Incidence and case fatality of acute myocardial infarction in Norway 2013-2021. / Insidens og letalitet av akutt hjerteinfarkt i Norge 2013­21.

Background: Previous studies of the incidence and case fatality of acute myocardial infarction in Norway are based on administrative data that do not distinguish between myocardial infarction with ST segment elevation (STEMI) and without ST segment elevation (NSTEMI). The aim of this study was to investigate the incidence, case fatality and patient characteristics for different types of myocardial infarction in the period 2013-2021. Material and method: The Norwegian Myocardial Infarction Registry, the Norwegian Patient Registry and the Norwegian Cause of Death Registry were linked in order to identify all patients with myocardial infarction. We calculated age-adjusted incidence and 30-day case fatality. Results: Incidence of all types of myocardial infarction in total fell by 3.8 % per year on average (95 % CI 3.6-4.1). There was a reduction of 2.3 % (95 % CI 1.8-2.8) for STEMI, 3.1 % (95 % CI 2.8-3.4) for NSTEMI, and 6.5 % (95 % CI 5.9-7.1) for out-of-hospital deaths from myocardial infarction. Thirty-day case fatality for all types of myocardial infarction in total was 21.3 % in 2013 and 17.5 % in 2021. Case fatality for all infarctions fell by an average of 2.8 % per year (95 % CI 2.3-3.3), case fatality for NSTEMI fell by 4.4 % per year (95 % CI 3.3-5.5) per year, while case fatality for STEMI was unchanged. Interpretation: Incidence of all types of myocardial infarction declined in the period 2013-2021. Thirty-day case fatality remains high, despite a fall in case fatality for all myocardial infarctions in total and for NSTEMI. There was no change in case fatality for STEMI.

Treatment and 30-Day Mortality after Myocardial Infarction in Prostate Cancer Patients: A Population-Based Study from Norway.

INTRODUCTION: There is limited knowledge about the use of invasive treatment and mortality after acute myocardial infarction (AMI) in prostate cancer (PCa) patients. We therefore wanted to compare rates of invasive treatment and 30-day mortality between AMIs in patients with PCa and AMIs in the general Norwegian male population. METHODS: Norwegian population-based registry data from 2013 to 2019 were used in this cohort study to identify AMIs in patients with a preceding PCa diagnosis. We compared invasive treatment rates and 30-day mortality in AMI patients with PCa to the same outcomes in all male AMI patients in Norway. Invasive treatment was defined as performed angiography with or without percutaneous coronary intervention or coronary artery bypass graft surgery. Standardized mortality (SMR) and incidence ratios, and logistic regression were used to evaluate the association between PCa risk groups and invasive treatment. RESULTS: In 1,018 patients with PCa of all risk groups, the total rates of invasive treatment for AMIs were similar to the rates in the general AMI population. In patients with ST-segment elevation AMIs, rates were lower in metastatic PCa compared to localized PCa (OR 0.15, 95% CI: 0.04-0.49). For non-ST-segment elevation AMIs, there were no differences between PCa risk groups. The 30-day mortality after AMI was lower in PCa patients than in the total population of similarly aged AMI patients (SMR 0.77, 95% CI: 0.61-0.97). CONCLUSION: Except for patients with metastatic PCa experiencing an ST-segment elevation AMI, PCa patients were treated as frequent with invasive treatment for their AMI as the general AMI population. 30-day all-cause mortality was lower after AMI in PCa patients compared to the general AMI population.

Drug-Eluting versus Bare-Metal Stents in Saphenous Vein Grafts Compared to Native Coronary Vessels: The Norwegian Coronary Stent Trial Study.

