Cardiovascular risk prediction in type 2 diabetes before and after widespread screening: a derivation and validation study.

BACKGROUND: Until recently, most patients with diabetes worldwide have been diagnosed when symptomatic and have high cardiovascular risk, meaning most should be prescribed cardiovascular preventive medications. However, in New Zealand, a world-first national programme led to approximately 90% of eligible adults being screened for diabetes by 2016, up from 50% in 2012, identifying many asymptomatic patients with recent-onset diabetes. We hypothesised that cardiovascular risk prediction equations derived before widespread screening would now significantly overestimate risk in screen-detected patients. METHODS: New Zealanders aged 30-74 years with type 2 diabetes and without known cardiovascular disease, heart failure, or substantial renal impairment were identified from the 400 000-person PREDICT primary care cohort study between Oct 27, 2004, and Dec 30, 2016, covering the period before and after widespread screening. Sex-specific equations estimating 5-year risk of cardiovascular disease were developed using Cox regression models, with 18 prespecified predictors, including diabetes-related and renal function measures. Equation performance was compared with an equivalent equation derived in the New Zealand Diabetes Cohort Study (NZDCS), which recruited between 2000 and 2006, before widespread screening. FINDINGS: 46 652 participants were included in the PREDICT-1° Diabetes subcohort, of whom 4114 experienced first cardiovascular events during follow-up (median 5·2 years, IQR 3·3-7·4). 14 829 (31·8%) were not taking oral hypoglycaemic medications or insulin at baseline. Median 5-year cardiovascular risk estimated by the new equations was 4·0% (IQR 2·3-6·8) in women and 7·1% (4·5-11·2) in men. The older NZDCS equation overestimated median cardiovascular risk by three times in women (median 14·2% [9·7-20·0]) and two times in men (17·1% [4·5-20·0]). Model and discrimination performance measures for PREDICT-1° Diabetse equations were also significantly better than for the NZDCS equation (eg, for women: R2=32% [95% CI 29-34], Harrell's C=0·73 [0·72-0·74], Royston's D=1·410 [1·330-1·490] vs R2=24% [21-26], C=0·69 [0·67-0·70], and D=1·147 [1·107-1·187]). INTERPRETATION: International treatment guidelines still consider most people with diabetes to be at high cardiovascular risk; however, we show that recent widespread diabetes screening has radically changed the cardiovascular risk profile of people with diabetes in New Zealand. Many of these patients have normal renal function, are not dispensed glucose-lowering medications, and have low cardiovascular risk. These findings have clear international implications as increased diabetes screening is inevitable due to increasing obesity, simpler screening tests, and the introduction of new-generation glucose-lowering medications that prevent cardiovascular events. Cardiovascular risk prediction equations derived from contemporary diabetes populations, with multiple diabetes-related and renal function predictors, will be required to better differentiate between low-risk and high-risk patients in this increasingly heterogeneous population and to inform appropriate non-pharmacological management and cost-effective targeting of expensive new medications. FUNDING: Health Research Council of New Zealand, Heart Foundation of New Zealand, and Healthier Lives National Science Challenge.

Cardiovascular disease preventive medication dispensing for almost every New Zealander 65 years and over: a preventive treatment paradox?

OBJECTIVE: To describe the dispensing of cardiovascular disease (CVD) preventive medications among older New Zealanders with and without prior CVD or diabetes. METHODS: New Zealanders aged ≥65 years in 2013 were identified using anonymised linkage of national administrative health databases. Dispensing of blood pressure lowering (BPL), lipid lowering (LL) or antithrombotic (AT) medications, was documented, stratified by age and by history of CVD, diabetes, or neither. RESULTS: Of the 593,549 people identified, 32% had prior CVD, 14% had diabetes (of whom half also had prior CVD) and 61% had neither diagnosis. For those with prior CVD, between 79-87% were dispensed BPL and 73-79% were dispensed AT medications, across all age groups. In contrast, LL dispensing was lower than either BPL or AT in every age group, falling from 75% at age 65-69 years to 43% at 85+ years. For people with diabetes, BPL and LL dispensing was similar to those with prior CVD, but AT dispensing was approximately 20% lower. Among people without prior CVD or diabetes, both BPL and AT dispensing increased with age (from 39% and 17% at age 65-69 years to 56% and 35% at 85+ years respectively), whereas LL dispensing was 26-31% across the 65-84 year age groups, falling to 17% at 85+ years. CONCLUSION: The much higher dispensing of BPL and AT compared to LL medications with increasing age suggests a preventive treatment paradox for older people, with the medications most likely to cause adverse effects being dispensed most often.

