Prevention Of Major Cardiovascular Events Research Articles

Effect of CPAP Treatment on Cardiovascular Outcomes

IntroductionRandomized controlled trials (RCT) have not demonstrated a role for continuous positive airway pressure (CPAP) on the secondary prevention of major cardiovascular events in obstructive sleep apnea (OSA) patients. However, participants in RCTs are substantially different from real-world patients. Therefore, we aimed to assess the effect of CPAP treatment on major cardiovascular events in real-world OSA patients. MethodsPopulation-based longitudinal observational study including all OSA patients with an active CPAP prescription at the beginning of 2011 in Catalonia, Spain, that terminated CPAP treatment during 2011 and did not have CPAP prescriptions between 2012-2015; and propensity-score-matched OSA patients that continued CPAP treatment until the end of 2015 or death. Adjusted hazard ratios were used to assess the association between CPAP treatment and overall and cardiovascular mortality, cardiovascular hospitalizations, or major adverse cardiovascular events (MACEs). Results3638 CPAP terminators and 10,914 propensity-score-matched continuators were included (median age 67 [57–77] years, 71.4% male). During a median follow-up of 47.9 months CPAP continuators showed a lower risk of cardiovascular death than terminators (hazard ratio [HR]: 0.61; 95% confidence interval [CI]: 0.50–0.75) after adjusting by age, sex and key comorbidities. Similar results were found for cardiovascular hospitalizations (HR: 0.87; 95% CI: 0.76–0.99) and MACEs (HR: 0.84; 95% CI: 0.75–0.95). ConclusionCPAP treatment continuation could be associated with a significantly lower risk of major cardiovascular events in real-world OSA patients. This result highlights the importance of including real-world patients in studies on OSA.

Polypill Strategy in Secondary Cardiovascular Prevention.

The polypill strategy, originally developed to improve medication adherence, has demonstrated efficacy in improving baseline systolic blood pressures and cholesterol levels in multiple clinical trials. However, the long-term clinical impact of improved major cardiovascular events (MACE) outcomes by the polypill remains uncertain. Recent trials with long-term follow-up, which included minority groups and people with low socioeconomic status, have shown non-inferiority with no difference in adverse effects rates for the secondary prevention of MACE. Although the polypill strategy was initially introduced to improve adherence to guideline-directed medical therapy (GDMT) for cardiovascular complications, the strategy has surpassed standard medical treatment for secondary prevention of MACE outcomes. Studies also showed improved medication compliance in underserved populations.

Abstract P305: Room for Improved Secondary Prevention of Major Cardiovascular Events Among the Population With New Onset Diabetes: A Longitudinal Latent Class Trajectory Analysis

Background: After a diagnosis of diabetes, specialist physicians may play a key role in the secondary prevention of major cardiovascular events (MACE). Yet, trajectories of visits to specialists are heterogenous and their efficacy in the prevention of MACE remains unexplored. Goal: To assess whether trajectories of visits to specialists are associated with MACE among new cases of diabetes. Methods: Using the Quebec Integrated Chronic Disease Surveillance System, we identified new cases of diabetes ≥20 years old during fiscal year 2013, who had no prior history of MACE (ischemic cardiopathy, stroke, myocardial infarction or cardiovascular death). Firstly, individual trajectories according to the presence/absence of ≥1 ambulatory visit to a specialist (cardiologist, internist, endocrinologist) were compiled over consecutive 3-month periods up to 2 years following diagnosis. Patients with no visit were compiled in a “primary care only” group, while others were classified in groups using latent class growth analysis. Patients who had a MACE during this period were excluded. Secondly, the risk of MACE occuring after the 2 years following diagnosis up to December 31 st 2019 was compared between groups using a marginal Cox proportional hazards regression model, adjusted with inverse probability weighting and providing adjusted hazard ratio (aHR) with 95% confidence intervals (CI). Results: Among the 24,782 patients included, 5 groups were identified ( Figure 1 ). A total of 2,837 MACE occurred. Compared with the “primary care only group”, those who consulted a specialist were at higher risk of MACE (Regular/frequent visits: aHR: 1.50 [95% CI: 1.26 to 1.66]; Late visits: aHR: 1.41 [1.13 to 1.73]; Regular/sparce visits: 1.38 [1.27 to 1.51]; Early visits: 1.36 [1.19 to 1.54]), while no difference was observed between these groups. Conclusions: Although confounding by indication cannot be totally ruled out, these results may suggest room for improvement in the secondary prevention of MACE after a diabetes diagnosis.

Down the rabbit hole: reviewing the evidence for primary prevention of cardiovascular disease in people with obesity.

