Search

Key Points: Question: What are the outcomes of transcatheter mitral valve repair for isolated degenerative mitral regurgitation (MR) in a real-world setting? Findings: In this registry-based cohort study of 19 088 consecutive patients with isolated moderate to severe or severe degenerative MR who underwent nonemergent transcatheter mitral valve repair, MR success (defined as moderate or less residual MR without severe stenosis) was achieved in 88.9% of patients and associated with significantly lower 1-year mortality (14.0%) vs those with an unsuccessful procedure (26.7%). Among patients with MR success, the lowest 1-year mortality (11.4%) was observed in patients who had both mild or less residual MR and mean mitral gradients of 5 mm Hg or less vs those with an unsuccessful procedure (26.7%). Meaning: Transcatheter mitral valve repair may be a reasonable treatment option in patients with high surgical risk and isolated degenerative MR. Importance: There are limited data on the outcomes of transcatheter edge-to-edge mitral valve repair for degenerative mitral regurgitation (MR) in a real-world setting. Objective: To evaluate the outcomes of transcatheter mitral valve repair for degenerative MR. Design, Setting, and Participants: Cohort study of consecutive patients in the Society of Thoracic Surgeons/American College of Cardiology Transcatheter Valve Therapies Registry who underwent nonemergent transcatheter mitral valve repair for degenerative MR in the US from 2014 through 2022. Exposure: Transcatheter edge-to-edge mitral valve repair with the MitraClip device (Abbott). Main Outcomes and Measures: The primary end point was MR success, defined as moderate or less residual MR and a mean mitral gradient of less than 10 mm Hg. Clinical outcomes were evaluated based on the degree of residual MR (mild or less MR or moderate MR) and mitral valve gradients (≤5 mm Hg or >5 to <10 mm Hg). Results: A total of 19 088 patients with isolated moderate to severe or severe degenerative MR who underwent transcatheter mitral valve repair were analyzed (median age, 82 years; 48% women; median Society of Thoracic Surgeons predicted risk of mortality with surgical mitral valve repair, 4.6%). MR success was achieved in 88.9% of patients. At 30 days, the incidence of death was 2.7%; stroke, 1.2%; and mitral valve reintervention, 0.97%. MR success compared with an unsuccessful procedure was associated with significantly lower mortality (14.0% vs 26.7%; adjusted hazard ratio, 0.49; 95% CI, 0.42-0.56; P <.001) and heart failure readmission (8.4% vs 16.9%; adjusted hazard ratio, 0.47; 95% CI, 0.41-0.54; P <.001) at 1 year. Among patients with MR success, the lowest mortality was observed in patients who had both mild or less residual MR and mean mitral gradients of 5 mm Hg or less compared with those with an unsuccessful procedure (11.4% vs 26.7%; adjusted hazard ratio, 0.40; 95% CI, 0.34-0.47; P <.001). Conclusions and Relevance: In this registry-based study of patients with degenerative MR undergoing transcatheter mitral valve repair, the procedure was safe and resulted in successful repair in 88.9% of patients. The lowest mortality was observed in patients with mild or less residual MR and low mitral gradients. This cohort study assesses residual mitral regurgitation and mitral gradient outcomes as well as clinical outcomes after transcatheter mitral valve repair in a registry of patients with moderate to severe or severe degenerative mitral regurgitation. [ABSTRACT FROM AUTHOR]

This study uses National Health and Nutrition Examination Survey data to examine lipid control among adults in the US with coronary artery disease from January 2015 to March 2020. [ABSTRACT FROM AUTHOR]

The study attempts to evaluate the factors and comparative determinants of 4-year cardiovascular event rates in stable outpatients at risk of or with atherothrombosis. The results indicate that such kinds of clinical descriptors can help physicians identify high-risk patients at risk.

A study was conducted to evaluate and assess the relationship between hospital primary angioplasty volume in ST-segment elevation myocardial infarction (STEMI) with quality and outcomes of care. Results indicated that higher-volume primary angioplasty centers were associated with shorter door-to-balloon (DBT) times and more evidence-based therapies.