Ten-year trends in cardiac implantable electronic devices in New Zealand: a national data linkage study (ANZACS-QI 51).

BACKGROUND: Implant rates for cardiac implantable electronic devices (CIED), including permanent pacemakers (PPM) and implantable cardioverter defibrillators (ICD), have increased globally in recent decades. AIMS: This is the first national study providing a contemporary analysis of national CIED implant trends by sex-specific age groups over an extended period. METHODS: Patient characteristics and device type were identified for 10 years (2009-2018) using procedure coding in the National Minimum Datasets, which collects all New Zealand (NZ) public hospital admissions. CIED implant rates represent implants/million population. RESULTS: New PPM implant rates increased by 4.6%/year (P < 0.001), increasing in all age groups except patients <40 years. Males received 60.1% of new PPM implants, with higher implant rates across all age groups compared with females. The annual increase in age-standardised implant rates was similar for males and females (3.4% vs 3.0%; P = 0.4). By 2018 the overall PPM implant rate was 538/million. New ICD implant rates increased by 4.2%/year (P < 0.001), increasing in all age groups except patients <40 and ≥ 80 years. Males received 78.1% of new ICD implants, with higher implant rates across all age groups compared to females. The annual increase in age-standardised implant rates was higher in males compared with females (3.5% vs 0.7%; P < 0.001). By 2018 the overall ICD implant rate was 144/million. CONCLUSION: CIED implant rates have increased steadily in NZ over the past decade but remain low compared with international benchmarks. Males had substantially higher CIED implant rates compared with females, with a growing gender disparity in ICD implant rates.

Regional variation in cardiac implantable electronic device implants trends in New Zealand over the past decade (ANZACS-QI 54).

BACKGROUND: Permanent pacemaker (PPM) and implantable cardioverter defibrillator (ICD) implant rates have increased in New Zealand over the past decade. AIMS: To provide a contemporary analysis of regional variation in implant rates. METHODS: New PPM and ICD implants in patients aged ≥15 years were identified for 10 years (2009-2018) using procedure coding in the National Minimum Datasets, which collects all New Zealand public hospital admissions. Age-standardised new implant rates per million adult population were calculated for each of the four regions (Northern, Midland, Central and Southern) and the 20 district health boards (DHB) across those regions. Trend analysis was performed using joinpoint regression. RESULTS: New PPM implant rates increased nationally by 3.4%/year (P < 0.001). The Northern region had the highest new PPM implant rate, increasing by 4.5%/year (P < 0.001). Excluding DHB with <50 000 people, the new PPM implant rate for 2017/2018 was highest in Counties Manukau DHB (854.3/million; 95% confidence interval (CI): 774.9-933.6/million) and lowest in Canterbury DHB (488.6/million; 95% CI: 438.1-539.0/million). New ICD implant rates increased nationally by 3.0%/year (P = 0.002). The Midland region had the highest new ICD implant rate, increasing by 3.8%/year (P = 0.013). Excluding DHB with <50 000 people, the new ICD implant rate for 2017-2018 was highest in the Bay of Plenty DHB (228.5/million; 95% CI: 180.4-276.6/million) and lowest in Canterbury DHB (90.2/million; 95% CI: 69.9-110.4/million). CONCLUSION: There was significant variation in PPM and ICD implant rates across regions and DHB, suggesting potential inequity in patient access across New Zealand.

Guideline-Directed Medical Therapy Before and After Primary Prevention Implantable Cardioverter Defibrillator Implantation in New Zealand (ANZACS-QI 66).

INTRODUCTION: Guidelines recommend angiotensin converting enzyme inhibitors (ACEi)/angiotensin receptor blockers (ARB)/angiotensin receptor neprilysin inhibitors (ARNI); beta blockers; and mineralocorticoid receptor antagonists (MRA) in patients with symptomatic heart failure and reduced left ventricular ejection fraction before consideration of primary prevention implantable cardioverter defibrillator (ICD). This study aims to investigate dispensing rates of guideline-directed medical therapy (GDMT) before and after primary prevention ICD implantation in New Zealand. METHODS: All patients receiving a primary prevention ICD between 2009 and 2018 were identified using nationally collected data on all public hospital admissions in New Zealand. This was anonymously linked to national pharmaceutical data to obtain medication dispensing. Medications were categorised as low dose (<50% of target dose), 50-99% of target dose or target dose based on international guidelines. RESULTS: Of the 1,698 patients identified, ACEi/ARB/ARNI, beta blockers and MRA were dispensed in 80.2%, 83.6% and 45.4%, respectively, prior to ICD implant. However, ≥50% target doses of each medication class were dispensed in only 51.8%, 51.8% and 34.5%, respectively. Only 15.8% of patients were receiving ≥50% target doses of all three classes of medications. In the 1,666 patients who survived 1 year after ICD implant, the proportions of patients dispensed each class of medications remained largely unchanged. CONCLUSION: Dispensing of GDMT was suboptimal in patients before and after primary prevention ICD implantation in New Zealand, and only a minority received ≥50% target doses of all classes of medication. Interventions are needed to optimise use of these standard evidence-based medications to improve clinical outcomes and avoid unnecessary device implantation.

