Risk Of Nonfatal Myocardial Infarction Research Articles

Ezetimibe for the prevention of cardiovascular disease and all-cause mortality events.

Cardiovascular disease (CVD) remains an important cause of mortality and morbidity, and high levels of blood cholesterol are thought to be the major modifiable risk factors for CVD. The use of statins is the preferred treatment strategy for the prevention of CVD, but some people at high-risk for CVD are intolerant to statin therapy or unable to achieve their treatment goals with the maximal recommended doses of statin. Ezetimibe is a selective cholesterol absorption inhibitor, whether it has a positive effect on CVD events remains uncertain. Results from clinical studies are inconsistent and a thorough evaluation of its efficacy and safety for the prevention of CVD and mortality is necessary. To assess the efficacy and safety of ezetimibe for the prevention of CVD and all-cause mortality. We searched the CENTRAL, MEDLINE, Embase and Web of Science on 27 June 2018, and two clinical trial registry platforms on 11 July 2018. We checked reference lists from primary studies and review articles for additional studies. No language restrictions were applied. We included randomised controlled trials (RCTs) that compared ezetimibe versus placebo or ezetimibe plus other lipid-modifying drugs versus other lipid-modifying drugs alone in adults, with or without CVD, and which had a follow-up of at least 12 months. Two review authors independently selected studies for inclusion, extracted data, assessed risk of bias and contacted trialists to obtain missing data. We performed statistical analyses according to the Cochrane Handbook for Systematic Reviews of Interventions and used the GRADE to assess the quality of evidence. We included 26 RCTs randomising 23,499 participants. All included studies assessed effects of ezetimibe plus other lipid-modifying drugs compared with other lipid-modifying drugs alone or plus placebo. Our findings were driven by the largest study (IMPROVE-IT), which had weights ranging from 41.5% to 98.4% in the different meta-analyses.Ezetimibe with statins probably reduces the risk of major adverse cardiovascular events compared with statins alone (risk ratio (RR) 0.94, 95% confidence interval (CI) 0.90 to 0.98; a decrease from 284/1000 to 267/1000, 95% CI 256 to 278; 21,727 participants; 10 studies; moderate-quality evidence). Trials reporting all-cause mortality used ezetimibe with statin or fenofibrate and found they have little or no effect on this outcome (RR 0.98, 95% CI 0.91 to 1.05; 21,222 participants; 8 studies; high-quality evidence). Adding ezetimibe to statins probably reduces the risk of non-fatal myocardial infarction (MI) (RR 0.88, 95% CI 0.81 to 0.95; a decrease from 105/1000 to 92/1000, 95% CI 85 to 100; 21,145 participants; 6 studies; moderate-quality evidence) and non-fatal stroke (RR 0.83, 95% CI 0.71 to 0.97; a decrease 32/1000 to 27/1000, 95% CI 23 to 31; 21,205 participants; 6 studies; moderate-quality evidence). Trials reporting cardiovascular mortality added ezetimibe to statin or fenofibrate, probably having little or no effect on this outcome (RR 1.00, 95% CI 0.89 to 1.12; 19457 participants; 6 studies; moderate-quality evidence). The need for coronary revascularisation might be reduced by adding ezetimibe to statin (RR 0.94, 95% CI 0.89 to 0.99; a decrease from 196/1000 to 184/1000, 95% 175 to 194; 21,323 participants; 7 studies); however, no difference in coronary revascularisation rate was observed when a sensitivity analysis was limited to studies with a low risk of bias.In terms of safety, adding ezetimibe to statins may make little or no difference in the risk of hepatopathy (RR 1.14, 95% CI 0.96 to 1.35; 20,687 participants; 4 studies; low-quality evidence). It is uncertain whether ezetimibe increase or decrease the risk of myopathy (RR 1.31, 95% CI 0.72 to 2.38; 20,581 participants; 3 studies; very low-quality evidence) and rhabdomyolysis, given the wide CIs and low event rate. Little or no difference in the risk of cancer, gallbladder-related disease and discontinuation due to adverse events were observed between treatment groups. For serum lipids, adding ezetimibe to statin or fenofibrate might further reduce the low-density lipoprotein cholesterol (LDL-C), total cholesterol and triglyceride levels and likely increase the high-density lipoprotein cholesterol levels; however, substantial heterogeneity was detected in most analyses.None of the included studies reported on health-related quality of life. Moderate- to high-quality evidence suggests that ezetimibe has modest beneficial effects on the risk of CVD endpoints, primarily driven by a reduction in non-fatal MI and non-fatal stroke, but it has little or no effect on clinical fatal endpoints. The cardiovascular benefit of ezetimibe might involve the reduction of LDL-C, total cholesterol and triglycerides. There is insufficient evidence to determine whether ezetimibe increases the risk of adverse events due to the low and very low quality of the evidence. The evidence for beneficial effects was mainly obtained from individuals with established atherosclerotic cardiovascular disease (ASCVD, predominantly with acute coronary syndrome) administered ezetimibe plus statins. However, there is limited evidence regarding the role of ezetimibe in primary prevention and the effects of ezetimibe monotherapy in the prevention of CVD, and these topics thus requires further investigation.

