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BACKGROUND: We examined whether the primary composite outcome (cardiovascular death or heart failure hospitalization) was related to differences in background use and dosing of guideline-directed medical therapy in patients with heart failure with reduced ejection fraction enrolled in VICTORIA (Vericiguat Global Study in Subjects with Heart Failure with Reduced Ejection Fraction), a randomized trial of vericiguat versus placebo. METHODS: We evaluated the adherence to guideline use of angiotensin-converting enzyme inhibitors, angiotensin-receptor blockers, angiotensin receptor-neprilysin inhibitors, beta-blockers, and mineralocorticoid receptor antagonists. We assessed basic adherence; indication-corrected adherence accounting for guideline indications and contraindications; and dosecorrected adherence (indication-corrected adherence+=50% of drug dose target). Associations between study treatment and the primary composite outcome according to the adherence to guidelines were assessed using multivariable adjustment; adjusted hazard ratios with 95% CIs and Pinteraction are reported. RESULTS: Of 5050 patients, 5040 (99.8%) had medication data at baseline. For angiotensin-converting enzyme inhibitor, angiotensin-receptor blockers, and angiotensin receptor-neprilysin inhibitors, basic adherence to guidelines was 87.4%, indication-corrected was 95.7%, and dose-corrected was 50.9%. For beta-blockers, basic adherence was 93.1%, indicationcorrected was 96.2%, and dose-corrected was 45.4%. For mineralocorticoid receptor antagonists, basic adherence was 70.3%, indication-corrected was 87.1%, and dose-corrected was 82.2%. For triple therapy (angiotensin-converting enzyme inhibitors, angiotensin-receptor blockers, or angiotensin receptor-neprilysin inhibitors+beta-blocker+mineralocorticoid receptor antagonist), basic adherence was 59.7%, indication-corrected was 83.3%, and dose-corrected was 25.5%. Using basic or dose-corrected adherence, the treatment effect of vericiguat was consistent across adherence to guidelines groups, with or without multivariable adjustment with no treatment heterogeneity. CONCLUSIONS: Patients in VICTORIA were well treated with heart failure with reduced ejection fraction medications. The efficacy of vericiguat was consistent across background therapy with very high adherence to guidelines accounting for patient-level indications, contraindications, and tolerance. [ABSTRACT FROM AUTHOR]

BACKGROUND: Randomized controlled trials (RCTs) often target enrollment of patients with demographics and outcomes less representative of the broader population of interest. To provide context for the VICTORIA trial (Vericiguat Global Study in Subjects With Heart Failure With Reduced Ejection Fraction), we designed a registry of hospitalized patients with worsening heart failure to characterize their clinical profile, outcomes, and reasons for their nonparticipation in a RCT. METHODS: Fifty-one RCT sites in Canada and the United States participated. Eligible patients included those with chronic heart failure, hospitalized for heart failure, and an ejection fraction <45%; no other exclusions were applied. Sites identified patients between 2017 and 2019 during the RCT enrollment period. RCT eligibility criteria were applied, and non-mutually exclusive reasons for nonenrollment were captured. Mortality at 1 year was estimated via the Meta-Analysis Global Group in Chronic Heart Failure risk score or as observed in the RCT. RESULTS: Overall, 2056 patients were enrolled in the registry; 61% (n=1256) were ineligible for the RCT, 37% (n=766) were eligible but not enrolled, and 2% (n=34) were also enrolled in the RCT. Registry participants had a median age of 70, 33% were women, and 63% were White. The median risk score predicted a 20.9% 1-year mortality, higher than in the RCT (predicted 14.7% and observed 11.5%). Major reasons for ineligibility in the RCT included the use of nitrates (23%), systolic blood pressure <100 mm Hg (12%), and substance use (11%) with other exclusion criteria <10%. For eligible patients, reasons for nonparticipation in the RCT included lack of interest in participating (28%), poor compliance (25%), inability to complete follow-up (23%), too sick (20%), unable to provide consent (17%), and distance from site (15%). CONCLUSIONS: Patients with worsening heart failure in routine clinical practice exhibit high-risk features, and approximately one-third were eligible for an RCT but excluded. The majority of these nonparticipating patients had modifiable reasons. [ABSTRACT FROM AUTHOR]

Advances in cardiovascular medicine fueled by innovative clinical trials have dramatically improved the lives of patients worldwide. Commensurate with this progress has been a decline in morbid and mortal events. Accordingly, an increased propensity to collate patient outcomes in clinical trials has emerged that combines death and nonfatal complications into a single composite event. Despite the acknowledged benefits in trial efficiency from such an approach, this method assumes uniform directionality of each component, does not distinguish the relative clinical significance of each, and counts only the first occurrence of any event in the final tally within a conventional time to first event analysis. In this article, we evaluate the criticisms that have been leveled at this approach and provide an overview of recently published phase III cardiovascular trials using primary composite end points. We then explore what to anticipate from the large cohort of as-yet unpublished clinical trials in this arena. Last, we propose a variety of novel approaches that use composite end points and suggest a path forward to enhancing their use in future clinical trials. [ABSTRACT FROM AUTHOR]

The article discusses the health condition known as acute heart failure. It explores the nature of the condition by characterizing its clinical features, practice patterns as well as in-hospital results of acute heart failure patients. According to the authors, in-hospital mortality was higher compared with patients who usually participate in randomized clinical trials.