Results of a study to identify gene variants that influence the clinical efficacy of clopidogrel therapy have revealed that the CYP2C19*2 genotype was associated with decreased platelet response to clopidogrel therapy. The major benefits of genomic profiling are also highlighted.

Importance: High lipid concentrations are a modifiable risk factor for cardiovascular disease. Little is known about how population-level lipid concentrations, as well as trends in lipid control, have changed over the past decade among US adults.Objective: To determine whether lipid concentrations and rates of lipid control changed among US adults and whether these trends differed by sex and race and ethnicity, from 2007 to 2018.Design, Setting, and Participants: Serial cross-sectional analysis of 33 040 US adults aged 20 years or older, weighted to be nationally representative, from the National Health and Nutrition Examination Surveys (2007-2008 to 2017-2018).Main Outcomes and Measures: Lipid concentrations among US adults and rates of lipid control among adults receiving statin therapy. Lipid control was defined as a total cholesterol concentration of 200 mg/dL or less.Results: The mean age of the study population was 47.4 years, and 51.4% were women; of the 33 040 participants, 12.0% were non-Hispanic Black; 10.3%, Mexican American; 6.4%, other Hispanic American; 62.7%, non-Hispanic White; and 8.5%, other race and ethnicities (including non-Hispanic Asian. Among all US adults, age-adjusted total cholesterol improved significantly in the overall population from 197 mg/dL in 2007-2008 to 189 mg/dL in 2017-2018 (difference, -8.6 mg/dL [95% CI, -12.2 to -4.9 mg/dL]; P for trend <.001), with similar patterns for men and women. Black, Mexican American, other Hispanic, and White adults experienced significant improvements in total cholesterol, but no significant change was observed for Asian adults. Among adults receiving statin therapy, age-adjusted lipid control rates did not significantly change from 78.5% in 2007-2008 to 79.5% in 2017-2018 (difference, 1.1% [95% CI, -3.7% to 5.8%]; P for trend = .27), and these patterns were similar for men and women. Across all racial and ethnic groups, only Mexican Americans experienced a significant improvement in age-adjusted lipid control (P for trend = .008). In 2015-2018, age-adjusted rates of lipid control were significantly lower for women than for men (OR, 0.54 [95% CI, 0.40 to 0.72]). In addition, when compared with White adults, rates of lipid control while taking statins were significantly lower among Black adults (OR, 0.66 [95% CI, 0.47 to 0.94]) and other Hispanic adults (OR, 0.59 [95% CI, 0.37 to 0.95]); no significant differences were observed for other racial and ethnic groups.Conclusions and Relevance: In this serial cross-sectional study, lipid concentrations improved in the US adult population from 2007-2008 through 2017-2018. These patterns were observed across all racial and ethnic subgroups, with the exception of non-Hispanic Asian adults. [ABSTRACT FROM AUTHOR]

A study is conducted to evaluate whether weight loss and metabolic effects of rimonobant are successful in reducing the onset of coronary artery disease in patients with abdominal obesity and metabolic syndrome. Results conclude that rimonobant is not very effective but does help in weight loss and reduction in waist size, improves lipid profiles and so is good in prevention of coronary heart disease.

An international study was conducted to establish one-year cardiovascular (CV) event rates in outpatients with established arterial disease or with multiple risk factors for atherothrombosis. Results of the study indicated that patients experienced relatively high annual CV event rates, and multiple disease locations increased the one-year risk of CV events.

A study was conducted to determine whether atherosclerosis risk factor prevalence and treatment would demonstrate comparable patterns in many countries around the world. The large international contemporary database shows that classic cardiovascular risk factors are consistent and common but are largely undertreated and undercontrolled in many regions of the world.

