Perspectives in Managing Kidney Disease and Atherosclerotic Cardiovascular Disease.

INTRODUCTION: Chronic kidney disease (CKD) and atherosclerotic cardiovascular disease (ASCVD) share a complex and dependent link with each other and other cardiometabolic conditions. Currently, there is insufficient data regarding patient and provider perceptions about this important clinical overlap. This study sought to evaluate healthcare provider (HCP) and patient attitudes and perceptions about CKD and ASCVD, including risk, diagnosis, and management of both conditions. METHODS: Cross-sectional surveys of 58 nephrologists and 74 cardiologists who treat patients with CKD and ASCVD and 195 patients who self-reported having CKD and ASCVD were conducted in the US between May and June 2021. RESULTS: Most nephrologists agreed that the presence of cardiometabolic comorbidities increased patients' risk of developing CKD; 86% agreed that type 2 diabetes (T2D) increased the risk, and 67% agreed that ASCVD increased the risk. However, only 52% of the nephrologists reported they typically discuss the risk of developing CKD with patients prior to diagnosing them. Slightly more than one-third of patients (35%) reported their HCP discussed other conditions' impact on the development of CKD; of all HCPs surveyed, nephrologists were the least likely to discuss CKD risk with their patients. Most nephrologists (83%) also reported they recommended lifestyle modification to patients; however, only about half of patients (53%) reported they were currently using a lifestyle change to treat CKD and/or ASCVD. CONCLUSIONS: Although CKD and ASCVD are known to have a bidirectional relationship, HCPs in our study did not report routinely educating patients about the risk of developing one or both conditions. As HCPs with perhaps the deepest understanding of the interplay between CKD and cardiorenal comorbidities, nephrologists are well positioned to help patients understand the link between cardiovascular and renal health, help identify strategies to limit risk, and appropriately treat the conditions.

Cardiorenal care coordination: holistic patient care opportunities in the primary care setting for patients with chronic kidney disease and atherosclerotic cardiovascular disease.

OBJECTIVES: Chronic kidney disease (CKD) and atherosclerotic cardiovascular disease (ASCVD) are closely linked conditions, and the presence of each condition promotes incidence and progression of the other. In this study, we sought to better understand the medical journey of patients with CKD and ASCVD and to uncover patients' and healthcare providers' (HCPs) perceptions and attitudes toward CKD and ASCVD diagnosis, treatment, and care coordination. METHODS: Cross-sectional, US-population-based online surveys were conducted between May 18, 2021, and June 17, 2021, among 239 HCPs (70 of whom were primary care physicians, or PCPs) and 195 patients with CKD and ASCVD. RESULTS: PCPs reported personally diagnosing CKD in 78% and ASVD in 64% of their patients, respectively. PCPs reported they are more likely to serve as the overall coordinator of their patient's care (89%), while slightly more than half of PCPs self-identified as a patient's coordinator of care specifically for CKD (54%) or ASCVD (59%). In contrast, patients viewed their PCP as their coordinator of care for CKD (25%) or ASCVD (9%). PCPs who personally treated patients with CKD and ASCVD most often recalled primarily prescribing or recommending pharmacologic treatments for CKD and ASCVD; however, patients reported that lifestyle modification was the most common treatment modality they had ever used to manage CKD and ASCVD. CONCLUSION: CKD and ASCVD are interrelated cardiometabolic conditions with underlying risk factors that can be managed in a primary care setting. However, few patients in our study considered their PCP to be the coordinator of their care for CKD or ASCVD. PCPs can and should take a more active role in educating patients and coordinating care for those with CKD and ASCVD.

Chronic kidney disease (CKD) is a medical condition where the kidneys are damaged, and their function is reduced. CKD is often linked to other health problems. Atherosclerotic cardiovascular disease (ASCVD) is a condition where cholesterol builds up in the arteries, leading to reduced blood flow and heart issues. This study wanted to understand what patients and healthcare providers (HCPs) know about these two conditions and how they are managed. We sent questionnaires to 195 patients with CKD and ASCVD as well as 239 HCPs who treat patients with CKD and ASCVD. The results showed primary care physicians (PCPs) are the main healthcare providers for most patients, but specialists are often involved in managing CKD and ASCVD. PCPs play a crucial role in helping patients understand how other health care conditions can impact their risk for CKD and ASCVD. PCPs can also guide patients on making lifestyle changes to lower their risk of these diseases and can refer patients to specialists, while still providing guidance on management of these conditions.