BACKGROUND: Drug-eluting stents (DES) reduce target lesion revascularization (TLR) with no effect on mortality or myocardial infarction (MI) compared to bare-metal stents (BMS) in native vessels. Randomized stent studies in saphenous vein grafts (SVG) are few and the reported effects are ambiguous. The Norwegian Coronary Stent Trial study is the first to randomize lesions to percutaneous coronary intervention in native vessels and SVG. AIMS: The aim of this study was to compare the rate of mortality, MI, and TLR across stent and vessel types. METHODS: In this substudy, 6,087 patients with a single lesion in native vessels and 164 in SVG were followed for 5 years. RESULTS: MI was more frequent in SVG (subdistributional hazard ratio [SHR] 4.95 (3.75-6.54, p < 0.001), but not affected by stent type. In the first 500 days, DES reduced TLR in native vessels (SHR 0.21 (0.15-0.30) p < 0.001) and SVG (SHR 0.18 (0.04-0.80) p = 0.02). Thereafter, DES and BMS were equivalent in native vessels, but DES had a higher TLR rate than BMS in SVG (SHR 3.31 (1.23-8.94) p = 0.02). After 5 years, the TLR rate was still significantly lower for DES in native vessels (3.2% vs. 7.8%, p < 0.001) but not in SVG (21.4% vs. 18. 4%). CONCLUSION: In SVG, no difference in TLR between DES and BMS was observed after 5 years in contrast to persistent benefit in native vessels. The high rate of TLR and MI in SVG makes treatment of native vessels a preference whenever feasible and better treatment options for SVG are warranted.

Influenza vaccination and risk for cardiovascular events: a nationwide self-controlled case series study.

BACKGROUND: US and European guidelines diverge on whether to vaccinate adults who are not at high risk for cardiovascular events against influenza. Here, we investigated the associations between influenza vaccination and risk for acute myocardial infarction, stroke and pulmonary embolism during the 2009 pandemic in Norway, when vaccination was recommended to all adults. METHODS: Using national registers, we studied all vaccinated Norwegian individuals who suffered AMI, stroke, or pulmonary embolism from May 1, 2009 through September 30, 2010. We defined higher-risk individuals as those using anti-diabetic, anti-obesity, anti-thrombotic, pulmonary or cardiovascular medications (i.e. individuals to whom vaccination was routinely recommended); all other individuals were regarded as having lower-risk. We estimated incidence rate ratios with 95% CI using conditional Poisson regression in the pre-defined risk periods up to 180 days following vaccination compared to an unexposed time-period, with adjustment for season or daily temperature. RESULTS: Overall, we observed lower risk for cardiovascular events following influenza vaccination. When stratified by baseline risk, we observed lower risk across all three outcomes in association with vaccination among higher-risk individuals. In this subgroup, relative risks were 0.72 (0.59-0.88) for AMI, 0.77 (0.59-0.99) for stroke, and 0.73 (0.45-1.19) for pulmonary embolism in the period 1-14 days following vaccination when compared to the background period. These associations remained essentially the same up to 180 days after vaccination. In contrast, the corresponding relative risks among subjects not using medications were 4.19 (2.69-6.52), 1.73 (0.91-3.31) and 2.35 (0.78-7.06). CONCLUSION: In this nationwide study, influenza vaccination was associated with overall cardiovascular benefit. This benefit was concentrated among those at higher cardiovascular risk as defined by medication use. In contrast, our results demonstrate no comparable inverse association with thrombosis-related cardiovascular events following vaccination among those free of cardiovascular medications at baseline. These results may inform the risk-benefit balance for universal influenza vaccination.

Does a history of cardiovascular disease or cancer affect mortality after SARS-CoV-2 infection? / Hva betyr tidligere hjerte- og karsykdom eller kreft for risiko for død etter påvist SARS-CoV-2?