Dual versus single long-acting bronchodilator use could raise acute coronary syndrome risk by over 50%: A population-based nested case-control study.

BACKGROUND: Coronary heart disease occurs more frequently among patients with chronic obstructive pulmonary disease (COPD) compared to those without COPD. While some research suggests that long-acting bronchodilators might confer an additional risk of acute coronary syndrome (ACS), information from real-world clinical practice about the cardiovascular impact of using two versus one long-acting bronchodilator for COPD is limited. We undertook a population-based nested case-control study to estimate the risk of ACS in users of both a long-acting muscarinic antagonist (LAMA) and a long-acting beta2-agonist (LABA) relative to users of a LAMA. METHODS: The study was based on the primary care PREDICT Cardiovascular Disease Cohort and linked data from regional laboratories and the New Zealand Ministry of Health's national data collections. The underlying cohort (n = 29,993) comprised patients aged 45-84 years, who initiated treatment with a LAMA and/or LABA for COPD between 1 February 2006 and 11 October 2016. 1490 ACS cases were matched to 13,550 controls by date of birth, sex, date of cohort entry (first long-acting bronchodilator dispensing), and COPD severity. RESULTS: Relative to current use of LAMA therapy, current use of LAMA and LABA dual therapy was associated with a significantly higher risk of ACS (adjusted OR = 1.72; [95% CI: 1.28-2.31]). CONCLUSION: Dual long-acting bronchodilator therapy, rather than LAMA mono-therapy, could increase the risk of ACS by more than 50%. This has important implications for decisions about the potential benefit/harm ratio of COPD treatment intensification, given the modest benefits of dual therapy.

Rationale, design and population description of the CREDENCE study: cardiovascular risk equations for diabetes patients from New Zealand and Chinese electronic health records.

The cardiovascular risk equations for diabetes patients from New Zealand and Chinese electronic health records (CREDENCE) study is a unique prospectively designed investigation of cardiovascular risk in two large contemporary cohorts of people with type 2 diabetes from New Zealand (NZ) and China. The study was designed to derive equivalent cardiovascular risk prediction equations in a developed and a developing country, using the same epidemiological and statistical methodology. Two similar cohorts of people with type 2 diabetes were identified from large general population studies in China and New Zealand, which had been generated from longitudinal electronic health record systems. The CREDENCE study aims to determine whether cardiovascular risk prediction equations derived in patients with type 2 diabetes in a developed country are applicable in a developing country, and vice versa, by deriving and validating equivalent diabetes-specific cardiovascular risk prediction models from the two countries. Baseline data in CREDENCE was collected from October 2004 in New Zealand and from January 2010 in China. In the first stage of CREDENCE, a total of 93,207 patients (46,649 from NZ and 46,558 from China) were followed until December 31st 2018. Median follow-up was 7.0 years (New Zealand) and 5.7 years (China). There were 5926 (7.7% fatal) CVD events in the New Zealand cohort and 3650 (8.8% fatal) in the Chinese cohort. The research results have implications for policy makers, clinicians and the public and will facilitate personalised management of cardiovascular risk in people with type 2 diabetes worldwide.

Risk of major bleeding by ethnicity and socioeconomic deprivation among 488,107 people in primary care: a cohort study.