Obesity is a prevalent chronic disorder and a well-known risk factor for cardiovascular disease. However, the evidence of treating obesity for primary prevention of major cardiovascular events is still scarce and controversial. In this review, we provided a comprehensive description of the current evidence in treating obesity regarding cardiovascular protection. Bariatric surgery appears to be the most robust method to reduce events in people without established cardiovascular disease. High compliance to lifestyle interventions can further reduce cardiovascular risk. Concerning pharmacological therapies, a post hoc analysis from SUSTAIN-6 and a meta-analysis from STEP trials suggest that semaglutide, a GLP-1 receptor agonist, could reduce cardiovascular events in people without established cardiovascular disease. The first study addressed specifically a high-risk population with diabetes and, the second, low- or intermediary-risk individuals without diabetes. Tirzepatide, a novel dual GIP/GLP-1 agonist, although not yet tested in specific cardiovascular outcomes trials, could be an alternative since it induces loss in weight similar to the achieved by bariatric surgery. Therefore, extrapolated data in distinct baseline cardiovascular risk populations suggest that these two drugs could be used in primary prevention with the aim of preventing cardiovascular events, but the grade of this evidence is still low. Specifically designed studies are needed to address this specific topic.

A meta-analysis evaluating efficacy and safety of colchicine for prevention of major cardiovascular events in patients with coronary artery disease.

Inflammatory plays a key role in the development of coronary artery disease (CAD). Colchicine as an anti-inflammatory treatment for CAD has attracted much attention, its efficacy and safety are controversial and deserved further exploration. To evaluate the efficacy and safety of colchicine for patients with CAD, relevant randomized controlled trials (RCTs) were identified by searching several databases including PubMed, Web of Science, and EMBASE from January 1992 to May 2022. Fourteen eligible trials of colchicine therapy include populations with chronic coronary syndrome (CCS) (N = 2), acute coronary syndrome (ACS) (N = 5), and percutaneous coronary intervention (PCI) or coronary artery bypass grafting (CABG) (N = 7), and involve a total of 13,235 patients which include 6654 subjects in colchicine group and 6581 subjects in the respective control arms. The outcome was reported as odds ratio (OR) and 95% confidence interval (CI), as the relative measure of association. Overall, the incidences of major adverse cardiovascular events (MACEs) (OR 0.65; 95% CI 0.54-0.77, p < 0.01), new ACS (OR 0.68; 95% CI 0.57-0.81, p < 0.01), coronary revascularization (OR 0.65; 95% CI 0.53-0.78, p < 0.01), and stroke (OR 0.51; 95% CI 0.32-0.82, p < 0.01), were lower in the colchicine group than in the placebo arm. We did not find a significant reduction in the incidence of atrial fibrillation (OR 0.84; 95% CI 0.68-1.04, p = 0.11), all-cause mortality (OR 1.06; 95% CI 0.83-1.35, p = 0.83), cardiovascular mortality (OR 0.77; 95% CI 0.52-1.15, p = 0.21). However, we found that colchicine did increase non-cardiovascular mortality (OR 1.44; 95% CI 1.04-2.01, p = 0.03). Although the incidence of gastrointestinal events in the colchicine treatment group was higher than that in the placebo arms (OR 2.08; 95% CI 1.39-3.12, p < 0.01), the symptoms disappeared rapidly after drug withdrawal and could be tolerated by most patients. Colchicine did not increase the incidence of infections (OR 1.42; 95% CI 0.82-2.46, p = 0.22), pneumonia (OR 1.55; 95% CI 0.58-4.18, p = 0.39), cancers (OR 0.98; 95% CI 0.79-1.22, p = 0.88), bleeding (OR 1.14; 95% CI 0.41-3.14, p = 0.80). Colchicine is an effective, relatively safe drug that could be considered for the treatment of CAD. However, we need to pay attention to the increasing occurrence of non-cardiovascular mortality and infection especially pneumonia possibly caused by colchicine. Efficacy and safety of colchicine for patients with CAD. CAD coronary artery disease; RCTs randomized controlled trials; OR odds ratio; MACEs major adverse cardiovascular events; ACS acute coronary syndrome; NNT number needed to treat; NNH number needed to harm.

LP(a): Structure, Genetics, Associated Cardiovascular Risk, and Emerging Therapeutics.

