Canagliflozin and Cardiovascular and Renal Outcomes in Type 2 Diabetes Mellitus and Chronic Kidney Disease in Primary and Secondary Cardiovascular Prevention Groups

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

Canagliflozin and renal outcomes in type 2 diabetes and nephropathy

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

Equiangular Spiral Antenna Backed by a Shallow Cavity With Absorbing Strips

When a conducting shallow cavity is placed behind an equiangular spiral to obtain a unidirectional beam, the inherent wideband characteristics of the spiral deteriorate. To restore the wideband characteristics, a ring-shaped absorbing strip (R-ABS) is placed under the spiral arms. Analysis of the equiangular spiral with the R-ABS is performed using the finite-difference time-domain method. It is found that the R-ABS successfully restores the wideband characteristics. Subsequently, the R-ABS is divided into two absorbing strips, each specified by an arc-angle . Analysis reveals that the radiation characteristics obtained using the R-ABS are reproduced when the arc-angle is greater than . Throughout this paper an extremely small cavity depth is selected for the analysis: 0.07 wavelength at the lower operating design frequency of 3 GHz

Unbalanced-Mode Spiral Antenna Backed by an Extremely Shallow Cavity

This paper describes a two-arm Archimedean spiral antenna backed by a conducting cavity, where only one arm is directly excited, with the other arm being parasitically excited; in other words, the spiral arms are excited in an unbalanced mode. A balun circuit required for a conventional two-arm spiral is not used for this unbalanced-mode spiral. The design of the unbalanced-mode spiral is performed over a frequency range of fLd = 3 GHz to fHd = 9 GHz (1:3 bandwidth), where the antenna height is selected to be extremely small (7 mm = 0.07 wavelength at fLd) to realize a low-profile antenna. For reference, a corresponding spiral antenna excited in balanced mode is also analyzed. It is found that the unbalanced-mode spiral shows an acceptably small VSWR over the design frequency range of fLd to fHd. The radiation is circularly polarized around the antenna axis normal to the spiral plane. The gain shows behavior similar to that of the balanced-mode spiral. Results for other antenna heights (5 mm, 10.5 mm, and 14 mm) are also presented and briefly discussed. It can be said that the unbalanced-mode spiral is a circularly polarized wideband antenna with a simple feed system

Low-Profile Equiangular Spiral Antenna Backed by an EBG Reflector

The bi-directional beam from an equiangular spiral antenna (EAS) is changed to a unidirectional beam using an electromagnetic band gap (EBG) reflector. The antenna height, measured from the upper surface of the EBG reflector to the spiral arms, is chosen to be extremely small to realize a low-profile antenna: 0.07 wavelength at the lowest analysis frequency of 3 GHz. The analysis shows that the EAS backed by the EBG reflector does not reproduce the inherent wideband axial ratio characteristic observed when the EAS is isolated in free space. The deterioration in the axial ratio is examined by decomposing the total radiation field into two field components: one component from the equiangular spiral and the other from the EBG reflector. The examination reveals that the amplitudes and phases of these two field components do not satisfy the constructive relationship necessary for circularly polarized radiation. Based on this finding, next, the EBG reflector is modified by gradually removing the patch elements from the center region of the reflector, thereby satisfying the required constructive relationship between the two field components. This equiangular spiral with a modified EBG reflector shows wideband characteristics with respect to the axial ratio, input impedance and gain within the design frequency band (4-9 GHz). Note that, for comparison, the antenna characteristics for an EAS isolated in free space and an EAS backed by a perfect electric conductor are also presented