BACKGROUND: Antithrombotic medications (antiplatelets and anticoagulants) reduce the risk of cardiovascular disease (CVD), but with the disadvantage of increasing bleeding risk. Ethnicity and socioeconomic deprivation are independent predictors of major bleeds among patients without CVD, but it is unclear whether they are also predictors of major bleeds among patients with CVD or atrial fibrillation (AF) after adjustment for clinical variables. METHODS: Prospective cohort study of 488,107 people in New Zealand Primary Care (including 64,420 Maori, the indigenous people of New Zealand) aged 30-79 years who had their CVD risk assessed between 2007 and 2016. Participants were divided into three mutually exclusive subgroups: (1) AF with or without CVD (n = 15,212), (2) CVD and no AF (n = 43,790), (3) no CVD or AF (n = 429,105). Adjusted hazards ratios (adjHRs) were estimated from Cox proportional hazards models predicting major bleeding risk for each of the three subgroups to determine whether ethnicity and socioeconomic deprivation are independent predictors of major bleeds in different cardiovascular risk groups. RESULTS: In all three subgroups (AF, CVD, no CVD/AF), Maori (adjHR 1.63 [1.39-1.91], 1.24 [1.09-1.42], 1.57 [95% CI 1.45-1.70], respectively), Pacific people (adjHR 1.90 [1.58-2.28], 1.30 [1.12-1.51], 1.62 [95% CI 1.49-1.75], respectively) and Chinese people (adjHR 1.53 [1.08-2.16], 1.15 [0.90-1.47], 1.13 [95% CI 1.01-1.26], respectively) were at increased risk of a major bleed compared to Europeans, although for Chinese people the effect did not reach statistical significance in the CVD subgroup. Compared to Europeans, Maori and Pacific peoples were generally at increased risk of all bleed types (gastrointestinal, intracranial and other bleeds). An increased risk of intracranial bleeds was observed among Chinese and Other Asian people and, in the CVD and no CVD/AF subgroups, among Indian people. Increasing socioeconomic deprivation was also associated with increased risk of a major bleed in all three subgroups (adjHR 1.07 [1.02-1.12], 1.07 [1.03-1.10], 1.10 [95% CI 1.08-1.12], respectively, for each increase in socioeconomic deprivation quintile). CONCLUSION: Ethnicity and socioeconomic status should be considered in bleeding risk assessments to guide the use of antithrombotic medication for the management of AF and CVD.

Increases in early discharge following acute coronary syndrome hospitalisations and associated clinical outcomes in New Zealand between 2006 and 2015: ANZACS-QI-43 study.

BACKGROUND: International guidelines recommend early discharge for uncomplicated acute coronary syndrome (ACS) patients within 3 days; however, there is a paucity of contemporary literature regarding the safety of this strategy. AIMS: To report the trends in the proportion of ACS hospitalisations discharged within 3 days and their outcomes in New Zealand. METHODS: ACS hospitalisations 2006-2015 using national routinely collected data were categorised by length of stay (LOS) into ≤3, 4-5 and >5 days, excluding deaths during the index admission. Trend analysis of death, cardiovascular and bleeding events and their composites (net adverse clinical events) at 30-day and 1-year post-discharge were performed using generalised linear mixed regression models adjusting for covariates by LOS subgroups. RESULTS: Among 130 037 ACS hospitalisations, LOS ≤ 3 days increased from 32% in 2006 to 44% in 2016. This trend was observed for all demographics, ACS subtypes and management strategies. Event rates at 30 days and 1 year were the lowest for the LOS ≤3 days subgroup (all-cause mortality 1.6% and 9.1% respectively). Thirty-day and 1-year all-cause mortality rates were unchanged over time for this subgroup (adjusted odds ratio (95% confidence interval) of 1.011 (0.985-1.038) and 0.991 (0.979-1.003)), while net adverse clinical event rates significantly decreased (0.962 (0.950-0.973) and 0.972 (0.964-0.980) respectively). CONCLUSION: There was a substantial increase in early discharge post-ACS over 10 years. These patients were associated with reduction in adverse clinical events up to 1 year and no increase in all-cause mortality. These findings from a comprehensive national register suggest that guideline recommendations on early discharge after uncomplicated ACS are safe and appropriate.

Trends in Ischaemic Heart Disease in Australia, 2001-2015: A Comparison of Urban and Rural Populations.

