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Aims
We previously reported that in the EMPA-REG OUTCOME(R) trial, empagliflozin added to standard of care reduced the risk of 3-point major adverse cardiovascular events, cardiovascular and all-cause death, and hospitalization for heart failure in patients with type 2 diabetes and high cardiovascular risk. We have now further investigated heart failure outcomes in all patients and in subgroups, including patients with or without baseline heart failure.
Methods and results
Patients were randomized to receive empagliflozin 10 mg, empagliflozin 25 mg, or placebo. Seven thousand and twenty patients were treated; 706 (10.1%) had heart failure at baseline. Heart failure hospitalization or cardiovascular death occurred in a significantly lower percentage of patients treated with empagliflozin 265/4687 patients (5.7%)] than with placebo 198/2333 patients (8.5%)] hazard ratio, HR: 0.66 (95% confidence interval: 0.55-0.79); P < 0.001], corresponding to a number needed to treat to prevent one heart failure hospitalization or cardiovascular death of 35 over 3 years. Consistent effects of empagliflozin were observed across subgroups defined by baseline characteristics, including patients with vs. without heart failure, and across categories of medications to treat diabetes and/or heart failure. Empagliflozin improved other heart failure outcomes, including hospitalization for or death from heart failure 2.8 vs. 4.5%; HR: 0.61 (0.47-0.79); P < 0.001] and was associated with a reduction in all-cause hospitalization 36.8 vs. 39.6%; HR: 0.89 (0.82-0.96); P = 0.003]. Serious adverse events and adverse events leading to discontinuation were reported by a higher proportion of patients with vs. without heart failure at baseline in both treatment groups, but were no more common with empagliflozin than with placebo.
Conclusion
In patients with type 2 diabetes and high cardiovascular risk, empagliflozin reduced heart failure hospitalization and cardiovascular death, with a consistent benefit in patients with and without baseline heart failure.
Hintergrund:
Kardiovaskuläre Erkrankungen sind die führende Todesursache in Ländern der westlichen Welt. Die Koronare Herzkrankheit (KHK) macht über die Hälfte dieser Todesfälle aus. Obwohl die Risikofaktoren der KHK in den vergangenen Jahrzehnten ausreichend erforscht wurde, ist in in den letzten Jahren ein weiterer potentieller Risikofaktor von Interesse geworden: die Depression. Es konnte gezeigt werden, dass eine gehäufte Komorbidität zwischen KHK und depressiver Symptomatik besteht und dass das gleichzeitige Vorliegen von KHK und Depression mit schlechterer Prognose und erhöhter Mortalität verknüpft ist. Die vorliegende retrospektive Arbeit beschäftigte sich mit dem postoperativen Outcome von Patienten mit depressiver Erkrankung, die sich einem herzchirurgischen Eingriff unterzogen hatten, im Vergleich zu einem Kollektiv psychisch gesunder Patienten. Studienhypothese war, dass Depression das Risiko von postoperativer Mortalität, peri- und postoperativer Komplikationen und stationären Wiederaufnahmen erhöht.
Material und Methoden:
Insgesamt wurden 294 Patienten, die im Zeitraum von Januar 2008 bis einschließlich März 2013 in der Klinik für Thorax-, Herz- und thorakale Gefäßchirurgie des Universitätsklinikum Würzburg am Herzen operiert wurden, eingeschlossen. Es wurden prä-, peri- und postoperative Daten aus den digitalen Patientenakten, Anästhesie- und Operationsprotokollen erhoben und in Erhebungsbögen festgehalten. An statistischen Test wurden der T-Test und der Chi-Quadrat-Test benutzt. Als primären Endpunkt definierten wir die postoperative 30-Tages-Mortalität.
Resultate:
In der Gruppe der depressiven Patienten verstarben 8 Patienten und 11 Patienten wurden in der Herz-Thorax-Chirurgie wiederaufgenommen. Wir konnten keinen Unterschied zu den nicht depressiven Patienten feststellen (Mortalität p=0,213, Rehospitalisation p=0,578). Es konnte ein hoch-signifkanter Zusammenhang zwischen Depression und dem Risiko für postoperatives Delir gezeigt werden (p=0,002).
Konklusion: Wir konnten keinen Unterschied zwischen der 30-Tages-Letalität und der Rehospitaliseriungsrate nach Herzoperation zwischen präoperativ depressiven und nicht depressiven Patienten feststellen. Wir konnten zeigen, dass Patienten mit präoperativer Depression ein erhöhtes Risiko haben postoperatives Delir zu erleiden. Wir zogen daraus die Schlussfolgerung, dass die Diagnosestellung und Therapie von Depression und depressiver Symptomatik in Patienten mit koronarer Herzkrankheit von klinischer Relevanz ist um eine optimale chirurgische Behandlung zu gewährleisten.
Background:
To assess heart failure therapies in diabetic patients with preserved as compared to impaired systolic ventricular function.
Methods:
3304 patients with heart failure from 9 different studies were included (mean age 63 +/- 14 years); out of these, 711 subjects had preserved left ventricular ejection fraction (>= 50%) and 994 patients in the whole cohort suffered from diabetes.
Results:
The majority (>90%) of heart failure patients with reduced ejection fraction (SHF) and diabetes were treated with an ACE inhibitor (ACEi) or angiotensin receptor blocker (ARB) or with beta-blockers. By contrast, patients with diabetes and preserved ejection fraction (HFNEF) were less likely to receive these substance classes (p < 0.001) and had a worse blood pressure control (p < 0.001). In comparison to patients without diabetes, the probability to receive these therapies was increased in diabetic HFNEF patients (p < 0.001), but not in diabetic SHF patients. Aldosterone receptor blockers were given more often to diabetic patients with reduced ejection fraction (p < 0.001), and the presence and severity of diabetes decreased the probability to receive this substance class, irrespective of renal function.
Conclusions:
Diabetic patients with HFNEF received less heart failure medication and showed a poorer control of blood pressure as compared to diabetic patients with SHF. SHF patients with diabetes were less likely to receive aldosterone receptor blocker therapy, irrespective of renal function.
Family studies suggest a genetic component to the etiology of chronic kidney disease (CKD) and end stage renal disease (ESRD). Previously, we identified 16 loci for eGFR in genome-wide association studies, but the associations of these single nucleotide polymorphisms (SNPs) for incident CKD or ESRD are unknown. We thus investigated the association of these loci with incident CKD in 26,308 individuals of European ancestry free of CKD at baseline drawn from eight population-based cohorts followed for a median of 7.2 years (including 2,122 incident CKD cases defined as eGFR < 60ml/min/1.73m(2) at follow-up) and with ESRD in four case-control studies in subjects of European ancestry (3,775 cases, 4,577 controls). SNPs at 11 of the 16 loci (UMOD, PRKAG2, ANXA9, DAB2, SHROOM3, DACH1, STC1, SLC34A1, ALMS1/NAT8, UBE2Q2, and GCKR) were associated with incident CKD; p-values ranged from p = 4.1e-9 in UMOD to p = 0.03 in GCKR. After adjusting for baseline eGFR, six of these loci remained significantly associated with incident CKD (UMOD, PRKAG2, ANXA9, DAB2, DACH1, and STC1). SNPs in UMOD (OR = 0.92, p = 0.04) and GCKR (OR = 0.93, p = 0.03) were nominally associated with ESRD. In summary, the majority of eGFR-related loci are either associated or show a strong trend towards association with incident CKD, but have modest associations with ESRD in individuals of European descent. Additional work is required to characterize the association of genetic determinants of CKD and ESRD at different stages of disease progression.