Aspirin Use and Cardiovascular Outcome in Patients With Type 2 Diabetes Mellitus and Heart Failure: A Population-Based Cohort Study.

BackgroundAspirin is of uncertain benefit for primary prevention in patients with type 2 diabetes mellitus (T2D). We assessed whether primary prevention with aspirin is beneficial in patients with T2D and heart failure (HF).Methods and ResultsData from The Health Improvement Network, a UK multicenter prospective primary care database, were analyzed. Those with T2D and HF, age ≥55 years, and no previous history of myocardial infarction and/or coronary artery disease, stroke, peripheral artery disease, or atrial fibrillation were included. We compared outcomes for those on aspirin to no aspirin after diagnosis of HF and T2D and assessed the role of a >75‐mg dose. The primary outcome was a composite of all‐cause mortality and hospitalization for HF; secondary outcomes were nonfatal stroke, nonfatal myocardial infarction, or major bleeding. There were 5967 participants on aspirin and 6567 not on aspirin. The mean age (SD) was 75.3 (9.6) years, 53.9% were men, and the mean follow‐up (SD) was for 5 (4.2) years. After propensity‐score matching and further multivariable adjustment, aspirin was significantly associated with a decrease in the primary outcome and all‐cause mortality (hazard ratio=0.88, 95% confidence interval 0.82‐0.93; 0.88, 0.83‐0.94], respectively); and an increased risk of nonfatal myocardial infarction (hazard ratio=1.66; 95% confidence interval 1.49‐1.85) and nonfatal stroke (hazard ratio=1.23, 1.01‐1.50). Major bleedings and hospitalization for HF were not significantly higher with aspirin (hazard ratio=0.68, 0.45‐1.03; 0.87, 0.66‐1.15, respectively). There was no additional benefit for a dose >75 mg.ConclusionsPrimary prevention with aspirin in patients with T2D and HF is associated with lower all‐cause mortality.

Deepwater Horizon oil spill exposures and nonfatal myocardial infarction in the GuLF STUDY

BackgroundWorkers involved in the response and clean-up of the 2010 Deepwater Horizon oil spill faced possible exposures to crude oil, burning oil, dispersants and other pollutants in addition to physical and emotional stress. These exposures may have increased risk of myocardial infarction (MI) among oil spill workers.MethodsGulf Long-term Follow-up (GuLF) STUDY participants comprise individuals who either participated in the Deepwater Horizon response efforts or registered for safety training but were not hired. Oil spill-related exposures were assessed during enrollment interviews conducted in 2011–2013. We estimated risk ratios (RR) and 95% confidence intervals for the associations of clean-up work characteristics with self-reported nonfatal MI up to three years post-spill.ResultsAmong 31,109 participants without history of MI prior to the spill, 77% worked on the oil spill. There were 192 self-reported MI during the study period; 151 among workers. Among the full cohort, working on the oil spill clean-up (vs not working on the clean-up) and living in proximity to the oil spill (vs further away) were suggestively associated with a possible increased risk of nonfatal MI [RR: 1.22 (0.86, 1.73) and 1.15 (0.82, 1.60), respectively]. Among oil spill workers, working for > 180 days was associated with MI [RR for > 180 days (vs 1–30 days): 2.05 (1.05, 4.01)], as was stopping working due to heat [RR: 1.99 (1.43, 2.78)]. There were suggestive associations of maximum total hydrocarbon exposure ≥3.00 ppm (vs < 0.30 ppm) [RR: 1.69 (0.90, 3.19)] and working on decontaminating oiled equipment (vs administrative support) [1.72 (0.96, 3.09)] with nonfatal MI.ConclusionThis is the first study to assess the associations between oil spill exposures and MI. Results suggest that working on the spill for > 180 days and stopping work due to heat increased risk of nonfatal MI. Future research should evaluate whether the observed associations are related to specific chemical exposures or other stressors associated with the spill.

In which individuals should aspirin be used for primary prevention of cardiovascular disease?

EVIDENCE-BASED ANSWER In patients older than 40 years without cardiovascular disease (CVD), aspirin use decreases the risk of nonfatal myocardial infarction (MI) by 22% and allcause mortality by 6%. However, aspirin has no effect on stroke or all-cause mortality and may increase the risk of hemorrhage and other nontrivial bleeding (SOR: B, meta-analysis of heterogeneous RCTs). Low-dose aspirin should be given to adults 50 to 69 years old with a 10% or higher 10-year risk of CVD who are not at increased risk of bleeding and have a life expectancy of at least 10 years. The decision should be individualized for adults 60 to 69 years old (SOR: C, expert opinion).