Lipoprotein(a) [Lp(a)] is a molecule bound to apolipoprotein(a) with some similarity to low-density lipoprotein cholesterol (LDL-C), which has been found to be a risk factor for cardiovascular disease (CVD). Lp(a) appears to induce inflammation, atherogenesis, and thrombosis. Approximately 20% of the world's population has increased Lp(a) levels, determined predominantly by genetics. Current clinical practices for the management of dyslipidemia are ineffective in lowering Lp(a) levels. Evolving RNA-based therapeutics, such as the antisense oligonucleotide pelacarsen and small interfering RNA olpasiran, have shown promising results in reducing Lp(a) levels. Phase III pivotal cardiovascular outcome trials [Lp(a)HORIZON and OCEAN(a)] are ongoing to evaluate their efficacy in secondary prevention of major cardiovascular events in patients with elevated Lp(a). The future of cardiovascular residual risk reduction may transition to a personalized approach where further lowering of either LDL-C, triglycerides, or Lp(a) is selected after high-intensity statin therapy based on the individual risk profile and preferences of each patient.

Effects of continuous positive airway pressure on cardiac events and metabolic components in patients with moderate to severe obstructive sleep apnea and coronary artery disease: a meta-analysis.

This meta-analysis aimed to systematically assess the effects of continuous positive airway pressure (CPAP) in secondary prevention of major cardiovascular events (MACEs) in patients with moderate-to-severe obstructive sleep apnea and coronary artery disease. PubMed, Embase, the Cochrane Library, and ClinicalTrials.gov were searched for observational studies and randomized controlled trials that compared CPAP with usual care in patients with moderate-to-severe obstructive sleep apnea with coronary artery disease. The primary outcomes were MACEs, all-cause death, acute coronary syndrome, rehospitalization for heart failure, repeat revascularization, and arrhythmia. A total of 11 studies (5 randomized controlled trials and 6 observational studies) with 5,410 patients reported outcomes of MACEs. Treatment with CPAP was associated with a modest risk reduction in MACEs (risk ratio [RR] 0.87, 95% confidence interval [CI] 0.78 to 0.98; P = .02). Similarly, CPAP significantly reduced the risk of all-cause and cardiovascular death by 23% (RR 0.77, 95% CI 0.60 to 0.99; P = .04; I2 = 0%). Subgroup analysis revealed that CPAP adherence time ≥ 4 hours/night had a greater benefit on MACEs by 42% (RR 0.58, 95% CI 0.42 to 0.79; P < .001; I2 = 0%) and repeat revascularization by 44% (RR 0.56, 95% CI 0.34 to 0.92; P = .02; I2 = 0%). Also, CPAP had a positive effect on systolic and diastolic blood pressure. CPAP therapy might prevent subsequent MACEs and all-cause death among patients with moderate to severe obstructive sleep apnea and concomitant coronary artery disease. CPAP use exceeding 4 hours/night may add more benefits on MACEs, repeat revascularization, and blood pressure. Registry: PROSPERO database; Name: Effects of Continuous Positive Airway Pressure on Cardiovascular Events and Metabolic Components in Patients with Obstructive Sleep Apnea and Coronary Artery Disease; URL: https://www.crd.york.ac.uk/prospero/display_record.php?ID= CRD42020213546; Identifier: CRD42020213546. Yang D, Li L, Dong J, Yang W, Liu Z. Effects of continuous positive airway pressure on cardiac events and metabolic components in patients with moderate to severe obstructive sleep apnea and coronary artery disease: a meta-analysis. J Clin Sleep Med. 2023;19(12):2015-2025.

Cardiovascular prevention: Mediterranean or low-fat diet?

The international scientific community has long agreed on the fact that a low-fat diet is actually able to bring benefits to cardiovascular health and beyond. By low-fat diet, experts mean a diet where the average calories assimilated daily are made up of no more than 30% fat. The Mediterranean Diet, on the other hand, identifies a nutritional model inspired by the traditional eating habits of the countries bordering the Mediterranean Sea. It began to be studied scientifically in the 1950s and it is still today one of the diets that have a positive impact on our health when associated with correct lifestyles. Although epidemiological and mechanistic studies show similar results, there is no evidence from large-scale, long-term clinical trials on the efficacy of the Mediterranean Diet compared with another active group, particularly in secondary prevention. A convincing response has been obtained from the recent CORDIOPREV study (CORonary Diet Intervention with Olive oil and cardiovascular PREVention) which randomized ∼1000 patients with documented coronary artery disease to a Mediterranean Diet or a low-fat dietary intervention. In a 7-year follow-up, the Mediterranean Diet was superior to the low-fat diet in the prevention of major cardiovascular events.

Dual Antiplatelet Therapy Versus Antiplatelet Monotherapy Plus Oral Anticoagulation in Patients with Acute Coronary Syndrome and Coronary Artery Ectasia: Design and Rationale of OVER-TIME Randomized Clinical Trial.