Background: Baseline Q waves may provide additional value compared with time from the onset of symptoms in predicting outcomes for patients with ST-segment elevation. We evaluated whether baseline Q waves superseded time from symptom onset as a prognostic marker of one-year mortality in patients with ST-segment elevation acute coronary syndrome. Our study was derived from data from patients undergoing primary percutaneous coronary intervention within 24 hours in the PLATelet inhibition and patient Outcomes trial Methods: Q waves on the baseline electrocardiogram were evaluated by a blinded core laboratory. We assessed the associations between baseline Q waves and time from symptom onset to percutaneous coronary intervention with peak biomarkers, ST-segment resolution on the discharge electrocardiogram, and one-year all-cause and vascular mortality. Results: Of 4341 patients with ST-segment elevation, 46% had baseline Q waves. Compared to those without Q waves, those with baseline Q waves were older, more frequently male, had higher heart rates, more advanced Killip class and had a longer time between the onset of symptoms and percutaneous coronary intervention. They also had higher one-year all-cause mortality than patients without baseline Q waves (baseline Q waves: 4.9%; no baseline Q waves: 2.8%; hazard ratio [HR] 1.78, 95% confidence interval [CI] 1.29-2.45, p < 0.001). Complete ST-segment resolution was greatest and all-cause mortality lowest among those with symptom onset three hours or less before percutaneous coronary intervention and no baseline Q waves. After multivariable adjustment, baseline Q waves, but not time from symptom onset, were associated with a significant increase in all-cause mortality (adjusted HR 1.42, 95% CI 1.10-2.01, p = 0.046) and vascular mortality (adjusted HR 1.58, 95% CI 1.09-2.28, p = 0.02). Interpretation: The presence of baseline Q waves provides useful additional prognostic insight into the clinical outcome of patients with ST-segment elevation. [ABSTRACT FROM AUTHOR]

Objectives: The aim of this study was to obtain a valid estimate of the clinical effects of primary percutaneous coronary intervention (PPCI) in relation to age. Background: Treatment with PPCI is most beneficial in high-risk myocardial infarction patients. Paradoxically, elderly patients, who are at increased risk of adverse outcome, are often withheld PPCI. Methods: Individual patient data were obtained from 22 randomized trials (n = 6,763) evaluating the clinical effects of PPCI versus fibrinolysis (FL). Differences in 30-day death, repeat myocardial infarction, and stroke between patients randomized to FL and PPCI were determined in 5 age-strata: ≤50, >50 to 60, >60 to 70, >70 to 80, and >80 years. Treatment effects are reported as odds ratios (ORs) and 95% confidence intervals (CI). Multivariable logistic regression analyses, which included age × treatment interaction, were applied to examine evidence of heterogeneity in age-specific ORs. Results: Thirty-day death increased with increasing age and ranged from 1.1% (FL) and 1.8% (PPCI) in patients ≤50 years to 26.4% and 18.3% in patients >80 years of age. The point estimate of treatment effect (overall adjusted OR: 0.65; 95% CI: 0.52 to 0.79) was compatible with a mortality reduction favoring PPCI in all age-strata (except in patients ≤50 years of age), and 95% CIs were largely overlapping. There was no evidence of heterogeneity in ORs between age categories. Similar results were observed for repeat myocardial infarction and stroke. Conclusions: In this analysis of randomized trials, the reduction in clinical end points by PPCI was not influenced by age. Hence, age per se should not be considered an exclusion criterion for the application of PPCI. [Copyright &y& Elsevier]

The article compares percutaneous coronary intervention with fibrinolysis for treatment of ST-segment elevation myocardial infarction (PCI)in patients with diabetes mellitus. Results reveal that diabetic patients with ST-segment elevation myocardial infarction treated with reperfusion therapy have increased mortality compared with patients without diabetes. The beneficial effects of primary PCI compared with fibrinolysis in diabetic patients are in harmony with effects in nondiabetics.