Examining risk factors for cardiovascular disease among food bank members in Vancouver.

Food banks provide supplemental food to low-income households, yet little is known about the cardiovascular health of food banks members. This study therefore described cardiovascular disease (CVD) risk factors among food bank members and explored associations between food insecurity and CVD risk.Adults ≥18 years (n = 77) from three food bank sites in metro Vancouver, British Columbia completed surveys and physical assessments examining a range of socio-demographic variables and CVD risk factors. A composite measure of myocardial infarction (MI) risk called the INTERHEART score was assessed and household food insecurity was measured using the Household Food Security Survey Module. Regression models were used to explore associations between food insecurity and CVD risk measures, including the INTERHEART score.Ninety-seven percent of food bank members reported experiencing food insecurity, 65% were current smokers, 53% reported either chronic or several periods of stress in the past year, 55% reported low physical activity levels and 80% reported consuming fewer than five servings of fruit and vegetables daily. Prevalence of self-reported diabetes and hypertension were 13% and 29% respectively. Fifty-two percent of the sample were at high risk of non-fatal MI. No statistically significant associations were found between increased severity of food insecurity and CVD risk factors among this sample where both severe food insecurity and high CVD risks were prevalent.Food bank members were at elevated risk for CVD compared with the general population. Strategies are needed to reduce prevalence of food insecurity and CVD risk factors, both of which disproportionately affected food bank members.

PAI-1 level and the PAI-1 4G/5G polymorphism in relation to risk of non-fatal myocardial infarction: results from the Stockholm Heart Epidemiology Program (SHEEP).

This study examines the relationship between plasma Plasminogen Activator Inhibitor-1 (PAI-1) activity and the PAI-1 4G/5G polymorphism, and their association with the risk of myocardial infarction (MI). Furthermore, this study explores whether a high level of PAI-1 or whether the PAI-1 4G/5G polymorphism synergistically interacts with any established environmental risk factor for MI. This case-referent study of subjects aged 45-70 and living in Stockholm includes 851 men and 361 women with first-time MI and 1051 men and 505 women who were randomly chosen as referents from a population register. The adjusted odds ratio (OR) of MI was 1.9 (95% confidence interval [CI] 1.4-2.8) for men with a plasma PAI-1 activity level greater than the 90 th percentile value of referents. The corresponding OR for women was 1.5 (95% CI 0.9-2.5). A strong indication of synergistic interaction was found in men for the co-exposure to high plasma PAI-1 activity and current smoking, an adjusted synergy index score of 3.9 (95% CI 1.2-13.2). In women, the 4G allele was associated slightly with an increased risk of MI, OR 1.4 (95% CI 1.0-1.9). This association was not found in men. There were no clear indications of synergistic interaction effects involving the PAI-1 4G/5G polymorphism and the environmental exposures considered (cigarette smoking, physical inactivity, overweight, diabetes mellitus, hypercholesterolaemia, hypertension, high C-reactive protein and hypertriglyceridaemia).

Comparison of mid- to long-term clinical outcomes between anatomical testing and usual care in patients with suspected coronary artery disease: A meta-analysis of randomized trials.

Controversies remain regarding clinical outcomes following initial strategies of coronary computed tomography angiography (CCTA) vs usual care with functional testing in patients with suspected coronary artery disease (CAD). CCTA as initial diagnostic strategy results in better mid- to long-term outcomes than usual care in patients with suspected CAD. We searched PubMed, Embase, and Cochrane Library for randomized controlled trials comparing clinical outcomes during ≥6 months' follow-up between initial anatomical testing by CCTA vs usual care with functional testing in patients with suspected CAD. Occurrence of all-cause mortality, nonfatal myocardial infarction (MI), and major adverse cardiovascular events (MACE), and use of invasive coronary angiography and coronary revascularization, were compared between the 2 diagnostic strategies. Twelve trials were included (20 014 patients; mean follow-up, 20.5 months). Patients undergoing CCTA as initial noninvasive testing had lower risk of nonfatal MI compared with those treated with usual care (risk ratio [RR]: 0.70, 95% confidence interval [CI]: 0.52-0.94, P = 0.02). There was a tendency for reduced MACE following initial CCTA strategy, but not for risk of all-cause mortality. Compared with functional testing, the CCTA strategy increased use of invasive coronary angiography (RR: 1.53, 95% CI: 1.12-2.09, P = 0.007) and coronary revascularization (RR: 1.49, 95% CI: 1.11-2.00, P = 0.007). Anatomical testing with CCTA as the initial noninvasive diagnostic modality in patients with suspected CAD resulted in lower risk of nonfatal MI than usual care with functional testing, at the expense of more frequent use of invasive procedures.

