BACKGROUND:Despite advances in therapy, data on long-term survival and temporal mortality patterns in real-world heart failure (HF) populations, particularly during the critical early period after diagnosis or clinical destabilization, remain scarce. This study aimed to analyze long-term survival and identify factors associated with mortality in a prospective Russian real-world HF cohort that is relatively underrepresented in the international registry literature. METHODS:A prospective 5-years registry study consecutively enrolled 150 patients with HF in February-May 2018. Participants underwent comprehensive assessment of clinical state, traditional cardiovascular risk factors (RF), psychosocial RF, quality of life, perception of illness, cognitive function, and treatment characteristics. Survival was analyzed using the Kaplan-Meier method, and mortality trends were assessed over time. The Cox proportional hazard model, with calculation of hazard ratio (HR) and 95% coincidence interval (CI), was used for univariate and multivariate regression analyses. RESULTS:The cohort (median age 69 years, 57% male) was elderly and multimorbid, with high prevalence of coronary artery disease (95%), hypertension (91%), and chronic kidney disease (56%). Guideline-directed medical therapy was suboptimal: while beta-blocker and diuretic use was high (87% and 79%, respectively), utilization of aldosterone antagonists and ARNI was low (40% and 0.7%, respectively). Only 32.7% received multicomponent HF therapy. The overall 5-years (0.02-5.09) survival rate was 59.9%. Approximately half (48%) of patients died in the first year, the remaining deaths occurred in 2-nd, 3-rd and 4-th years (15%, 17%, and 20%, respectively), and deaths were recorded during 5-th and 6-th years of follow-up. Kaplan-Meier survival analysis showed that left ventricular ejection fraction (LV EF) was strongly associated with 5-years survival. In patients with reduced and moderately reduced LV EF 5-years survival was significantly lower than that in those with preserved LV EF (50.0% and 45.7% versus 70.4%, respectively). No significant difference was found only when comparing the survival curves of patients with moderately reduced and reduced LV EF (chi-square = 0.014; p = 0.906). The leading cause of death was decompensation of HF (65.2%), followed by sudden cardiac death (15.2%). Multivariate analysis showed that age (HR 1.03 per 1-year increase; 95% CI 1.01-1.06; p = 0.017), weight loss >4.5 kg in 5 days in response to therapy (HR 3.49; 95% CI 1.82-6.68; p < 0.001), anemia (HR 2.83; 95% CI 1.47-5.46; p = 0.002), obstructive sleep apnea syndrome (HR 4.43; 95% CI 1.91-10.28; p = 0.001), and HF NYHA functional class IV (HR 4.79; 95% CI 1.50-15.34; p = 0.008) were independent predictors of 5-years all-cause mortality in HF patients. CONCLUSION:This study identifies a high early mortality phenotype in a real-world HF population, strongly associated with significant gaps in guideline-directed therapy. The findings underscore the urgent need for early aggressive optimization of treatment, particularly in the high-risk period following diagnosis or destabilization of HF, to improve long-term survival.

Kontsevaya, Anna V; Bates, Katie; Goryachkin, Evgeny A; Bobrova, Natalia; Syromiatnikova, Liudmila I; Popova, Yulia V; Platonov, Dmitry Yu; Osipova, Irina V; Nedbaikin, Andrei M; Malorodova, Tatyana N; +10 more... Mirolyubova, Olga A; Kryuchkov, Dmitry V; Khaisheva, Larisa A; Galyavich, Albert S; Franz, Maria V; Efanov, Alexey Yu; Duplyakov, Dmitry V; Drapkina, Oxana M; Leon, David; McKee, Martin; (2018) Hospital Stage of Myocardial Infarction Treatment in 13 Regions of Russian Federation by Results of the International Research. RATIONAL PHARMACOTHERAPY IN CARDIOLOGY, 14 (4). pp. 474-487. ISSN 1819-6446 DOI: https://doi.org/10.20996/1819-64462018-14-4-474-487