Sex differences in device-measured physical activity after transcatheter aortic valve replacement.

OBJECTIVE: Physical activity (PA) is an important clinical and quality of life outcome after transcatheter aortic valve replacement (TAVR). We examined the effect of TAVR on objectively measured PA in patients with cardiac implanted electronic devices (CIEDs). METHODS: Daily accelerometer data was obtained from CIEDs. Patients in the University of North Carolina Health System with continuous PA data at least 6 months before TAVR and 12 months after TAVR were included. Changes in activity pre- and post-TAVR were analyzed with linear mixed-effects models using a random intercept for each patient. An interaction term was included to determine differences in PA between men and women pre- and post-TAVR. RESULTS: Of the 306 patients with CIEDs who underwent TAVR, 24,655 patient-days of data from 46 patients, mean age of 82 years old, 44% of whom were female met inclusion criteria. A significant and sustained increase of 14.7% in daily PA was seen after TAVR [10.15 minutes per day, 95% confidence interval (CI) 8.75 to 11.56 P < .001] after adjusting for sex, obesity, race, history of depression, and Charlson Comorbidity Index. Effects were more prominent in women (18.57 [95% CI 16.36 to 20.79, P < .001] minute increase post-TAVR) compared to men (4.51 [95% CI 3.87 to 5.16] minute increase post-TAVR, P < .001). CONCLUSIONS: This study demonstrates PA increases after TAVR with effects more pronounced in women than men. Further, this study highlights the potential use of remote monitoring data for monitoring functional outcomes in device patients after a procedure.

Patients and Their Physician's Perspectives About Oral Anticoagulation in Patients With Atrial Fibrillation Not Receiving an Anticoagulant.

Importance: The underuse of oral anticoagulation in patients with nonvalvular atrial fibrillation (AF) is a major issue that is not well understood. Objective: To understand the lack of anticoagulation by assessing the perceptions of patients with AF who are not receiving anticoagulation and their physician's about the risk of stroke and the benefits and risks of anticoagulation. Design, Setting, and Participants: This cohort study included patients with nonvalvular AF and a CHA2DS2-VASc score of 2 or more (calculated as congestive heart failure, hypertension, age 75 years and older, diabetes, stroke or transient ischemic attack, vascular disease, age 65 to 74 years, and sex category) who were not receiving anticoagulation and were enrolled from 19 sites within the National Cardiovascular Data Registry (NCDR) Practice Innovation and Clinical Excellence Registry (PINNACLE Registry) between January 18, 2017, and May 7, 2018. Data were collected from January 18, 2017, to September 30, 2019, and analyzed from April 2022 to March 2023. Exposure: Each patient enrolled in the study completed a survey, and their treating physician then conducted a clinical review of their care. Main Outcomes and Measures: Assessment of willingness for anticoagulation treatment and its appropriateness after central review by a panel of 4 cardiologists. Use of anticoagulation at 1 year follow-up was compared vs similar patients at other centers in the PINNACLE Registry. Results: Of the 817 patients enrolled, the median (IQR) age was 76.0 (69.0-83.0) years, 369 (45.2%) were women, and the median (IQR) CHA2DS2-VASc score was 4.0 (3.0-6.0). The top 5 reasons physicians cited for no anticoagulation were low AF burden or successful rhythm control (278 [34.0%]), patient refusal (272 [33.3%]), perceived low risk of stroke (206 [25.2%]), fall risk (175 [21.4%]), and high bleeding risk (167 [20.4%]). After rereview, 221 physicians (27.1%) would reconsider prescribing oral anticoagulation as compared with 311 patients (38.1%), including 67 (24.6%) whose physician cited patient refusal. Of 647 patients (79.2%) adjudicated as appropriate or may be appropriate for anticoagulation, physicians would reconsider anticoagulation for only 177 patients (21.2%), while 527 patients (64.5%) would either agree to starting anticoagulation (311 [38.1%]) or were neutral (216 [27.3%]) to starting anticoagulation. Upon follow-up, 119 patients (14.6%) in the BOAT-AF study were prescribed anticoagulation, as compared with 55 879 of 387 975 similar patients (14.4%) at other centers in the PINNACLE Registry. Conclusions and Relevance: The findings of this cohort study suggest that patients with AF who are not receiving anticoagulation are more willing to consider anticoagulation than their physicians. These data emphasize the need to revisit any prior decision against anticoagulation in a shared decision-making manner.