Chronic Kidney Disease, Basal Insulin Glargine, and Health Outcomes in People with Dysglycemia: The ORIGIN Study

BackgroundEarly stages of chronic kidney disease are associated with an increased cardiovascular risk in patients with established type 2 diabetes and macrovascular disease. The role of early stages of chronic kidney disease on macrovascular outcomes in prediabetes and early type 2 diabetes mellitus is not known. In the Outcome Reduction with an Initial Glargine Intervention (ORIGIN) trial, the introduction of insulin had no effect on cardiovascular outcomes compared with standard therapy. In this post hoc analysis of ORIGIN, we compared cardiovascular outcomes in subjects without to those with mild (Stages 1-2) or moderate chronic kidney disease (Stage 3). MethodsΤwo co-primary composite cardiovascular outcomes were assessed. The first was the composite end point of nonfatal myocardial infarction, nonfatal stroke, or death from cardiovascular causes; and the second was a composite of any of these events plus a revascularization procedure, or hospitalization for heart failure. Several secondary outcomes were prespecified, including microvascular outcomes, incident diabetes, hypoglycemia, weight, and cancers. ResultsComplete renal function data were available in 12,174 of 12,537 ORIGIN participants. A total of 8114 (67%) had no chronic kidney disease, while 4060 (33%) had chronic kidney disease stage 1-3. When compared with nonchronic kidney disease participants, the risk of developing the composite primary outcome (nonfatal myocardial infarction, nonfatal stroke, or cardiovascular death) in those with mild to moderate chronic kidney disease was 87% higher; hazard ratio (HR) 1.87; 95% confidence interval (CI), 1.71-2.04 (P < .0001). The presence of chronic kidney disease 1-3 was also associated with a greater than twofold higher risk for both all-cause mortality (HR 2.17; 95% CI, 1.98-2.38; P < .0001) and cardiovascular mortality (HR 2.39; 95% CI, 2.13-2.69; P < .0001). Moreover, patients with mild to moderate chronic kidney disease had significantly higher risk for nonfatal myocardial infarction (50%), nonfatal stroke (68%), any stroke (84%), the above composite primary end point plus revascularization or heart failure requiring hospitalization (59%), or a major coronary artery disease event (56%). Furthermore, in patients with chronic kidney disease and early diabetes mellitus type 2, the primary end point occurred 83% more frequently as compared with nonchronic kidney disease participants (HR 1.83; 95% CI, 1.67-2.01; P < .001) and in patients with prediabetes and chronic kidney disease 67% more frequently (HR 1.67; 95% CI,1.25-2.24; P < .001). ConclusionsIn high-risk patients with dysglycemia (prediabetes and early diabetes), mild and moderate chronic kidney disease significantly increased cardiovascular events.

Social Integration and Reduced Risk of Coronary Heart Disease in Women: The Role of Lifestyle Behaviors.

Higher social integration is associated with lower cardiovascular mortality; however, whether it is associated with incident coronary heart disease (CHD), especially in women, and whether associations differ by case fatality are unclear. This study sought to examine the associations between social integration and risk of incident CHD in a large female prospective cohort. Seventy-six thousand three hundred and sixty-two women in the Nurses' Health Study, free of CHD and stroke at baseline (1992), were followed until 2014. Social integration was assessed by a simplified Berkman-Syme Social Network Index every 4 years. End points included nonfatal myocardial infarction and fatal CHD. Two thousand three hundred and seventy-two incident CHD events occurred throughout follow-up. Adjusting for demographic, health/medical risk factors, and depressive symptoms, being socially integrated was significantly associated with lower CHD risk, particularly fatal CHD. The most socially integrated women had a hazard ratio of 0.55 (95% confidence interval, 0.41-0.73) of developing fatal CHD compared with those least socially integrated (P for trend <0.0001). When additionally adjusting for lifestyle behaviors, findings for fatal CHD were maintained but attenuated (P for trend =0.02), whereas the significant associations no longer remained for nonfatal myocardial infarction. The inverse associations between social integration and nonfatal myocardial infarction risk were largely explained by health-promoting behaviors, particularly through differences in cigarette smoking; however, the association with fatal CHD risk remained after accounting for these behaviors and, thus, may involve more direct biological mechanisms. Social integration is inversely associated with CHD incidence in women, but is largely explained by lifestyle/behavioral pathways.

Glucose targets for preventing diabetic kidney disease and its progression.