The use and predictors of early invasive management strategies in high-risk patients with non-ST-segment elevation acute coronary syndromes (NSTE ACS) is determined and the association of early invasive management with mortality is examined. It is found out that an early invasive management strategy is not utilized in the majority of high-risk patients with NSTE ACS.

Importance: Current guidelines recommend against use of intravenous alteplase in patients with acute ischemic stroke who are taking non-vitamin K antagonist oral anticoagulants (NOACs).Objective: To evaluate the safety and functional outcomes of intravenous alteplase among patients who were taking NOACs prior to stroke and compare outcomes with patients who were not taking long-term anticoagulants.Design, Setting, and Participants: A retrospective cohort study of 163 038 patients with acute ischemic stroke either taking NOACs or not taking anticoagulants prior to stroke and treated with intravenous alteplase within 4.5 hours of symptom onset at 1752 US hospitals participating in the Get With The Guidelines-Stroke program between April 2015 and March 2020, with complementary data from the Addressing Real-world Anticoagulant Management Issues in Stroke registry.Exposures: Prestroke treatment with NOACs within 7 days prior to alteplase treatment.Main Outcomes and Measures: The primary outcome was symptomatic intracranial hemorrhage occurring within 36 hours after intravenous alteplase administration. There were 4 secondary safety outcomes, including inpatient mortality, and 7 secondary functional outcomes assessed at hospital discharge, including the proportion of patients discharged home.Results: Of 163 038 patients treated with intravenous alteplase (median age, 70 [IQR, 59 to 81] years; 49.1% women), 2207 (1.4%) were taking NOACs and 160 831 (98.6%) were not taking anticoagulants prior to their stroke. Patients taking NOACs were older (median age, 75 [IQR, 64 to 82] years vs 70 [IQR, 58 to 81] years for those not taking anticoagulants), had a higher prevalence of cardiovascular comorbidities, and experienced more severe strokes (median National Institutes of Health Stroke Scale score, 10 [IQR, 5 to 17] vs 7 [IQR, 4 to 14]) (all standardized differences >10). The unadjusted rate of symptomatic intracranial hemorrhage was 3.7% (95% CI, 2.9% to 4.5%) for patients taking NOACs vs 3.2% (95% CI, 3.1% to 3.3%) for patients not taking anticoagulants. After adjusting for baseline clinical factors, the risk of symptomatic intracranial hemorrhage was not significantly different between groups (adjusted odds ratio [OR], 0.88 [95% CI, 0.70 to 1.10]; adjusted risk difference [RD], -0.51% [95% CI, -1.36% to 0.34%]). There were no significant differences in the secondary safety outcomes, including inpatient mortality (6.3% for patients taking NOACs vs 4.9% for patients not taking anticoagulants; adjusted OR, 0.84 [95% CI, 0.69 to 1.01]; adjusted RD, -1.20% [95% CI, -2.39% to -0%]). Of the secondary functional outcomes, 4 of 7 showed significant differences in favor of the NOAC group after adjustment, including the proportion of patients discharged home (45.9% vs 53.6% for patients not taking anticoagulants; adjusted OR, 1.17 [95% CI, 1.06 to 1.29]; adjusted RD, 3.84% [95% CI, 1.46% to 6.22%]).Conclusions and Relevance: Among patients with acute ischemic stroke treated with intravenous alteplase, use of NOACs within the preceding 7 days, compared with no use of anticoagulants, was not associated with a significantly increased risk of intracranial hemorrhage. [ABSTRACT FROM AUTHOR]