The optimal anti-thrombotic therapy to prevent recurrent ischemic events in patients with acute coronary syndrome and coronary artery ectasia (CAE) remains unclear. To assess the efficacy and safety of antiplatelet plus anticoagulant therapy versus dual antiplatelet therapy in patients with acute coronary syndromes and coronary artery ectasia. OVER-TIME is an investigator initiated, exploratory, open label, single center, randomized clinical trial comparing dual antiplatelet therapy (acetyl-salicylic acid plus a P2Y12 inhibitor) with the combination of an antiplatelet monotherapy (a P2Y12 inhibitor) plus a low dose anticoagulant (rivaroxaban, 15mg oral dose) for the prevention of recurrent ischemic events among patients with CAE. We aim to enroll approximately 60 patients with CAE and acute coronary syndromes. After recruitment, patients are randomized to (a) standard of care (dual antiplatelet regimen) or (b) the combination of antiplatelet monotherapy and low dose anticoagulant. Patients will be followed for at least 12 months. The OVER-TIME study aims to assess the efficacy of the regimen in prevention of major cardiovascular events and its security in bleeding events in acute coronary syndromes among patients with CAE. Expected results and conclusions: OVER-TIME is the first randomized controlled trial to assess different antithrombotic strategies in patients with CAE and acute coronary syndrome, and its results will offer preliminary data for the prevention of major cardiovascular events and bleeding events in this group of patients. NCT05233124 (ClinicalTrials.gov), date of registration: February 10, 2022.

IDF21-0652 Blood pressure-lowering for prevention of major cardiovascular diseases in persons with and without type 2 diabetes

Background: There is insufficient randomised evidence as to whether the effect of blood pressure (BP)-lowering treatment differs in people with type 2 diabetes versus those without this metabolic condition, particularly at a normal or high-normal BP level. Aim: To investigate the effects of BP-lowering treatment on the risk of major cardiovascular events in people with and without type 2 diabetes, and by baseline levels of systolic and diastolic BP. Method: We used the resource provided by the Blood Pressure Lowering Treatment Trialists' Collaboration (BPLTTC) to conduct a one-stage individual participant data meta-analysis of major randomised trials. The primary outcome was total major cardiovascular events, defined as the first occurrence of fatal or non-fatal stroke or cerebrovascular disease, fatal or non-fatal myocardial infarction, and heart failure causing death or requiring hospitalisation. The analysis was stratified for type 2 diabetes status at baseline, and baseline categories of systolic BP (in 10 mm Hg increments from <120 mm Hg to ≥170 mm Hg) and diastolic BP from <70 mm Hg to ≥110 mm Hg diastolic). Cox proportional hazard model stratified by the trial was used to estimate hazard ratio (HR). A Poisson regression model with an identity link was used to calculate the absolute risk reduction (ARR). Results: Data for 358,533 participants (58.4% men) from 51 randomised clinical trials were included in the analysis, in which 28.8% (n=103,325) of the participants had diagnosis of type 2 diabetes at baseline. Baseline mean systolic/diastolic BPs were 149/84 mm Hg in participants with type 2 diabetes (n=103,325) and 153/88 mm Hg in participants without type 2 diabetes (n=255,208). The incidence risks of primary events during the study follow-up time in participants with and without type 2 diabetes were 16.5% and 10.2%, respectively. Over 4.2 years of median follow-up, a fixed value of 5-mm Hg reduction in systolic BP was associated with a lower risk of major cardiovascular events both in participants with type 2 diabetes (HR 0.94 [95% CI 0.91 to 0.98]; ARR -0.015 [95% CI -0.020 to -0.010]) and in those without history of type 2 diabetes (HR 0.89 [95% CI 0.87 to 0.92]; ARR =-0.016 [95% CI -0.018 to -0.013]). In stratified analyses, we did not find reliable evidence for heterogeneity of treatment effects by baseline systolic or diastolic BP level in participants with or without type 2 diabetes (all P for interaction > 0.78). Discussion: The effect of BP reduction for primary and secondary prevention of major cardiovascular events was broadly comparable among people with and without type 2 diabetes, with no clinically important evidence that the level of systolic or diastolic BP at baseline is a determinant of treatment effect. Recommendations by guidelines on different BP reduction treatment in people with and without diabetes, or initiation of BP reduction therapy at a specific BP threshold, are not substantiated by these findings. This work will be presented on behalf of the Blood Pressure Lowering Treatment Trialists' Collaboration. Working group: Milad Nazarzadeh, Zeinab Bidel, Dexter Canoy, Emma Copland, Abbas Dehghan, Derrick A Bennett, George Davey Smith, Rury R. Holman, Mark Woodward, Ajay Gupta, Amanda Adler, Naveed Sattar, Richard J McManus, Koon Teo, Barry R Davis, John Chalmers, Carl J. Pepine, Kazem Rahimi.

Polypill for prevention of cardiovascular diseases with focus on non-alcoholic steatohepatitis: the PolyIran-Liver trial.