Coordinated Care to Optimize Cardiovascular Preventive Therapies in Type 2 Diabetes: A Randomized Clinical Trial.

Importance: Evidence-based therapies to reduce atherosclerotic cardiovascular disease risk in adults with type 2 diabetes are underused in clinical practice. Objective: To assess the effect of a coordinated, multifaceted intervention of assessment, education, and feedback vs usual care on the proportion of adults with type 2 diabetes and atherosclerotic cardiovascular disease prescribed all 3 groups of recommended, evidence-based therapies (high-intensity statins, angiotensin-converting enzyme inhibitors [ACEIs] or angiotensin receptor blockers [ARBs], and sodium-glucose cotransporter 2 [SGLT2] inhibitors and/or glucagon-like peptide 1 receptor agonists [GLP-1RAs]). Design, Setting, and Participants: Cluster randomized clinical trial with 43 US cardiology clinics recruiting participants from July 2019 through May 2022 and follow-up through December 2022. The participants were adults with type 2 diabetes and atherosclerotic cardiovascular disease not already taking all 3 groups of evidence-based therapies. Interventions: Assessing local barriers, developing care pathways, coordinating care, educating clinicians, reporting data back to the clinics, and providing tools for participants (n = 459) vs usual care per practice guidelines (n = 590). Main Outcomes and Measures: The primary outcome was the proportion of participants prescribed all 3 groups of recommended therapies at 6 to 12 months after enrollment. The secondary outcomes included changes in atherosclerotic cardiovascular disease risk factors and a composite outcome of all-cause death or hospitalization for myocardial infarction, stroke, decompensated heart failure, or urgent revascularization (the trial was not powered to show these differences). Results: Of 1049 participants enrolled (459 at 20 intervention clinics and 590 at 23 usual care clinics), the median age was 70 years and there were 338 women (32.2%), 173 Black participants (16.5%), and 90 Hispanic participants (8.6%). At the last follow-up visit (12 months for 97.3% of participants), those in the intervention group were more likely to be prescribed all 3 therapies (173/457 [37.9%]) vs the usual care group (85/588 [14.5%]), which is a difference of 23.4% (adjusted odds ratio [OR], 4.38 [95% CI, 2.49 to 7.71]; P < .001) and were more likely to be prescribed each of the 3 therapies (change from baseline in high-intensity statins from 66.5% to 70.7% for intervention vs from 58.2% to 56.8% for usual care [adjusted OR, 1.73; 95% CI, 1.06-2.83]; ACEIs or ARBs: from 75.1% to 81.4% for intervention vs from 69.6% to 68.4% for usual care [adjusted OR, 1.82; 95% CI, 1.14-2.91]; SGLT2 inhibitors and/or GLP-1RAs: from 12.3% to 60.4% for intervention vs from 14.5% to 35.5% for usual care [adjusted OR, 3.11; 95% CI, 2.08-4.64]). The intervention was not associated with changes in atherosclerotic cardiovascular disease risk factors. The composite secondary outcome occurred in 23 of 457 participants (5%) in the intervention group vs 40 of 588 participants (6.8%) in the usual care group (adjusted hazard ratio, 0.79 [95% CI, 0.46 to 1.33]). Conclusions and Relevance: A coordinated, multifaceted intervention increased prescription of 3 groups of evidence-based therapies in adults with type 2 diabetes and atherosclerotic cardiovascular disease. Trial Registration: ClinicalTrials.gov Identifier: NCT03936660.

