiographic end point of diameter stenosis >50% of main vessel and occlusion of the side branch after 8 months was found in 5.3% in the MV group and 5.1% in the MV+SB group (P=NS). Conclusions— Independent of stenting strategy, excellent clinical and angiographic results were obtained with percutaneous treatment of de novo coronary artery bifurcation lesions with sirolimus-eluting stents. The simple stenting strategy used in the MV group was associated with reduced procedure and fluoroscopy times and lower rates of procedure-related biomarker elevation. Therefore, this strategy can be recommended as the routine bifurcation stenting technique.

Drug-Eluting or Bare-Metal Stents for Coronary Artery Disease

BACKGROUND Limited data are available on the long-term effects of contemporary drug-eluting stents versus contemporary bare-metal stents on rates of death, myocardial infarction, repeat revascularization, and stent thrombosis and on quality of life. METHODS We randomly assigned 9013 patients who had stable or unstable coronary artery disease to undergo percutaneous coronary intervention (PCI) with the implantation of either contemporary drug-eluting stents or bare-metal stents. In the group receiving drug-eluting stents, 96% of the patients received either everolimus- or zotarolimus-eluting stents. The primary outcome was a composite of death from any cause and nonfatal spontaneous myocardial infarction after a median of 5 years of follow-up. Secondary outcomes included repeat revascularization, stent thrombosis, and quality of life. RESULTS At 6 years, the rates of the primary outcome were 16.6% in the group receiving drug-eluting stents and 17.1% in the group receiving bare-metal stents (hazard ratio, 0.98; 95% confidence interval [CI], 0.88 to 1.09; P=0.66). There were no significant between-group differences in the components of the primary outcome. The 6-year rates of any repeat revascularization were 16.5% in the group receiving drug-eluting stents and 19.8% in the group receiving bare-metal stents (hazard ratio, 0.76; 95% CI, 0.69 to 0.85; P<0.001); the rates of definite stent thrombosis were 0.8% and 1.2%, respectively (P=0.0498). Quality-of-life measures did not differ significantly between the two groups. CONCLUSIONS In patients undergoing PCI, there were no significant differences between those receiving drug-eluting stents and those receiving bare-metal stents in the composite outcome of death from any cause and nonfatal spontaneous myocardial infarction. Rates of repeat revascularization were lower in the group receiving drug-eluting stents. (Funded by the Norwegian Research Council and others; NORSTENT ClinicalTrials.gov number, NCT00811772 .).

Randomized Comparison of Coronary Bifurcation Stenting With the Crush Versus the Culotte Technique Using Sirolimus Eluting Stents The Nordic Stent Technique Study

Background—In a number of coronary bifurcation lesions, both the main vessel and the side branch need stent coverage. Using sirolimus eluting stents, we compared 2 dedicated bifurcation stent techniques, the crush and the culotte techniques in a randomized trial with separate clinical and angiographic end-points. Methods and Results—A total of 424 patients with a bifurcation lesion were randomized to crush (n=209) and culotte (n=215) stenting. The primary end point was major adverse cardiac events; cardiac death, myocardial infarction, target vessel revascularization, or stent thrombosis after 6 months. At 6 months there were no significant differences in major adverse cardiac event rates between the groups; crush 4.3%, culotte 3.7% (P=0.87). Procedure and fluoroscopy times and contrast volumes were similar in the 2 groups. The rates of procedure-related increase in biomarkers of myocardial injury were 15.5% in crush versus 8.8% in culotte group (P=0.08). A total of 324 patients had a quantitative coronary assessment at the index procedure and after 8 months. The angiographic end-points of in-segment and in-stent restenosis of main vessel and/or side branch after 8 months were found in 12.1% versus 6.6% (P=0.10) and in 10.5% versus 4.5% (P=0.046) in the crush and culotte groups, respectively. Conclusions—Both the crush and the culotte bifurcation stenting techniques were associated with similar and excellent clinical and angiographic results. Angiographically, there was a trend toward less in-segment restenosis and significantly reduced in-stent restenosis following culotte stenting.