BACKGROUND: Cardiovascular disease and cancer have been described as possible risk factors for COVID-19 mortality. The purpose of this study was to investigate whether a history of cardiovascular disease or cancer affects the risk of dying after a COVID-19 diagnosis in Norway. MATERIAL AND METHOD: Data were compiled from the Norwegian Surveillance System for Communicable Diseases, the Norwegian Cardiovascular Disease Registry and the Cancer Registry of Norway. Univariable and multivariable regression models were used to calculate both relative and absolute risk. RESULTS: In the first half of 2020, 8 809 people tested positive for SARS-CoV-2 and 260 COVID-19-associated deaths were registered. Increasing age, male sex (relative risk (RR): 1.5; confidence interval (CI): 1.2-2.0), prior stroke (RR: 1.5; CI: 1.0-2.1) and cancer with distant metastasis at the time of diagnosis (RR: 3.0; CI: 1.1-8.2) were independent risk factors for death after a diagnosis of COVID-19. After adjusting for age and sex, myocardial infarction, atrial fibrillation, heart failure, hypertension, and non-metastatic cancer were no longer statistically significant risk factors for death. INTERPRETATION: The leading risk factor for death among individuals who tested positive for SARS-CoV-2 was age. Male sex, and a previous diagnosis of stroke or cancer with distant metastasis were also associated with an increased risk of death after a COVID-19 diagnosis.

Completeness and correctness of acute myocardial infarction diagnoses in a medical quality register and an administrative health register.

Aims: Health registers are used for administrative purposes, disease surveillance, quality assessment, and research. The value of the registers is entirely dependent on the quality of their data. The aim of this study was to investigate and compare the completeness and correctness of the acute myocardial infarction (AMI) diagnosis in the Norwegian Myocardial Infarction Register and in the Norwegian Patient Register. Methods: All Norwegian patients admitted directly to St Olavs hospital, Trondheim University Hospital, Trondheim University Hospital from 1 July to 31 December 2012 and who had plasma levels of cardiac troponin T measured during their hospitalization (n=4835 unique individuals, n=5882 hospitalizations) were identified in the hospital biochemical database. A gold standard for AMI was established by evaluation of maximum troponin T levels and by review of the information in the medical records. Cases of AMI in the registers were classified as true positive, false positive, true negative, and false negative according to the gold standard. We calculated sensitivity, positive predictive value (PPV), specificity, and negative predictive value (NPV). Results: The Norwegian Myocardial Infarction Register had a sensitivity of 86.0% (95% confidence interval (CI) 82.8-89.3%), PPV of 97.9% (96.4-99.3%), and specificity of 99.9% and NPV of 98.9% (98.6-99.2%) (99.8-100%). The corresponding figures for the Norwegian Patient Register were 85.8% (95% CI 82.5-89.1%), 95.1% (92.9-97.2%), and 99.7% (99.5-99.8%) and 98.9% (98.6-99.2%), respectively. Both registers had a sensitivity higher than 95% when compared to hospital discharge diagnoses. The results were similar for men and women and for cases below and above 80 years of age. Conclusions: The Norwegian Myocardial Infarction Register and the Norwegian Patient Register are adequately complete and correct for administrative purposes, disease surveillance, quality assessment, and research.

Treatment of ST-elevation myocardial infarction - an observational study. / Behandling av hjerteinfarkt med ST-elevasjon ­ en observasjonsstudie.

BACKGROUND: ST-elevation myocardial infarction is treated with reperfusion, either in the form of primary percutaneous coronary intervention (PCI) or thrombolytic therapy. The choice of treatment depends on transport time to the nearest PCI centre. Norway's geography means that thrombolytic therapy will be appropriate for many patients. Irrespective of treatment choice, it is important to avoid delays. We wished to compare the outcomes of primary PCI and thrombolytic therapy in our healthcare region and to examine whether reperfusion therapy was administered within the recommended time window. MATERIAL AND METHOD: Using registry data and patient medical records, we compared the outcomes of primary PCI and thrombolytic therapy in cases of ST-elevation myocardial infarction in the Central Norway Regional Health Authority in the period 2015-16. The outcomes analysed were 30-day mortality, ejection fraction measured by echocardiography during the hospital stay, incidence of bleeding complications, and time from diagnosis to start of treatment. RESULTS: The study population comprised 648 patients with ST-elevation myocardial infarction. Of these, 382 were treated with primary PCI and 266 received thrombolytic therapy. The 30-day mortality was 5.5 % in the primary PCI group and 5.6 % in the thrombolysis group (p = 1.0). There were no significant differences in ejection fraction and no cases of serious bleeding. In 45 % of the total population, reperfusion therapy was started later than recommended in guidelines. INTERPRETATION: There was no statistically significant difference in mortality or ejection fraction when comparing primary PCI and thrombolytic therapy in an unselected population with ST-elevation myocardial infarction. Many patients experienced delayed start of treatment . It is important to take action to reduce delays at all stages of the therapeutic chain. Thrombolytic therapy should be considered when it is unclear whether transport time to a PCI centre will exceed that recommended in guidelines.