Epidemiology and Outcomes of Aortic Stenosis in Acute Decompensated Heart Failure: The ARIC Study.

BACKGROUND: Few studies characterize the epidemiology and outcomes of aortic stenosis (AS) in acute decompensated heart failure (ADHF). This study investigates the significance of AS in contemporary patients who have experienced an ADHF hospitalization. METHODS: The ARIC study (Atherosclerosis Risk in Communities) surveilled ADHF hospitalizations for residents ≥55 years of age in 4 US communities. ADHF cases were stratified by left ventricular ejection fraction (LVEF). Demographic differences in AS burden and the association of varying AS severities with mortality were estimated using multivariable logistic regression. RESULTS: From 2005 through 2014, there were 3597 (weighted n=16 692) ADHF hospitalizations of which 48.6% had an LVEF <50% and 51.4% an LVEF ≥50%. AS prevalence was 12.1% and 18.7% in those with an LVEF <50% and ≥50%, respectively. AS was less likely in Black than White patients regardless of LVEF: LVEF <50% (odds ratio [OR], 0.34 [95% CI, 0.28-0.42]); LVEF ≥50% (OR, 0.51 [95% CI, 0.44-0.59]). Higher AS severity was independently associated with 1-year mortality in both LVEF subgroups: LVEF <50% (OR, 1.16 [95% CI, 1.04-1.28]); LVEF ≥50% (OR, 1.40 [95% CI, 1.28-1.54]). Sensitivity analyses excluding severe AS patients detected that mild/moderate AS was independently associated with 1-year mortality in both LVEF subgroups: LVEF <50% (OR, 1.23 [95% CI, 1.02-1.47]); LVEF ≥50% (OR, 1.31 [95% CI, 1.14-1.51]). CONCLUSIONS: Among patients who have experienced an ADHF hospitalization, AS is prevalent and portends poor mortality outcomes. Notably, mild/moderate AS is independently associated with 1-year mortality in this high-risk population.

Coordinating Cardiology clinics randomized trial of interventions to improve outcomes (COORDINATE) - Diabetes: rationale and design.

Several medications that are proven to reduce cardiovascular events exist for individuals with type 2 diabetes mellitus (T2DM) and atherosclerotic cardiovascular disease, however they are substantially underused in clinical practice. Clinician, patient, and system-level barriers all contribute to these gaps in care; yet, there is a paucity of high quality, rigorous studies evaluating the role of interventions to increase utilization. The COORDINATE-Diabetes trial randomized 42 cardiology clinics across the United States to either a multifaceted, site-specific intervention focused on evidence-based care for patients with T2DM or standard of care. The multifaceted intervention comprised the development of an interdisciplinary care pathway for each clinic, audit-and-feedback tools and educational outreach, in addition to patient-facing tools. The primary outcome is the proportion of individuals with T2DM prescribed three key classes of evidence-based medications (high-intensity statin, angiotensin converting enzyme inhibitor or angiotensin receptor blocker, and either a sodium/glucose cotransporter-2 inhibitor (SGLT-2i) inhibitor or glucagon-like peptide 1 receptor agonist (GLP-1RA) and will be assessed at least 6 months after participant enrollment. COORDINATE-Diabetes aims to identify strategies that improve the implementation and adoption of evidence-based therapies.

Role of Primary Care Clinicians in the Management of Patients With Type 2 Diabetes and Cardiorenal Diseases.

Individuals with type 2 diabetes are at increased risk of both renal and cardiovascular events. The convergence of type 2 diabetes, chronic kidney disease, and cardiovascular disease, including heart failure, requires management by a multidisciplinary health care team. Primary care clinicians are likely to be the first and most frequent point of contact for individuals with type 2 diabetes who are at high risk of cardiorenal disease and therefore play a pivotal role in early diagnosis, establishment of effective treatment strategies, and coordination of care. This article presents a clinical perspective with multidisciplinary collaboration on a patient case representative of those seen in routine clinical practice. The authors assess reasons why patients may not receive evidence-based care and identify opportunities to initiate therapies that reduce cardiovascular and renal events in the primary care setting.