Individuals with non-alcoholic steatohepatitis or elevated liver enzymes have increased cardiovascular mortality but are often excluded from prevention trials. We investigated the effectiveness of fixed-dose combination therapy for the prevention of major cardiovascular events (MCVE) among individuals with and without presumed non-alcoholic steatohepatitis (pNASH). Two thousand four hundred participants over 50 were randomized into the intervention and control groups. Consent was obtained post-randomization. Consenting participants in the intervention group were given a pill containing aspirin, atorvastatin, hydrochlorothiazide, and valsartan (polypill). Participants were followed for 5 years. Presumed non-alcoholic steatohepatitis was diagnosed by ultrasonography and elevated liver enzymes. The primary outcome was MCVE. ClinicalTrials.gov: NCT01245608. Among the originally randomized population, 138 of 1249 in the intervention group (11.0%) and 137 of 1017 controls (13.5%) had MCVE during the 5-year follow-up [unadjusted risk ratio (RR) 0.83, 95% confidence interval (CI) 0.66-1.03]. Of the 1508 participants who consented to additional measurements and treatment, 63 of 787 (8.0%) intervention group participants and 86 of 721 (11.9%) controls had MCVE (adjusted RR 0.61, 95% CI 0.44-0.83). Although the adjusted relative risk of MCVE in participants with pNASH (0.35, 95% CI 0.17-0.74) was under half that for participants without pNASH (0.73, 95% CI 0.49-1.00), the difference did not reach statistical significance. There was no change in liver enzymes in participants taking polypill but among those with pNASH, there was a significant decrease after 60 months of follow-up (intragroup -12.0 IU/L, 95% CI -14.2 to -9.6). Among patients consenting to receive fixed-dose combination therapy, polypill is safe and effective for the prevention of MCVE, even among participants with fatty liver and increased liver enzymes.

Abstract 9893: Polypills for Primary Prevention of Cardiovascular Disease: A Systematic Review and Meta-Analysis of Clinical Trials

Background: Single pills with fixed-dose combinations (FDC) of lipid and blood pressure lowering medications have been proposed for the treatment of cardiovascular disease. Although polypills have proven to be effective in secondary prevention of major cardiovascular events, there is a lack of evidence regarding polypill use in primary prevention in intermediate and high-risk patients. This systematic review and meta-analysis was conducted to evaluate the effect of polypills on primary prevention of cardiovascular (CV) events using data from clinical trials. Methods: We searched Pubmed, Web of Science, EBSCO, and SCOPUS through May 2021. Two authors independently screened articles for fulfillment of inclusion criteria. The RevMan (version 5.4) software was used to calculate the pooled risk ratios (RRs) and mean differences (MDs), along with their associated confidence intervals (95% CI). Results: Eight trials with a total of 20653 patients were included. There was a significant reduction in total fatal and non-fatal CV events among the polypill group [RR (95% CI) = 0.71 (0.63, 0.80); P &lt; 0.001]. Moreover, this reduction was present for both the intermediate [RR (95% CI) = 0.76 (0.65, 0.89); P &lt; 0.001] and high-risk [RR (95% CI) = 0.63 (0.52, 0.76); P &lt; 0.001] group of patients. Subgroup analysis based on the follow up duration revealed this benefit was only evident in the five-year follow up duration group [RR (95% CI) = 0.70 (0.62, 0.79); P&lt; 0.001] and was absent in the one-year or less interval group [RR (95% CI) = 0.77 (0.47, 1.29); P= 0.330]. Furthermore, there was a significant reduction in 10-year predicted cardiovascular risk in the polypill group [MD (95% CI) = -3.74 (-5.96, -1.51); P&lt; 0.001] compared to controls. Conclusion: A polypill strategy decreases the incidence of fatal and non-fatal CV events in patients with intermediate and high cardiovascular risk and may be an effective component in the care of these patients.

Anti-inflammatory therapy in ischaemic heart disease: from canakinumab to colchicine.

Four large trials have recently evaluated the effects of anti-inflammatory drugs in the secondary prevention of major cardiovascular events (MACE) in over 25 000 patients followed for 1.9–3.7 years. CANTOS tested subcutaneous canakinumab [an anti-interleukin (IL) 1β antibody] 300 mg every 3 months against placebo in patients with a history of myocardial infarction (MI) and serum C-reactive protein (CRP) >2 mg/L, demonstrating efficacy in preventing MACE but increased rates of fatal infections. COLCOT (in patients with recent MI) and LoDoCo2 (in patients with chronic coronary syndromes) tested oral colchicine (an NLRP3 inflammasome inhibitor) 0.5 mg daily vs. placebo, demonstrating prevention of MACE with a slightly increased risk of pneumonia in COLCOT (0.9 vs. 0.4%) but not in LoDoCo2. CIRT tested oral methotrexate (an anti-rheumatic anti-nuclear factor-kB) 15–20 mg per week against placebo in ischaemic heart disease patients with diabetes or metabolic syndrome, without significant reduction in MACE rates or in circulating IL6 or CRP levels, and with increased risk of skin cancers. In summary, canakinumab and colchicine have shown efficacy in preventing MACE in ischaemic heart disease patients, but only colchicine has acceptable safety (and cost) for use in secondary cardiovascular prevention. Clinical results are expected with the anti-IL6 ziltivekimab.