Diabetes is the leading cause of end-stage kidney disease (ESKD) around the world. Blood pressure lowering and glucose control are used to reduce diabetes-associated disability including kidney failure. However there is a lack of an overall evidence summary of the optimal target range for blood glucose control to prevent kidney failure. To evaluate the benefits and harms of intensive (HbA1c < 7% or fasting glucose levels < 120 mg/dL versus standard glycaemic control (HbA1c ≥ 7% or fasting glucose levels ≥ 120 mg/dL for preventing the onset and progression of kidney disease among adults with diabetes. We searched the Cochrane Kidney and Transplant Specialised Register up to 31 March 2017 through contact with the Information Specialist using search terms relevant to this review. Studies contained in the Specialised Register are identified through search strategies specifically designed for CENTRAL, MEDLINE, and EMBASE; handsearching conference proceedings; and searching the International Clinical Trials Register (ICTRP) Search Portal and ClinicalTrials.gov. Randomised controlled trials evaluating glucose-lowering interventions in which people (aged 14 year or older) with type 1 or 2 diabetes with and without kidney disease were randomly allocated to tight glucose control or less stringent blood glucose targets. Two authors independently assessed studies for eligibility and risks of bias, extracted data and checked the processes for accuracy. Outcomes were mortality, cardiovascular complications, doubling of serum creatinine (SCr), ESKD and proteinuria. Confidence in the evidence was assessing using GRADE. Summary estimates of effect were obtained using a random-effects model, and results were expressed as risk ratios (RR) and their 95% confidence intervals (CI) for dichotomous outcomes, and mean difference (MD) and 95% CI for continuous outcomes. Fourteen studies involving 29,319 people with diabetes were included and 11 studies involving 29,141 people were included in our meta-analyses. Treatment duration was 56.7 months on average (range 6 months to 10 years). Studies included people with a range of kidney function. Incomplete reporting of key methodological details resulted in uncertain risks of bias in many studies. Using GRADE assessment, we had moderate confidence in the effects of glucose lowering strategies on ESKD, all-cause mortality, myocardial infarction, and progressive protein leakage by kidney disease and low or very low confidence in effects of treatment on death related to cardiovascular complications and doubling of serum creatinine (SCr).For the primary outcomes, tight glycaemic control may make little or no difference to doubling of SCr compared with standard control (4 studies, 26,874 participants: RR 0.84, 95% CI 0.64 to 1.11; I2= 73%, low certainty evidence), development of ESKD (4 studies, 23,332 participants: RR 0.62, 95% CI 0.34 to 1.12; I2= 52%; low certainty evidence), all-cause mortality (9 studies, 29,094 participants: RR 0.99, 95% CI 0.86 to 1.13; I2= 50%; moderate certainty evidence), cardiovascular mortality (6 studies, 23,673 participants: RR 1.19, 95% CI 0.73 to 1.92; I2= 85%; low certainty evidence), or sudden death (4 studies, 5913 participants: RR 0.82, 95% CI 0.26 to 2.57; I2= 85%; very low certainty evidence). People who received treatment to achieve tighter glycaemic control probably experienced lower risks of non-fatal myocardial infarction (5 studies, 25,596 participants: RR 0.82, 95% CI 0.67 to 0.99; I2= 46%, moderate certainty evidence), onset of microalbuminuria (4 studies, 19,846 participants: RR 0.82, 95% CI 0.71 to 0.93; I2= 61%, moderate certainty evidence), and progression of microalbuminuria (5 studies, 13,266 participants: RR 0.59, 95% CI 0.38 to 0.93; I2= 75%, moderate certainty evidence). In absolute terms, tight versus standard glucose control treatment in 1,000 adults would lead to between zero and two people avoiding non-fatal myocardial infarction, while seven adults would avoid experiencing new-onset albuminuria and two would avoid worsening albuminuria. This review suggests that people who receive intensive glycaemic control for treatment of diabetes had comparable risks of kidney failure, death and major cardiovascular events as people who received less stringent blood glucose control, while experiencing small clinical benefits on the onset and progression of microalbuminuria and myocardial infarction. The adverse effects of glycaemic management are uncertain. Based on absolute treatment effects, the clinical impact of targeting an HbA1c < 7% or blood glucose < 6.6 mmol/L is unclear and the potential harms of this treatment approach are largely unmeasured.

PCSK9 variant, long-chain n–3 PUFAs, and risk of nonfatal myocardial infarction in Costa Rican Hispanics1–3