Trends in Percutaneous Balloon Mitral Valvuloplasty Complications for Mitral Stenosis in the United States (the National Inpatient Sample [2008 to 2018]).

The epidemiology of mitral stenosis (MS) continues to evolve in the United States. Although the incidence of rheumatic MS has decreased in high-income countries, there is a paucity of data surrounding trends in percutaneous balloon mitral valvuloplasty (PBMV), the current first-line management strategy. This study aimed to identify contemporary trends in PBMV in the United States. Hospitalizations for adults (≥18 years) with MS who underwent PBMV were identified from the National Inpatient Sample from 2008 to 2018. Baseline co-morbidities and outcomes over the study period were determined using Poisson regression. There were 3,980 weighted PBMV cases, 70% of which were women. PBMV hospitalizations decreased from 603 in 2008 to 210 in 2018 (p <0.001). From 2008 to 2018, the age at hospitalization was unchanged in both female and male patients. In contrast, the Charlson Co-morbidity Index increased in both. Baseline heart failure (39% to 64%), hypertension (38% to 43%), and diabetes mellitus (17% to 26%) all substantially increased over the study period. In-hospital mortality occurred in 2% of female and 5% of male patients and was unchanged from 2008 to 2018. Vascular complications (12%) and acute kidney injury (10%) were the most frequent postprocedural complications during the 11-year study period. A composite of mortality or any postprocedural complication did not vary by gender (odds ratio 1.23, 95% confidence interval 0.88 to 1.72). In conclusion, the use of PBMV significantly decreased from 2008 to 2018, and patients with MS who underwent PBMV over this period had an increased burden of co-morbidities, elevated postprocedural complication rate, and no change in in-hospital mortality.

Use of Lipid-, Blood Pressure-, and Glucose-Lowering Pharmacotherapy in Patients With Type 2 Diabetes and Atherosclerotic Cardiovascular Disease.

Importance: Based on contemporary estimates in the US, evidence-based therapies for cardiovascular risk reduction are generally underused among patients with type 2 diabetes and atherosclerotic cardiovascular disease (ASCVD). Objective: To determine the use of evidence-based cardiovascular preventive therapies in a broad US population with diabetes and ASCVD. Design, Setting, and Participants: This multicenter cohort study used health system-level aggregated data within the National Patient-Centered Clinical Research Network, including 12 health systems. Participants included patients with diabetes and established ASCVD (ie, coronary artery disease, cerebrovascular disease, and peripheral artery disease) between January 1 and December 31, 2018. Data were analyzed from September 2020 until January 2021. Exposures: One or more health care encounters in 2018. Main Outcomes and Measures: Patient characteristics by prescription of any of the following key evidence-based therapies: high-intensity statin, angiotensin-converting enzyme inhibitor (ACEI) or angiotensin-receptor blocker (ARB) and sodium glucose cotransporter-2 inhibitors (SGLT2I) or glucagon-like peptide-1 receptor agonist (GLP-1RA). Results: The overall cohort included 324 706 patients, with a mean (SD) age of 68.1 (12.2) years and 144 169 (44.4%) women and 180 537 (55.6%) men. A total of 59 124 patients (18.2% ) were Black, and 41 470 patients (12.8%) were Latinx. Among 205 885 patients with specialized visit data from the prior year, 17 971 patients (8.7%) visited an endocrinologist, 54 330 patients (26.4%) visited a cardiologist, and 154 078 patients (74.8%) visited a primary care physician. Overall, 190 277 patients (58.6%) were prescribed a statin, but only 88 426 patients (26.8%) were prescribed a high-intensity statin; 147 762 patients (45.5%) were prescribed an ACEI or ARB, 12 724 patients (3.9%) were prescribed a GLP-1RA, and 8989 patients (2.8%) were prescribed an SGLT2I. Overall, 14 918 patients (4.6%) were prescribed all 3 classes of therapies, and 138 173 patients (42.6%) were prescribed none. Patients who were prescribed a high-intensity statin were more likely to be men (59.9% [95% CI, 59.6%-60.3%] of patients vs 55.6% [95% CI, 55.4%-55.8%] of patients), have coronary atherosclerotic disease (79.9% [95% CI, 79.7%-80.2%] of patients vs 73.0% [95% CI, 72.8%-73.3%] of patients) and more likely to have seen a cardiologist (40.0% [95% CI, 39.6%-40.4%] of patients vs 26.4% [95% CI, 26.2%-26.6%] of patients). Conclusions and Relevance: In this large cohort of US patients with diabetes and ASCVD, fewer than 1 in 20 patients were prescribed all 3 evidence-based therapies, defined as a high-intensity statin, either an ACEI or ARB, and either an SGLT2I and/or a GLP-1RA. These findings suggest that multifaceted interventions are needed to overcome barriers to the implementation of evidence-based therapies and facilitate their optimal use.