Safety in simple versus complex stenting of coronary artery bifurcation lesions. The Nordic Bifurcation Study 14-month follow-up results

AIMS The risk of stent thrombosis has been reported to increase with percutaneous coronary intervention (PCI) complexity. The present study reports the pre-specified secondary endpoint of a 14-month stent thrombosis and major adverse cardiac events in patients stented with a simple versus a complex bifurcation technique using sirolimus eluting stents (SES). METHODS AND RESULTS A total of 413 patients with a coronary bifurcation lesion were randomised to a simple treatment strategy; stenting of main vessel and optional stenting of side branch (MV group), or to a complex stenting strategy; stenting of both main vessel and side branch (MV+SB group). Mortality data were available in all patients and 14-month clinical follow-up data in 395 (96%) of the patients. After 14 months, the rates of definite, probable and possible stent thrombosis (ARC criteria) were 1.0% vs. 0.5%, 1.0% vs. 0% and 0.5% vs. 0% (ns) in the MV and in the MV+SB groups, respectively. Rates of MACE were 9.5% in the MV group and 8.2% in the MV+SB group (ns). Total death was seen in 2.4% vs. 1.0% and non-PCI related myocardial infarction in 2.0% vs. 1.0% in the MV and the MV+SB groups, respectively. CONCLUSIONS After 14 months, two months after recommended cessation of dual antiplatelet therapy, the rates of stent thrombosis and major adverse cardiac events were low and independent of treatment complexity in patients treated with SES for coronary artery bifurcation lesions.

Age and gender differences in incidence and case fatality trends for myocardial infarction: a 30-year follow-up. The Tromsø Study:

Background: Although the mortality of coronary heart disease (CHD) has declined in Western countries during the last decades, studies have suggested that the prevention and treatment of CHD may not have been as effective in women as in men. We examined gender- and age-specific trends in incidence, case fatality and the severity of first myocardial infarction (MI) in a large Norwegian population-based study. Design: Prospective population-based cohort study. Methods: A total of 31,323 participants enrolled between 1974 and 2001 were followed throughout 2004 for a total of 400,572 person-years. Suspected coronary events were adjudicated by a review of hospital records and death certificates. A total of 1669 events fulfilled standardized criteria of first-ever fatal or non-fatal MI. Results: In the age group 35–79 years, the age-adjusted incidence of MI declined significantly in men, whereas an increase was observed in women. For men and women ≥80 years the incidence rates remained unchanged. The severity of MI and the 28-day and 1-year case fatality rates declined significantly and similarly in men and women. Conclusion: Trends in MI incidence differed by sex and age; in the age group 35–79 years a marked decrease was observed among men but an increase was observed among women, while no change was observed among older patients. MI severity and case fatality were clearly reduced for both sexes. These data suggest that the burden of CHD is shifting from middle-aged men toward middle-aged women and elderly patients.

Trends in Modifiable Risk Factors Are Associated With Declining Incidence of Hospitalized and Nonhospitalized Acute Coronary Heart Disease in a Population.

Background— Few studies have used individual person data to study whether contemporary trends in the incidence of coronary heart disease are associated with changes in modifiable coronary risk factors. Methods and Results— We identified 29 582 healthy men and women ≥25 years of age who participated in 3 population surveys conducted between 1994 and 2008 in Tromsø, Norway. Age- and sex-adjusted incidence rates were calculated for coronary heart disease overall, out-of-hospital sudden death, and hospitalized ST-segment–elevation and non–ST-segment–elevation myocardial infarction. We measured coronary risk factors at each survey and estimated the relationship between changes in risk factors and changes in incidence trends. A total of 1845 participants had an incident acute coronary heart disease event during 375 064 person-years of follow-up from 1994 to 2010. The age- and sex-adjusted incidence of total coronary heart disease decreased by 3% (95% confidence interval, 2.0–4.0; P<0.001) each year. This decline was driven by decreases in out-of-hospital sudden death and hospitalized ST-segment–elevation myocardial infarction. Changes in coronary risk factors accounted for 66% (95% confidence interval, 48–97; P<0.001) of the decline in total coronary heart disease. Favorable changes in cholesterol contributed 32% to the decline, whereas blood pressure, smoking, and physical activity each contributed 14%, 13%, and 9%, respectively. Conclusions— We observed a substantial decline in the incidence of coronary heart disease that was driven by reductions in out-of-hospital sudden death and hospitalized ST-segment–elevation myocardial infarction. Changes in modifiable coronary risk factors accounted for 66% of the decline in coronary heart disease events.

Seasonal variation in cardiovascular disease risk factors in a subarctic population: the Tromsø Study 1979–2008

Background Seasonal changes in cardiovascular disease (CVD) risk factors may be due to exposure to seasonal environmental variables like temperature and acute infections or seasonal behavioural patterns in physical activity and diet. Investigating the seasonal pattern of risk factors should help determine the causes of the seasonal pattern in CVD. Few studies have investigated the seasonal variation in risk factors using repeated measurements from the same individual, which is important as individual and population seasonal patterns may differ. Methods The authors investigated the seasonal pattern in systolic and diastolic blood pressure, heart rate, body weight, total cholesterol, triglycerides, high-density lipoprotein cholesterol, C reactive protein and fibrinogen. Measurements came from 38 037 participants in the population-based cohort, the Tromsø Study, examined up to eight times from 1979 to 2008. Individual and population seasonal patterns were estimated using a cosinor in a mixed model. Results All risk factors had a highly statistically significant seasonal pattern with a peak time in winter, except for triglycerides (peak in autumn), C reactive protein and fibrinogen (peak in spring). The sizes of the seasonal variations were clinically modest. Conclusions Although the authors found highly statistically significant individual seasonal patterns for all risk factors, the sizes of the changes were modest, probably because this subarctic population is well adapted to a harsh climate. Better protection against seasonal risk factors like cold weather could help reduce the winter excess in CVD observed in milder climates.