Age-stratified and blood-pressure-stratified effects of blood-pressure-lowering pharmacotherapy for the prevention of cardiovascular disease and death: an individual participant-level data meta-analysis

SummaryBackgroundThe effects of pharmacological blood-pressure-lowering on cardiovascular outcomes in individuals aged 70 years and older, particularly when blood pressure is not substantially increased, is uncertain. We compared the effects of blood-pressure-lowering treatment on the risk of major cardiovascular events in groups of patients stratified by age and blood pressure at baseline.MethodsWe did a meta-analysis using individual participant-level data from randomised controlled trials of pharmacological blood-pressure-lowering versus placebo or other classes of blood-pressure-lowering medications, or between more versus less intensive treatment strategies, which had at least 1000 persons-years of follow-up in each treatment group. Participants with previous history of heart failure were excluded. Data were obtained from the Blood Pressure Lowering Treatment Triallists' Collaboration. We pooled the data and categorised participants into baseline age groups (<55 years, 55–64 years, 65–74 years, 75–84 years, and ≥85 years) and blood pressure categories (in 10 mm Hg increments from <120 mm Hg to ≥170 mm Hg systolic blood pressure and from <70 mm Hg to ≥110 mm Hg diastolic). We used a fixed effects one-stage approach and applied Cox proportional hazard models, stratified by trial, to analyse the data. The primary outcome was defined as either a composite of fatal or non-fatal stroke, fatal or non-fatal myocardial infarction or ischaemic heart disease, or heart failure causing death or requiring hospital admission.FindingsWe included data from 358 707 participants from 51 randomised clinical trials. The age of participants at randomisation ranged from 21 years to 105 years (median 65 years [IQR 59–75]), with 42 960 (12·0%) participants younger than 55 years, 128 437 (35·8%) aged 55–64 years, 128 506 (35·8%) 65–74 years, 54 016 (15·1%) 75–84 years, and 4788 (1·3%) 85 years and older. The hazard ratios for the risk of major cardiovascular events per 5 mm Hg reduction in systolic blood pressure for each age group were 0·82 (95% CI 0·76–0·88) in individuals younger than 55 years, 0·91 (0·88–0·95) in those aged 55–64 years, 0·91 (0·88–0·95) in those aged 65–74 years, 0·91 (0·87–0·96) in those aged 75–84 years, and 0·99 (0·87–1·12) in those aged 85 years and older (adjusted pinteraction=0·050). Similar patterns of proportional risk reductions were observed for a 3 mm Hg reduction in diastolic blood pressure. Absolute risk reductions for major cardiovascular events varied by age and were larger in older groups (adjusted pinteraction=0·024). We did not find evidence for any clinically meaningful heterogeneity of relative treatment effects across different baseline blood pressure categories in any age group.InterpretationPharmacological blood pressure reduction is effective into old age, with no evidence that relative risk reductions for prevention of major cardiovascular events vary by systolic or diastolic blood pressure levels at randomisation, down to less than 120/70 mm Hg. Pharmacological blood pressure reduction should, therefore, be considered an important treatment option regardless of age, with the removal of age-related blood-pressure thresholds from international guidelines.FundingBritish Heart Foundation, National Institute of Health Research Oxford Biomedical Research Centre, Oxford Martin School.

Impact of compliance with lifestyle recommendations and medication adherence on 1-year prevention of major cardiovascular events in diabetic patients undergoing partial foot amputation