OBJECTIVE: Ischaemic heart disease (IHD) is a major source of disease burden worldwide. Recent trends show incidence is declining but it is unclear whether the trends are similar in urban and rural populations. This study examines the trends of IHD events (i.e. hospitalisations and deaths) in New South Wales, Australia by rurality. METHODS: This was a retrospective analysis of linked administrative data for hospitalisation and death records across NSW between 2001 and 2015. Participants were NSW residents aged 15-105 years who died or were hospitalised with a principal diagnosis of IHD. The main outcome measures were annual age-standardised mortality and hospitalisations for IHD by calendar year and rurality. RESULTS: Between 2001 and 2015, age-standardised annual IHD hospitalisations declined in urban areas from 587 to 260 and in rural areas from 766 to 395 per 100,000 people. The annual decline in hospitalisations was greater in urban than rural areas, with Annual Percentage Change (APC) of -5.6% (95% CI, -6.1%, -5.0%) and -4.5% (95% CI, -5.0%, -4.0%), respectively (p=0.012). Ischaemic heart disease mortality declined at a similar rate in urban and rural regions (APC -7.6% and -6.7% per annum, p=0.28). Absolute inequalities in IHD deaths persisted until 2015 when there were 49 (urban) and 70 (rural) IHD deaths per 100,000 people. CONCLUSIONS: Ischaemic heart disease hospitalisations and mortality have declined considerably between 2001 and 2015 in both rural and urban areas, yet inequalities persist, suggesting more intensive preventive efforts are required to further reduce the burden of IHD in rural populations.

Eligibility and subsequent burden of cardiovascular disease of four strategies for blood pressure-lowering treatment: a retrospective cohort study.

BACKGROUND: Worldwide treatment recommendations for lowering blood pressure continue to be guided predominantly by blood pressure thresholds, despite strong evidence that the benefits of blood pressure reduction are observed in patients across the blood pressure spectrum. In this study, we aimed to investigate the implications of alternative strategies for offering blood pressure treatment, using the UK as an illustrative example. METHODS: We did a retrospective cohort study in primary care patients aged 30-79 years without cardiovascular disease, using data from the UK's Clinical Practice Research Datalink linked to Hospital Episode Statistics and Office for National Statistics mortality. We assessed and compared four different strategies to determine eligibility for treatment: using 2011 UK National Institute for Health and Care Excellence (NICE) guideline, or proposed 2019 NICE guideline, or blood pressure alone (threshold ≥140/90 mm Hg), or predicted 10-year cardiovascular risk alone (QRISK2 score ≥10%). Patients were followed up until the earliest occurrence of a cardiovascular disease diagnosis, death, or end of follow-up period (March 31, 2016). For each strategy, we estimated the proportion of patients eligible for treatment and number of cardiovascular events that could be prevented with treatment. We then estimated eligibility and number of events that would occur during 10 years in the UK general population. FINDINGS: Between Jan 1, 2011, and March 31, 2016, 1 222 670 patients in the cohort were followed up for a median of 4·3 years (IQR 2·5-5·2). 271 963 (22·2%) patients were eligible for treatment under the 2011 NICE guideline, 327 429 (26·8%) under the proposed 2019 NICE guideline, 481 859 (39·4%) on the basis of a blood pressure threshold of 140/90 mm Hg or higher, and 357 840 (29·3%) on the basis of a QRISK2 threshold of 10% or higher. During follow-up, 32 183 patients were diagnosed with cardiovascular disease (overall rate 7·1 per 1000 person-years, 95% CI 7·0-7·2). Cardiovascular event rates in patients eligible for each strategy were 15·2 per 1000 person-years (95% CI 15·0-15·5) under the 2011 NICE guideline, 14·9 (14·7-15·1) under the proposed 2019 NICE guideline, 11·4 (11·3-11·6) with blood pressure threshold alone, and 16·9 (16·7-17·1) with QRISK2 threshold alone. Scaled to the UK population, we estimated that 233 152 events would be avoided under the 2011 NICE guideline (28 patients needed to treat for 10 years to avoid one event), 270 233 under the 2019 NICE guideline (29 patients), 301 523 using a blood pressure threshold (38 patients), and 322 921 using QRISK2 threshold (27 patients). INTERPRETATION: A cardiovascular risk-based strategy (QRISK2 ≥10%) could prevent over a third more cardiovascular disease events than the 2011 NICE guideline and a fifth more than the 2019 NICE guideline, with similar efficiency regarding number treated per event avoided. FUNDING: National Institute for Health Research.

On Meat, Butter, and Fudge.