Background: Previous studies have indicated that the cardioprotective effects of long-chain (LC) n–3 (ω-3) polyunsaturated fatty acids (PUFAs) may vary across various ethnic populations. Emerging evidence has suggested that the gene-environment interaction may partly explain such variations. Proprotein convertase subtilisin/kexin type 9 (PCSK9) was shown to have a mutually regulating relation with LC n–3 PUFAs and also to reduce the risk of cardiovascular diseases (CVDs). Therefore, we hypothesized that certain PCSK9 genetic variants may modify the association between LC n–3 PUFA intake and CVD risk.Objective: We determined whether a PCSK9 variant (rs11206510), which has been identified for early onset myocardial infarction (MI), modified the association of LC n–3 PUFAs with nonfatal MI risk in Costa Rican Hispanics.Design: We analyzed cross-sectional data from 1932 case subjects with a first nonfatal MI and 2055 population-based control subjects who were living in Costa Rica to examine potential gene-environment interactions. Two-sided P values <0.05 were considered significant.Results: We observed a significant interaction between the PCSK9 rs11206510 genotype and LC n–3 PUFA intake on nonfatal MI risk (P-interaction = 0.012). The OR of nonfatal MI was 0.84 (95% CI: 0.72, 0.98) per 0.1% increase in total energy intake from LC n–3 PUFAs in protective-allele (C-allele) carriers, whereas the corresponding OR (95% CI) in non–C-allele carriers was 1.02 (95% CI: 0.95, 1.10). Similar results were observed when we examined the association between docosahexaenoic acid, which is one type of LC n–3 PUFA, and nonfatal MI risk (P-interaction = 0.003).Conclusion: LC n–3 PUFA intake is associated with a lower risk of nonfatal MI in C-allele carriers of PCSK9 rs11206510 (n = 799) but not in non–C-allele carriers (n = 3188).

The Role of Antiplatelet Therapy in Primary Prevention. A Review.

The efficacy of antiplatelet therapy for the secondary prevention of cardiovascular disease after an ischemic event is well established. However, the role for antiplatelet therapy for the primary prevention of cardiovascular disease is more complex because of the interplay of efficacy vs safety in individuals without established cardiovascular disease who have a relatively low, but linear trajectory of cardiovascular risk. Several large randomized trials have investigated the efficacy and safety of antiplatelet therapy (primarily aspirin) for patients without established cardiovascular disease. The pharmacological profile of the most commonly used primary prevention antiplatelet agent, aspirin, has been delineated by randomized clinical trials and showcased in practice guidelines for reducing cardiovascular risk. For this indication, aspirin has been consistently shown to reduce the risk of non-fatal myocardial infarction with little impact on cardiovascular death, but with a consistent increased risk of bleeding. These divergent results have contributed to differences in the recommendations from international practice guidelines and highlight controversy at the forefront of considerations for anti-platelet therapy for primary prevention. However, further studies in specific sub-groups of patients without established cardiovascular disease such as those with Diabetes Mellitus, chronic kidney disease, or the elderly may clarify which patient groups will benefit the most from aspirin treatment for the primary prevention of a cardiovascular event.

Legacy effect of statins: 20-year follow up of the West of Scotland Coronary Prevention Study (WOSCOPS).

The West of Scotland Coronary Prevention Study (WOSCOPS) was a randomized, placebo- controlled, primary prevention trial of pravastatin in men aged 45 to 64 (mean age of 55 years) with no history of myocardial infarction at randomization. A total of 6,595 men, with a mean (SD) plasma cholesterol level of 272 (23) mg/dL and mean (SD) low density lipoprotein cholesterol (LDL-C) of 192 (17) mg/dL were randomly assigned to receive pravastatin 40 mg daily or placebo for five years. The primary outcome was a composite of death from coronary heart disease (CHD) and nonfatal myocardial infarction. There was a 31% relative reduction in the primary outcome with pravastatin. There was similar reduction in risk of nonfatal myocardial infarction, death from CHD and death from all cardiovascular causes with no increased risk of death from non-cardiovascular causes nor an increase in incident cancers.

Habitual intake of anthocyanins and flavanones and risk of cardiovascular disease in men ,

Background: Although increased fruit intake reduces cardiovascular disease (CVD) risk, which fruits are most beneficial and what key constituents are responsible are unclear. Habitual intakes of flavonoids, specifically anthocyanins and flavanones, in which >90% of habitual intake is derived from fruit, are associated with decreased CVD risk in women, but associations in men are largely unknown.Objective: We examined the relation between habitual anthocyanin and flavanone intake and coronary artery disease and stroke in the Health Professionals Follow-Up Study.Design: We followed 43,880 healthy men who had no prior diagnosed CVD or cancer. Flavonoid intake was calculated with the use of validated food-frequency questionnaires.Results: During 24 y of follow-up, 4046 myocardial infarction (MI) and 1572 stroke cases were confirmed by medical records. Although higher anthocyanin intake was not associated with total or fatal MI risk, after multivariate adjustment an inverse association with nonfatal MI was observed (HR: 0.87; 95% CI: 0.75, 1.00; P = 0.04; P-trend = 0.098); this association was stronger in normotensive participants (HR: 0.81; 95% CI: 0.69, 0.96; P-interaction = 0.03). Anthocyanin intake was not associated with stroke risk. Although flavanone intake was not associated with MI or total stroke risk, higher intake was associated with a lower risk of ischemic stroke (HR: 0.78; 95% CI: 0.62, 0.97; P = 0.03, P-trend = 0.059), with the greatest magnitude in participants aged ≥65 y (P-interaction = 0.04).Conclusions: Higher intakes of fruit-based flavonoids were associated with a lower risk of nonfatal MI and ischemic stroke in men. Mechanistic studies and clinical trials are needed to unravel the differential benefits of anthocyanin- and flavanone-rich foods on cardiovascular health.