Abstract Funding Acknowledgements Type of funding sources: None. Background Partial foot amputation (PFA) is generally not considered a high-risk surgery. However, 3 years survival rate is less than 50-60%. The purpose of the study was to evaluate the impact of compliance with lifestyle recommendations and medication adherence on 1-year prevention of major cardiovascular events (MACE) in patients with type 2 diabetes mellitus (T2DM) after PFA. Methods In this prospective single-center interventional cohort study, 785 consecutive T2DM patients after PFA were included in the 1-year follow-up. Physical examination and laboratory tests were performed at baseline and every month after PFA for 1 year. Patients were considered as compliant with lifestyle recommendations if they followed a healthy diet, smoking cessation, and at least ≥30 min/day physical exercise. Patients were defined as adherent to medication if they followed ≥80% prescribed medication intake. MACE was defined as a composite endpoint including cardiovascular death, myocardial infarction (MI), stent thrombosis, acute stroke, or unstable arrhythmia. Results During 1-year follow-up MACE occurred in 63/535 patients who were medication adherent compared to 137/249 non-adherent patients (Chi square = 167,2, p &amp;lt; 0,001). Among lifestyle compliant patients, 55/498 had MACE compare with 145/286 non-compliant patients (Chi square = 150.3, p &amp;lt; 0,001). The COX regression analysis was conducted to present the adjusted effect of compliance and adherence to the incidence of MACE (B = 0.989, p &amp;lt; 0.001, and B= 1.096, p &amp;lt; 0.001, respectively) (Table). The potential confounders such as age and previous MI were statistically significant (Table). Gender, smoking, diabetes severity, HbA1c, hypertension, symptomatic coronary artery disease, history of ischemic events, heart revascularization were not statistically significant. Conclusion. Failure to follow lifestyle recommendations in T2DM patients after PFA increases the OR of the incidence of MACE 2.7 fold, non-adherence to medication 3 fold. Our results indicate that optimizing preventive interventions is of outmost importance for patients with diabetes undergoing PFA Cox Regression Results for predictors of Indicator Odds ratio B Standard error P-value Age 1.031 0.031 0.009 0.007 History of myocardial infarction 4.017 1.391 0.184 &amp;lt;0.001 Non-compliance to lifestyle changes 2.688 0.989 0.198 &amp;lt;0.001 Medication non-adherence 2.992 1.096 0.186 &amp;lt;0.001

Fixed Dose Combination Therapy for Secondary Prevention of Major Cardiovascular Events: Review of Literature and Design for Persian Polypill, A Randomized Clinical Trial.

This is a review on clinical trials assessing polypill in secondary prevention of cardiovascular diseases (CVD), followed by design of Persian Polypill study. We identified six completed studies and three ongoing trials having at least 10% of their participants with established CVD. Evaluation of these trials showed insufficient data to support polypill as a strategy to reduce major adverse cardiovascular events (MACE) in CVD patients, and a lack of studies in low and middle income countries. Persian Polypill will be an open labeled, parallel two arm, randomized clinical trial conducting on patients hospitalized because of an acute myocardial infarction (AMI). It is planned to randomize 1200 patients to one of the two arms, either receiving polypill or usual care and follow them for 34 months. The primary outcome will be a composite clinical outcome of MACE and the secondary outcome will be cost-effectiveness of polypill treatment. Results of this study might support comprising polypill in routine management of AMI, especially in developing countries.

Effects of vitamin supplements on clinical cardiovascular outcomes: Time to move on! - A comprehensive review.

Background & aimsVitamin supplementations have increasingly been advertised on media and reported to be widely used by the general public to improve cardiovascular health. Due to the COVID-19 pandemic, people have become more interested in ways to improve and maintain their health. Increased awareness of people on healthy lifestyle is translating into inquisition regarding dietary supplements. Aim: First, focus on the most commonly used vitamin supplements and comprehensively review the evidence for and against recommending them to patients to improve and/or maintain cardiovascular health. Second, illustrate how the interest in studies shifted over time from Vitamin A, E, C, and B to Vitamin D and observational studies led to randomized controlled trials.MethodsA thorough PubMed search with the phrase: “Vitamin supplements and cardiovascular health” was performed. In the present review, focus was maintained on the evidence for the use of vitamin supplements in the prevention of major cardiovascular events and/or the maintenance of cardiovascular health by comprehensively reviewing all previous studies indexed in PubMed. Studies with clinical ‘hard’ end-points were included only.ResultsA total of 87 studies met the inclusion criteria and were reviewed in the present article. High-quality evidence suggesting benefits for the use of vitamin supplements to maintain or improve cardiovascular health in people is minimal to non-existent.ConclusionsVitamin supplementation does not improve clinical cardiovascular outcomes in general population. Counseling on the importance of maintaining a healthy lifestyle with adequate and nutritious food intake seems more appropriate to improve and maintain cardiovascular health.