Was the Annals of Internal Medicine recently acting as a mouthpiece for meat-industry propaganda? Five papers underpinned recommendations on meat consumption; their central deceit was to review only randomized controlled trials and cohort studies, which, in research on the associations between common foods and disease outcomes, are nearer to the bottom than the top of the evidence hierarchy. Despite concluding that their own recommendations were "weak and based on low certainty evidence", the authors were happy to recommend that there is "No need to reduce red or processed meat consumption for good health." What we actually know is that: red meat consumption is an order of magnitude higher now than through most of human history; red meat is a probable, and processed meat is a definite, human carcinogen; saturated fat increases risk of heart disease; and vegans and vegetarians have better lipid profiles, lower risk of chronic disease, and greater longevity than meat eaters. There are other consequences of meat consumption too, including: altered sexual development; widespread antimicrobial resistance; and disrupted planetary health, including depletion of aquifers, groundwater pollution, and increased greenhouse gases. The pseudoscience presented in the Annals of Internal Medicine appears to have been written solely to create doubt and confusion in the wider population. Scientists and journals should hold themselves to a higher standard.

Predicting Bleeding Risk to Guide Aspirin Use for the Primary Prevention of Cardiovascular Disease: A Cohort Study.

Background: Many prognostic models for cardiovascular risk can be used to estimate aspirin's absolute benefits, but few bleeding risk models are available to estimate its likely harms. Objective: To develop prognostic bleeding risk models among persons in whom aspirin might be considered for the primary prevention of cardiovascular disease (CVD). Design: Prospective cohort study. Setting: New Zealand primary care. Participants: The study cohort comprised 385 191 persons aged 30 to 79 years whose CVD risk was assessed between 2007 and 2016. Those with indications for or contraindications to aspirin and those who were already receiving antiplatelet or anticoagulant therapy were excluded. Measurements: For each sex, Cox proportional hazards models were developed to predict major bleeding risk; participants were censored at the earliest of the date on which they first met an exclusion criterion, date of death, or study end date (30 June 2017). The main models included the following predictors: demographic characteristics (age, ethnicity, and socioeconomic deprivation), clinical measurements (systolic blood pressure and ratio of total-high-density lipoprotein cholesterol), family history of premature CVD, medical history (smoking, diabetes, bleeding, peptic ulcer disease, cancer, chronic liver disease, chronic pancreatitis, or alcohol-related conditions), and medication use (nonsteroidal anti-inflammatory agents, corticosteroids, and selective serotonin reuptake inhibitors). Results: During 1 619 846 person-years of follow-up, 4442 persons had major bleeding events (of which 313 [7%] were fatal). The main models predicted a median 5-year bleeding risk of 1.0% (interquartile range, 0.8% to 1.5%) in women and 1.1% (interquartile range, 0.7% to 1.6%) in men. Plots of predicted-against-observed event rates showed good calibration throughout the risk range. Limitation: Hemoglobin level, platelet count, and body mass index were excluded from the main models because of high numbers of missing values, and the models were not externally validated in non-New Zealand populations. Conclusion: Prognostic bleeding risk models were developed that can be used to estimate the absolute bleeding harms of aspirin among persons in whom aspirin is being considered for the primary prevention of CVD. Primary Funding Source: The Health Research Council of New Zealand.

Personalized Prediction of Cardiovascular Benefits and Bleeding Harms From Aspirin for Primary Prevention: A Benefit-Harm Analysis.

Background: Whether the benefits of aspirin for the primary prevention of cardiovascular disease (CVD) outweigh its bleeding harms in some patients is unclear. Objective: To identify persons without CVD for whom aspirin would probably result in a net benefit. Design: Individualized benefit-harm analysis based on sex-specific risk scores and estimates of the proportional effect of aspirin on CVD and major bleeding from a 2019 meta-analysis. Setting: New Zealand primary care. Participants: 245 028 persons (43.6% women) aged 30 to 79 years without established CVD who had their CVD risk assessed between 2012 and 2016. Measurements: The net effect of aspirin was calculated for each participant by subtracting the number of CVD events likely to be prevented (CVD risk score × proportional effect of aspirin on CVD risk) from the number of major bleeds likely to be caused (major bleed risk score × proportional effect of aspirin on major bleeding risk) over 5 years. Results: 2.5% of women and 12.1% of men were likely to have a net benefit from aspirin treatment for 5 years if 1 CVD event was assumed to be equivalent in severity to 1 major bleed, increasing to 21.4% of women and 40.7% of men if 1 CVD event was assumed to be equivalent to 2 major bleeds. Net benefit subgroups had higher baseline CVD risk, higher levels of most established CVD risk factors, and lower levels of bleeding-specific risk factors than net harm subgroups. Limitations: Risk scores and effect estimates were uncertain. Effects of aspirin on cancer outcomes were not considered. Applicability to non-New Zealand populations was not assessed. Conclusion: For some persons without CVD, aspirin is likely to result in net benefit. Primary Funding Source: Health Research Council of New Zealand.