Inhibition of p38 MAP kinase in patients with ST-elevation myocardial infarction - findings from the LATITUDE-TIMI 60 trial.

BACKGROUND: p38 mitogen activated kinase (MAPK) mediates the response to pro-inflammatory cytokines following myocardial infarction (MI) and is inhibited by losmapimod. METHODS: LATITUDE-TIMI 60 (ClinicalTrials.gov NCT02145468) randomized patients with MI to losmapimod or placebo for 12 weeks (24 weeks total follow-up). In this pre-specified analysis, we examined outcomes based on MI type [ST-segment elevation MI (STEMI) (865, 25%) and non-STEMI (2624, 75%)]. RESULTS: In patients with STEMI, inflammation, measured by hs-CRP, was significantly attenuated with losmapimod at 48 hours (P <0.001) and week 12 (P = 0.01). Losmapimod lowered NT-proBNP in patients with STEMI at 48 hours (P = 0.04) and week 12 (P = 0.02). The effects of losmapimod on CV death (CVD), MI, or severe recurrent ischemia requiring urgent coronary artery revascularization at 24 weeks [MACE] differed in patients with STEMI (7.0% vs 10.8%; HR 0.65, 95%CI 0.41 - 1.03; P= 0.06) and NSTEMI (11.4% vs 8.5%; HR 1.30, 95%CI 1.02 - 1.66; P = 0.04; p[int] = 0.009). CVD or HHF among patients with STEMI were 5.6% (losmapimod) and 8.3% (placebo) (HR 0.66; 95%CI 0.40 - 1.11; P = 0.12) and in NSTEMI were 4.8% (losmapimod) and 4.4% (placebo) (HR 1.09; 95%CI 0.76 - 1.56) in patients with NSTEMI. CONCLUSIONS: Patients with STEMI treated with losmapimod had an attenuated inflammatory response. Our collective findings raise the hypothesis that mitigating the inflammatory response may result in different outcomes in patients with STEMI and NSTEMI. While the difference in outcomes is exploratory, these findings do support separate examination of patients with STEMI and NSTEMI and increased emphasis on heart failure in future investigation of modulators of inflammation in MI.

Ischemic Events Occur Early in Patients Undergoing Percutaneous Coronary Intervention and Are Reduced With Cangrelor: Findings From CHAMPION PHOENIX.