Aims Stroke is an uncommon but serious complication after non-ST-segment elevation acute coronary syndrome (NSTE-ACS). We aimed to identify predictors of stroke within 30 days in patients who suffered NSTE-ACS. [ABSTRACT FROM PUBLISHER]

Background: Patient sex has been shown to differentially affect mortality from unstable angina (UA) and acute myocardial infarction (AMI). However, to our knowledge, no prior population-based studies have examined both cohorts simultaneously to explain this intriguing variation. Hence, we undertook to explore and explain sex differences in 5-year mortality after UA and AMI. Methods: We used an administrative database of 22 967 patients with AMI and 8441 patients with UA discharged from acute care hospitals in Alberta between April 1, 1993, and March 31, 2000. Results: Women were older with more baseline comorbidities, more frequently had a diagnosis of UA, and had 30% lower relative odds of undergoing revascularization than men. Kaplan-Meier estimates of 5-year mortality were similar between sexes after UA (women vs men, 21.6% vs 19.5%; P = .09) but markedly higher for women after AMI (38.5% vs 26.6%, P<.001). After adjustment for baseline characteristics and revascularization, the hazard ratios (95% confidence intervals) for women vs men were 0.81 (0.72-0.92) after UA and 0.99 (0.93-1.05) after AMI. Only women younger than 65 years were at a significantly higher risk after AMI. The reasons for this difference in sex-related outcomes between UA and AMI may relate to greater disparities in the AMI cohort with respect to age, comorbidities, neighborhood incomes, and referrals to cardiovascular specialists. Conclusions: Relative to UA, AMI has a more serious impact on women than men, such that women have a survival advantage when afflicted with UA but lose that advantage with AMI. Additional investigation into the causes, treatment, and policy implications of the age-sex interaction is warranted. [ABSTRACT FROM AUTHOR]

Abstract: Purpose: To assess the effects of socioeconomic status on mortality in patients with acute myocardial infarction. Material and Methods: We studied a retrospective cohort of 5622 patients who presented to a hospital emergency department with an initial episode of acute myocardial infarction between April 1998 and March 2002 in the Province of Alberta, Canada. Our main outcome measure was 1-year all-cause mortality following the index emergency department visit; we used socioeconomic status (measured by neighborhood median household income) as our main predictor after controlling for patient and hospital characteristics and revascularization. Results: Socioeconomic status profoundly affected the rate of emergency department presentation and the process and outcome of acute myocardial infarction care. In patients belonging to the lowest versus the highest socioeconomic status quartile, the risk of presenting to the emergency department was 72% higher (P <.001); at 1 year, revascularization was lower (36% vs 48%, P <.001), and mortality higher (19.1% vs 9.1%, P <.001). Socioeconomic status was independently associated with 1-year mortality after adjustment for baseline characteristics and 1-year revascularization, and socioeconomic status was especially influential in non-revascularized patients. Conclusions: Given the influence of socioeconomic status on mortality after acute myocardial infarction and the key role of revascularization in modulating this relationship, our study has important implications for access to and process of cardiac care. [Copyright &y& Elsevier]

: PurposeTo assess the potential long-term beneficial effects of statin use after successful abdominal aortic surgery.: MethodsBetween 1991 and 2001, 570 patients underwent abdominal aortic aneurysm repair at the Erasmus Medical Center. Of the 519 patients (91%) who survived surgery beyond 30 days, 510 (98%) were followed for a median of 4.7 years (interquartile range, 2.7 to 7.3 years). These patients were evaluated for use of statins and beta-blockers, and for clinical risk factors (e.g., advanced age; prior myocardial infarction; diabetes mellitus; renal dysfunction; chronic pulmonary disease; history of heart failure, stroke, or angina), and their association with all-cause and cardiovascular mortality.: ResultsA total of 205 patients (40%) died during follow-up; 140 due to cardiovascular causes. The incidence of all-cause (18% [27/154] vs. 50% [178/356], P <0.001) and cardiovascular (11% [17/154] vs. 34% [122/356], P <0.001) mortality was significantly lower in statin users than in nonstatin users. After adjusting for clinical risk factors and beta-blocker use, the association between statin use and reduced all-cause (hazard ratio [HR] = 0.4; 95% confidence interval [CI]: 0.3 to 0.6; P <0.001) and cardiovascular (HR = 0.3; 95% CI: 0.2 to 0.6; P <0.001) mortality persisted. Beta-blocker use was also associated with a significant reduction in all-cause (HR = 0.6; 95% CI: 0.5 to 0.9; P = 0.003) and cardiovascular (HR = 0.7; 95% CI: 0.4 to 0.9; P = 0.03) mortality. There was no evidence of an association between statin use and all-cause and cardiovascular mortality according to beta-blocker use or clinical risk factors.: ConclusionLong-term statin use is associated with reduced all-cause and cardiovascular mortality irrespective of clinical risk factors and beta-blocker use. [Copyright &y& Elsevier]