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.

Comparison of the validity of stroke diagnoses in a medical quality register and an administrative health register.

AIMS: Health registers are essential sources of data used in a wide range of stroke research, including epidemiological, clinical and healthcare studies. Regardless of the type of register, the data must be of high quality to be useful. In this study, we investigated and compared the correctness and completeness of the Norwegian Patient Register (an administrative health register) and the Norwegian Stroke Register (a medical quality register for acute stroke). METHODS: We reviewed the medical records for 5192 admissions to hospital in 2012 and defined cases of stroke in the two registers as true positive, false positive, true negative or false negative. We calculated the sensitivity, specificity, positive predictive value (PPV) and negative predictive value with 95% confidence intervals assuming a normal approximation of the binomial distribution. RESULTS: The Norwegian Stroke Register was highly correct and relatively complete (sensitivity 88.1%, specificity 100% and PPV 98.6%). The Norwegian Patient Register was more complete, but less correct, when we included both the main and secondary diagnoses of stroke (sensitivity 96.8%, specificity 99.6% and PPV 79.7%); restricting the analyses to the main diagnoses of stroke resulted in less complete and more correct registrations (sensitivity 86.1%, specificity 99.9% and PPV 93.5%). CONCLUSIONS: The Norwegian Stroke Register and the Norwegian Patient Register are adequately complete and correct to serve as valuable sources of data for epidemiological, clinical and healthcare studies, as well as for administrative purposes.

Mind the intention-behavior gap: a qualitative study of post-myocardial infarction patients' beliefs and experiences with long-term supervised and self-monitored physical exercise.

BACKGROUND: Many post-myocardial infarction (MI) patients struggle with physical activity behavior change (BC) for life-long secondary prevention. There is limited knowledge about factors influencing long-term physical activity BC among post-MI patients. This qualitative study aimed to explore the beliefs and experiences related to post-MI patients' physical activity BC process following a year's participation in a supervised and self-monitored exercise program: the Norwegian Trial of Physical Exercise After MI (NorEx). METHODS: We conducted a qualitative study, performing in-depth semi-structured interviews with a randomly selected sample of NorEx participants when they were scheduled for cardiopulmonary exercise testing after one year of participation. Interviews were transcribed verbatim and the data was analyzed by applying reflexive thematic analysis. RESULTS: Seventeen participants (n = 4 female [24%]; median age, 61 years; median time since index MI, 4 years) were recruited and interviewed once. Analysis resulted in four main themes (nine sub-themes): (1) Personal responsibility to exercise (Exercise is safe, Health benefits, Habitual exercise); (2) Peer social support for a sense of safety and belonging (Social exercise, Supervision is preferred); (3) Research participation transformed exercise beliefs (High-intensity exercise is superior, Personal Activity Intelligence (PAI) promotes exercise adherence); and (4) Mind the intention-behavior gap (Initial anxiety, Lack of continued follow-up). CONCLUSIONS: Several participants reported that they were able to maintain exercise BC during a year's participation in NorEx. Nevertheless, a perceived lack of continued and individualized follow-up made some participants struggle with motivation and self-regulation, leading to an intention-behavior gap. Therefore, our findings suggest there is a need for individualized and continued social support and supervision from health and exercise professionals to maintain long-term exercise BC for secondary prevention among post-MI patients. TRIAL REGISTRATION: The NorEx study has been registered at ClinicalTrials.gov (NCT04617639, registration date 2020-10-21).