Niacin: Time to Believe Outcomes Over Surrogate Outcomes

Long-acting niacin, a blockbuster drug for many years, emerged during an era in which the simple assumption was that favorably modifying patients’ lipid profiles was tantamount to lowering their risks for cardiovascular disease. The implicit assumption in the medical community and among regulators was that improving lipid profiles would improve outcomes even as the mechanism of the drug action was not clear. This approach holds sway today as evidenced by the recent approval of the PCSK9 inhibitor drugs before the completion of the definitive phase 3 outcome trials.1,2 The evidence suggests that the way in which a risk factor is modified matters for whether it produces a benefit.3 Long-acting niacin is a particularly interesting case because it was included in one of the earliest outcome trials, the Coronary Drug Project, initiated in 1966, although the results were equivocal.4 With 5 to 8 years of follow-up, niacin failed to improve mortality, the primary end point. The 5-year rates of death were 21.2% for niacin and 20.9% for placebo. Death rates because of coronary heart disease were also close and not significantly different: 15.9% for niacin and 16.2% for placebo. The niacin group did have a lower risk of nonfatal myocardial infarction, one of the secondary end points. It should also be noted that because …

The prognostic value of transient arterial hypertension in patients with chronic heart insufficiency and preserved left ventricular ejection function

The study included 169patients (74 men and 95 women) with CHI (mean age 56,3±10,9 yr). All of them had PEF higher than 50%. 105 patients had FCII CHI, 64 ones FCIII CHI. Stage IIA was documented in 136 and stage IIB in 33 patients. Duration of the study 24 months. The combined end point included non-fatal myocardial infarction and cardiovascular death. Arterial hypotension at office AP was diagnosed in 16 (9,5%) patients, transient arterial hypotension based at 24 hr AP monitoring in 104 (61,6%) patients. A total of 8 combined end points were documented during the study period. All these patients had transient systole-diastolic and/or systolic arterial hypotension . No myocardial infarction or lethal outcome developed in CHI patients without episodes of arterial hypotension (x=4,28, р=0,04). 24 hr AP monitoring in CHI-PEF patients permits to significantly increase the frequency of detection ofpotentially dangerous changes of AP. Transient arterial pressure occurs in 61.6% of the FCII-III CHI-PEF patients. Transient systole-diastolic arterial hypotension significantly increases the risk of non-fatal myocardial infarction and cardiovascular death in CHI-PEF patients

Aspirin for the Primary Prevention of Cardiovascular Events: A Systematic Evidence Review for the U.S. Preventive Services Task Force.

Cardiovascular disease (CVD) is the leading cause of death in the United States. To update a systematic review about the benefits of aspirin for the primary prevention of cardiovascular events in adults aged 40 years or older and to evaluate effect modification in subpopulations. MEDLINE, PubMed, Cochrane Central Register of Controlled Trials (January 2008 to January 2015), and Cochrane Database of Systematic Reviews. Two investigators independently reviewed 3396 abstracts and 65 articles according to prespecified criteria. All included trials evaluated aspirin for the primary prevention of cardiovascular events. Two investigators assessed study quality; data were abstracted by 1 reviewer and checked by a second. Two good-quality and 9 fair-quality randomized, controlled trials were identified. In analyses of all doses, aspirin reduced the risk for nonfatal myocardial infarction (MI) (relative risk [RR], 0.78 [95% CI, 0.71 to 0.87]) but not nonfatal stroke; aspirin showed little or no benefit for all-cause or cardiovascular mortality. Benefits began within the first 5 years. Older adults achieved greater relative MI reduction, but no other effect modifications were found in analyzed subpopulations. In trials with aspirin doses of 100 mg or less per day, the reduction in nonfatal MI benefit persisted (absolute risk reduction, 0.15 to 1.43 events per 1000 person-years) and a 14% reduction in nonfatal stroke benefit was noted, but no benefit was found for all-cause mortality (RR, 0.95 [CI, 0.89 to 1.01]) or cardiovascular mortality (RR, 0.97 [CI, 0.85 to 1.10]). Evidence for aspirin in primary prevention is heterogeneous and limited by rare events and few credible subgroup analyses. The beneficial effect of aspirin for the primary prevention of CVD is modest and occurs at doses of 100 mg or less per day. Older adults seem to achieve a greater relative MI benefit. Agency for Healthcare Research and Quality.

Efficacy of Angiotensin-Converting Enzyme Inhibitors and Angiotensin-Receptor Blockers in Coronary Artery Disease without Heart Failure in the Modern Statin Era: a Meta-Analysis of Randomized-Controlled Trials.