Importance: Acute coronary syndromes (ACS) are characterized by a sudden reduction in blood supply to the heart and include ST-segment elevation myocardial infarction (STEMI), non-STEMI (NSTEMI), and unstable angina. Each year, an estimated more than 7 million people in the world are diagnosed with ACS, including more than 1 million patients hospitalized in the US.Observations: Chest discomfort at rest is the most common presenting symptom of ACS and affects approximately 79% of men and 74% of women presenting with ACS, although approximately 40% of men and 48% of women present with nonspecific symptoms, such as dyspnea, either in isolation or, more commonly, in combination with chest pain. For patients presenting with possible ACS, electrocardiography should be performed immediately (within 10 minutes of presentation) and can distinguish between STEMI and non-ST-segment elevation ACS (NSTE-ACS). STEMI is caused by complete coronary artery occlusion and accounts for approximately 30% of ACS. ACS without significant ST-segment elevation on electrocardiography, termed NSTE-ACS, account for approximately 70% of ACS, are caused by partial or intermittent occlusion of the artery and are associated with ST-segment depressions (approximately 31%), T-wave inversions (approximately 12%), ST-segment depressions combined with T-wave inversions (16%), or neither (approximately 41%). When electrocardiography suggests STEMI, rapid reperfusion with primary percutaneous coronary intervention (PCI) within 120 minutes reduces mortality from 9% to 7%. If PCI within 120 minutes is not possible, fibrinolytic therapy with alteplase, reteplase, or tenecteplase at full dose should be administered for patients younger than 75 years without contraindications and at half dose for patients 75 years or older (or streptokinase at full dose if cost is a consideration), followed by transfer to a facility with the goal of PCI within the next 24 hours. High-sensitivity troponin measurements are the preferred test to evaluate for NSTEMI. In high-risk patients with NSTE-ACS and no contraindications, prompt invasive coronary angiography and percutaneous or surgical revascularization within 24 to 48 hours are associated with a reduction in death from 6.5% to 4.9%.Conclusions and Relevance: Each year, an estimated more than 7 million people are diagnosed with ACS worldwide. For patients with STEMI, coronary catheterization and PCI within 2 hours of presentation reduces mortality, with fibrinolytic therapy reserved for patients without access to immediate PCI. For high-risk patients with NSTE-ACS without contraindications, prompt invasive coronary angiography followed by percutaneous or surgical revascularization is associated with lower rates of death. [ABSTRACT FROM AUTHOR]

Importance: Influenza is temporally associated with cardiopulmonary morbidity and mortality among those with cardiovascular disease who may mount a less vigorous immune response to vaccination. Higher influenza vaccine dose has been associated with reduced risk of influenza illness.Objective: To evaluate whether high-dose trivalent influenza vaccine compared with standard-dose quadrivalent influenza vaccine would reduce all-cause death or cardiopulmonary hospitalization in high-risk patients with cardiovascular disease.Design, Setting, and Participants: Pragmatic multicenter, double-blind, active comparator randomized clinical trial conducted in 5260 participants vaccinated for up to 3 influenza seasons in 157 sites in the US and Canada between September 21, 2016, and January 31, 2019. Patients with a recent acute myocardial infarction or heart failure hospitalization and at least 1 additional risk factor were eligible.Interventions: Participants were randomly assigned to receive high-dose trivalent (n = 2630) or standard-dose quadrivalent (n = 2630) inactivated influenza vaccine and could be revaccinated for up to 3 seasons.Main Outcomes and Measures: The primary outcome was the time to the composite of all-cause death or cardiopulmonary hospitalization during each enrolling season. The final date of follow-up was July 31, 2019. Vaccine-related adverse events were also assessed.Results: Among 5260 randomized participants (mean [SD] age, 65.5 [12.6] years; 3787 [72%] men; 3289 [63%] with heart failure) over 3 influenza seasons, there were 7154 total vaccinations administered and 5226 (99.4%) participants completed the trial. In the high-dose trivalent vaccine group, there were 975 primary outcome events (883 hospitalizations for cardiovascular or pulmonary causes and 92 deaths from any cause) among 884 participants during 3577 participant-seasons (event rate, 45 per 100 patient-years), whereas in the standard-dose quadrivalent vaccine group, there were 924 primary outcome events (846 hospitalizations for cardiovascular or pulmonary causes and 78 deaths from any cause) among 837 participants during 3577 participant-seasons (event rate, 42 per 100 patient-years) (hazard ratio, 1.06 [95% CI, 0.97-1.17]; P = .21). In the high-dose vs standard-dose groups, vaccine-related adverse reactions occurred in 1449 (40.5%) vs 1229 (34.4%) participants and severe adverse reactions occurred in 55 (2.1%) vs 44 (1.7%) participants.Conclusions and Relevance: In patients with high-risk cardiovascular disease, high-dose trivalent inactivated influenza vaccine, compared with standard-dose quadrivalent inactivated influenza vaccine, did not significantly reduce all-cause mortality or cardiopulmonary hospitalizations. Influenza vaccination remains strongly recommended in this population.Trial Registration: ClinicalTrials.gov Identifier: NCT02787044. [ABSTRACT FROM AUTHOR]