Exploring variation in timely reperfusion treatment in ST-segment elevation myocardial infarction in Norway: a national register-based cohort study.

OBJECTIVES: This study aimed to investigate determinants of reperfusion within recommended time limits (timely reperfusion) for ST-segment elevation myocardial infarction patients, exploring the impact of geography, patient characteristics and socio-economy. DESIGN: National register-based cohort study. SETTING: Multilevel logistic regression models were applied to examine the associations between timely reperfusion and residency in hospital referral areas and municipalities, patient characteristics, and socio-economy. PARTICIPANTS: 7607 Norwegian ST-segment elevation myocardial infarction patients registered in the Norwegian Registry of Myocardial Infarction during 2015-2018. MAIN OUTCOME MEASURES: The odds of timely reperfusion by primary percutaneous coronary intervention (PCI) or fibrinolysis. RESULTS: Among 7607 ST-segment elevation myocardial infarction patients in Norway, 56% received timely reperfusion. The Norwegian goal is 85%. While 81% of the patients living in the Oslo hospital referral area received timely reperfusion, only 13% of the patients living in Finnmark did so.Patients aged 75-84 years had lower odds of timely reperfusion than patients below 55 years of age (OR 0.73, 95% CI 0.61 to 0.87). Patients with moderate or high comorbidity had lower odds than patients without (OR 0.81, 95% CI 0.68 to 0.95 and OR 0.61, 95% CI 0.44 to 0.84). More than 2 hours from symptom onset to first medical contact gave lower odds than less than 30 min (OR 0.63, 95% CI 0.54 to 0.72). 1-2 hours of travel time to a PCI centre (OR 0.39, 95% CI 0.31 to 0.49) and more than 2 hours (OR 0.22, 95% CI 0.16 to 0.30) gave substantially lower odds than less than 1 hour of travel time. CONCLUSIONS: The varying proportion of patients receiving timely reperfusion across hospital referral areas implies inequity in fundamental healthcare services, not compatible with established Norwegian health policy. The importance of travel time to PCI centre points at the expanded use of prehospital pharmacoinvasive strategy to obtain the goals of timely reperfusion in Norway.

Lipid Levels During Adult Lifetime in Men and Women With and Without a Subsequent Incident Myocardial Infarction: A Longitudinal Analysis of Data From the Tromsø Study 1974 to 2016.

Background The atherosclerotic effect of an adverse lipid profile is assumed to accumulate throughout life, leading to increased risk of myocardial infarction (MI). Still, little is known about age at onset and duration of unfavorable lipid levels before MI. Methods and Results Longitudinal data on serum lipid levels for 26 130 individuals (50.5% women, aged 20-89 years) were obtained from 7 population-based health surveys in Tromsø, Norway. Diagnoses of MI were obtained from national registers. A linear mixed model was applied to compare age- and sex-specific mean values of total cholesterol, high-density lipoprotein cholesterol (HDL-C), and triglyceride concentration by MI status (MI versus non-MI). Already from young adulthood, 20 to 35 years before the incident MI, individuals with a subsequent incident MI had on average more adverse lipid levels than individuals of the same age and sex without MI. Analogous to a dose-response relationship, there was a clear trend toward more severe adverse lipid levels the lower the age at incident MI (P<0.001, test for trend through ordered categories <55, 55-74, ≥75 years). This trend was particularly pronounced for high-density lipoprotein cholesterol in percentage of total cholesterol (both sexes) and for the relative relationship between triglyceride, high-density lipoprotein cholesterol, and total cholesterol level (women). The difference in mean lipid level by MI status was just as large in women as in men, but the age pattern differed (P≤0.05, tests of 3-way interaction). Conclusions Compared with general population mean levels, adverse lipid levels were seen 20 to 35 years before the incident MI in both men and women.