Contrasting Trends in Acute Coronary Syndrome Hospitalisation and Coronary Revascularisation in New Zealand 2006-2016: A National Data Linkage Study (ANZACS-QI 27).

BACKGROUND: Evaluating trends in acute coronary syndrome (ACS) and invasive coronary procedures, including coronary angiography, percutaneous coronary intervention (PCI) and coronary artery bypass grafting (CABG) can identify areas for improvement in clinical care and inform future health planning. This national data-linkage study reports trends in ACS hospitalisations and procedure rates in New Zealand between 2006 and 2016. METHODS: All adult ACS hospitalisations and associated angiography and revascularisation procedures were identified from hospital discharge codes. Crude and age-standardised ACS incidence and procedure rates were calculated for each calendar year. RESULTS: Between 2006 and 2016 there were 188,264 ACS admissions. During this time, there was a steady decline in hospitalisation rates, from 685 to 424 per 100,000 per year. This decline was observed in both sexes and in all age groups. There were also significant increases in coronary angiography and revascularisation rates, from 29.8% to 54.3% and 20.6% to 37.3%, respectively, between 2006 and 2016. The rate of revascularisation by PCI increased from 16.0% to 31.0%, a greater increase than revascularisation by CABG, which increased from 4.6% to 6.5%. Increases in procedures were observed in all age groups and both sexes. The proportions of coronary angiograms that resulted in revascularisation each year consistently ranged from 67 to 70% throughout the period. CONCLUSIONS: Acute coronary syndrome hospitalisation rates in New Zealand decreased by nearly 40% between 2006 and 2016, while the use of coronary angiography and revascularisation after ACS nearly doubled. The similar proportions of angiograms that resulted in revascularisation each year suggests that, despite the doubling of angiograms over the 10-year study period, they are not over-utilised.

Cardiovascular disease risk prediction equations in 400 000 primary care patients in New Zealand: a derivation and validation study.

BACKGROUND: Most cardiovascular disease risk prediction equations in use today were derived from cohorts established last century and with participants at higher risk but less socioeconomically and ethnically diverse than patients they are now applied to. We recruited a nationally representative cohort in New Zealand to develop equations relevant to patients in contemporary primary care and compared the performance of these new equations to equations that are recommended in the USA. METHODS: The PREDICT study automatically recruits participants in routine primary care when general practitioners in New Zealand use PREDICT software to assess their patients' risk profiles for cardiovascular disease, which are prospectively linked to national ICD-coded hospitalisation and mortality databases. The study population included male and female patients in primary care who had no prior cardiovascular disease, renal disease, or congestive heart failure. New equations predicting total cardiovascular disease risk were developed using Cox regression models, which included clinical predictors plus an area-based deprivation index and self-identified ethnicity. Calibration and discrimination performance of the equations were assessed and compared with 2013 American College of Cardiology/American Heart Association Pooled Cohort Equations (PCEs). The additional predictors included in new PREDICT equations were also appended to the PCEs to determine whether they were independent predictors in the equations from the USA. FINDINGS: Outcome events were derived for 401 752 people aged 30-74 years at the time of their first PREDICT risk assessment between Aug 27, 2002, and Oct 12, 2015, representing about 90% of the eligible population. The mean follow-up was 4·2 years, and a third of participants were followed for 5 years or more. 15 386 (4%) people had cardiovascular disease events (1507 [10%] were fatal, and 8549 [56%] met the PCEs definition of hard atherosclerotic cardiovascular disease) during 1 685 521 person-years follow-up. The median 5-year risk of total cardiovascular disease events predicted by the new equations was 2·3% in women and 3·2% in men. Multivariable adjusted risk increased by about 10% per quintile of socioeconomic deprivation. Maori, Pacific, and Indian patients were at 13-48% higher risk of cardiovascular disease than Europeans, and Chinese or other Asians were at 25-33% lower risk of cardiovascular disease than Europeans. The PCEs overestimated of hard atherosclerotic cardiovascular disease by about 40% in men and by 60% in women, and the additional predictors in the new equations were also independent predictors in the PCEs. The new equations were significantly better than PCEs on all performance metrics. INTERPRETATION: We constructed a large prospective cohort study representing typical patients in primary care in New Zealand who were recommended for cardiovascular disease risk assessment. Most patients are now at low risk of cardiovascular disease, which explains why the PCEs based mainly on old cohorts substantially overestimate risk. Although the PCEs and many other equations will need to be recalibrated to mitigate overtreatment of the healthy majority, they also need new predictors that include measures of socioeconomic deprivation and multiple ethnicities to identify vulnerable high-risk subpopulations that might otherwise be undertreated. FUNDING: Health Research Council of New Zealand, Heart Foundation of New Zealand, and Healthier Lives National Science Challenge.