BACKGROUND: Thrombotic events are reduced with cangrelor, an intravenous P2Y12 inhibitor. We sought to characterize the timing, number, and type of early events (within 2 hours of randomization) in CHAMPION PHOENIX (A Clinical Trial Comparing Cangrelor to Clopidogrel Standard of Care Therapy in Subjects Who Require Percutaneous Coronary Intervention). METHODS: CHAMPION PHOENIX was a double-blind, placebo-controlled trial that randomized patients undergoing percutaneous coronary intervention to cangrelor or clopidogrel. For this analysis, we evaluated the efficacy of cangrelor in the first 2 hours postrandomization with regards to the primary end point (death, myocardial infarction, ischemia-driven revascularization, or stent thrombosis). Sensitivity analyses were performed evaluating a secondary, post hoc end point (death, Society of Coronary Angiography and Intervention myocardial infarction, ischemia-driven revascularization, or Academic Research Consortium definite stent thrombosis). RESULTS: The majority of events (63%) that occurred in the trial occurred within 2 hours of randomization. The most common early event was myocardial infarction; next were stent thrombosis, ischemia driven revascularization, and death. In the first 2 hours after randomization, cangrelor significantly decreased the primary composite end point compared with clopidogrel (4.1% versus 5.4%; hazard ratio, 0.76 [95% CI, 0.64-0.90], P=0.002). Similar findings were seen for the composite end point of death, Society of Coronary Angiography and Intervention myocardial infarction, ischemia-driven revascularization, or Academic Research Consortium stent thrombosis at 2 hours (0.9% versus 1.6%; hazard ratio, 0.57 [95% CI, 0.40-0.80], P=0.001). Between 2 and 48 hours, there was no difference in the primary composite end point (0.6% versus 0.5%; odds ratio, 1.17 [95% CI, 0.71-1.93]; P=0.53). Early (≤2 hours of randomization) GUSTO (Global Use of Strategies to Open Occluded Coronary Arteries) moderate or severe bleeding events were infrequent, and there was no significant difference with cangrelor compared with clopidogrel (0.2% [n=10] versus 0.1% [n=4]; adjusted odds ratio, 1.41 [95% CI, 0.37-5.40]; P=0.62). CONCLUSIONS: The reductions in ischemic events and overall efficacy seen with cangrelor in CHAMPION PHOENIX occurred early and during the period of time in which patients were being actively treated with cangrelor. These findings provide evidence that supports the importance of potent platelet inhibition during percutaneous coronary intervention. Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT01156571.

Cardiovascular outcomes with sodium-glucose cotransporter-2 inhibitors vs other glucose-lowering drugs in 13 countries across three continents: analysis of CVD-REAL data.

BACKGROUND: Randomized, controlled cardiovascular outcome trials may not be fully representative of the management of patients with type 2 diabetes across different geographic regions. We conducted analyses of data from the multinational CVD-REAL consortium to determine the association between initiation of sodium-glucose cotransporter-2 inhibitors (SGLT-2i) and cardiovascular outcomes, including subgroup analyses based on patient characteristics. METHODS: De-identified health records from 13 countries across three continents were used to identify patients newly-initiated on SGLT-2i or other glucose-lowering drugs (oGLDs). Propensity scores for SGLT-2i initiation were developed in each country, with 1:1 matching for oGLD initiation. In the matched groups hazard ratios (HRs) for hospitalization for heart failure (HHF), all-cause death (ACD), the composite of HHF or ACD, myocardial infarction (MI) and stroke were estimated by country, and pooled using a weighted meta-analysis. Multiple subgroup analyses were conducted across patient demographic and clinical characteristics to examine any heterogeneity in treatment effects. RESULTS: Following matching, 440,599 new users of SGLT-2i and oGLDs were included in each group. Mean follow-up time was 396 days for SGLT-2i initiation and 406 days for oGLDs initiation. SGLT-2i initiation was associated with a lower risk of HHF (HR: 0.66, 95%CI 0.58-0.75; p < 0.001), ACD (HR: 0.52, 95%CI 0.45-0.60; p < 0.001), the composite of HHF or ACD (HR: 0.60, 95%CI 0.53-0.68; p < 0.001), MI (HR: 0.85, 95%CI 0.78-0.92; p < 0.001), and stroke (HR: 0.78, 95%CI 0.72-0.85; p < 0.001); regardless of patient characteristics, including established cardiovascular disease, or geographic region. CONCLUSIONS: This CVD-REAL study extends the findings from the SGLT-2i clinical trials to the broader setting of an ethnically and geographically diverse population, and across multiple subgroups. Trial registration NCT02993614.