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 non-winter 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.

Validating Acute Myocardial Infarction Diagnoses in National Health Registers for Use as Endpoint in Research: The Tromsø Study.

PURPOSE: To assess whether acute myocardial infarction (MI) diagnoses in national health registers are sufficiently correct and complete to replace manual collection of endpoint data for a population-based, epidemiological study. PATIENTS AND METHODS: Using the Tromsø Study Cardiovascular Disease Register for 2013-2014 as gold standard, we calculated correctness (defined as positive predictive value (PPV)) and completeness (defined as sensitivity) of MI cases in the Norwegian Myocardial Infarction Register and the Norwegian Patient Register separately and in combination. We calculated the sensitivity and PPV with 95% confidence intervals using the Clopper-Pearson Exact test. RESULTS: We identified 153 MI cases in the gold standard. In the Norwegian Myocardial Infarction Register, we found a PPV of 97.1% (95% confidence interval (CI) 92.8-99.2) and a sensitivity of 88.2% (95% CI 82.0-92.9). In the Norwegian Patient Register, the PPV was 96.3% (95% CI 91.6-98.8) and the sensitivity was 85.6% (95% CI 79.0-90.8). The combined dataset of the Norwegian Myocardial Infarction Register and the Norwegian Patient Register had a PPV of 96.6% (95% CI 92.1-98.9) and a sensitivity of 91.5% (95% CI 85.9-95.4). CONCLUSION: MI diagnoses in both the Norwegian Myocardial Infarction Register and the Norwegian Patient Register were highly correct and complete, and each of the registers could be considered as endpoint sources for the Tromsø Study. A combination of the two national registers seemed, however, to represent the most comprehensive data source overall. The benefits of using data from national registers as endpoints in epidemiological studies include faster, less resource-intensive access to nationwide data and considerably lower loss to follow-up, compared to manual data collection in a limited geographical area.

Incidence and risk factors for major bleeding among patients undergoing percutaneous coronary intervention: Findings from the Norwegian Coronary Stent Trial (NORSTENT).

INTRODUCTION: Bleeding is a concern after percutaneous coronary intervention (PCI) and subsequent dual antiplatelet therapy (DAPT). We herein report the incidence and risk factors for major bleeding in the Norwegian Coronary Stent Trial (NORSTENT). MATERIALS AND METHODS: NORSTENT was a randomized, double blind, pragmatic trial among patients with acute coronary syndrome or stable coronary disease undergoing PCI during 2008-11. The patients (N = 9,013) were randomized to receive either a drug-eluting stent or a bare-metal stent, and were treated with at least nine months of DAPT. The patients were followed for a median of five years, with Bleeding Academic Research Consortium (BARC) 3-5 major bleeding as one of the safety endpoints. We estimated cumulative incidence of major bleeding by a competing risks model and risk factors through cause-specific Cox models. RESULTS: The 12-month cumulative incidence of major bleeding was 2.3%. Independent risk factors for major bleeding were chronic kidney disease, low bodyweight (< 60 kilograms), diabetes mellitus, and advanced age (> 80 years). A myocardial infarction (MI) or PCI during follow-up increased the risk of major bleeding (HR = 1.67, 95% CI 1-29-2.15). CONCLUSIONS: The 12-month cumulative incidence of major bleeding in NORSTENT was higher than reported in previous, explanatory trials. This analysis strengthens the role of chronic kidney disease, advanced age, and low bodyweight as risk factors for major bleeding among patients receiving DAPT after PCI. The presence of diabetes mellitus or recurrent MI among patients is furthermore a signal of increased bleeding risk. CLINICAL TRIAL REGISTRATION: Unique identifier NCT00811772; http://www.clinicaltrial.gov.

Homocysteine lowering and cardiovascular events after acute myocardial infarction.