Importance: Earlier administration of intravenous tissue plasminogen activator (tPA) in acute ischemic stroke is associated with reduced mortality by the time of hospital discharge and better functional outcomes at 3 months. However, it remains unclear whether shorter door-to-needle times translate into better long-term outcomes.Objective: To examine whether shorter door-to-needle times with intravenous tPA for acute ischemic stroke are associated with improved long-term outcomes.Design, Setting, and Participants: This retrospective cohort study included Medicare beneficiaries aged 65 years or older who were treated for acute ischemic stroke with intravenous tPA within 4.5 hours from the time they were last known to be well at Get With The Guidelines-Stroke participating hospitals between January 1, 2006, and December 31, 2016, with 1-year follow-up through December 31, 2017.Exposures: Door-to-needle times for intravenous tPA.Main Outcomes and Measures: The primary outcomes were 1-year all-cause mortality, all-cause readmission, and the composite of all-cause mortality or readmission.Results: Among the 61 426 patients treated with tPA within 4.5 hours, the median age was 80 years and 43.5% were male. The median door-to-needle time was 65 minutes (interquartile range, 49-88 minutes). The 48 666 patients (79.2%) who were treated with tPA and had door-to-needle times of longer than 45 minutes, compared with those treated within 45 minutes, had significantly higher all-cause mortality (35.0% vs 30.8%, respectively; adjusted HR, 1.13 [95% CI, 1.09-1.18]), higher all-cause readmission (40.8% vs 38.4%; adjusted HR, 1.08 [95% CI, 1.05-1.12]), and higher all-cause mortality or readmission (56.0% vs 52.1%; adjusted HR, 1.09 [95% CI, 1.06-1.12]). The 34 367 patients (55.9%) who were treated with tPA and had door-to-needle times of longer than 60 minutes, compared with those treated within 60 minutes, had significantly higher all-cause mortality (35.8% vs 32.1%, respectively; adjusted hazard ratio [HR], 1.11 [95% CI, 1.07-1.14]), higher all-cause readmission (41.3% vs 39.1%; adjusted HR, 1.07 [95% CI, 1.04-1.10]), and higher all-cause mortality or readmission (56.8% vs 53.1%; adjusted HR, 1.08 [95% CI, 1.05-1.10]). Every 15-minute increase in door-to-needle times was significantly associated with higher all-cause mortality (adjusted HR, 1.04 [95% CI, 1.02-1.05]) within 90 minutes after hospital arrival, but not after 90 minutes (adjusted HR, 1.01 [95% CI, 0.99-1.03]), higher all-cause readmission (adjusted HR, 1.02; 95% CI, 1.01-1.03), and higher all-cause mortality or readmission (adjusted HR, 1.02 [95% CI, 1.01-1.03]).Conclusions and Relevance: Among patients aged 65 years or older with acute ischemic stroke who were treated with tissue plasminogen activator, shorter door-to-needle times were associated with lower all-cause mortality and lower all-cause readmission at 1 year. These findings support efforts to shorten time to thrombolytic therapy. [ABSTRACT FROM AUTHOR]