One in four major ischaemic heart disease events are fatal and 60% are pre-hospital deaths: a national data-linkage study (ANZACS-QI 8).

Aims: The aim of this study is to determine proportions of major ischaemic heart disease (IHD) events that are fatal and where they occur, in an era of rapidly falling IHD mortality. Methods and Results: Individual person linkage of national data sets identified all IHD hospitalizations and deaths in New Zealand from December 2008 to November 2010. Outcome measures were proportions of people: (i) hospitalized with IHD and alive at 28 days; (ii) hospitalized with IHD and died within 28 days; (iii) hospitalized for a non-IHD cause and died from IHD within 28 days; and (iv) not hospitalized and died from IHD. Three event definitions were used [broad-balanced: IHD deaths and IHD hospitalizations, unbalanced: IHD deaths and myocardial infarction (MI) hospitalizations, and narrow-balanced: MI deaths and MI hospitalizations]. About 37 867 IHD hospitalizations and 9409 IHD deaths were identified using the broad IHD definition. Approximately one-quarter of IHD events were fatal: 4% were deaths within 28 days of an IHD hospitalization, 6% were IHD deaths within 28 days of a non-IHD hospitalization, and 14% were non-hospitalized IHD deaths. Using different event definitions, overall case fatality varied from 24­25% (broad and narrow balanced) to 37­39% (unbalanced), whereas the proportion of all deaths that were non-hospitalized was approximately 60%. Forty per cent of deaths were first-ever events that manifested as non-hospitalized IHD deaths. Conclusion: About one-quarter of IHD are fatal, although the proportion is dependent on disease definitions and age. About 60% of all IHD deaths occur out of hospital, and of these 60% are in people not previously hospitalized for IHD.

Annual Risk of Major Bleeding Among Persons Without Cardiovascular Disease Not Receiving Antiplatelet Therapy.

Importance: A decision to initiate aspirin therapy for primary prevention of cardiovascular disease (CVD) requires consideration of both treatment benefits and harms. The most significant harm associated with aspirin is major bleeding, yet there is a paucity of data on bleeding risk in suitable community populations. Objective: To determine the risk of major bleeding among people without CVD who are not receiving antiplatelet therapy. Design, Setting, and Participants: Prospective cohort study of 359 166 individuals aged 30 to 79 years receiving primary care in New Zealand who had CVD risk assessment between 2002 and 2015. Participants were censored at the earliest date on which they had a first major bleeding event, died, or met any baseline cohort exclusion criteria or the study end date of December 31, 2015. Analyses were repeated after excluding people with medical conditions associated with increased bleeding risk (non-high-risk cohort; n=305 057) and after further excluding people receiving other medications associated with increased bleeding risk (nonmedication cohort; n=240 254). Exposures: Sex and age group in 10-year bands from 30 to 79 years. Main Outcomes and Measures: Risk of a major bleeding event (hospitalization or death associated with bleeding); nonfatal gastrointestinal tract bleeding; and gastrointestinal tract bleeding-related case fatality. Results: Mean participant age was 54 years (SD, 10 years), 44% were women, and 57% were European. Among the 359 166 individuals in the baseline cohort, 3976 had a major bleeding event during 1 281 896 person-years of follow-up. Most had gastrointestinal (GI) bleeding (n=2910 [73%]). There were 274 fatal bleeding events (7%), of which 153 were intracerebral. The risk of a nonfatal GI bleeding event per 1000 person-years was 2.19 (95% CI, 2.11-2.27), 1.77 (95% CI, 1.69-1.85) and 1.61 (95% CI, 1.52-1.69), in the baseline, non-high-risk, and nonmedication cohorts, respectively. Case fatality associated with GI bleeding was 3.4% (95% CI, 2.2%-4.1%), 4.0% (95% CI, 3.2%-5.1%), and 4.6% (95% CI, 3.6%-6.0%) in the baseline, non-high-risk, and nonmedication cohorts, respectively. Conclusions and Relevance: In a population not receiving antiplatelet therapy, the annual risk of major bleeding events and nonfatal major bleeding was estimated. These findings could inform population-level guidelines for primary prevention of CVD.