Seasonal variation in incidence of acute myocardial infarction in a sub-Arctic population: the Tromsø Study 1974-2004

Background: A seasonal pattern with higher winter morbidity and mortality has been reported for acute myocardial infarction (MI). The magnitude of the difference between peak and nadir season has been associated with latitude, but results are inconsistent. Studies of seasonal variation of MI in population-based cohorts, based on adjudicated MI cases, are few. We investigated the monthly and seasonal variation in first-ever nonfatal and fatal MI in the population of Tromsø in northern Norway, a region with a harsh climate and extreme seasonal variation in daylight exposure. Design: Prospective population-based cohort study. Methods: A total of 37 392 participants from the Tromsø Study enrolled between 1974 and 2001 were followed throughout 2004. Each incident case of MI was validated by the review of medical records and death certificates. MI incidence rates for months and seasons were analyzed for seasonal patterns with Poisson regression and the Cosinor procedure. All analyses were stratified by sex, age and smoking status. Results: A total of 1893 first-ever MIs were registered, of which 592 were fatal. There was an 11 % (95% confidence interval: 1.00–1.23, P = 0.04) increased risk of incident MI during winter (November-January) compared with nonwinter seasons, with no statistically significant interaction with sex, age, smoking or calendar year. Other seasonal modelling gave similar but not statistically significant results. Conclusion: We found a small increase in risk of incident MI during the darkest winter months. Populations living in sub-Arctic areas may be adapted to face climate exposure during winter through behavioural protection.

The effect of daily weather conditions on myocardial infarction incidence in a subarctic population: the Tromsø Study 1974–2004

Background Meteorological factors like cold temperatures and heavy snowfalls have been reported to increase myocardial infarction (MI) incidence, but there are inconsistencies in results as well as in methodology in previous studies. The objective of this study was to examine the impact of meteorological factors on incidence of MI in a population-based study in Tromsø, Norway (69°39′N). Methods A total of 32 110 participants from the Tromsø Study enrolled between 1974 and 2001 were followed throughout 2004. Each incident case of MI was validated by the review of medical records and death certificates. Meteorological data from the Tromsø Weather Station were collected from the Norwegian Meteorological Institute database. Poisson regression models were applied to analyse the impact of meteorological factors on MI incidence. All analyses were stratified by sex and age. Results A total of 1882 first-ever MIs were registered. The main finding was an increase in MI incidence among persons older than 65 years with decreasing temperatures (p=0.016) and increasing snowfall (p=0.030). When comparing the lower and upper limits of the temperature distribution (−10°C with 20°C), the MI risk increased by 47% (RR=1.47, 95% CI 1.09 to 2.13). Comparing limits of the snowfall distribution (10 with 0 mm), the MI risk increased by 44% (RR=1.44, 95% CI 1.07 to 1.94). Conclusions In this subarctic population, MI incidence was little affected by the weather, probably due to behavioural protection. However, cold weather and heavy snowfall may be associated with increased risk of MI among older people.

Coronary bypass graft patency cannot be determined by multidetector spiral computed tomography

Objectives. Angiography by selective catheterization is the reference standard for coronary bypass graft patency assessment but carries a risk of serious complications. We have investigated whether 16-slice multidetector spiral computed tomography (MDCT) can substitute for selective angiography. Design. Two to three years after coronary artery bypass grafting, 45 patients with a total of 156 bypasses (100 single and 28 sequential grafts) were examined with both MDCT and conventional selective angiography on the same day. The bypasses were classified as patent, stenotic or occluded. Results. The likelihood ratio for MDCT-detected occlusion was 40, reflecting a fairly high combined sensitivity and specificity. However, 24% of the distal anastomoses could not be evaluated by MDCT, mainly because of respiratory movements, artifacts due to metal clips, and small vessel dimensions. Moreover, seven out of 117 bypasses (6%) deemed evaluable by MDCT were wrongly classified by this method. Conclusions. At present, 16-slice MDCT cannot replace selective angiography for assessment of coronary bypass graft patency since 24% of bypasses could not be evaluated by this method, and an error rate of 6% is unacceptable.