Importance: Recent guidelines endorse using history of menopause before age 40 years to refine atherosclerotic cardiovascular disease risk assessments among middle-aged women. Robust data on cardiovascular disease risk in this population are lacking.Objective: To examine the development of cardiovascular diseases and cardiovascular risk factors in women with natural and surgical menopause before age 40 years.Design, Setting, and Participants: Cohort study (UK Biobank), with adult residents of the United Kingdom recruited between 2006 and 2010. Of women who were 40 to 69 years old and postmenopausal at study enrollment, 144 260 were eligible for inclusion. Follow-up occurred through August 2016.Exposures: Natural premature menopause (menopause before age 40 without oophorectomy) and surgical premature menopause (bilateral oophorectomy before age 40). Postmenopausal women without premature menopause served as the reference group.Main Outcomes and Measures: The primary outcome was a composite of incident coronary artery disease, heart failure, aortic stenosis, mitral regurgitation, atrial fibrillation, ischemic stroke, peripheral artery disease, and venous thromboembolism. Secondary outcomes included individual components of the primary outcome, incident hypertension, hyperlipidemia, and type 2 diabetes.Results: Of 144 260 postmenopausal women included (mean [SD] age at enrollment, 59.9 [5.4] years), 4904 (3.4%) had natural premature menopause and 644 (0.4%) had surgical premature menopause. Participants were followed up for a median of 7 years (interquartile range, 6.3-7.7). The primary outcome occurred in 5415 women (3.9%) with no premature menopause (incidence, 5.70/1000 woman-years), 292 women (6.0%) with natural premature menopause (incidence, 8.78/1000 woman-years) (difference vs no premature menopause, +3.08/1000 woman-years [95% CI, 2.06-4.10]; P < .001), and 49 women (7.6%) with surgical premature menopause (incidence, 11.27/1000 woman-years) (difference vs no premature menopause, +5.57/1000 woman-years [95% CI, 2.41-8.73]; P < .001). For the primary outcome, natural and surgical premature menopause were associated with hazard ratios of 1.36 (95% CI, 1.19-1.56; P < .001) and 1.87 (95% CI, 1.36-2.58; P < .001), respectively, after adjustment for conventional cardiovascular disease risk factors and use of menopausal hormone therapy.Conclusions and Relevance: Natural and surgical premature menopause (before age 40 years) were associated with a small but statistically significant increased risk for a composite of cardiovascular diseases among postmenopausal women. Further research is needed to understand the mechanisms underlying these associations. [ABSTRACT FROM AUTHOR]

Importance: The relationship between exposure to lower low-density lipoprotein cholesterol (LDL-C) and lower systolic blood pressure (SBP) with the risk of cardiovascular disease has not been reliably quantified.Objective: To assess the association of lifetime exposure to the combination of both lower LDL-C and lower SBP with the lifetime risk of cardiovascular disease.Design, Setting, and Participants: Among 438 952 participants enrolled in the UK Biobank between 2006 and 2010 and followed up through 2018, genetic LDL-C and SBP scores were used as instruments to divide participants into groups with lifetime exposure to lower LDL-C, lower SBP, or both. Differences in plasma LDL-C, SBP, and cardiovascular event rates between the groups were compared to estimate associations with lifetime risk of cardiovascular disease.Exposures: Differences in plasma LDL-C and SBP compared with participants with both genetic scores below the median. Genetic risk scores higher than the median were associated with lower LDL-C and lower SBP.Main Outcomes and Measures: Odds ratio (OR) for major coronary events, defined as coronary death, nonfatal myocardial infarction, or coronary revascularization.Results: The mean age of the 438 952 participants was 65.2 years (range, 40.4-80.0 years), 54.1% were women, and 24 980 experienced a first major coronary event. Compared with the reference group, participants with LDL-C genetic scores higher than the median had 14.7-mg/dL lower LDL-C levels and an OR of 0.73 for major coronary events (95% CI, 0.70-0.75; P < .001). Participants with SBP genetic scores higher than the median had 2.9-mm Hg lower SBP and an OR of 0.82 for major coronary events (95% CI, 0.79-0.85, P < .001). Participants in the group with both genetic scores higher than the median had 13.9-mg/dL lower LDL-C, 3.1-mm Hg lower SBP, and an OR of 0.61 for major coronary events (95% CI, 0.59-0.64; P < .001). In a 4 × 4 factorial analysis, exposure to increasing genetic risk scores and lower LDL-C levels and SBP was associated with dose-dependent lower risks of major coronary events. In a meta-regression analysis, combined exposure to 38.67-mg/dL lower LDL-C and 10-mm Hg lower SBP was associated with an OR of 0.22 for major coronary events (95% CI, 0.17-0.26; P < .001), and 0.32 for cardiovascular death (95% CI, 0.25-0.40; P < .001).Conclusions and Relevance: Lifelong genetic exposure to lower levels of low-density lipoprotein cholesterol and lower systolic blood pressure was associated with lower cardiovascular risk. However, these findings cannot be assumed to represent the magnitude of benefit achievable from treatment of these risk factors. [ABSTRACT FROM AUTHOR]