BACKGROUND: Homocysteine is a risk factor for cardiovascular disease. We evaluated the efficacy of homocysteine-lowering treatment with B vitamins for secondary prevention in patients who had had an acute myocardial infarction. METHODS: The trial included 3749 men and women who had had an acute myocardial infarction within seven days before randomization. Patients were randomly assigned, in a two-by-two factorial design, to receive one of the following four daily treatments: 0.8 mg of folic acid, 0.4 mg of vitamin B12, and 40 mg of vitamin B6; 0.8 mg of folic acid and 0.4 mg of vitamin B12; 40 mg of vitamin B6; or placebo. The primary end point during a median follow-up of 40 months was a composite of recurrent myocardial infarction, stroke, and sudden death attributed to coronary artery disease. RESULTS: The mean total homocysteine level was lowered by 27 percent among patients given folic acid plus vitamin B12, but such treatment had no significant effect on the primary end point (risk ratio, 1.08; 95 percent confidence interval, 0.93 to 1.25; P=0.31). Also, treatment with vitamin B6 was not associated with any significant benefit with regard to the primary end point (relative risk of the primary end point, 1.14; 95 percent confidence interval, 0.98 to 1.32; P=0.09). In the group given folic acid, vitamin B12, and vitamin B6, there was a trend toward an increased risk (relative risk, 1.22; 95 percent confidence interval, 1.00 to 1.50; P=0.05). CONCLUSIONS: Treatment with B vitamins did not lower the risk of recurrent cardiovascular disease after acute myocardial infarction. A harmful effect from combined B vitamin treatment was suggested. Such treatment should therefore not be recommended. (ClinicalTrials.gov number, NCT00266487.).

Cancer incidence and mortality after treatment with folic acid and vitamin B12.

CONTEXT: Recently, concern has been raised about the safety of folic acid, particularly in relation to cancer risk. OBJECTIVE: To evaluate effects of treatment with B vitamins on cancer outcomes and all-cause mortality in 2 randomized controlled trials. DESIGN, SETTING, AND PARTICIPANTS: Combined analysis and extended follow-up of participants from 2 randomized, double-blind, placebo-controlled clinical trials (Norwegian Vitamin Trial and Western Norway B Vitamin Intervention Trial). A total of 6837 patients with ischemic heart disease were treated with B vitamins or placebo between 1998 and 2005, and were followed up through December 31, 2007. INTERVENTIONS: Oral treatment with folic acid (0.8 mg/d) plus vitamin B(12) (0.4 mg/d) and vitamin B(6) (40 mg/d) (n = 1708); folic acid (0.8 mg/d) plus vitamin B(12) (0.4 mg/d) (n = 1703); vitamin B(6) alone (40 mg/d) (n = 1705); or placebo (n = 1721). MAIN OUTCOME MEASURES: Cancer incidence, cancer mortality, and all-cause mortality. RESULTS: During study treatment, median serum folate concentration increased more than 6-fold among participants given folic acid. After a median 39 months of treatment and an additional 38 months of posttrial observational follow-up, 341 participants (10.0%) who received folic acid plus vitamin B(12) vs 288 participants (8.4%) who did not receive such treatment were diagnosed with cancer (hazard ratio [HR], 1.21; 95% confidence interval [CI], 1.03-1.41; P = .02). A total of 136 (4.0%) who received folic acid plus vitamin B(12) vs 100 (2.9%) who did not receive such treatment died from cancer (HR, 1.38; 95% CI, 1.07-1.79; P = .01). A total of 548 patients (16.1%) who received folic acid plus vitamin B(12) vs 473 (13.8%) who did not receive such treatment died from any cause (HR, 1.18; 95% CI, 1.04-1.33; P = .01). Results were mainly driven by increased lung cancer incidence in participants who received folic acid plus vitamin B(12). Vitamin B(6) treatment was not associated with any significant effects. CONCLUSION: Treatment with folic acid plus vitamin B(12) was associated with increased cancer outcomes and all-cause mortality in patients with ischemic heart disease in Norway, where there is no folic acid fortification of foods. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT00671346.