Rivaroxaban Plus Aspirin in Obese and Overweight Patients With Vascular Disease in the COMPASS Trial

BackgroundDirect oral anticoagulants are administered in fixed doses irrespective of body weight, but guidelines recommend against their use in patients with extremes of body weight. ObjectivesThis study determined the effects of dual-pathway inhibition antithrombotic regimen (rivaroxaban 2.5 mg twice daily plus aspirin 100 mg/day) compared with aspirin Halone across a range of patient body mass indexes (BMIs) and body weights. MethodsThis was a secondary analysis of the COMPASS (Cardiovascular OutcoMes for People using Anticoagulation StrategieS) trial, which included patients with chronic coronary artery disease or peripheral artery disease. Efficacy and safety outcomes were studied in relation to BMI: (normal 18.5 ≤BMI <25 kg/m2, overweight 25 ≤BMI <30 kg/m2, obese ≥30 kg/m2) and body weight (≤70 kg, 70 < weight ≤90 kg, and >90 kg; as well as ≤120 kg vs. >120 kg). ResultsAmong 27,395 randomized patients, 6,459 (24%) had normal BMI, 12,047 (44%) were overweight, and 8,701 (32%) were obese. The combination of rivaroxaban and aspirin compared with aspirin produced a consistent reduction in the primary outcome of cardiovascular death, stroke, or myocardial infarction, irrespective of BMI or body weight. For 18.5 ≤BMI <25 kg/m2: 3.5% vs. 5.0%; hazard ratio (HR): 0.73 (95% credible interval [CrI]: 0.58 to 0.90); 25 ≤ BMI <30 kg/m2: 4.3% vs. 5.1%; HR: 0.80 (95% CrI: 0.66 to 0.96); BMI ≥30 kg/m2: 4.2% vs. 6.1%; HR: 0.71 (95% CrI: 0.57 to 0.86). For body weight ≤70 kg: 4.1% vs. 5.3%; HR: 0.75 (95% CrI: 0.62 to 0.91); 70 < weight ≤90 kg: 4.1% vs. 5.3%; HR: 0.76 (95% CrI: 0.65 to 0.89); >90 kg: 4.2% vs. 5.7%; HR: 0.74 (95% CrI: 0.61 to 0.90). Effects on bleeding, mortality, and net clinical benefit were consistent irrespective of BMI or bodyweight. ConclusionsThe effects of dual-pathway antithrombotic therapy are consistent irrespective of BMI or body weight, suggesting no need for dose adjustments in the ranges of weights and BMI of patients enrolled in the COMPASS trial. Further studies need to address this problem in relation to greater extremes of body weight. (Rivaroxaban for the Prevention of Major Cardiovascular Events in Coronary or Peripheral Artery Disease [COMPASS]; NCT01776424)

Chronic ischaemic heart disease and rivaroxaban: which patients derive the greatest benefit?

Patients with established cardiovascular (CV) disease may suffer further CV events, despite receiving optimal medical treatment. Although platelet inhibition plays a central role in the prevention of new events, the use of anticoagulant therapies to reduce events in atheromatous disease has, until recently, been overlooked. The recent Rivaroxaban for the Prevention of Major Cardiovascular Events in Coronary or Peripheral Artery Disease (COMPASS) trial showed that rivaroxaban 2.5 mg twice daily given with low-dose aspirin reduces the incidence of the composite endpoint of stroke, heart attack, and death in patients with stable coronary artery disease. Although there are some limitations to the study, COMPASS offers promising conclusions and may change secondary prevention in patients with stable CV disease. This article reviews the results of the COMPASS study and how these results may affect patient management in everyday clinical practice.

Estimation of the major cardiovascular events prevention with Inclisiran

Background and aimsThe ORION 10–11 trials have reported the efficacy of Inclisiran on low-density lipoprotein cholesterol (LDLc) reduction, and also suggested prevention of major cardiovascular events (MACE) incidence. MethodsWe have performed a meta-analysis of the available studies, involving PCSK9 inhibitors or Inclisiran for >6 months, that reported the incidence of MACE. The primary endpoint was MACE incidence, as reported in outcomes-based randomized clinical trials (OB-RCT) and non OB-RCT. Analyses were performed using fixed effect models and fractional polynomial regression. ResultsThe meta-analysis included a total of 57,431 patients, 1592 treated with Inclisiran and 28,259 with PSCK9 inhibitors (17,244 with evolocumab and 11,015 with alirocumab). Baseline mean LDLc was 104.1 (12.9) mg globally. On-treatment mean LDLc was 40.1 (7.8) mg/dl and mean absolute LDLc reduction was 60.6 (10.3) mg/dl. A total of 5389 MACE were reported, 2482 in patients receiving the study drug and 2907 in patients assigned to placebo. Treatment was associated with OB-RCT and no heterogeneity was observed. The estimation of MACE reduction associated with LDLc reduction, adjusted by age, diabetes, hypertension and baseline LDLc, provided a linear trend in the risk of MACE and LDLc reduction that was linear and all studies fitted properly. ConclusionsThe results of the ORION 10–11 trials are in concordance with results of trials involving treatment with PCSK9 inhibitors. The results of the ORION-4 trial will provide definite evidence on the effects of Inclisiran on MACE reduction.