Importance: There is concern that long-acting muscarinic antagonists increase cardiovascular morbidity or mortality in patients with chronic obstructive pulmonary disease (COPD).Objective: To determine the cardiovascular safety (noninferiority) and efficacy (superiority) of aclidinium bromide, 400 μg twice daily, in patients with COPD and cardiovascular disease or risk factors.Design, Setting, and Participants: Multicenter, randomized, placebo-controlled, double-blind, parallel-design study conducted at 522 sites in North America. A total of 3630 patients with moderate to very severe COPD and either a history of cardiovascular disease or at least 2 atherothrombotic risk factors were randomized; follow-up occurred for up to 3 years until at least 122 major adverse cardiovascular events (MACE) occurred. The first patient was enrolled on October 16, 2013 and the last on August 22, 2016. The final patient completed follow-up on September 21, 2017.Interventions: Patients were randomized to receive aclidinium (n = 1812) or placebo (n = 1818) by dry-powder inhaler, twice daily for up to 3 years.Main Outcomes and Measures: The primary safety end point was time to first MACE over up to 3 years (hazard ratio [HR] 1-sided 97.5% CI noninferiority margin = 1.8). The primary efficacy end point was the annual COPD exacerbation rate during the first year of treatment. Secondary outcomes included an expanded MACE definition (time to first MACE or serious cardiovascular event of interest) and annual rate of exacerbations requiring hospitalization.Results: Among 3589 patients analyzed (mean age, 67.2 years; 58.7% male), 2537 (70.7%) completed the study. Of these, 69 (3.9%) aclidinium and 76 (4.2%) placebo patients had a MACE (HR, 0.89; 1-sided 97.5% CI, 0-1.23); the expanded MACE definition included 168 (9.4%) aclidinium vs 160 (8.9%) placebo patients with events (HR, 1.03; 1-sided 97.5% CI, 0-1.28). Annual moderate to severe exacerbation rates (aclidinium, 0.44; placebo, 0.57; rate ratio, 0.78; 2-sided 95% CI, 0.68-0.89; P < .001) and rate of exacerbations requiring hospitalization (aclidinium, 0.07; placebo, 0.10; rate ratio, 0.65; 2-sided 95% CI, 0.48-0.89; P = .006) decreased significantly with aclidinium vs placebo. The most common adverse events were pneumonia (aclidinium, 109 events [6.1%]; placebo, 105 events [5.8%]), urinary tract infection (aclidinium, 93 events [5.2%]; placebo, 89 events [5.0%]), and upper respiratory tract infection (aclidinium, 86 events [4.8%]; placebo, 101 events [5.6%]).Conclusions and Relevance: Among patients with COPD and increased cardiovascular risk, aclidinium was noninferior to placebo for risk of MACE over 3 years. The rate of moderate to severe COPD exacerbations was reduced over the first year.Trial Registration: ClinicalTrials.gov Identifier: NCT01966107. [ABSTRACT FROM AUTHOR]