Current practice guidelines support the use of angiotensin-converting enzyme inhibitors (ACEi) and angiotensin-receptor blockers (ARBs) in patients with coronary artery disease (CAD) without heart failure (HF). However, a number of cited trials were performed prior to the era of prevalent statin use. Our objective was to evaluate the effectiveness of ACEi and ARBs in reducing cardiovascular events as well as the impact of statin therapy. We searched the MEDLINE and EMBASE databases for randomized-controlled trials (1/1/1980 - 8/31/2015) with ACEi or ARBs as the single intervention for patients with CAD without HF. We assessed the outcomes of non-fatal myocardial infarction (MI), stroke, cardiovascular mortality and all-cause mortality. The relationship between these outcomes and the percentages of patients on statin therapy was evaluated using meta-regression analysis. A total of ten ACEi trials and five ARB trials were included for analysis, with 78,761 patients followed for a mean of 36months. Treatment with ACEi was associated with decreased non-fatal MI (RR 0.83; 95% CI 0.75-0.91), stroke (RR 0.76; 95% CI 0.68-0.86), cardiovascular mortality (RR 0.83; 95% CI 0.72-0.95), and all-cause mortality (RR 0.86; 95% CI 0.80-0.93). Treatment with ARBs was associated only with a decreased incidence of stroke (RR 0.92; 95% CI 0.87-0.98). When adjusted for statin use, there was a trend towards an attenuated effect of ACEi in reducing cardiovascular mortality with increased use of statins (p-value = 0.063). In CAD patients without HF, ACEi, but not ARBs decreases the risk of non-fatal MI, cardiovascular mortality and all-cause mortality, while both ACEi and ARBs decrease the risk of stroke.

Safety and efficacy of health supplement for weight loss

Purpose: The aim of this review is to evaluate the safety and efficacy of a product named acai berry ABC and to understand the marketing issues implemented by this product. Methodology: A review regarding registration of product was conducted by examining the registration in Pharmaceutical Division Services, Ministry of Health of Malaysia and the profile of product was evaluated by assessing the online MIMS. Besides that, an electronic search was conducted through searching at Cochrane Library, EMBASE, PubMed to assess the safety and efficacy of the product. Malaysia Advertisement Board was referred to evaluate the marketing issue in acai berry ABC. Results: According to Pharmaceutical Division Services, Ministry of Health, acai berry ABC is listed under product adulterated with poison which is contained sibutramine as an active ingredient which is against the Sale of Drugs Act 1952. Acai berry ABC widely advertised throughout social media such as Facebook, website services, and online marketing. Thus, there are a few issues related to marketing that against the Medicine Advertisement Board. Moreover, a review on safety and efficacy of sibutramine reported that sibutramine is effective in weight loss and it also may increase slightly in blood pressure (BP). Sibutramine should be used cautiously in patients with borderline or high BP. However, the Sibutramine Cardiovascular Outcome Trial (SCOUT) trial showed that long-term use of sibutramine among the subject with cardiovascular disease had a risk of nonfatal myocardial infarction and nonfatal stroke, but not of cardiovascular death or death from any cause. Due to SCOUT trial, physician and pharmacist are recommended by the European Medicine Agency have to stop selling products containing sibutramine. Malaysia also banned this product since 2010. However, still there is a company selling the herbal weight loss product adulterated with sibutramine such as acai berry ABC. Conclusions: Ministry of Health has banned the selling of acai berry ABC in Malaysia due to adulteration with sibutramine which may risk and harmful to cardiovascular disease patient. As for Malaysian, it is not safe to consume the product that contains with control poison without consultation from physician or pharmacist. It is a pharmacist responsibility to educate people to consume an only product that registered with Ministry of Health. Malaysian should always consult with a physician or pharmacist if any confusion regarding any product that they have been consumed.

Developments in Diabetology in 2016

Two major trials, LEADER and SUSTAIN 6, published in 2016, reported the cardiovascular and microvascular benefits of liraglutide and semaglutide respectively. This communication describes the results of these trials, and analyses the subtle differences in their outcomes. While semaglutide significantly reduces the risk of non-fatal myocardial infarction (primary prevention), liraglutide reduces the risk of all-cause mortality and cardiovascular mortality (secondary prevention). Both drugs significantly improve renal outcomes, but semaglutide increased the risk of retinal events. The time taken to achieve benefit was much less (4-6 months) with semaglutide than with liraglutide (12–18 months). LEADER and SUSTAIN 6 have made 2016 a landmark year in the history of diabetes care. Their positive results will help promote better, comprehensive diabetes care, using minimal drugs (therapeutic parsimony), encourage use of rational combinations to improve outcomes, and stimulate exaptation of these drugs for non-glycemic purposes.