Creator: Alexandria Bartley, PharmD. Candidate, Florida Agricultural & Mechanical College, Faculty of Pharmacy and Pharmaceutical Sciences
Canagliflozin lowered threat of cardiovascular dying and hospitalizations as a result of coronary heart failure by 31%.
It’s recognized that sufferers with each sort 2 diabetes and continual kidney illness are at the next threat of creating coronary heart failure. This examine is a secondary analysis of the Canagliflozin and Renal Occasions in Diabetes with Established Nephropathy Medical Analysis (CREDENCE) trial. Within the CREDENCE trial, canagliflozin, a sodium-glucose co-transporter 2 (SGLT-2) inhibitor, was confirmed to be superior to placebo in glucose management and the variety of opposed occasions in sufferers with sort 2 diabetes and recognized heart problems. A earlier related trial was the Empagliflozin Cardiovascular End result Occasion Trial in Kind 2 Diabetes Mellitus Sufferers (EMPA-REG OUTCOME). Nevertheless, the EMPA-REG OUTCOME trial evaluated sufferers with sort 2 diabetes who had been high-risk sufferers for heart problems, not like the CREDENCE trial, which evaluated sufferers with sort 2 diabetes and established heart problems.
The aim of this trial was to find out if the results of canagliflozin on the composite of cardiovascular dying and hospitalizations as a result of coronary heart failure differ within the subgroups primarily based on sufferers’ traits. In line with the researchers, this trial was a randomized, double-blinded, placebo-controlled, multicenter worldwide trial. On this trial, randomizations had been performed in a 1:1 ratio. The canagliflozin arm had 2,202 sufferers, and the placebo arm had 2,199 sufferers. Sufferers had follow-ups at weeks 3,13, and 26, and after that, they adopted up each 13 weeks. The affected person inhabitants needed to be older than 30 years previous, have sort 2 diabetes, and glycosylated hemoglobin greater than 6.5% however lower than 12%. Additionally, sufferers needed to have continual kidney illness with an estimated glomerular filtration charge of 30 to lower than 90, albuminuria, and a steady dose of both an angiotensin-converting enzyme inhibitor (ACEi) or angiotensin-receptor blocker (ARB) for longer than 4 weeks earlier than randomization. The sufferers couldn’t have been handled with immunosuppression remedy for his or her kidney illness, have a historical past of dialysis or a kidney transplant, and couldn’t be a affected person with sort 1 diabetes. The first consequence was an end-stage renal illness (ESRD), doubling serum creatinine, renal or cardiovascular (CV) dying. The secondary outcomes had been all-cause mortality, cardiovascular dying, myocardial infarction, stroke, hospitalization for coronary heart failure/unstable angina, amputation, and glycosylated hemoglobin discount. The statistical design used was Cox regression fashions for the hazard ratios and 95% confidence intervals and Kaplan Meier curves for subgroups of curiosity.
The outcomes of canagliflozin on this examine, primarily based on hazard ratio and confidence intervals, had been considerably constant in sufferers with totally different ages, genders, and histories of heart problems. General, canagliflozin lowered the danger of cardiovascular dying or hospitalization of coronary heart failure with a hazard ratio of 0.69 and a confidence interval of 0.57-0.83. The chance of cardiovascular dying and hospitalizations as a result of coronary heart failure was lowered by 31%. The end result of canagliflozin on hospitalization as a result of coronary heart failure alone was related among the many totally different subgroups with a hazard ratio of 0.61 and a confidence interval of 0.47-0.80. The results of canagliflozin primarily based on the historical past of coronary heart failure estimated glomerular filtration charge, albuminuria, and loop diuretic use weren’t important individually primarily based on p interplay worth. The chance of cardiovascular dying and hospitalization as a result of coronary heart failure was lowered by canagliflozin irrespective primarily based on a loop diuretic. Additionally, no matter age, intercourse, and estimated glomerular filtration charge, canagliflozin advantages didn’t differ considerably.
The CREDENCE trial ended early because of the overwhelming profit. Baseline traits had been properly balanced between the 2 remedy arms. Within the subgroups of the composite consequence, the P interplay values weren’t important. Important ends in the subgroups had been difficult to perform because of the smaller pattern sizes.
- Canagliflozin was in a position to steadily cut back the danger of cardiovascular dying and hospitalizations as a result of coronary heart failure in sufferers with each sort 2 diabetes and continual kidney illness.
- The sufferers at the next threat of cardiovascular dying and hospitalizations as a result of coronary heart failure had been sufferers with a historical past of heart problems or coronary heart failure.
- Research analyzing key affected person traits assist prescribers to make better-informed choices for an individualized care plan.
Zeeuw D, Arnott C, Li J-W, et al. The effects of canagliflozin on heart failure and cardiovascular death by baseline participant characteristics: analysis of the CREDENCE trial. EASD Digital Congress. Printed 2020. Accessed October 12, 2020.
Alexandria Bartley, PharmD. Candidate, Florida Agricultural & Mechanical College, Faculty of Pharmacy and Pharmaceutical Sciences