Background: Canagliflozin reduces the risk of kidney failure in patients with type 2 diabetes mellitus and chronic kidney disease, but effects on specific cardiovascular outcomes are uncertain, as are effects in people without previous cardiovascular disease (primary prevention). Methods: In CREDENCE (Canagliflozin and Renal Events in Diabetes With Established Nephropathy Clinical Evaluation), 4401 participants with type 2 diabetes mellitus and chronic kidney disease were randomly assigned to canagliflozin or placebo on a background of optimized standard of care. Results: Primary prevention participants (n=2181, 49.6%) were younger (61 versus 65 years), were more often female (37% versus 31%), and had shorter duration of diabetes mellitus (15 years versus 16 years) compared with secondary prevention participants (n=2220, 50.4%). Canagliflozin reduced the risk of major cardiovascular events overall (hazard ratio [HR], 0.80 [95% CI, 0.67-0.95]; P=0.01), with consistent reductions in both the primary (HR, 0.68 [95% CI, 0.49-0.94]) and secondary (HR, 0.85 [95% CI, 0.69-1.06]) prevention groups (P for interaction=0.25). Effects were also similar for the components of the composite including cardiovascular death (HR, 0.78 [95% CI, 0.61-1.00]), nonfatal myocardial infarction (HR, 0.81 [95% CI, 0.59-1.10]), and nonfatal stroke (HR, 0.80 [95% CI, 0.56-1.15]). The risk of the primary composite renal outcome and the composite of cardiovascular death or hospitalization for heart failure were also consistently reduced in both the primary and secondary prevention groups (P for interaction >0.5 for each outcome). Conclusions: Canagliflozin significantly reduced major cardiovascular events and kidney failure in patients with type 2 diabetes mellitus and chronic kidney disease, including in participants who did not have previous cardiovascular disease.

BACKGROUND:Type 2 diabetes mellitus is the leading cause of kidney failure worldwide, but few effective long-term treatments are available. In cardiovascular trials of inhibitors of sodium-glucose cotransporter 2 (SGLT2), exploratory results have suggested that such drugs may improve renal outcomes in patients with type 2 diabetes. METHODS:In this double-blind, randomized trial, we assigned patients with type 2 diabetes and albuminuric chronic kidney disease to receive canagliflozin, an oral SGLT2 inhibitor, at a dose of 100 mg daily or placebo. All the patients had an estimated glomerular filtration rate (GFR) of 30 to <90 ml per minute per 1.73 m2 of body-surface area and albuminuria (ratio of albumin [mg] to creatinine [g], >300 to 5000) and were treated with renin-angiotensin system blockade. The primary outcome was a composite of end-stage kidney disease (dialysis, transplantation, or a sustained estimated GFR of <15 ml per minute per 1.73 m2), a doubling of the serum creatinine level, or death from renal or cardiovascular causes. Prespecified secondary outcomes were tested hierarchically. RESULTS:The trial was stopped early after a planned interim analysis on the recommendation of the data and safety monitoring committee. At that time, 4401 patients had undergone randomization, with a median follow-up of 2.62 years. The relative risk of the primary outcome was 30% lower in the canagliflozin group than in the placebo group, with event rates of 43.2 and 61.2 per 1000 patient-years, respectively (hazard ratio, 0.70; 95% confidence interval [CI], 0.59 to 0.82; P = 0.00001). The relative risk of the renal-specific composite of end-stage kidney disease, a doubling of the creatinine level, or death from renal causes was lower by 34% (hazard ratio, 0.66; 95% CI, 0.53 to 0.81; P<0.001), and the relative risk of end-stage kidney disease was lower by 32% (hazard ratio, 0.68; 95% CI, 0.54 to 0.86; P = 0.002). The canagliflozin group also had a lower risk of cardiovascular death, myocardial infarction, or stroke (hazard ratio, 0.80; 95% CI, 0.67 to 0.95; P = 0.01) and hospitalization for heart failure (hazard ratio, 0.61; 95% CI, 0.47 to 0.80; P<0.001). There were no significant differences in rates of amputation or fracture. CONCLUSIONS:In patients with type 2 diabetes and kidney disease, the risk of kidney failure and cardiovascular events was lower in the canagliflozin group than in the placebo group at a median follow-up of 2.62 years. (Funded by Janssen Research and Development; CREDENCE ClinicalTrials.gov number, NCT02065791.).

Background: Death rates from cardiovascular disease in Russia are among the highest in the world. In recent years, the Russian government has invested substantially in the healthcare system, with a particular focus on improving access to advanced technology, especially for acute myocardial infarction (AMI). This protocol describes a study to understand the management of AMI in different Russian regions, investigating the role of patient, clinical, and health system characteristics. Methods: A prospective observational study has recruited a representative sample of AMI patients within 16 hospitals from 13 regions across Russia. Criteria for inclusion are being aged 35-70 years with a confirmed diagnosis of AMI and surviving until the day after admission. Information being collected includes health system contacts and features of clinical management prior to the event and in the 12 months following discharge from hospital. Following initial exploration of the data to generate hypotheses, multivariate analyses will be applied to assess the role of these characteristics in both treatment decisions and any delays in time critical interventions. Between June 2015 and August 2016, 1,122 patients have been recruited at baseline and follow-up to 12 months post-discharge is scheduled to be completed by autumn 2017. The study is unique in examining patient factors, clinical management prior to admission and in hospital in the acute phase and throughout the critical first year of recovery across a diverse range of geographies and facilities. It uses standardized instruments to collect data from patients and health care providers and includes regions that are diverse in terms of geography and development of cardiology capacity. However, given the limited health services research capacity in the Russian Federation, it was not possible to obtain a sample that was truly nationally representative.